ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد ایتم قابل مشاهده باقیمانده : 4 مورد

Trimethoprim-sulfamethoxazole (co-trimoxazole): Drug information

Trimethoprim-sulfamethoxazole (co-trimoxazole): Drug information
(For additional information see "Trimethoprim-sulfamethoxazole (co-trimoxazole): Patient drug information" and see "Trimethoprim-sulfamethoxazole (co-trimoxazole): Pediatric drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
Brand Names: US
  • Bactrim;
  • Bactrim DS;
  • Sulfatrim Pediatric
Brand Names: Canada
  • APO-Sulfatrim;
  • Septra;
  • Sulfatrim;
  • Sulfatrim DS;
  • Sulfatrim Pediatric;
  • TEVA-Trimel;
  • TEVA-Trimel DS
Pharmacologic Category
  • Antibiotic, Miscellaneous;
  • Antibiotic, Sulfonamide Derivative
Dosing: Adult

Note: Weight-based dosing recommendations are based on the trimethoprim (TMP) component. Each double-strength tablet contains TMP 160 mg and sulfamethoxazole (SMX) 800 mg. Each single-strength tablet contains TMP 80 mg and SMX 400 mg. The undiluted IV solution contains TMP 16 mg per mL and SMX 80 mg per mL. IV solutions must be diluted in D5W prior to use. Diluted IV solutions have limited stability and can precipitate unpredictably; refer to a detailed IV compatibility reference.

General dosing guidelines:

Oral: 1 to 2 double-strength tablets every 12 to 24 hours. Note: Serum creatinine and potassium concentrations should be monitored in outpatients receiving high-dose therapy (>5 mg/kg/day [TMP component]) (Gentry 2013).

IV: 8 to 20 mg/kg/day (TMP component) divided every 6 to 12 hours.

Bite wound infection, prophylaxis or treatment (animal or human bite) (alternative agent) (off-label use): Oral: 1 double-strength tablet twice daily; in combination with an appropriate agent for anaerobic coverage. Duration of therapy for prophylaxis is 3 to 5 days (IDSA [Stevens 2014]); duration of therapy for established infection is typically 5 to 14 days (Baddour 2021a; Baddour 2021b).

Chronic obstructive pulmonary disease, acute exacerbation (alternative agent): Note: Avoid use in patients with risk factors for Pseudomonas infection or poor outcomes (eg, ≥65 years of age with major comorbidities, FEV1 <50% predicted, frequent exacerbations) (Sethi 2020).

Oral: 1 double-strength tablet every 12 hours for 3 to 7 days (GOLD 2021; Sethi 2020; manufacturer's labeling).

Diabetic foot infection, mild (methicillin-resistant Staphylococcus aureus) (off-label use): Oral: 2 double-strength tablets twice daily, usually for 1 to 2 weeks (IDSA [Lipsky 2012]; Lipsky 2004). Note: When used as empiric therapy, must be used in combination with other appropriate agents. Some experts also use this agent for selected moderate infections (Lipsky 2012).

Diarrhea, infectious:

Cyclosporiasis (off-label use):

Immunocompromised (AIDS-associated): Limited data available: Oral: 1 double-strength tablet twice daily for 14 days, followed by secondary prophylaxis with 1 double-strength tablet 3 times weekly (Pape 1994; Weller 2021).

Immunocompetent: Oral: 1 double-strength tablet twice daily for 7 to 10 days (CDC 2013a; Hoge 1995).

Cystoisosporiasis (isosporiasis) (off-label use):

Immunocompromised (AIDS-associated): Oral, IV: 160 mg (TMP component) twice daily for 7 to 10 days; if symptoms worsen or persist, may increase dose to 160 mg (TMP component) 4 times daily and/or prolong duration to 21 to 28 days. In patients with CD4 <200 cells/mm3, follow treatment with secondary prophylaxis of one double-strength tablet orally 3 times weekly (HHS [OI adult 2020]).

Immunocompetent (usually self-limited; treatment not always indicated): Oral: 1 double-strength tablet twice daily for 7 to 10 days (CDC 2013b).

Shigellosis (widespread resistance [alternative agent if susceptibility is documented]): Oral: 1 double-strength tablet twice daily for 5 to 7 days (Agha 2021).

Intra-abdominal infection (off-label use) (alternative agent):

Diverticulitis, acute (for uncomplicated infection that meets criteria for outpatient therapy or as step-down therapy after clinical improvement on initial parenteral therapy):

Note: Some experts suggest deferring antibiotics in otherwise healthy immunocompetent patients with mild disease; however, data on this approach in outpatients are limited (AGA [Stollman 2015]; Desai 2019; Shah 2017; SIS [Mazuski 2017]; van Dijk 2020).

Oral: 1 double-strength tablet every 12 hours in combination with metronidazole for 7 to 10 days (Pemberton 2021).

Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess (alternative agent for methicillin-resistant S. aureus) (off-label use): IV: 5 mg/kg/dose (TMP component) every 8 to 12 hours (IDSA [Liu 2011]; Sexton 2019a; Sexton 2019b; Southwick 2019). Duration generally ranges from 4 to 8 weeks for brain abscess and spinal epidural abscess and 6 to 8 weeks for intracranial epidural abscess (Sexton 2019a; Sexton 2019b; Southwick 2019).

Melioidosis ( Burkholderia pseudomallei ) infection (off-label use):

Initial intensive therapy (as a potential add-on to primary therapy [ceftazidime or a carbapenem] in focal disease of the CNS, prostate, bone, joint, skin, or soft tissue): Oral, IV:

40 to 60 kg: 240 mg (TMP component) twice daily (Currie 2021; Lipsitz 2012).

>60 kg: 320 mg (TMP component) twice daily (Currie 2021; Lipsitz 2012).

Duration: ≥14 days; a longer duration may be necessary depending on disease severity and site of infection (Currie 2021; Lipsitz 2012).

Eradication therapy (begin after completion of initial intensive therapy): Oral:

40 to 60 kg: 240 mg (TMP component) twice daily (Lipsitz 2012).

>60 kg: 320 mg (TMP component) twice daily (Lipsitz 2012).

Duration: ≥3 months; extend to 6 months for bone or CNS involvement. Longer duration may be necessary following vascular surgery with graft for mycotic aneurysm (Currie 2021; Lipsitz 2012).

Meningitis, bacterial (alternative agent for methicillin-resistant S. aureus, L. monocytogenes, E. coli, and other Enterobacteriaceae) (off-label use): IV: 5 mg/kg/dose (TMP component) every 6 to 12 hours (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). Note: Some experts prefer 5 mg/kg/dose (TMP component) every 8 hours (Hasbun 2021).

Nocardiosis (off-label use): Limited data available to guide treatment. Due to concerns for resistance, susceptibility testing should be performed on isolates (CDC 2016).

Cutaneous infections (superficial; no other organ involvement): Oral: 5 to 10 mg/kg/day (TMP component) in 2 divided doses (Spelman 2021b).

Pulmonary infection (mild to moderate):

Immunocompetent patients: Oral: 5 to 10 mg/kg/day (TMP component) in 2 divided doses (Spelman 2021b).

Immunocompromised patients: Oral: 15 mg/kg/day (TMP component) in 3 to 4 divided doses (Spelman 2021b).

Pulmonary infection (severe), CNS, disseminated, or multi-site infection: IV: 15 mg/kg/day (TMP component) in 3 to 4 divided doses (Spelman 2021b). Note: When used as empiric therapy, must be used in combination with 1 to 2 additional agents. Consult an infectious diseases specialist for specific treatment recommendations.

Duration: Prolonged treatment is required (range: 3 months to ≥1 year [combined parenteral/oral therapy]) (Spelman 2021b).

Osteomyelitis due to methicillin-resistant S. aureus (alternative agent) (off-label use): Oral, IV: 4 mg/kg/dose (TMP component) every 12 hours with rifampin (IDSA [Liu 2011]).

Peritonitis, spontaneous bacterial (prevention) (off-label use):

High-risk patients (eg, hospitalized patients with Child-Pugh class B or C cirrhosis and active GI bleeding): Oral: 1 double-strength tablet twice daily (Runyon 2021).

Long-term secondary SBP prophylaxis: Oral: 1 double-strength tablet once daily (Runyon 2021).

Pneumocystis pneumonia:

Prophylaxis, primary and secondary:

Patients with HIV: Oral: 1 double-strength tablet once daily or 1 single-strength tablet once daily (preferred regimens) or 1 double-strength tablet 3 times weekly (alternative regimen). Note: In patients also requiring prophylaxis for toxoplasmosis, 1 double-strength tablet once daily should be used (HHS [OI adult 2020]).

Duration in patients with HIV receiving ART: Continue until undetectable viral load and CD4 count >200 cells/mm3 for >3 months (HHS [OI adult 2020]); some experts discontinue primary prophylaxis in patients with CD4 counts between 100 and 200 cells/mm3 who are receiving ART and have had an undetectable viral load for ≥3 to 6 months (COHERE 2010; HHS [OI adult 2020]).

Immunocompromised host, HIV-uninfected (eg, transplant recipients, cancer-related, hematopoietic stem cell transplant [HSCT]): Oral: 1 double-strength tablet once daily or 1 single-strength tablet once daily (preferred regimens); alternatively, 1 double-strength tablet 3 times weekly (Fishman 2001; Montoya 2001; Tomblyn 2009).

Duration after solid organ transplant (except lung): ≥6 to 12 months and during periods of increased immunosuppression (eg, treatment for acute rejection) (Fishman 2020; Martin 2013).

Duration after lung transplant: Lifelong therapy should be considered (Martin 2013; Palmer 2019).

Duration for cancer-related (including HSCT) in patients at high risk for PCP infection: Based on expert opinion, continue until risk factor(s) for PCP infection are no longer present (Neumann 2013, Thomas 2017). Consult other specialized databases for more detailed information.

Treatment (HHS [OI adult 2020]; ATS [Limper 2011]; Thomas 2017): Note: Secondary prophylaxis should be initiated immediately upon completion of therapy.

Moderate to severe infection: IV: 15 to 20 mg/kg/day (TMP component) in 3 or 4 divided doses for 21 days; may switch to oral therapy after clinical improvement. Note: Patients with moderate or severe infection (PaO2 <70 mm Hg at room air or alveolar-arterial oxygen gradient ≥35 mm Hg) should receive adjunctive glucocorticoids.

Mild to moderate infection: Oral: 15 to 20 mg/kg/day (TMP component) in 3 divided doses for 21 days or two double-strength tablets 3 times daily.

Prostatitis (off-label use):

Acute bacterial prostatitis: Oral: 1 double-strength tablet twice daily for 4 to 6 weeks (Lipsky 2010; Meyrier 2020a).

Chronic bacterial prostatitis (alternative agent): Oral: 1 double-strength tablet twice daily for ≥6 weeks (Lipsky 2010; Meares 1975; Meyrier 2021).

Prosthetic joint infection (off-label use): Oral continuation therapy for methicillin-resistant S. aureus and Enterobacteriaceae (following pathogen-specific IV therapy in patients undergoing 1-stage exchange or debridement with retention of prosthesis):

Oral: 1 double-strength tablet twice daily. For S. aureus infections, combine with rifampin (Berbari 2019; IDSA [Osmon 2013]). Duration is a minimum of 3 months, depending on patient-specific factors (Berbari 2019).

Q fever (C. burnetii), acute symptomatic (off-label use): Note: Treatment is most effective if given within the first 3 days of symptoms (CDC [Anderson 2013]).

Nonpregnant patients (alternative agent): Note: Reserve for patients unable to tolerate first-line agents and not at risk for complications (eg, patients without endocarditis or underlying valvular disease, negative antiphospholipid antibodies) (CDC [Anderson 2013]; Raoult 2020).

Oral: 1 double-strength tablet twice daily for 14 days (CDC [Anderson 2013]; Raoult 2020).

Pregnant patients: Oral: 1 double-strength tablet twice daily until 32 weeks' gestation; administer with folic acid supplementation. Note: Discontinue therapy for the final 8 weeks of pregnancy due to hyperbilirubinemia risk (CDC [Anderson 2013]; Raoult 2020).

Septic arthritis (without prosthetic material) due to methicillin-resistant S. aureus (alternative agent following initial IV therapy with an appropriate antibiotic) (off-label use): Oral: 2 double-strength tablets twice daily or 4 mg/kg/dose (TMP component) twice daily (maximum: 320 mg [TMP component]/dose) for completion of 3- to 4-week total treatment course (IV and oral) (Goldenberg 2019; IDSA [Liu 2011]).

Sexually transmitted infections:

Epididymitis in patients ≥35 years of age and who are at low risk for sexually transmitted infections (ie, likely to be caused by enteric organisms) (alternative agent) (off-label use): Oral: 1 double-strength tablet twice daily for 10 days (Eyre 2021).

Granuloma inguinale (donovanosis) (alternative agent) (off-label use): Oral: 1 double-strength tablet every 12 hours for at least 3 weeks and until lesions have healed (CDC [Workowski 2015]). Note: If symptoms do not improve within the first few days of therapy, another agent (eg, aminoglycoside) can be added (CDC [Workowski 2015]).

Skin and soft tissue infection (off-label use):

Cellulitis, nonpurulent with risk for methicillin-resistant S. aureus: Oral: 1 to 2 double-strength tablets twice daily (IDSA [Liu 2011]; IDSA [Stevens 2014]; Miller 2015). Some experts suggest adding an additional agent (eg, amoxicillin, cephalexin) for coverage of beta-hemolytic streptococci (IDSA [Liu 2011]; IDSA [Stevens 2014]).

Cellulitis, purulent or abscess: Oral: 1 to 2 double-strength tablets twice daily (IDSA [Liu 2011]; IDSA [Stevens 2014]). Note: Systemic antibiotics only indicated for abscess in certain instances (eg, immunocompromised patients, signs of systemic infection, large or multiple abscesses, indwelling device, high risk for adverse outcome with endocarditis). If at risk for gram-negative bacilli, use in combination with an appropriate agent (IDSA [Stevens 2014]; Spelman 2021a).

Duration: Treat for ≥5 days but may extend up to 14 days depending on severity and clinical response (IDSA [Stevens 2014]; Spelman 2021a).

Cellulitis, long-term suppression of recurrent infection: Note: For patients with ≥3 episodes/year of known or presumed staphylococcal cellulitis when predisposing factors cannot be controlled (Spelman 2021a).

Oral: 1 double-strength tablet twice daily after completion of treatment (Spelman 2021a).

Impetigo or ecthyma if methicillin-resistant S. aureus is suspected or confirmed: Note: For impetigo, reserve systemic therapy for patients with numerous lesions or in outbreak settings to decrease transmission (IDSA [Stevens 2014]).

Oral: 1 to 2 double-strength tablets twice daily for 7 days (Baddour 2021c; IDSA [Stevens 2014]).

Stenotrophomonas maltophilia infections (hospital-acquired or ventilator-associated pneumonia, bacteremia, or other sites) (off-label use): IV: 15 mg/kg/day (TMP component) in 3 or 4 divided doses. Duration depends on site of infection; 14 days for bacteremia and 7 days for pneumonia in an immunocompetent host with evidence of clinical improvement (Lewis 2021; Looney 2009).

Toxoplasma gondii encephalitis (AIDS associated) (off-label use):

Primary prophylaxis: Oral: 1 double-strength tablet once daily (preferred) or 1 double-strength tablet 3 times weekly or 1 single-strength tablet once daily; primary prophylaxis is indicated for T. gondii IgG-positive patients with CD4 count <100 cells/mm3. Continue primary prophylaxis following initiation of ART until CD4 count >200 cells/mm3 for >3 months; some experts discontinue primary prophylaxis in patients with a CD4 count between 100 to 200 cells/mm3 who are receiving ART and have had an undetectable viral load for ≥3 to 6 months (HHS [OI adult 2020]).

Treatment (alternative agent): Oral, IV: 10 mg/kg/day (TMP component) in 2 divided doses for at least 6 weeks; longer duration may be needed if clinical or radiologic disease is extensive or response is incomplete at 6 weeks (HHS [OI adult 2020]).

Secondary prophylaxis (chronic maintenance therapy) (alternative agent): Oral: 1 double-strength tablet twice daily or, alternatively, 1 double-strength tablet once daily (lower dose may be associated with increased relapse risk). Continue following initiation of ART until CD4 count >200 cells/mm3 for >6 months (HHS [OI adult 2020]).

Urinary tract infection:

Cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection), treatment: Note: Avoid use if resistance prevalence is >20% or if patient has risk factors for multidrug-resistant gram-negative infection (Hooton 2021a; Hooton 2021b):

Oral: 1 double-strength tablet twice daily; treat females for 3 days and males for 7 days (Hooton 2021a; Hooton 2021b; IDSA/ESCMID [Gupta 2011]).

Cystitis, prophylaxis for recurrent infection: Note: May be considered in nonpregnant women with bothersome, frequently recurrent cystitis despite nonantimicrobial preventive measures. The optimal duration has not been established; duration ranges from 3 to 12 months, with periodic reassessment (AUA/CUA/SUFU [Anger 2019]; Hooton 2021c).

Continuous prophylaxis: Oral: One-half of a single-strength tablet once daily or 3 times weekly (AUA/CUA/SUFU [Anger 2019]; Stamm 1980).

Postcoital prophylaxis (females with cystitis temporally related to sexual intercourse): Oral: One-half to 1 single-strength tablet as a single dose immediately before or after sexual intercourse (AUA/CUA/SUFU [Anger 2019]; Stapleton 1990).

Urinary tract infection, complicated (including pyelonephritis) (outpatient targeted therapy [if the isolate is known to be susceptible]):

Oral: 1 double-strength tablet twice daily for 14 days (IDSA/ESCMID [Gupta 2011]); for women who have a rapid response to treatment, some experts treat for 7 to 10 days (Hooton 2021d). Note: Oral therapy should generally follow appropriate parenteral therapy (Hooton 2021d; IDSA/ESCMID [Gupta 2011]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: Weight-based dosing recommendations are based on the trimethoprim (TMP) component. Each double-strength (DS) tablet contains TMP 160 mg and sulfamethoxazole (SMX) 800 mg. Each single-strength (SS) tablet contains TMP 80 mg and SMX 400 mg.

Sulfamethoxazole/Trimethoprim Dose Adjustments for Kidney Impairment - Oral

Dose Adjustments for Kidney Impairmenta: Oralb

CrCl (mL/minute)

If usual recommended dose is 1 DS tablet every 24 hours or 3 times per week

If usual recommended dose is 1 DS tablet every 12 hours

If usual recommended dose is 2 DS tablets every 12 hours

If usual recommended dose is 2 DS tablets every 8 hours

aExpert opinion derived from Golightly 2013, HHS (OI adult 2020), Nahata 1995, Nemecek 2019

bAbbreviations: DS: Double strength; SS: Single strength.

cFor severe infections, some experts recommend giving unadjusted doses for the first 1 to 2 days (Nahata 1995).

dRecommended by HHS (OI adult 2020) for treatment of Pneumocystis pneumonia in dialysis patients (administer once daily [on dialysis days administer post HD]).

>30

No dosage adjustment necessary.

No dosage adjustment necessary.

No dosage adjustment necessary.

No dosage adjustment necessary.

15 to 30c

Reduce dose to ~50% of usual dose.

Example: 1 SS tablet every 24 hours or 3 times per week

Reduce dose to ~50% of usual dose.

Example: 1 DS tablet once, followed by 1 SS tablet every 12 hours

Reduce dose to ~50% of usual dose.

Example: 1 DS tablet every 12 hours

Reduce dose to ~50% of usual dose.

Example: 2 DS tablets every 12 hours

<15

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 1 SS tablet every 24 hours or 3 times per week

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 1 DS tablet once, followed by 1 SS tablet every 12 or 24 hours

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 1 DS tablet every 12 hours or 1 DS tablet once, followed by 1 SS tablet every 12 hours

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 1 to 2 DS tablets every 12 hours or 2 DS tablets every 24 hoursd

Sulfamethoxazole/Trimethoprim Dose Adjustments for Kidney Impairment - IV

Dose Adjustments for Kidney Impairmenta: IV

CrCl (mL/minute)

If usual recommended daily dose is 10 mg/kg/day (TMP component)

If usual recommended daily dose is 8 to 12 mg/kg/day (TMP component)

If usual recommended daily dose is 15 to 20 mg/kg/day (TMP component)

aExpert opinion derived from Golightly 2013, HHS (OI adult 2020), Nahata 1995, Nemecek 2019.

bIn severe infections, some experts recommend giving unadjusted doses for the first 1 to 2 days (Nahata 1995).

>30

No dosage adjustment necessary.

No dosage adjustment necessary.

No dosage adjustment necessary.

15 to 30b

Reduce dose to ~50% of usual dose.

Example: 5 mg/kg once daily

Reduce dose to ~50% of usual dose.

Example: 4 to 6 mg/kg/day in 2 divided doses

Reduce dose to ~50% of usual dose.

Example: 7.5 to 10 mg/kg/day in 2 to 4 divided doses

<15

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 2.5 to 5 mg/kg once daily. Note: When treating toxoplasmosis encephalitis, use 5 mg/kg once daily or use alternative agent (HHS [OI Adult 2020]

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 2 to 3 mg/kg once daily or 4 to 6 mg/kg every 24 to 48 hours

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 4 to 5 mg/kg once daily or 7.5 to 10 mg/kg every 24 to 48 hours

Hemodialysis, intermittent (thrice weekly): Dialyzable (44% of trimethoprim and 57% sulfamethoxazole and its metabolites over 4 hours utilizing a low-flux filter [Nissenson 1987]):

Oral, IV: Follow dose recommendations for patients with CrCl <15 mL/minute not on dialysis; doses due on dialysis days should be administered after hemodialysis (Golightly 2013; HHS [OI adult 2020]).

Note: If treating Pneumocystis pneumonia, consider utilizing therapeutic drug monitoring to optimize therapy (target TMP concentration: 5 to 8 mcg/mL) (HHS [OI adult 2020]).

Peritoneal dialysis: Oral, IV: Not efficiently dialyzed (Singlas 1982). Follow dose recommendations for a patient with a CrCl <15 mL/minute. (Singlas 1982; Walker 1989).

Note: If treating Pneumocystis pneumonia, consider utilizing therapeutic drug monitoring to optimize therapy (target TMP concentration: 5 to 8 mcg/mL) (HHS [OI adult 2020]).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations assume high-flux dialyzers and flow rates of ~1,500 to 3,000 mL/hour, unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions due to drug accumulation is important.

CVVH/CVVHD/CVVHDF: Oral, IV: Sulfamethoxazole and trimethoprim are substantially removed by CRRT (Curkovic 2010; Kesner 2014). No dosage adjustment necessary (Brown 2014, Curkovic 2010).

PIRRT (eg, sustained low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions due to drug accumulation is important.

Oral, IV (blood and dialysate flow rates 170 mL/minute; 6- to 8-hour session): No dosage adjustment necessary (Brown 2014; Clajus 2013).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in manufacturer’s labeling. Use with caution; use is contraindicated in cases of marked hepatic damage.

Dosing: Pediatric

(For additional information see "Trimethoprim-sulfamethoxazole (co-trimoxazole): Pediatric drug information")

Note: Dosage recommendations are based on the trimethoprim (TMP) component:

General dosing, susceptible infection: Infants ≥2 months, Children, and Adolescents: Oral, IV: 6 to 12 mg TMP/kg/day in divided doses every 12 hours; maximum single dose: 160 mg TMP/dose (Red Book [AAP 2015])

Catheter (peritoneal dialysis); exit-site or tunnel infection: Limited data available: Infants, Children, and Adolescents: Oral: 5 to 10 mg TMP/kg/dose once daily; maximum dose: 80 mg TMP/dose (ISPD [Warady 2012])

Cyclosporiasis: Limited data available: Infants ≥2 months, Children, and Adolescents: Oral: 8 to 10 mg TMP/kg/day in divided doses twice daily for 7 to 10 days; maximum single dose: 160 mg TMP (Red Book [AAP 2015])

Meningitis: Infants ≥2 months, Children, and Adolescents: IV: 10 to 20 mg TMP/kg/day divided every 6 to 12 hours for 7 to 21 days; duration dependent on the pathogen and clinical course (Tunkel 2004)

MRSA, community-acquired mild to moderate skin/soft tissue infection: Infants ≥2 months, Children, and Adolescents: Oral: 8 to 12 mg TMP/kg/day in divided doses every 12 hours (Liu 2011); alternatively, use of 20 mg TMP/kg/day in divided doses every 6 hours has been reported (Long 2012). If using empirically, consider addition of group A streptococcal coverage.

Otitis media, acute: Infants ≥2 months, Children, and Adolescents: Oral: 6 to 10 mg TMP/kg/day in divided doses every 12 hours for 10 days. Note: Due to resistance of S. pneumoniae, should not be used in patients that fail first-line amoxicillin therapy (AAP [Lieberthal 2013]).

Pneumocystis jirovecii pneumonia (PCP) (HIV-exposed/-positive):

Prophylaxis:

Infants (at least 4 weeks of age) and Children: Oral: 5 to 10 mg TMP/kg/day or 150 mg TMP/m2/day; dose may be given as a single daily dose or in divided doses every 12 hours given 2 to 3 days per week on consecutive days or alternating days; maximum daily dose: TMP 320 mg/day (HHS [OI pediatric 2016])

Adolescents: Oral: 80 to 160 mg TMP daily or alternatively, 160 mg TMP 3 times weekly (HHS [OI adult 2017]):

Treatment:

Infants >2 months and Children: Initial: IV: 15 to 20 mg TMP/kg/day in divided doses every 6 hours for 21 days; as acute pneumonitis subsides in patients with mild to moderate disease and no malabsorption issues nor diarrhea, may transition to oral therapy of same daily dose (15 to 20 mg/kg/day TMP) administered in divided doses 3 or 4 times daily (HHS [OI pediatric 2016])

Adolescents (HHS [OI adult 2017]):

Mild to moderate: Oral: 15 to 20 mg TMP/kg/day in 3 divided doses for 21 days or alternatively, 320 mg TMP 3 times daily for 21 days

Moderate to severe: Initial: IV: 15 to 20 mg TMP/kg/day in 3 to 4 divided doses for 21 days; may switch to oral after clinical improvement

Q-Fever ( Coxiella burnetii ); mild infection (doxycycline therapeutic failure): Limited data available, dose should be based on severity of illness: Children <8 years: Oral: Usual dose range: 8 to 10 mg TMP/kg/day in divided doses twice daily for 14 days; a wider dose range of 4 to 20 mg TMP/kg/day divided twice daily has been suggested to address varying degrees of severity; however, reported pediatric efficacy experience (eg, case series) are lacking; monitor patients receiving doses at the high and low end of the range closely for efficacy and possible adverse effects (Bradley 2017; CDC 2013)

Shigellosis: Infants ≥2 months, Children, and Adolescents: Note: Due to reported widespread resistance empiric therapy with sulfamethoxazole and trimethoprim is not recommended (CDC-NARMS 2010; WHO 2005)

Oral:

Manufacturer's labeling: 8 mg TMP/kg/day in divided doses every 12 hours for 5 days; maximum single dose: 160 mg TMP

Alternate dosing: IDSA recommendations for infectious diarrhea: 10 mg TMP/kg/day in divided doses every 12 hours for 3 days (for immunocompetent patients) or 7 to 10 days (for immunocompromised patients); maximum single dose: 160 mg TMP (Guerrant 2001)

IV: 8 to 10 mg TMP/kg/day in divided doses every 6, 8, or 12 hours for up to 5 days

Toxoplasmosis (HIV-exposed/infected):

Prophylaxis, primary:

Infants ≥2 months and Children: Oral: 150 mg TMP/m2/day; dose may be administered as a single daily dose (preferred) or in divided doses every 12 hours; alternatively, may also be given 3 times weekly for 3 consecutive or alternating days (HHS [OI pediatric 2016])

Adolescents: Oral: 160 mg TMP daily (preferred) or 160 mg TMP 3 times weekly or 80 mg TMP daily (HHS [OI adult 2017])

Treatment, encephalitis: Adolescents: Oral, IV: 10 mg/kg/day TMP in two divided doses for at least 6 weeks; longer duration may be required in some patients; following treatment all patients should receive chronic maintenance therapy daily (HHS [OI adult 2017])

Secondary prophylaxis (chronic suppressive therapy, alternative regimen): Note: Only use when pyrimethamine is unavailable or not tolerated:

Infants and Children: Oral: 150 mg TMP/m2/day once daily (HHS [OI pediatric 2016])

Adolescents: Maintenance therapy; postencephalitis treatment: Oral: 160 mg TMP once or twice daily: May discontinue when asymptomatic and CD4 count >200 cells/mm3 for >6 months in response to ART. Note: Once-daily dosing may be associated with an increased risk of relapse; if used, a gradual transition (eg, follow acute treatment with 4 to 6 weeks of 160 mg TMP twice daily before lowering to once-daily dosing) may be beneficial (HHS [OI adult 2017])

Urinary tract infection:

Treatment:

Oral:

Infants and Children 2 to 24 months: 6 to 12 mg TMP/kg/day in divided doses every 12 hours for 7 to 14 days (AAP 2011)

Children >24 months and Adolescents: 8 mg TMP/kg/day in divided doses every 12 hours for 3 days; longer duration may be required in some patients; maximum single dose: 160 mg TMP

IV: Infants ≥2 months, Children, and Adolescents: 8 to 10 mg TMP/kg/day in divided doses every 6, 8, or 12 hours for up to 14 days with serious infections

Prophylaxis: Infants ≥2 months, Children, and Adolescents: Oral: 2 mg TMP/kg/dose once daily (Mattoo 2007; Red Book [AAP 2012])

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

Manufacturer’s labeling: Infants ≥2 months, Children, and Adolescents: Oral, IV:

CrCl >30 mL/minute: No adjustment required.

CrCl 15 to 30 mL/minute: Administer 50% of recommended dose.

CrCl <15 mL/minute: Use is not recommended.

Alternative recommendations:

Children and Adolescents (Veltri 2004): Note: Renally adjusted dose recommendations are based on doses of 3 to 5 mg/kg/dose every 12 hours. IV, Oral:

CrCl 10 to 50 mL/minute/1.73 m2: 3 to 5 mg TMP/kg/dose every 18 hours

CrCl <10 mL/minute/1.73 m2: 3 to 5 mg TMP/kg/dose every 24 hours

Hemodialysis: 3 to 5 mg TMP/kg/dose every 24 hours; administer 2.5 mg TMP/kg/dose after each dialysis session

CRRT (CAVH/CVVH/CAVHD/CVVHD):

Combined dialysis flow + ultrafiltration rate <1,500 mL/m2/hour: 3 to 5 mg TMP/kg/dose every 18 hours

Combined dialysis flow + ultrafiltration rate ≥ 1,500 mL/m2/hour: 4 to 5 mg TMP/kg/dose every 18 hours

Pneumocystis jirovecii pneumonia (PCP):

Treatment (Veltri 2004):

Children: Note: Renally adjusted dose recommendations are based on doses of 5 mg/kg/dose every 6 hours. IV, Oral:

CrCl 10 to 50 mL/minute/1.73 m2: 5 mg TMP/kg/dose every 8 hours

CrCl <10 mL/minute/1.73 m2: 5 mg TMP/kg/dose every 12 hours

Hemodialysis: 5 mg/kg/dose every 12 hours; administer 2.5 mg TMP/kg/dose after each dialysis session

Continuous renal replacement therapy (CRRT): CAVH/CVVH/CAVHD/CVVHD: 5 mg TMP/kg/dose every 8 hours

Adolescents (HHS [OI adult 2016]): IV, Oral:

CrCl 10 to 30 mL/minute: 5 mg TMP/kg/dose IV every 12 hours or 320 mg TMP orally every 12 hours

CrCl <10 mL/minute: 5 mg TMP/kg/dose IV every 24 hours or 160 mg TMP orally every 12 hours or 320 mg TMP orally every 24 hours

Hemodialysis: 5 mg TMP/kg/dose IV or 320 mg TMP orally; administer dose after dialysis on dialysis days

Prophylaxis (Masur 2002): Adolescents: Oral:

CrCl 15 to 30 mL/minute: 40 mg or 80 mg TMP daily or 80 mg TMP 3 times weekly

CrCl <15 mL/minute: 40 mg or 80 mg TMP daily or 80 mg TMP 3 times weekly. While the guidelines do acknowledge the alternative of giving 80 mg TMP daily, this may be inadvisable in the uremic/ESRD patient.

Hemodialysis: 40 mg or 80 mg TMP after each dialysis session

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; use is contraindicated in cases of marked hepatic damage.

Dosing: Geriatric

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: Sulfamethoxazole 80 mg and trimethoprim 16 mg per mL (5 mL, 10 mL, 30 mL)

Suspension, Oral:

Sulfatrim Pediatric: Sulfamethoxazole 200 mg and trimethoprim 40 mg per 5 mL (473 mL) [contains alcohol, usp, fd&c red #40, fd&c yellow #6 (sunset yellow), methylparaben, polysorbate 80, propylene glycol, propylparaben, saccharin sodium]

Sulfatrim Pediatric: Sulfamethoxazole 200 mg and trimethoprim 40 mg per 5 mL (473 mL [DSC]) [contains alcohol, usp, fd&c red #40, fd&c yellow #6 (sunset yellow), methylparaben, polysorbate 80, propylene glycol, propylparaben, saccharin sodium; cherry flavor]

Generic: Sulfamethoxazole 200 mg and trimethoprim 40 mg per 5 mL (20 mL, 473 mL)

Tablet, Oral:

Bactrim: Sulfamethoxazole 400 mg and trimethoprim 80 mg [scored; contains sodium benzoate]

Bactrim DS: Sulfamethoxazole 800 mg and trimethoprim 160 mg [scored; contains sodium benzoate]

Generic: Sulfamethoxazole 400 mg and trimethoprim 80 mg, Sulfamethoxazole 800 mg and trimethoprim 160 mg

Generic Equivalent Available: US

Yes

Dosage Forms Considerations

The 5:1 ratio (SMX:TMP) remains constant in all dosage forms.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Septra: Sulfamethoxazole 80 mg and trimethoprim 16 mg per mL (5 mL) [contains alcohol, usp, propylene glycol, sodium metabisulfite]

Suspension, Oral:

Generic: Sulfamethoxazole 200 mg and trimethoprim 40 mg per 5 mL (100 mL, 400 mL, 800 mL)

Tablet, Oral:

Sulfatrim Pediatric: Sulfamethoxazole 100 mg and trimethoprim 20 mg

Generic: Sulfamethoxazole 400 mg and trimethoprim 80 mg, Sulfamethoxazole 800 mg and trimethoprim 160 mg

Administration: Adult

IV: Infuse diluted solution over 60 to 90 minutes (administration over 30 to 60 minutes has also been described [Septra Canadian product monograph]); not for IM injection.

Oral: Administer without regard to meals. Administer with at least 8 ounces of water.

Administration: Pediatric

Oral: Administer without regard to meals. Shake suspension well before use.

Parenteral: IV infusion: Do not administer IM. Must be diluted in D5W prior to administration. Inspect solution for evidence of cloudiness or precipitation prior to administration; infuse diluted solution IV over 60 to 90 minutes (administration over 30 to 60 minutes has also been described [Septra Canadian product monograph]).

Use: Labeled Indications

Oral: Treatment of urinary tract infection (UTI) due to Escherichia coli, Klebsiella and Enterobacter spp, Morganella morganii, Proteus mirabilis, and Proteus vulgaris; acute otitis media; acute exacerbations of chronic obstructive pulmonary disease due to susceptible strains of Haemophilus influenzae or Streptococcus pneumoniae; treatment and prophylaxis of Pneumocystis pneumonia (PCP); traveler's diarrhea due to enterotoxigenic E. coli; treatment of shigellosis caused by Shigella flexneri or Shigella sonnei.

IV: Treatment of PCP; treatment of shigellosis caused by S. flexneri or S. sonnei; treatment of severe or complicated UTIs due to E. coli, Klebsiella and Enterobacter spp, M. morganii, P. mirabilis, and P. vulgaris.

Use: Off-Label: Adult

Bite wound infection, prophylaxis or treatment (animal or human bite); Cellulitis, long-term suppression of recurrent infection; Cellulitis, nonpurulent with risk for methicillin-resistant Staphylococcus aureus; Cellulitis, purulent or abscess; Cyclosporiasis; Cystoisosporiasis (Isosporiasis); Diabetic foot infection; Epididymitis; Granuloma inguinale (Donovanosis); Impetigo or ecthyma; Intra-abdominal infection; Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess (methicillin-resistant Staphylococcus aureus); Melioidosis (Burkholderia pseudomallei) infection; Meningitis, bacterial; Nocardiosis; Osteomyelitis; Peritonitis, spontaneous bacterial (prevention); Prostatitis; Prosthetic joint infection; Q fever (Coxiella burnetii); Septic arthritis (methicillin-resistant Staphylococcus aureus); Stenotrophomonas maltophilia infections; Toxoplasma gondii encephalitis (prophylaxis/treatment/chronic maintenance) in patients with HIV

Medication Safety Issues
Sound-alike/look-alike issues:

Bactrim may be confused with bacitracin, Bactine, Bactroban

Co-trimoxazole may be confused with clotrimazole

Septra may be confused with Ceptaz, Sectral

Septra DS may be confused with Semprex-D

Geriatric Patients: High-Risk Medication:

Beers Criteria: Sulfamethoxazole and Trimethoprim is identified in the Beers Criteria as a potentially inappropriate medication to be used with caution in patients 65 years and older with decreased CrCl and on ACE inhibitors or ARBs due to increased risk of hyperkalemia (Beers Criteria [AGS 2019]).

Pediatric patients: High-risk medication:

KIDs List: Sulfonamides, when used in neonates, are identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be avoided due to risk of kernicterus (weak recommendation; very low quality of evidence) (PPA [Meyers 2020]).

Adverse Reactions (Significant): Considerations
Clostridioides difficile infection

Clostridioides difficile infection (CDI) has occurred with sulfamethoxazole/trimethoprim, specifically including diarrhea, abdominal pain, and Clostridioides difficile colitis (Ref).

Onset: Varied; may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref).

Risk factors:

• Antibiotic exposure (highest risk factor) (Ref)

• Long durations in a hospital or other health care setting (recent or current) (Ref)

• Older adults (Ref)

• Immunocompromised conditions (Ref)

• A serious underlying condition (Ref)

• GI surgery/manipulation (Ref)

• Antiulcer medications (eg, proton pump inhibitors and H2 blockers) (Ref)

• Chemotherapy (Ref)

Drug-induced liver injury

The most typical pattern of drug-induced liver injury (hepatotoxicity) observed with sulfamethoxazole/trimethoprim is a mixed hepatocellular cholestasis. Cholestasis without inflammation and hepatocellular necrosis (including fatalities) have also occurred (Ref). Some cases may be manifestations of drug reaction with eosinophilia and systemic symptoms (DRESS) (Ref). May also cause mild elevations in ALT that do not develop into more serious liver injury or jaundice (Ref).

Mechanism: Non-dose-related; immunologic. Delayed hypersensitivity reactions, including hepatotoxicity associated with DRESS, are mediated by T-cells which may be induced by the toxic hydroxylamine and nitroso metabolites of sulfonamide antimicrobials (Ref). Other immune mechanisms have been suggested, including action of complement within the immune complex disease or binding of complement activating antibodies to membranes of hepatocytes or bile ducts (Ref).

Onset: Intermediate; most cases occur 1 to 3 weeks after initiation (Ref). Upon rechallenge, symptoms may develop more rapidly, often within 3 days of initiation (Ref).

Risk factors:

• African Americans (Ref)

• Genetic risk factors (ie, HLA-B*35:01 in African Americans; HLA-B*14:01 in European Americans) (Ref)

• Patients with HIV (Ref)

Hematologic effects

Various blood dyscrasias (including fatalities) have been reported with sulfamethoxazole/trimethoprim, including agranulocytosis, hemolytic anemia, leukopenia, and thrombocytopenia (Ref). Some cases may be manifestations of a hypersensitivity drug reaction with eosinophilia and systemic symptoms (Ref). Thrombocytopenia usually resolves within 1 week following discontinuation of therapy.

Mechanism: Non-dose-related. Thrombocytopenia is an immune-mediated process caused by platelet destruction by drug-dependent platelet antibodies (Ref). Hemolytic anemia is also immune-related (Ref). The pathogenesis for agranulocytosis is unknown, although in some cases an immune-mediated mechanism may be responsible (Ref).

Onset: Varied; ranges from 6 days up to 5 weeks (Ref). Upon rechallenge, symptoms may develop within 1 hour (Ref).

Risk factors:

• HIV/AIDS (Ref)

• Glucose-6-phosphate dehydrogenase deficiency may be at risk for the development of hemolytic anemia (Ref); although, most patients are able to tolerate the drug (Ref).

Hyperkalemia

Hyperkalemia may occur with sulfamethoxazole/trimethoprim and be life threatening (Ref); usually reversible following discontinuation (Ref).

Mechanism: Dose-related; trimethoprim blocks sodium channels in the distal nephron, inhibiting potassium secretion. Results in decreased renal potassium excretion (Ref).

Onset: Variable; usually occurs within 5 to 10 days after sulfamethoxazole/trimethoprim is initiated (Ref).

Risk factors:

• High doses (trimethoprim 20 mg/kg/day) (Ref)

• Kidney impairment (Ref)

• Older patients (Ref)

• Hypoaldosteronism (Ref)

• Concomitant use of medications causing or exacerbating hyperkalemia (Ref)

Hypoglycemia

Hypoglycemia may occur with sulfamethoxazole/trimethoprim and be life threatening (Ref); usually reversible following discontinuation (Ref).

Mechanism: Proposed to be related to the sulfamethoxazole component binding to receptors on the pancreatic islet cells and causing the release of insulin (Ref).

Onset: Rapid; range from 1.5 hours to 5 days after initiation (Ref).

Risk factors:

• Kidney or hepatic impairment (Ref)

• Prolonged fasting conditions (Ref)

• Malnourished (Ref)

• Concomitant medications that decrease plasma glucose levels (Ref)

Hyponatremia

Severe and symptomatic hyponatremia may occur with sulfamethoxazole/trimethoprim and be life threatening (Ref); usually reversible following discontinuation of therapy (Ref).

Mechanism: Dose-related; large volume of fluid required for IV infusion and/or due to diuretic actions (blockade of epithelial sodium channels in the distal nephron) of trimethoprim (Ref).

Onset: Rapid; ~5 days after initiation of therapy (Ref).

Risk factors:

• Dose (trimethoprim >8 mg/kg/day) (Ref)

Hypersensitivity reactions (delayed)

Delayed hypersensitivity reactions may occur with sulfamethoxazole/trimethoprim, including maculopapular skin rash, fixed drug eruption, and severe cutaneous adverse reactions (SCARs) (Ref). SCARs include acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), Sweet’s syndrome, and toxic epidermal necrolysis (TEN) (Ref).

Mechanism: Non-dose-related; immunologic. T-cell mediated, which may be induced by the toxic hydroxylamine and nitroso metabolites of sulfonamide antimicrobials (Ref).

Onset: Variable; typically occur days to weeks after drug exposure but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref). In patients with HIV/AIDS, a morbilliform reaction with fever usually occurs 1 to 2 weeks after initiation of therapy (Ref).

Risk factors:

• HIV/AIDS (most often a maculopapular rash, often associated with fever) (Ref)

Note: Cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur, or at the very least this potential is extremely low (Ref). Drugs that should be avoided in patients who develop hypersensitivity reactions to sulfamethoxazole-trimethoprim include other sulfonamide antimicrobials (regardless of route of administration), dapsone, fosamprenavir, darunavir, and sulfasalazine (Ref). In addition, trimethoprim should also be avoided, as it is unknown whether this drug may have contributed or been responsible for the initial reaction (Ref). In patients with serious reactions (eg, SJS/TEN, DRESS), some clinicians may elect to avoid all sulfonamide medications (Ref).

Hypersensitivity reactions (immediate)

Immediate hypersensitivity reactions may occur with sulfamethoxazole/trimethoprim, including urticaria, angioedema, and anaphylaxis (Ref). The sulfonamide component is often implicated as the causative agent, but some patients may be reacting to the trimethoprim component (Ref). An immediate hypersensitivity reaction (“anaphylactic-like”) can occur in patients with HIV/AIDS that may resemble sepsis, with fever and hypotension; in some of these patients, pulmonary infiltrates and rash may be present (Ref).

Mechanism: Non-dose-related; immunologic (ie, IgE-mediated with antibodies to sulfamethoxazole and trimethoprim) (Ref). The N1-substitute and not the sulfonamide group has been found to have direct specificity to IgE antibodies (Ref). The mechanism for anaphylactic-like reactions in patients with HIV/AIDS is not known (Ref), although it may be caused by higher levels of IgE and tumor necrosis factor in patients with AIDS (Ref).

Onset: Rapid; typically occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Anaphylactic-like reactions usually occur within 4 hours of administration (Ref).

Risk factors:

• HIV/AIDS (Ref)

Note: Cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur, or at the very least this potential is extremely low (Ref). Cross-reactions due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides and antibiotic sulfonamides (Ref).

Kernicterus

Sulfa antibiotics have been shown to displace bilirubin from protein binding sites, which may potentially lead to hyperbilirubinemia and kernicterus in neonates and young infants. There are limited data with sulfamethoxazole; therefore, the risk for kernicterus is extrapolated from data with sulfisoxazole (Ref).

Mechanism: Displaces bilirubin from albumin, resulting in higher concentrations of free unconjugated bilirubin, leading to kernicterus (Ref).

Risk factors:

• Neonates and infants <2 month of age, especially those born premature

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Circulatory shock (Liu 2018), hypersensitivity myocarditis (Nayak 2013), polyarteritis nodosa, thrombophlebitis (migrans; Verne-Pignatelli 1989)

Dermatologic: Acute generalized exanthematous pustulosis (Anliker 2003), erythema multiforme, exfoliative dermatitis, skin photosensitivity, skin rash, Stevens-Johnson syndrome (Acharya 2020), Sweet’s syndrome (Azfar 2009), toxic epidermal necrolysis (Zhang 2019), urticaria

Endocrine & metabolic: Hyperkalemia (Alappan 1999), hyponatremia (Babyev 2013)

Gastrointestinal: Abdominal pain, anorexia, diarrhea, glossitis, nausea, pancreatitis, stomatitis, vomiting

Genitourinary: Crystalluria, diuresis, toxic nephrosis (with anuria and oliguria)

Hematologic & oncologic: Agranulocytosis (Andres 2003), aplastic anemia (IAAAS 1989), eosinophilia, hemolysis (with G6PD deficiency) (Calabrò 1989), hemolytic anemia (Williams 2017), Henoch-Schönlein purpura, hypoprothrombinemia, leukopenia (Gordin 1984), megaloblastic anemia (Kobrinsky 1981), methemoglobinemia (Carroll 2016), neutropenia, thrombocytopenia (Mitta 2019)

Hepatic: Cholestatic jaundice (Ogilvie 1980), hepatotoxicity (including hepatitis, cholestasis, and hepatic necrosis) (Slim 2017), hyperbilirubinemia, increased serum transaminases

Hypersensitivity: Angioedema, serum sickness (Platt 1988)

Immunologic: Drug reaction with eosinophilia and systemic symptoms (Kardaun 2013)

Local: Inflammation at injection site, infusion site irritation, infusion-site pain

Nervous system: Apathy, aseptic meningitis (Bruner 2014), ataxia, chills, depression, fatigue, hallucination, headache, insomnia, kernicterus (neonates), nervousness, peripheral neuritis, seizure, vertigo

Neuromuscular & skeletal: Arthralgia, asthenia, myalgia, rhabdomyolysis, systemic lupus erythematosus (Mahmood 2020)

Ophthalmic: Conjunctival injection, injected sclera, uveitis

Otic: Tinnitus

Renal: Interstitial nephritis, renal insufficiency

Respiratory: Acute respiratory failure, cough, dyspnea, eosinophilic pneumonitis (acute), interstitial pulmonary disease (Yuzurio 2010), pulmonary infiltrates, pulmonary injury (acute and delayed)

Miscellaneous: Fever (Gordin 1984)

Postmarketing:

Cardiovascular: Prolonged QT interval on ECG (Lopez 1987), torsades de pointes (Lopez 1987)

Endocrine & metabolic: Hypoglycemia (Nunnari 2010; Strevel 2006), metabolic acidosis (Porras 1998)

Gastrointestinal: Clostridioides difficile colitis (Brown 2013; Gordin 1994; Hensgens 2012), dysgeusia (Syed 2016)

Hematologic & oncologic: Thrombotic thrombocytopenic purpura (Bapani 2013)

Hypersensitivity: Anaphylaxis (Harle 1988; Kuyucu 2014), fixed drug eruption (Can 2014)

Renal: Acute kidney injury (Fraser 2012)

Respiratory: Acute respiratory distress syndrome (Miller 2019)

Contraindications

Hypersensitivity to any sulfa drug, trimethoprim, or any component of the formulation; history of drug induced-immune thrombocytopenia with use of sulfonamides or trimethoprim; megaloblastic anemia due to folate deficiency; infants <2 months (manufacturer's labeling), infants <4 weeks (CDC 2009); marked hepatic damage or severe renal disease (if patient not monitored); concomitant administration with dofetilide

Note: Although the FDA approved product labeling states this medication is contraindicated with other sulfonamide-containing drug classes, the scientific basis of this statement has been challenged. See “Warnings/Precautions” for more detail.

Canadian labeling: Additional contraindications (not in US labeling): Blood dyscrasias; pregnancy; breastfeeding; premature infants; acute porphyria.

Warnings/Precautions

Concerns related to adverse effects:

• Superinfection: Prolonged use may result in fungal or bacterial superinfection.

Disease-related concerns:

• Asthma/Allergies: Use with caution in patients with allergies or asthma.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended. Maintain adequate hydration to prevent crystalluria.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Special populations:

• Elderly: Use with caution in elderly patients; greater risk for more severe adverse reactions.

• Patients with potential for folate deficiency: Use with caution in patients with potential folate deficiency (malnourished, chronic anticonvulsant therapy, or elderly).

• Porphyria: Avoid use in patients with porphyria.

• Slow acetylators: May be more prone to adverse reactions.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP ["Inactive" 1997]; Zar 2007).

• Sulfite sensitivity: Injection may contain sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible persons. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic persons.

Other warnings/precautions:

• Appropriate use: When used for uncomplicated urinary tract infections, this combination should not be used if a single agent is effective. Additionally, sulfonamides should not be used to treat group A beta-hemolytic streptococcal infections.

Warnings: Additional Pediatric Considerations

Sulfa antibiotics have been shown to displace bilirubin from protein binding sites which may potentially lead to hyperbilirubinemia and kernicterus in neonates and young infants; do not use in neonates; avoid use in infants <2 months unless other options are not available (eg, Pneumocystis).

Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Amantadine: Trimethoprim may enhance the adverse/toxic effect of Amantadine. Specifically, the risk of myoclonus and/or delirium may be increased. Amantadine may increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Amantadine. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Amodiaquine: Trimethoprim may enhance the neutropenic effect of Amodiaquine. Trimethoprim may increase the serum concentration of Amodiaquine. Risk X: Avoid combination

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Angiotensin II Receptor Blockers: Trimethoprim may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Trimethoprim may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

AzaTHIOprine: Sulfamethoxazole may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy

AzaTHIOprine: Trimethoprim may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

Chloroprocaine: May diminish the therapeutic effect of Sulfonamide Antibiotics. Management: Avoid concurrent use of chloroprocaine and systemic sulfonamide-based antimicrobials whenever possible. Risk D: Consider therapy modification

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

CycloSPORINE (Systemic): Sulfonamide Antibiotics may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Sulfonamide Antibiotics may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

Dapsone (Systemic): Trimethoprim may increase the serum concentration of Dapsone (Systemic). Dapsone (Systemic) may increase the serum concentration of Trimethoprim. Risk C: Monitor therapy

Dapsone (Topical): Trimethoprim may enhance the adverse/toxic effect of Dapsone (Topical). More specifically, trimethoprim may increase the risk for hemolysis Risk C: Monitor therapy

Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Risk C: Monitor therapy

Digoxin: Trimethoprim may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Dofetilide: Trimethoprim may increase the serum concentration of Dofetilide. Risk X: Avoid combination

Eplerenone: Trimethoprim may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy

Fosphenytoin: May decrease the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Fosphenytoin. Management: Consider alternatives to this combination when possible, to avoid potential decreased trimethoprim efficacy and increased phenytoin concentrations/effects. Monitor patients receiving this combination closely for both of these possible effects. Risk D: Consider therapy modification

Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

LamiVUDine: Trimethoprim may increase the serum concentration of LamiVUDine. Risk C: Monitor therapy

Leucovorin Calcium-Levoleucovorin: May diminish the therapeutic effect of Trimethoprim. Management: Avoid concurrent use of leucovorin or levoleucovorin with trimethoprim (plus sulfamethoxazole) for Pneumocystis jirovecii pneumonia. If trimethoprim is used for another indication, monitor closely for reduced efficacy. Risk X: Avoid combination

Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Risk X: Avoid combination

Memantine: Trimethoprim may enhance the adverse/toxic effect of Memantine. Specifically, the risk of myoclonus and/or delirium may be increased. Trimethoprim may increase the serum concentration of Memantine. Memantine may increase the serum concentration of Trimethoprim. Risk C: Monitor therapy

Mercaptopurine: Sulfamethoxazole may enhance the myelosuppressive effect of Mercaptopurine. Risk C: Monitor therapy

Mercaptopurine: Trimethoprim may enhance the myelosuppressive effect of Mercaptopurine. Risk C: Monitor therapy

MetFORMIN: Trimethoprim may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Methenamine: May enhance the adverse/toxic effect of Sulfonamide Antibiotics. Specifically, the combination may result in the formation of an insoluble precipitate in the urine. Risk X: Avoid combination

Methotrexate: Trimethoprim may enhance the adverse/toxic effect of Methotrexate. Management: Consider avoiding concomitant use of methotrexate and either sulfamethoxazole or trimethoprim. If used concomitantly, monitor for the development of signs and symptoms of methotrexate toxicity (e.g., bone marrow suppression). Risk D: Consider therapy modification

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

MetroNIDAZOLE (Systemic): May enhance the adverse/toxic effect of Products Containing Propylene Glycol. A disulfiram-like reaction may occur. Risk X: Avoid combination

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Phenytoin: Trimethoprim may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Trimethoprim. Management: Consider alternatives to this combination when possible, to avoid potential decreased trimethoprim efficacy and increased phenytoin concentrations/effects. Monitor patients receiving this combination closely for both of these possible effects. Risk D: Consider therapy modification

Phenytoin: Sulfamethoxazole may increase the serum concentration of Phenytoin. Management: Avoid coadministration of phenytoin and sulfamethoxazole. If coadministered, monitor phenytoin concentrations and for evidence of phenytoin toxicity. Risk of toxicity is increased with sulfamethoxazole/trimethoprim combination product. Risk D: Consider therapy modification

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Potassium P-Aminobenzoate: May diminish the therapeutic effect of Sulfonamide Antibiotics. Risk X: Avoid combination

PRALAtrexate: Trimethoprim may increase the serum concentration of PRALAtrexate. More specifically, trimethoprim may decrease excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum level and/or possible toxicity with concomitant use of trimethoprim. Monitor for decreased pralatrexate levels with discontinuation of trimethoprim. Risk C: Monitor therapy

PRALAtrexate: Sulfamethoxazole may increase the serum concentration of PRALAtrexate. More specifically, sulfamethoxazole may decrease excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum level and/or possible toxicity with concomitant use of sulfamethoxazole. Monitor for decreased pralatrexate levels with discontinuation of sulfamethoxazole. Risk C: Monitor therapy

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy

Procainamide: Trimethoprim may increase serum concentrations of the active metabolite(s) of Procainamide. Trimethoprim may increase the serum concentration of Procainamide. Management: Consider alternatives to trimethoprim-containing regimens to avoid this interaction. If coadministered, monitor for increased procainamide adverse effects (increased QTc) if trimethoprim is initiated/dose increased. Risk D: Consider therapy modification

Procaine: May diminish the therapeutic effect of Sulfonamide Antibiotics. Risk X: Avoid combination

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Pyrimethamine: May enhance the adverse/toxic effect of Trimethoprim. Risk C: Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy

Repaglinide: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy

RifAMPin: Trimethoprim may increase the serum concentration of RifAMPin. RifAMPin may decrease the serum concentration of Trimethoprim. Risk C: Monitor therapy

RifAMPin: Sulfamethoxazole may increase the serum concentration of RifAMPin. RifAMPin may decrease the serum concentration of Sulfamethoxazole. Risk C: Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Sapropterin: Trimethoprim may decrease the serum concentration of Sapropterin. Specifically, trimethoprim may decrease tissue concentrations of tetrahydrobiopterin. Risk C: Monitor therapy

Secnidazole: Products Containing Propylene Glycol may enhance the adverse/toxic effect of Secnidazole. Risk X: Avoid combination

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Spironolactone: Trimethoprim may enhance the hyperkalemic effect of Spironolactone. Risk C: Monitor therapy

Sulfonylureas: Sulfonamide Antibiotics may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

Varenicline: Trimethoprim may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concomitant use of trimethoprim, particularly in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Sulfonamide Antibiotics may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Consider reducing the vitamin K antagonist dose by 10% to 20% prior to starting the sulfonamide antibiotic. Monitor INR closely to further guide dosing. Risk D: Consider therapy modification

Zidovudine: May enhance the neutropenic effect of Trimethoprim. Trimethoprim may increase the serum concentration of Zidovudine. Risk C: Monitor therapy

Reproductive Considerations

Sulfamethoxazole/trimethoprim is recommended for the acute treatment of Q fever (C. burnetii) in pregnant patients; however, it is an alternative agent in nonpregnant adults. Patients should avoid pregnancy for ≥1 month after treatment. Pregnancy testing is recommended in patients who may become pregnant prior to therapy (CDC [Anderson 2013]).

Sulfamethoxazole/trimethoprim may be appropriate for the treatment of bacterial prostatitis, a condition associated with sexual dysfunction (Lipsky 2010). Treatment of prostatitis may or may not improve semen quality. Sulfamethoxazole/trimethoprim may also be associated with transient disruption of spermatogenesis, but effects on semen parameters are conflicting (Drobnis 2017; Samplaski 2015).

Pregnancy Considerations

Sulfamethoxazole and trimethoprim cross the placenta.

An increased risk of congenital malformations (neural tube defects, cardiovascular malformations, urinary tract defects, oral clefts, club foot) following maternal use of sulfamethoxazole and trimethoprim during pregnancy has been observed. Trimethoprim interferes with folic acid metabolism, decreasing maternal levels. Adequate maternal folic acid supplementation may decrease the risk of some birth defects (Crider 2009; Czeizel 2001; Hernandez-Diaz 2000; Hernandez-Diaz 2001; Matok 2009).

Due to theoretical concerns that sulfonamides pass the placenta and may cause kernicterus in the newborn, neonatal health care providers should be informed if maternal sulfonamide therapy is used near the time of delivery (HHS [OI adult 2020]); avoidance of sulfamethoxazole/trimethoprim during the third trimester is recommended by some guidelines.

The pharmacokinetics of sulfamethoxazole and trimethoprim are similar to nonpregnant values in early pregnancy (Ylikorkala 1973).

Sulfamethoxazole/trimethoprim is recommended for the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in pregnant patients with HIV because of the considerable maternal benefits of therapy. However, due to the risk of birth defects, supplemental folic acid at high doses (>0.4 mg/day) may be considered during the first trimester only. When sulfamethoxazole/trimethoprim is used during the first trimester, a fetal ultrasound is recommended at 18 to 20 weeks' gestation to evaluate fetal anatomy (HHS [OI adult 2020]).

Sulfamethoxazole/trimethoprim is recommended for the primary treatment of symptomatic Isospora belli infection as well as secondary prophylaxis in pregnant patients with HIV. Treatment for secondary prophylaxis can be withheld during the first trimester due to concerns of birth defects associated with sulfamethoxazole/trimethoprim therapy (HHS [OI adult 2020]).

Sulfamethoxazole/trimethoprim is recommended for the acute treatment of Q fever (Coxiella burnetii) in pregnant patients (alternative agent in nonpregnant adults). Untreated first trimester maternal infection may lead to miscarriage; premature delivery may occur when infection occurs later in pregnancy. Acute infection during pregnancy also increases the risk of chronic maternal infection. Treatment decreases the risk of adverse pregnancy outcomes and adverse events in subsequent pregnancies. Treatment with sulfamethoxazole/trimethoprim is recommended throughout pregnancy up to 32 weeks' gestation (withhold sulfamethoxazole/trimethoprim during the last 8 weeks of gestation due to the risk of kernicterus). Monitoring should continue for 24 months after delivery to evaluate possible progression to chronic disease (CDC [Anderson 2013]).

Sulfamethoxazole/trimethoprim is recommended for the primary prophylaxis of Toxoplasma gondii encephalitis (TE) in pregnant patients with HIV. The risks of fetal exposure to sulfamethoxazole/trimethoprim during the first trimester should be balanced with the risk TE (HHS [OI adult 2020]).

Sulfamethoxazole/trimethoprim is approved for the treatment of urinary tract infections (UTIs) in adults. Some guidelines prefer alternative antibiotics for UTIs in pregnancy as well as avoiding use in the third trimester (Betschart 2020).

Sulfamethoxazole/trimethoprim is not recommended for the treatment of granuloma inguinale during pregnancy (recommended as an alternative therapy in nonpregnant patients) (CDC [Workowski 2015]).

Sulfamethoxazole/trimethoprim may be used as part of a treatment regimen when brucellosis is diagnosed during pregnancy (not the preferred treatment in nonpregnant patients). Untreated maternal brucellosis infection may cause adverse pregnancy outcomes including spontaneous abortion or transmission to the infant. Treatment with sulfamethoxazole/trimethoprim is not recommended after 36 weeks' gestation due to the risk of kernicterus (Bosilkovski 2020; CDC brucellosis reference guide 2017).

Breast-Feeding Considerations

Sulfamethoxazole and trimethoprim are present in breast milk.

The manufacturer states that the exposure of sulfamethoxazole and trimethoprim to the breastfeeding infant would be 2% to 5% of the recommended daily dose for infants >2 months of age (maternal dose, milk concentration, and infant dose not specified).

The relative infant dose (RID) of trimethoprim is 3% when compared to an infant therapeutic trimethoprim dose of 10 mg/kg/day. In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).

The RID of trimethoprim was calculated using a mean milk concentration of 2 mcg/mL, providing an estimated infant dose via breast milk of <0.3 mg/kg/day. Using an average sulfamethoxazole milk concentration of 5.34 mcg/mL, the estimated infant sulfamethoxazole dose via breast milk would be <0.8 mg/kg/day. These milk concentrations were obtained following a maternal dose of trimethoprim 80 mg/sulfamethoxazole 400 mg as either 2 tablets (n=40) or 3 tablets (n=10) twice daily for a minimum of 5 days to women within 5 days of delivery (Miller 1974).

A prospective cohort study evaluated the outcomes of breastfed infants whose mothers were taking various medications. Within the study, 12 mother-infant pairs reported sulfamethoxazole/trimethoprim exposure (dose, duration, relationship to breastfeeding not provided). There were no cases of diarrhea, drowsiness, or irritability in the breastfed infants. Poor feeding was noted in 2 infants (Ito 1993). In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances (WHO 2002).

The therapeutic use of sulfamethoxazole and trimethoprim is contraindicated in infants <2 months of age due to the possibility of bilirubin displacement resulting in kernicterus and hemolytic anemia caused by immature erythrocyte enzyme systems; theoretically, the risk of kernicterus and hemolytic anemia is present in breastfed infants exposed to sulfamethoxazole and trimethoprim via breast milk (Mitrano 2009). The manufacturer recommends that caution be used if administered to persons who are breastfeeding, especially if breastfeeding infants are ill, jaundiced, premature, or stressed due to the potential risk of bilirubin displacement and kernicterus. Avoid use of sulfamethoxazole in persons who are breastfeeding an infant with G6PD deficiency (WHO 2002) or hyperbilirubinemia (Della-Giustina 2003). The WHO considers sulfamethoxazole and trimethoprim compatible with breastfeeding in older, healthy, full-term infants with monitoring of the infant for jaundice and hemolysis (WHO 2002).

Dietary Considerations

Should be taken with 8 oz of water. May be taken without regard to meals.

Monitoring Parameters

CBC, electrolytes, renal function.

Mechanism of Action

Sulfamethoxazole interferes with bacterial folic acid synthesis and growth via inhibition of dihydrofolic acid formation from para-aminobenzoic acid; trimethoprim inhibits dihydrofolic acid reduction to tetrahydrofolate resulting in sequential inhibition of enzymes of the folic acid pathway

Pharmacodynamics and Pharmacokinetics

Absorption: Oral: Rapid; almost completely (90% to 100%)

Distribution: Both SMX and TMP distribute to middle ear fluid, sputum, vaginal fluid; TMP also distributes into bronchial secretions

Vd: TMP:

Newborns: ~2.7 L/kg (range: 1.3 to 4.1 hours) (Springer 1982)

Infants: 1.5 L/kg (Hoppu 1989)

Children 1 to 10 years: 0.86 to 1 L/kg (Hoppu 1987)

Adults: ~1.3 L/kg (Hoppu 1987)

Protein binding: SMX: ~70%, TMP: ~44%

Metabolism: Hepatic, both to multiple metabolites; SMX to hydroxy (via CYP2C9) and acetyl derivatives, and also conjugated with glucuronide; TMP to oxide and hydroxy derivatives; the free forms of both SMX and TMP are therapeutically active

Half-life elimination:

TMP: Prolonged in renal failure

Newborns: ~19 hours; range: 11 to 27 hours (Springer 1982)

Infants 2 months to 1 year: ~4.6 hours; range: 3 to 6 hours (Hoppu 1989)

Children 1 to 10 years: 3.7 to 5.5 hours (Hoppu 1987)

Children and Adolescents >10 years: 8.19 hours

Adults: 6 to 11 hours

SMX: 9 to 12 hours, prolonged in renal failure

Time to peak, serum: Oral: 1 to 4 hours

Excretion: Both are excreted in urine as metabolites and unchanged drug

Pharmacodynamics and Pharmacokinetics: Additional Considerations

Renal function impairment: Patients with severely impaired renal function exhibit an increase in the half-lives of both components, requiring dosage adjustments.

Geriatric: Total body clearance of trimethoprim was 19% lower in elderly patients.

Pricing: US

Solution (Sulfamethoxazole-Trimethoprim Intravenous)

400-80 mg/5 mL (per mL): $1.51 - $1.52

Suspension (Sulfamethoxazole-Trimethoprim Oral)

200-40 mg/5 mL (per mL): $0.46

Suspension (Sulfatrim Pediatric Oral)

200-40 mg/5 mL (per mL): $0.24

Tablets (Bactrim DS Oral)

800-160 mg (per each): $3.12

Tablets (Bactrim Oral)

400-80 mg (per each): $1.73

Tablets (Sulfamethoxazole-Trimethoprim Oral)

400-80 mg (per each): $0.66 - $0.78

800-160 mg (per each): $0.37 - $1.40

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Abacin (IT);
  • Acuco (ZA);
  • Alcorim-F (IN);
  • Anitrim (MX);
  • Avlotrin (BD);
  • Bacdan (TW);
  • Bacin (MY, SG, TH);
  • Bactelan (MX);
  • Bacteric (MX);
  • Bacterol (CL);
  • Bacterol Forte (CL);
  • Bacticel (AR);
  • Bactiver (MX);
  • Bactoprim (TH);
  • Bactramin (JP);
  • Bactrim (AE, AR, AT, AU, BB, BH, BR, CH, CY, CZ, DE, DK, EC, EE, FR, IN, IQ, IR, IT, JO, KW, LB, LV, LY, MT, MX, NO, OM, PK, PL, PT, SA, SE, SK, SY, TH, TR, UA, VN, YE);
  • Bactrim DS (AU, BB);
  • Bactrim F (CO);
  • Bactrim Forte (AT, BE, BH, FI, FR, LB, LU, PH, PT, SE);
  • Bactrimel (GR, VE);
  • Bactropin (MX);
  • Biseptol (BG, LV);
  • Brogamax (MX);
  • Chemotrim (EG, QA);
  • Co-Try (BD);
  • Colizole (IN);
  • Colizole DS (IN);
  • Comazole (MY);
  • Comex (EG);
  • Cotriinol (ZW);
  • Cotrim (BF, BJ, CI, ET, GH, GM, GN, KE, KR, LR, MA, ML, MR, MU, MW, MY, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM);
  • Cotrim DS (MY);
  • Cotrimel (HK);
  • Cotrix (AE, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE);
  • Cotrizol (TW);
  • Cotrizole (ZW);
  • Deprim (MT);
  • Dhatrim (MY);
  • Dibaprim (MX);
  • Diseptyl (IL);
  • Duocide (TW);
  • Duratrimet (DE);
  • Ectaprim (MX);
  • Epitrim (AE, CY, IQ, IR, JO, KW, LY, OM, RO, SA, SY, YE);
  • Escoprim (CH);
  • Espectrin (BR);
  • Eusaprim (AT, FI, IS, IT, NO, SE);
  • Eusaprim Forte (BE);
  • Farcotrim (QA);
  • Fectrim (GB);
  • Gantaprim (IT);
  • Gantrim (IT);
  • Ikaprim (ID);
  • Infectrim (PE);
  • Introcin (CL);
  • Isotrim (IT);
  • Kepinol (DE);
  • Lagatrim (AE, BF, BJ, CI, CY, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM);
  • Lagatrim Forte (BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, PR, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZM);
  • Lidaprim (AE, SA);
  • Lidaprim Forte (AE, AT, SA);
  • Mano-Trim (TH);
  • Mano-Trim Forte (TH);
  • Medixin (IT);
  • Metoxiprim (MX);
  • Metrim (TH);
  • Mezenol (ZW);
  • Mezenol DS (ZW);
  • Microtrim (DE);
  • Morbifurb (CN);
  • Mortin (VN, ZW);
  • Nopil (AE, CY, IQ, IR, JO, KW, LY, OM, QA, SA, SY, YE);
  • Novabact (ZW);
  • Octex (MX);
  • Omsat (BF, BJ, CI, DE, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM);
  • Oriprim (RU);
  • Oriprim DS (KE, TZ, UG);
  • Oxaprim (IT);
  • Politrim (BD);
  • Primzole (SG);
  • Purbal (ZA);
  • Resprim (AU);
  • Resprim Forte (AU);
  • Sanprima (ID);
  • Sanprima Forte (ID);
  • Septran (IN, PK, PY);
  • Septran Forte (CR, DO, GT, HN, NI, PA, SV);
  • Septrin (AE, AU, BF, BH, BJ, CI, CY, ES, ET, GB, GH, GM, GN, ID, IE, IQ, IR, JO, KE, KR, KW, LR, LY, MA, ML, MR, MT, MU, MW, MX, NE, NG, OM, PE, PH, SA, SC, SD, SG, SL, SN, SY, TN, TZ, UG, VN, YE, ZM, ZW);
  • Septrin D.S. (EG);
  • Septrin DS (BH, HK);
  • Septrin Forte (AU);
  • Servitrim (MX);
  • Sevatrim (KR);
  • Sigaprim (DE);
  • Sinersul (HR);
  • Soltrim (MX);
  • Suftrex (EC);
  • Sulfacet (DE);
  • Sulfoid Trimetho (MX);
  • Sulfotrimin (DE);
  • Sulotrim (HR);
  • Suntrim (TH);
  • Suntrim Forte (TH);
  • Suprim (PE);
  • Suprin (IT);
  • Tagremin (RO);
  • Timexole (MX);
  • TMS (DE);
  • Trim (IT, ZA);
  • Trimaxazole (SG);
  • Trimetoger (MX);
  • Trimexan (CR, DO, GT, HN, NI, PA, SV);
  • Trimexazol (MX);
  • Trimexazole (TH);
  • Trimezol (BG);
  • Trimol (BH, QA);
  • Trimol D.S. (QA);
  • Trimoprim (HK);
  • Trimox (TW);
  • Trimoxis (PH);
  • Triomax (JO);
  • Trisolvat (CO);
  • Trisul (BD, NZ);
  • Trizole (PH);
  • Tryseptol (UA);
  • Umoxazole (ZW);
  • Xepaprim (ID);
  • Xepaprim Forte (ID);
  • Zoltrim (EC);
  • Zultrop (ID);
  • Zultrop Forte (ID)


For country abbreviations used in Lexicomp (show table)

REFERENCES

  1. 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694. doi: 10.1111/jgs.15767. [PubMed 30693946]
  2. Acharya A, Acharya SP, Bhattarai TR. Cotrimoxazole induced Steven Johnson Syndrome: A Case Report. JNMA J Nepal Med Assoc. 2020;58(229):702-704. doi:10.31729/jnma.4999 [PubMed 33068096]
  3. Azfar RS, Cohn J, Schaffer A, Kim EJ. Trimethoprim sulfamethoxazole-induced sweet syndrome. Arch Dermatol. 2009;145(2):215-216. doi:10.1001/archderm.145.2.215 [PubMed 19221284]
  4. Agha R, Goldberg MB. Shigella infection: treatment and prevention in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 16, 2021.
  5. Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]
  6. Ahn YH, Goldman JM. Trimethoprim-sulfamethoxazole and hyponatremia. Ann Intern Med. 1985;103(1):161-162. doi:10.7326/0003-4819-103-1-161_3 [PubMed 3873890]
  7. Alappan R, Buller GK, Perazella MA. Trimethoprim-sulfamethoxazole therapy in outpatients: is hyperkalemia a significant problem?. Am J Nephrol. 1999;19(3):389-394. doi:10.1159/000013483 [PubMed 10393376]
  8. Alvarez RF, Mattos AA, Corrêa EB, Cotrim HP, Nascimento TV. Trimethoprim-sulfamethoxazole versus norfloxacin in the prophylaxis of spontaneous bacterial peritonitis in cirrhosis. Arq Gastroenterol. 2005;42(4):256-262. doi:10.1590/s0004-28032005000400012 [PubMed 16444382]
  9. American Academy of Pediatrics (AAP). In: Kimberlin DW, Brady MT, Jackson MA, Long SA, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015.
  10. American Academy of Pediatrics Subcommittee on Urinary Tract Infection, Steering Committee on Quality improvement and Management. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128(3):595-610. [PubMed 21873693]
  11. Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med. 2007;146(9):657-665. doi:10.7326/0003-4819-146-9-200705010-00009 [PubMed 17470834]
  12. Anderson A, Bijlmer H, Fournier PE, et al. Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group. MMWR Recomm Rep. 2013;62(RR-03):1-30. [PubMed 23535757]
  13. Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52. [PubMed 27060684]
  14. Andrès E, Noel E, Maloisel F. Trimethoprim-sulfamethoxazole-induced life-threatening agranulocytosis. Arch Intern Med. 2003;163(16):1975-1976. doi:10.1001/archinte.163.16.1975 [PubMed 12963573]
  15. Andrès E, Mourot-Cottet R. Non-chemotherapy drug-induced neutropenia - an update. Expert Opin Drug Saf. 2017;16(11):1235-1242. doi:10.1080/14740338.2017.1376645 [PubMed 28879784]
  16. Anger J, Lee U, Ackerman AL, et al. Recurrent uncomplicated urinary tract infections in women: AUA/CUA/SUFU guideline. J Urol. 2019;202(2):282-289. doi: 10.1097/JU.0000000000000296. [PubMed 31042112]
  17. Anliker MD, Wüthrich B. Acute generalized exanthematous pustulosis due to sulfamethoxazole with positive lymphocyte transformation test (LTT). J Investig Allergol Clin Immunol. 2003;13(1):66-68. [PubMed 12861854]
  18. Anti-infective drug use in relation to the risk of agranulocytosis and aplastic anemia. A report from the International Agranulocytosis and Aplastic Anemia Study. Arch Intern Med. 1989;149(5):1036-1040. [PubMed 2785785]
  19. Antoniou T, Gomes T, Juurlink DN, Loutfy MR, Glazier RH, Mamdani MM. Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. Arch Intern Med. 2010;170(12):1045-1049. [PubMed 20585070]
  20. Antoniou T, Gomes T, Mamdani MM, et al. Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study. BMJ. 2011;343. [PubMed 21911446]
  21. Antoniou T, Hollands S, Macdonald EM, et al. Trimethoprim-sulfamethoxazole and risk of sudden death among patients taking spironolactone. CMAJ. 2015;187(4):E138-143. [PubMed 25646289]
  22. Arndt PA, Garratty G, Wolf CF, Rivera M. Haemolytic anaemia and renal failure associated with antibodies to trimethoprim and sulfamethoxazole. Transfus Med. 2011;21(3):194-198. doi:10.1111/j.1365-3148.2010.01061.x [PubMed 21175904]
  23. Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians, 2007, 154.
  24. Ashkenazi S, Amir J, Waisman Y, et al, "A Randomized, Double-Blind Study Comparing Cefixime and Trimethoprim-Sulfamethoxazole in the Treatment of Childhood Shigellosis," J Pediatr, 1993, 123(5):817-21. [PubMed 8229498]
  25. Azfar RS, Cohn J, Schaffer A, Kim EJ. Trimethoprim sulfamethoxazole-induced sweet syndrome. Arch Dermatol. 2009;145(2):215-216. doi:10.1001/archderm.145.2.215 [PubMed 19221284]
  26. Babayev R, Terner S, Chandra S, Radhakrishnan J, Mohan S. Trimethoprim-associated hyponatremia. Am J Kidney Dis. 2013;62(6):1188-1192. doi:10.1053/j.ajkd.2013.06.007 [PubMed 23891358]
  27. Bactrim (sulfamethoxazole and trimethoprim) injection [prescribing information]. Cranbury, NJ: Sun Pharmaceuticals; May 2021.
  28. Bactrim and Bactrim DS (sulfamethoxazole and trimethoprim) [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries Inc; April 2021.
  29. Bactrim Pedatric Suspension (sulfamethoxazole and trimethoprim) [prescribing information]. Cranbury, NJ: Sun Pharmaceuticals; May 2021.
  30. Baddour LM, Harper M. Animal bites (dogs, cats, and other animals): evaluation and management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 20, 2021a.
  31. Baddour LM, Harper M. Human bites: evaluation and management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 28, 2021b.
  32. Baddour LM. Impetigo. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 22, 2021c.
  33. Bapani S, Epperla N, Kasirye Y, Mercier R, Garcia-Montilla R. ADAMTS13 deficiency and thrombotic thrombocytopenic purpura associated with trimethoprim-sulfamethoxazole. Clin Med Res. 2013;11(2):86-90. doi:10.3121/cmr.2012.1105 [PubMed 23262188]
  34. Ben Salem C, Badreddine A, Fathallah N, Slim R, Hmouda H. Drug-induced hyperkalemia. Drug Saf. 2014;37(9):677-692. [PubMed 25047526]
  35. Berbari E, Baddour LM, Chen AF. Prosthetic joint infection: treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 6, 2019.
  36. Berg PA, Daniel PT. Co-trimoxazole-induced hepatic injury--an analysis of cases with hypersensitivity-like reactions. Infection. 1987;15(suppl 5):S259-S264. doi:10.1007/BF01643200 [PubMed 3501774]
  37. Betschart C, Albrich WC, Brandner S, et al. Guideline of the Swiss Society of Gynaecology and Obstetrics (SSGO) on acute and recurrent urinary tract infections in women, including pregnancy. Swiss Med Wkly. 2020;150:w20236. doi:10.4414/smw.2020.20236 [PubMed 32365216]
  38. Bijl AM, Van der Klauw MM, Van Vliet AC, Stricker BH. Anaphylactic reactions associated with trimethoprim. Clin Exp Allergy. 1998;28(4):510-512. doi:10.1046/j.1365-2222.1998.00258.x [PubMed 9641580]
  39. Bissuel F, Cotte L, Crapanne JB, et al, “Trimethoprim-Sulphamethoxazole Rechallenge in 20 Previously Allergic HIV-Infected Patients After Homeopathic,” AIDS, 1995, 9(4):407-8. [PubMed 7794554]
  40. Björnsson E, Jerlstad P, Bergqvist A, Olsson R. Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden. Scand J Gastroenterol. 2005;40(9):1095-1101. doi:10.1080/00365520510023846 [PubMed 16165719]
  41. Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic allergy. Lancet. 2019;393(10167):183-198. doi:10.1016/S0140-6736(18)32218-9 [PubMed 30558872]
  42. Bosilkovski M, Arapović J, Keramat F. Human brucellosis in pregnancy - an overview. Bosn J Basic Med Sci. 2020;20(4):415-422. doi:10.17305/bjbms.2019.4499 [PubMed 31782698]
  43. Bowen AC, Carapetis JR, Currie BJ, Fowler V Jr, Chambers HF, Tong SYC. Sulfamethoxazole-Trimethoprim (Cotrimoxazole) for Skin and Soft Tissue Infections Including Impetigo, Cellulitis, and Abscess. Open Forum Infect Dis. 2017;4(4):ofx232. doi: 10.1093/ofid/ofx232. [PubMed 29255730]
  44. Brackett CC, Singh H, Block JH. Likelihood and mechanisms of cross-allergenicity between sulfonamide antibiotics and other drugs containing a sulfonamide functional group. Pharmacotherapy. 2004;24(7):856-870. doi:10.1592/phco.24.9.856.36106 [PubMed 15303450]
  45. Bradley JS, Nelson JD, Barnett E, et al. Nelson's Pediatric Antimicrobial Therapy. 23rd ed. American Academy of Pediatrics; 2017.
  46. Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]
  47. Brown GR. Cotrimoxazole - optimal dosing in the critically ill. Ann Intensive Care. 2014;4:13. doi:10.1186/2110-5820-4-13 [PubMed 24910807]
  48. Brown KA, Khanafer N, Daneman N, Fisman DN. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrob Agents Chemother. 2013;57(5):2326-2332. doi:10.1128/AAC.02176-12 [PubMed 23478961]
  49. Bruner KE, Coop CA, White KM. Trimethoprim-sulfamethoxazole-induced aseptic meningitis-not just another sulfa allergy. Ann Allergy Asthma Immunol. 2014;113(5):520-526. doi:10.1016/j.anai.2014.08.006 [PubMed 25240332]
  50. Buijs BS, van den Berk GE, Boateng CP, Hoepelman AI, van Maarseveen EM, Arends JE. Cross-reactivity between darunavir and trimethoprim-sulfamethoxazole in HIV-infected patients. AIDS. 2015;29(7):785-791. doi:10.1097/QAD.0000000000000612 [PubMed 25985401]
  51. Calabrò V, Cascone A, Malaspina P, Battistuzzi G. Glucose-6-phosphate dehydrogenase (G6PD) deficiency in southern Italy: a case of G6PD A(-) associated with favism. Haematologica. 1989;74(1):71-73. [PubMed 2498187]
  52. Can C, Akkelle E, Bay B, Arıcan O, Yalçın O, Yazicioglu M. Generalized fixed drug eruption in a child due to trimethoprim/sulfamethoxazole. Pediatr Allergy Immunol. 2014;25(4):413-415. doi:10.1111/pai.12204 [PubMed 24750132]
  53. Carroll TG, Carroll MG. Methemoglobinemia in a pediatric oncology patient receiving sulfamethoxazole/trimethoprim prophylaxis. Am J Case Rep. 2016;17:499-502. doi:10.12659/ajcr.897820 [PubMed 27424851]
  54. Centers for Disease Control and Prevention (CDC). Brucellosis reference guide: exposures, testing, and prevention. https://www.cdc.gov/brucellosis/pdf/brucellosi-reference-guide.pdf. Updated February 2017. Accessed August 2020.
  55. Centers for Disease Control and Prevention (CDC). DPDx - Laboratory identification of parasitic diseases of public health concern. Cystoisosporiasis. https://www.cdc.gov/dpdx. Updated November 29, 2013b. Accessed October 13, 2017.
  56. Centers for Disease Control and Prevention (CDC). FAQs for clinicians about C. diff. https://www.cdc.gov/cdiff/clinicians/faq.html. Updated March 27, 2020.
  57. Centers for Disease Control and Prevention (CDC), "Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children," MMWR Recomm Rep, 2009, 58(RR-11):1-166. Available at http://www.antimicrobe.org/h04c.files/history/CDC-HIV%20ExposeInfectChildren-2009.pdf
  58. Centers for Disease Control and Prevention (CDC). National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS): Human Isolates Final Report, 2010. Atlanta, Georgia: US Department of Health and Human Services, CDC, 2012. https://www.cdc.gov/narms/pdf/2010-annual-report-narms.pdf.
  59. Centers for Disease Control and Prevention (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]
  60. Centers for Disease Control and Prevention (CDC). Nocardiosis: laboratory diagnostics and treatment. https://www.cdc.gov/nocardiosis/health-care-workers/laboratory-diagnostics.html. Updated March 30, 2016. Accessed October 13, 2017.
  61. Centers for Disease Control and Prevention (CDC). Treatment for cyclosporiasis. https://www.cdc.gov/parasites/cyclosporiasis/health_professionals/tx.html. Updated January 10, 2013a. Accessed October 10, 2017.
  62. Chalasani N, Bonkovsky HL, Fontana R, et al. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148(7):1340-52.e7. doi:10.1053/j.gastro.2015.03.006 [PubMed 25754159]
  63. Chalasani N, Reddy KRK, Fontana RJ, et al. Idiosyncratic drug induced liver injury in African-Americans is associated with greater morbidity and mortality compared to Caucasians. Am J Gastroenterol. 2017;112(9):1382-1388. doi:10.1038/ajg.2017.215 [PubMed 28762375]
  64. Chantachaeng W, Chularojanamontri L, Kulthanan K, Jongjarearnprasert K, Dhana N. Cutaneous adverse reactions to sulfonamide antibiotics. Asian Pac J Allergy Immunol. 2011;29(3):284-289. [PubMed 22053600]
  65. Cheng AC, McBryde ES, Wuthiekanun V, et al. Dosing regimens of cotrimoxazole (trimethoprim-sulfamethoxazole) for melioidosis. Antimicrob Agents Chemother. 2009;53(10):4193-4199. doi: 10.1128/AAC.01301-08. [PubMed 19620336]
  66. Choo V, “UK Revises Indications for Co-Trimoxazole,” Lancet, 1995, 346(8968):175.
  67. Clajus C, Kühn-Velten WN, Schmidt JJ, et al. Cotrimoxazole plasma levels, dialyzer clearance and total removal by extended dialysis in a patient with acute kidney injury: risk of under-dosing using current dosing recommendations. BMC Pharmacol Toxicol. 2013;14:19. doi:10.1186/2050-6511-14-19 [PubMed 23551893]
  68. Cockerill FR and Edson RS, “Trimethoprim-Sulfamethoxazole,” Mayo Clin Proc, 1991, 66(12):1260-9. [PubMed 1749295]
  69. Cordero-Ampuero J, Esteban J, Garcia-Cimbrelo E, Munuera L, Escobar R. Low relapse with oral antibiotics and two-stage exchange for late arthroplasty infections in 40 patients after 2-9 years. Acta Orthopaedica. 2007;78(4):511-519. [PubMed 17966006]
  70. Crider KS, Cleves MA, Reefhuis J, et al, "Antibacterial Medication Use During Pregnancy and Risk of Birth Defects: National Birth Defects Prevention Study," Arch Pediatr Adolesc Med, 2009, 163(11):978-85. [PubMed 19884587]
  71. Curkovic I, Lüthi B, Franzen D, Ceschi A, Rudiger A, Corti N. Trimethoprim/Sulfamethoxazole pharmacokinetics in two patients undergoing continuous venovenous hemodiafiltration. Ann Pharmacother. 2010;44(10):1669‐1672. doi:10.1345/aph.1P160 [PubMed 20823279]
  72. Currie B, Anstey NM. Melioidosis: treatment and prevention. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 22, 2021.
  73. Czeizel AE, Rockenbauer M, Sørensen HT, et al, "The Teratogenic Risk of Trimethoprim-Sulfonamides: A Population Based Case-Control Study," Reprod Toxicol, 2001, 15(6):637-46. [PubMed 11738517]
  74. Della-Giustina K and Chow G, "Medications in Pregnancy and Lactation," Emerg Med Clin North Am, 2003, 21(3):585-613. [PubMed 12962348]
  75. Desai M, Fathallah J, Nutalapati V, Saligram S. Antibiotics versus no antibiotics for acute uncomplicated diverticulitis: a systematic review and meta-analysis. Dis Colon Rectum. 2019;62(8):1005-1012. doi:10.1097/DCR.0000000000001324 [PubMed 30664553]
  76. Don BR. The effect of trimethoprim on potassium and uric acid metabolism in normal human subjects. Clin Nephrol. 2001;55(1):45-52. [PubMed 11200867]
  77. Dorn JM, Alpern M, McNulty C, Volcheck GW. Sulfonamide drug allergy. Curr Allergy Asthma Rep. 2018;18(7):38. doi:10.1007/s11882-018-0791-9 [PubMed 29876667]
  78. Dow D. Trimethoprim-sulfamethoxazole in the treatment of chronic prostatitis. Can Med Assoc J. 1975;112(13 Spec No):26-27. [PubMed 1093649]
  79. Drobnis EZ, Nangia AK. Antimicrobials and male reproduction. Adv Exp Med Biol. 2017;1034:131-161. doi:10.1007/978-3-319-69535-8_10 [PubMed 29256130]
  80. Eliaszewicz M, Flahault A, Roujeau JC, et al. Prospective evaluation of risk factors of cutaneous drug reactions to sulfonamides in patients with AIDS. J Am Acad Dermatol. 2002;47(1):40-46. doi:10.1067/mjd.2002.120468 [PubMed 12077579]
  81. Eyre RC. Evaluation of acute scrotal pain in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 6, 2021.
  82. Fishman JA. Prevention of infection caused by Pneumocystis carinii in transplant recipients. Clin Infect Dis. 2001;33(8):1397-1405. [PubMed 11565082]
  83. Fishman JA, Alexander BD. Prophylaxis of infections in solid organ transplantation. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 23, 2020.
  84. Fraser TN, Avellaneda AA, Graviss EA, Musher DM. Acute kidney injury associated with trimethoprim/sulfamethoxazole. J Antimicrob Chemother. 2012;67(5):1271-1277. doi:10.1093/jac/dks030 [PubMed 22351681]
  85. Gaudel P, Qavi AH, Basak P. Life-threatening thrombocytopenia secondary to trimethoprim/sulfamethoxazole. Cureus. 2017;9(12):e1963. doi:10.7759/cureus.1963 [PubMed 29492352]
  86. Gentry CA, Nguyen AT. An evaluation of hyperkalemia and serum creatinine elevation associated with different dosage levels of outpatient trimethoprim-sulfamethoxazole with and without concomitant medications. Ann Pharmacother. 2013;47(12):1618-1626. doi: 10.1177/1060028013509973. [PubMed 24259630]
  87. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2021 report. https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf. Accessed July 16, 2021.
  88. Goldenberg DL, Sexton DJ. Septic arthritis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 6, 2019.
  89. Golightly LK, Teitelbaum I, Kiser TH, et al, eds. Renal Pharmacotherapy. New York, NY: Springer Science; 2013.
  90. Gordin FM, Simon GL, Wofsy CB, Mills J. Adverse reactions to trimethoprim-sulfamethoxazole in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1984;100(4):495-499. doi:10.7326/0003-4819-100-4-495 [PubMed 6230976]
  91. Gordin F, Gibert C, Schmidt ME. Clostridium difficile colitis associated with trimethoprim-sulfamethoxazole given as prophylaxis for Pneumocystis carinii pneumonia. Am J Med. 1994;96(1):94-95. doi:10.1016/0002-9343(94)90124-4 [PubMed 8304370]
  92. Greenberg S, Reiser IW, Chou SY, Porush JG. Trimethoprim-sulfamethoxazole induces reversible hyperkalemia. Ann Intern Med. 1993;119(4):291-295. doi:10.7326/0003-4819-119-4-199308150-00007 [PubMed 8328737]
  93. Grinlington L, Choo S, Cranswick N, Gwee A. Non-β-lactam antibiotic hypersensitivity reactions. Pediatrics. 2020;145(1):e20192256. doi:10.1542/peds.2019-2256 [PubMed 31796504]
  94. Guerrant RL, Van Gilder T, Steiner TS, et al; Infectious Diseases Society of America. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001;32(3):331-351. [PubMed 11170940]
  95. Gupta K, Hooton TM, Naber KG, et al; Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-e120. doi: 10.1093/cid/ciq257. [PubMed 21292654]
  96. Harle DG, Baldo BA, Smal MA, Van Nunen SA. An immunoassay for the detection of IgE antibodies to trimethoprim in the sera of allergic patients. Clin Allergy. 1987;17(3):209-216. doi:10.1111/j.1365-2222.1987.tb02005.x [PubMed 3608139]
  97. Harle DG, Baldo BA, Wells JV. Drugs as allergens: detection and combining site specificities of IgE antibodies to sulfamethoxazole. Mol Immunol. 1988;25(12):1347-1354. doi:10.1016/0161-5890(88)90050-8 [PubMed 3237218]
  98. Harris RC, Lucey JF, Maclean JR. Kernicterus in premature infants associated with low concentrations of bilirubin in the plasma. Pediatrics. 1958;21(6):875-884. [PubMed 13553575]
  99. Hasbun R. Initial therapy and prognosis of bacterial meningitis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 12, 2021.
  100. Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy. 2009;29(5):562-577. [PubMed 19397464]
  101. Hensgens MP, Goorhuis A, Dekkers OM, Kuijper EJ. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012;67(3):742-748. doi:10.1093/jac/dkr508 [PubMed 22146873]
  102. Hernández-Díaz S and Mitchell AA, Author reply, NEJM, 2001, 344(12): 934-5.
  103. Hernández-Díaz S, Werler MM, Walker AM, et al, "Folic Acid Antagonists During Pregnancy and the Risk of Birth Defects," N Engl J Med, 2000, 343(22):1608-14. [PubMed 11096168]
  104. Hoge CW, Shlim DR, Ghimire M, et al. Placebo-controlled trial of co-trimoxazole for cyclospora infections among travellers and foreign residents in Nepal Nepal [published correction appears in Lancet. 1995;345(8956):1060]. Lancet. 1995;345(8951):691-693. [PubMed 7885125]
  105. Hoosen K, Mosam A, Dlova NC, Grayson W. An update on adverse cutaneous drug reactions in HIV/AIDS. Dermatopathology (Basel). 2019;6(2):111-125. doi:10.1159/000496389 [PubMed 31700852]
  106. Hooton TM. Acute simple cystitis in men. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 11, 2021b.
  107. Hooton TM, Gupta K. Acute complicated urinary tract infection (including pyelonephritis) in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 20, 2021d.
  108. Hooton TM, Gupta K. Acute simple cystitis in women. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 16, 2021a.
  109. Hooton TM, Gupta K. Recurrent simple cystitis in women. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 13, 2021c.
  110. Hoppu K, "Age Differences in Trimethoprim Pharmacokinetics: Need for Revised Dosing in Children?" Clin Pharmacol Ther, 1987, 41(3):336-43. [PubMed 3816021]
  111. Hoppu K. Changes in trimethoprim pharmacokinetics after the newborn period. Arch Dis Child. 1989;64(3):343-345. [PubMed 2705795]
  112. Hughes W, Leoung G, Kramer F, et al, “Comparison of Atovaquone (566C80) With Trimethoprim-Sulfamethoxazole to Treat Pneumocystis carinii Pneumonia in Patients With AIDS,” N Engl J Med, 1993, 328(21):1521-7. [PubMed 8479489]
  113. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
  114. Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126. [PubMed 10891521]
  115. Ito S, Blajchman A, Stephenson M, Eliopoulos C, Koren G. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 1993;168(5):1393-1399. doi:10.1016/s0002-9378(11)90771-6 [PubMed 8498418]
  116. Jarosinki PF, Kennedy PE, and Gallelli JF, “Stability of Concentrated Trimethoprim-Sulfamethoxazole Admixtures,” AJHP, 1989, 46(4):732-7. [PubMed 2785757]
  117. Jick H and Derby LE, “A Large Population-Based Follow-Up Study of Trimethoprim-Sulfamethoxazole, Trimethoprim, and Cephalexin for Uncommon Serious Drug Toxicity,” Pharmacotherapy, 1995, 15(4):428-32. [PubMed 7479194]
  118. Jick H and Derby LE, “Is Co-Trimoxazole Safe?” Lancet, 1995, 345(8957):1118-9. [PubMed 7715367]
  119. Johnson MP, Goodwin SD, Shands JW Jr. Trimethoprim-sulfamethoxazole anaphylactoid reactions in patients with AIDS: case reports and literature review. Pharmacotherapy. 1990;10(6):413-416. [PubMed 2287564]
  120. Kardaun SH, Sekula P, Valeyrie-Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169(5):1071-1080. doi:10.1111/bjd.12501 [PubMed 23855313]
  121. Kesner JM, Yardman-Frank JM, Mercier RC, et al. Trimethoprim and sulfamethoxazole transmembrane clearance during modeled continuous renal replacement therapy. Blood Purif. 2014;38(3-4):195‐202. doi:10.1159/000368884 [PubMed 25531772]
  122. Khan DA, Knowles SR, Shear NH. Sulfonamide hypersensitivity: fact and fiction. J Allergy Clin Immunol Pract. 2019;7(7):2116-2123. doi:10.1016/j.jaip.2019.05.034 [PubMed 31495421]
  123. Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.
  124. Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015.
  125. Kobrinsky NL, Ramsay NK. Acute megaloblastic anemia induced by high-dose trimethoprim-sulfamethoxazole. Ann Intern Med. 1981;94(6):780-781. doi:10.7326/0003-4819-94-6-780 [PubMed 6972183]
  126. Kocak Z, Hatipoglu CA, Ertem G, et al. Trimethoprim-sulfamethoxazole induced rash and fatal hematologic disorders. J Infect. 2006;52(2):e49-e52. doi:10.1016/j.jinf.2005.05.008 [PubMed 15996741]
  127. Kuyucu S, Mori F, Atanaskovic-Markovic M, et al. Hypersensitivity reactions to non-betalactam antibiotics in children: an extensive review. Pediatr Allergy Immunol. 2014;25(6):534-543. doi:10.1111/pai.12273 [PubMed 25201401]
  128. Lee M, Bozzo P, Einarson A, et al, "Urinary Tract Infections in Pregnancy," Can Fam Physician, 2008, 54(6):853-4. [PubMed 18556490]
  129. Lee AJ, Maddix DS. Trimethoprim/sulfamethoxazole-induced hypoglycemia in a patient with acute renal failure. Ann Pharmacother. 1997;31(6):727-732. doi:10.1177/106002809703100611 [PubMed 9184713]
  130. Lerner PI. Nocardiosis. Clin Infect Dis. 1996;22(6):891-903. [PubMed 8783685]
  131. Lewis SS, Zaas A. Stenotrophomonas maltophilia. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 25, 2021.
  132. Li PK, Szeto CC, Piraino B, et al, "Peritoneal Dialysis-Related Infections Recommendations: 2010 Update," Perit Dial Int, 2010, 30(4):393-423 [PubMed 20628102]
  133. Li YJ, Phillips E, Dellinger A, et al. HLA-B*14:01 and HLA-B*35:01 are associated with trimethoprim-sulfamethoxazole induced liver injury [published online ahead of print, 2020 Apr 9]. Hepatology. 2020;10.1002/hep.31258. doi:10.1002/hep.31258 [PubMed 32270503]
  134. Lieberthal AS, Carroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media [published correction appears in Pediatrics. 2014;133(2):346]. Pediatrics. 2013;131(3):e964-999. [PubMed 23439909]
  135. Limper AH, Knox KS, Sarosi GA, et al; American Thoracic Society Fungal Working Group. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011;183(1):96-128. doi: 10.1164/rccm.2008-740ST. [PubMed 21193785]
  136. Lin D, Tucker MJ, Rieder MJ. Increased adverse drug reactions to antimicrobials and anticonvulsants in patients with HIV infection. Ann Pharmacother. 2006;40(9):1594-1601. doi:10.1345/aph.1G525 [PubMed 16912251]
  137. Linnik YA, Tsui EW, Martin IW, et al. The first reported case of concurrent trimethoprim-sulfamethoxazole-induced immune hemolytic anemia and thrombocytopenia. Transfusion. 2017;57(12):2937-2941. doi:10.1111/trf.14315 [PubMed 28905389]
  138. Lipsitz R, Garges S, Aurigemma R, et al. Workshop on treatment of and postexposure prophylaxis for Burkholderia pseudomallei and B. mallei Infection, 2010. Emerg Infect Dis. 2012;18(12):e2. doi: 10.3201/eid1812.120638. [PubMed 23171644]
  139. Lipsky BA. Medical treatment of diabetic foot infections. Clin Infect Dis. 2004;39(suppl 2):S104-S114. [PubMed 15306988]
  140. Lipsky BA, Byren I, Hoey CT. Treatment of bacterial prostatitis. Clin Infect Dis. 2010;50(12):1641-1652. doi:10.1086/652861 [PubMed 20459324]
  141. Lipsky BA, Berendt AR, Cornia PB, et al; Infectious Diseases Society of America. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012;54(12):e132-e173. doi: 10.1093/cid/cis346. [PubMed 22619242]
  142. Lipsky BA, Peters EJ, Senneville E, et al Expert opinion on the management of infections in the diabetic foot. Diabetes Metab Res Rev. 2012;28(suppl 1):163-178. doi: 10.1002/dmrr.2248. [PubMed 22271739]
  143. Liu C, Bayer A, Cosgrove SE, et al; Infectious Diseases Society of America. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18-e55. doi:10.1093/cid/ciq146 [PubMed 21208910]
  144. Liu P, Ranches GP, Gold JA. Trimethoprim-sulfamethoxazole induced circulatory shock in a human immunodeficiency virus uninfected patient: a case report and review. BMC Pharmacol Toxicol. 2018;19(1):76. doi:10.1186/s40360-018-0269-3 [PubMed 30458864]
  145. Long S, Pickering L, eds. Principles and Practice of Pediatric Infectious Diseases. 4th ed. Philadelphia, PA: Saunders Elsevier; 2012.
  146. Lontos S, Shelton E, Angus PW, et al. A randomized controlled study of trimethoprim-sulfamethoxazole versus norfloxacin for the prevention of infection in cirrhotic patients. J Dig Dis. 2014;15(5):260-267. doi:10.1111/1751-2980.12132 [PubMed 24612987]
  147. Looney WJ, Narita M, Mühlemann K. Stenotrophomonas maltophilia: an emerging opportunist human pathogen. Lancet Infect Dis. 2009;9(5):312-323. doi: 10.1016/S1473-3099(09)70083-0. [PubMed 19393961]
  148. Lopez JA, Harold JG, Rosenthal MC, Oseran DS, Schapira JN, Peter T. QT prolongation and torsades de pointes after administration of trimethoprim-sulfamethoxazole. Am J Cardiol. 1987;59(4):376-377. doi:10.1016/0002-9149(87)90824-1 [PubMed 3492908]
  149. Lundstrom TS and Sobel JD, “Vancomycin, Trimethoprim-Sulfamethoxazole, and Rifampin,” Infect Dis Clin North Am, 1995, 9(3):747-67. [PubMed 7490442]
  150. Mahmood SB, Abou Zahr Z. Systemic lupus erythematosus triggered by trimethoprim-sulfamethoxazole. Scand J Rheumatol. 2020;49(6):507-508. doi:10.1080/03009742.2020.1719543 [PubMed 32293218]
  151. Mainra RR, Card SE. Trimethoprim-sulfamethoxazole-associated hepatotoxicity - part of a hypersensitivity syndrome. Can J Clin Pharmacol. 2003;10(4):175-178. [PubMed 14712321]
  152. Markowitz N, Saravolatz LD. Use of trimethoprim-sulfamethoxazole in a glucose-6-phosphate dehydrogenase-deficient population. Rev Infect Dis. 1987;9(suppl 2):S218-S229. doi:10.1093/clinids/9.supplement_2.s218 [PubMed 3495027]
  153. Martin SI, Fishman JA; AST Infectious Diseases Community of Practice. Pneumocystis pneumonia in solid organ transplantation. Am J Transplant. 2013;13(suppl 4):272-279. doi: 10.1111/ajt.12119. [PubMed 23465020]
  154. Masur H, Kaplan JE, Holmes KK; US Public Health Service; Infectious Diseases Society of America. Guidelines for preventing opportunistic infections among HIV-Infected persons – 2002. Recommendations of the US Public Health Service and the Infectious Diseases Society of America. Ann Intern Med. 2002;137(5)(pt 2):435-478. [PubMed 12617574]
  155. Mathews WA, Manint JE, Kleiss J. Trimethoprim-sulfamethoxazole-induced hypoglycemia as a cause of altered mental status in an elderly patient. J Am Board Fam Pract. 2000;13(3):211-212. doi:10.3122/15572625-13-3-211 [PubMed 10826870]
  156. Matok I, Gorodischer R, Koren G, et al, "Exposure to Folic Acid Antagonists During the First Trimester of Pregnancy and the Risk of Major Malformations," Br J Clin Pharmacol, 2009, 68(6):956-62. [PubMed 20002091]
  157. Mattoo TK. Medical management of vesicoureteral reflux - quiz within the article. Don't overlook placebos. Pediatr Nephrol. 2007;22(8):1113-1120. [PubMed 17483966]
  158. Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised guidelines on the management of intra-abdominal infection. Surg Infect (Larchmt). 2017;18(1):1-76. doi:10.1089/sur.2016.261 [PubMed 28085573]
  159. McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48. doi:10.1093/cid/cix1085 [PubMed 29462280]
  160. Meares EM. Long-term therapy of chronic bacterial prostatitis with trimethoprim-sulfamethoxazole. Can Med Assoc J. 1975;112(13 Spec No):22-25. [PubMed 236820]
  161. Meyers RS, Thackray J, Matson KL, et al. Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List. J Pediatr Pharmacol Ther. 2020;25(3):175-191. [PubMed 32265601]
  162. Meyrier A, Fekete T. Acute bacterial prostatitis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 9, 2020a.
  163. Meyrier A, Fekete T. Chronic bacterial prostatitis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 23, 2021.
  164. Micheletti RG, Chiesa-Fuxench Z, Noe MH, et al. Stevens-johnson syndrome/toxic epidermal necrolysis: a multicenter retrospective study of 377 adult patients from the United States. J Invest Dermatol. 2018;138(11):2315-2321. doi:10.1016/j.jid.2018.04.027 [PubMed 29758282]
  165. Miller JO, Taylor J, Goldman JL. Severe acute respiratory failure in healthy adolescents exposed to trimethoprim-sulfamethoxazole. Pediatrics. 2019;143(6). [PubMed 31142578]
  166. Miller LG, Daum RS, Creech CB, et al; DMID 07-0051 Team. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015;372(12):1093-1103. doi: 0.1056/NEJMoa1403789. [PubMed 25785967]
  167. Miller RD, Salter AJ. The passage of trimethoprim/sulfamethoxazole into breast milk and its significance. Proceedings of the 8th international congress of chemotherapy, Athens. Hellenic Soc Chemother. 1974;1:687-691.
  168. Mitrano JA, Spooner LM, Belliveau P. Excretion of antimicrobials used to treat methicillin-resistant Staphylococcus aureus infections during lactation: safety in breastfeeding infants. Pharmacotherapy. 2009;29(9):1103-1109. [PubMed 19698015]
  169. Mitta A, Curtis BR, Reese JA, George JN. Drug-induced thrombocytopenia: 2019 update of clinical and laboratory data. Am J Hematol. 2019;94(3):E76-E78. doi:10.1002/ajh.25379 [PubMed 30549322]
  170. Mockenhaupt M, Viboud C, Dunant A, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol. 2008;128(1):35-44. doi:10.1038/sj.jid.5701033 [PubMed 17805350]
  171. Montoya JG, Giraldo LF, Efron B, et al. Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center. Clin Infect Dis. 2001;33(5):629-640. [PubMed 11486285]
  172. Mori H, Kuroda Y, Imamura S, et al. Hyponatremia and/or hyperkalemia in patients treated with the standard dose of trimethoprim-sulfamethoxazole. Intern Med. 2003;42(8):665-669. doi:10.2169/internalmedicine.42.665 [PubMed 12924488]
  173. Myers MW, Jick H. Hospitalization for serious blood and skin disorders following co-trimoxazole. Br J Clin Pharmacol. 1997;43(6):649-651. doi:10.1046/j.1365-2125.1997.00590.x [PubMed 9205827]
  174. Naber K, Vergin H, and Weigand W, “Pharmacokinetics of Co-trimoxazole and Co-tetroxazine in Geriatric Patients,” Infection, 1981, 9(5):239-43. [PubMed 6975241]
  175. Nahata MC. Dosage regimens of trimethoprim/sulfamethoxazole (TPM/SMX) in patients with renal dysfunction. Ann Pharmacother. 1995;29(12):1300. [PubMed 8672842]
  176. Nayak SU, Simon GL. Myocarditis after trimethoprim/sulfamethoxazole treatment for ehrlichiosis. Emerg Infect Dis. 2013;19(12):1975-1977. doi:10.3201/eid1912.121459 [PubMed 24274783]
  177. Nemecek BD, Hammond DA, eds. Demystifying Drug Dosing in Renal Dysfunction. Bethesda, MD: American Society of Health-System Pharmacists; 2019.
  178. Neumann S, Krause SW, Maschmeyer G, von Lilienfeld-Toal M; Infectious Diseases Working Party (AGIHO); German Society of Hematology and Oncology (DGHO). Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematological malignancies and solid tumors: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol. 2013;92(4):433-442. doi: 10.1007/s00277-013-1698-0. [PubMed 23412562]
  179. Nissenson AR, Wilson C, Holazo A. Pharmacokinetics of intravenous trimethoprim-sulfamethoxazole during hemodialysis. Am J Nephrol. 1987;7(4):270‐274. doi:10.1159/000167484 [PubMed 3500644]
  180. Noto H, Kaneko Y, Takano T, et al, “Severe Hyponatremia and Hyperkalemia Induced by Trimethoprim-Sulfamethoxazole in Patients With Pneumocystis carinii Pneumonia,” Intern Med, 1995, 34(2):96-9. [PubMed 7727887]
  181. Nunnari G, Celesia BM, Bellissimo F, et al. Trimethoprim-sulfamethoxazole-associated severe hypoglycaemia: a sulfonylurea-like effect. Eur Rev Med Pharmacol Sci. 2010;14(12):1015-1018. [PubMed 21375132]
  182. Odell GB, Hopkins J. In vitro studies of the effect of sulfonamides on bilirubin. AMA J Disease of Children. 1958;96:535-536. [PubMed Odell1958]
  183. Ogilvie AL, Toghill PJ. Cholestatic jaundice due to co-trimoxazole. Postgrad Med J. 1980;56(653):202-204. doi:10.1136/pgmj.56.653.202 [PubMed 7393813]
  184. Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE), Mocroft A, Reiss P, Kirk O, et al. Is it safe to discontinue primary Pneumocystis jiroveci pneumonia prophylaxis in patients with virologically suppressed HIV infection and a CD4 cell count <200 cells/microL? [published correction appears in Clin Infect Dis. 2010;51(9):1114]. Clin Infect Dis. 2010;51(5):611-619. doi: 10.1086/655761. [PubMed 20645862]
  185. Osmon DR, Berbari EF, Berendt AR, et al; Infectious Diseases Society of America. Diagnosis and management of prosthetic joint infection: clinical practice guideline by the Infectious Diseases Society of America. Clin Infect Dis. 2013,56(1):e1-e25. [PubMed 23223583]
  186. Oussalah A, Yip V, Mayorga C, et al. Genetic variants associated with T cell-mediated cutaneous adverse drug reactions: A PRISMA-compliant systematic review-An EAACI position paper. Allergy. 2020;75(5):1069-1098. doi:10.1111/all.14174 [PubMed 31899808]
  187. Palmer SM, Zaas A, Wolfe C. Fungal infections following lung transplantation. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 6, 2019.
  188. Pape JW, Verdier RI, Boncy M, Johnson WD Jr. Cyclospora infection in adults infected with HIV. Clinical manifestations, treatment, and prophylaxis. Ann Intern Med. 1994;121(9):654-657. [PubMed 7944073]
  189. Parekh TM, Raji M, Lin YL, Tan A, Kuo YF, Goodwin JS. Hypoglycemia after antimicrobial drug prescription for older patients using sulfonylureas. JAMA Intern Med. 2014;174(10):1605-1612. doi:10.1001/jamainternmed.2014.3293 [PubMed 25179404]
  190. Pemberton JH. Acute colonic diverticulitis: medical management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 8, 2021.
  191. Perazella MA. Trimethoprim-induced hyperkalaemia: clinical data, mechanism, prevention and management. Drug Saf. 2000;22(3):227-236. doi:10.2165/00002018-200022030-00006 [PubMed 10738846]
  192. Persichino J, Sutjita M. Anaphylactic-like reaction from trimethoprim-sulfamethoxazole in a patient with AIDS. Int J STD AIDS. 2016;27(7):595-597. doi:10.1177/0956462415587442 [PubMed 25999169]
  193. Platt R, Dreis MW, Kennedy DL, Kuritsky JN. Serum sickness-like reactions to amoxicillin, cefaclor, cephalexin, and trimethoprim-sulfamethoxazole. J Infect Dis. 1988;158(2):474-477. doi:10.1093/infdis/158.2.474 [PubMed 3261315]
  194. Porras MC, Lecumberri JN, Castrillón JL. Trimethoprim/sulfamethoxazole and metabolic acidosis in HIV-infected patients. Ann Pharmacother. 1998;32(2):185-189. doi:10.1345/aph.17042 [PubMed 9496402]
  195. Ransohoff DF, Jacobs G. Terminal hepatic failure following a small dose of sulfamethoxazole-trimethoprim. Gastroenterology. 1981;80(4):816-819. [PubMed 7202951]
  196. Raoult D. Treatment and prevention of Q fever. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 17, 2020.
  197. Reinke CM, Thomas JK, Graves AH. Apparent hemolysis in an AIDS patient receiving trimethoprim/sulfamethoxazole: case report and literature review. J Pharm Technol. 1995;11(6):256-295. doi:10.1177/875512259501100607 [PubMed 10157546]
  198. Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52(6):2065-2076. doi:10.1002/hep.23937 [PubMed 20949552]
  199. Runyon BA. Management of adult patients with ascites due to cirrhosis: update 2012. Alexandria, VA: American Association for the Study of Liver Diseases; 2012. https://www.aasld.org/sites/default/files/2019-06/AASLDPracticeGuidelineAsciteDuetoCirrhosisUpdate2012Edition4_.pdf. Accessed May 12, 2015.
  200. Runyon BA. Spontaneous bacterial peritonitis in adults: treatment and prophylaxis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 22, 2021.
  201. Samplaski MK, Nangia AK. Adverse effects of common medications on male fertility. Nat Rev Urol. 2015;12(7):401-413. doi:10.1038/nrurol.2015.145 [PubMed 26101108]
  202. Schiff D, Chan G, Stern L. Fixed drug combinations and the displacement of bilirubin from albumin. Pediatrics. 1971;48(1):139-141. [PubMed 5561865]
  203. Septra and Septra DS (sulfamethoxazole/trimethoprim) [prescribing information]. New York, NY: Pfizer; November 2020.
  204. Septra (sulfamethoxazole/trimethoprim) [product monograph]. Oakville, Ontario, Canada: Aspen Pharmacare Canada Inc; March 2021.
  205. Sethi S, Murphy TF. Management of infection in exacerbations of chronic obstructive pulmonary disease. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 31, 2020.
  206. Sexton DJ, Sampson JH. Intracranial epidural abscess. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 14, 2019a.
  207. Sexton DJ, Sampson JH. Spinal epidural abscess. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 14, 2019b.
  208. Shah SD, Cifu AS. Management of acute diverticulitis. JAMA. 2017;318(3):291-292. doi:10.1001/jama.2017.6373 [PubMed 28719679]
  209. Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017;65(12):e45-e80. doi:10.1093/cid/cix669 [PubMed 29053792]
  210. Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]
  211. Silverman WA, Andersen DH, Blanc WA, Crozier DN. A difference in mortality rate and incidence of kernicterus among premature infants allotted to two prophylactic antibacterial regimens. Pediatrics. 1956;18(4):614-625. [PubMed 13370229]
  212. Singh N, Gayowski T, Yu VL, Wagener MM. Trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in cirrhosis: a randomized trial. Ann Intern Med. 1995;122(8):595-598. doi:10.7326/0003-4819-122-8-199504150-00007 [PubMed 7887554]
  213. Singlas E, Colin JN, Rottembourg J, et al. Pharmacokinetics of sulfamethoxazole--trimethoprim combination during chronic peritoneal dialysis: effect of peritonitis. Eur J Clin Pharmacol. 1982;21(5):409‐415. doi:10.1007/BF00542328 [PubMed 7075646]
  214. Slatore CG, Tilles SA. Sulfonamide hypersensitivity. Immunol Allergy Clin North Am. 2004;24(3):477-vii. doi:10.1016/j.iac.2004.03.011 [PubMed 15242722]
  215. Slim R, Asmar N, Yaghi C, Honein K, Sayegh R, Chelala D. Trimethoprim-sulfamethoxazole-induced hepatotoxicity in a renal transplant patient. Indian J Nephrol. 2017;27(6):482-483. doi:10.4103/ijn.IJN_339_16 [PubMed 29217891]
  216. Snow V, Lascher S, Mottur-Pilson C; Joint Expert Panel on Chronic Obstructive Pulmonary Disease of the American College of Chest Physicians and the American College of Physicians-American Society of Internal Medicine. Evidence base for management of acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 2001;134(7):595-599. [PubMed 11281744]
  217. Southwick FS. Treatment and prognosis of bacterial brain abscess. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 6, 2019.
  218. Spelman D, Baddour LM. Cellulitis and skin abscess in adults: treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 11, 2021a.
  219. Spelman D. Treatment of nocardiosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 7, 2021b.
  220. Springer C, Eyal F, and Michel J, "Pharmacology of Trimethoprim-Sulfamethoxazole in Newborn Infants," J Pediatr, 1982, 100(4):647-50. [PubMed 7062219]
  221. Stamm WE, Counts GW, Wagner KF, et al. Antimicrobial prophylaxis of recurrent urinary tract infections: a double-blind, placebo-controlled trial. Ann Intern Med. 1980;92(6):770-775. doi: 10.7326/0003-4819-92-6-770. [PubMed 6992677]
  222. Stapleton A, Latham RH, Johnson C, Stamm WE. Postcoital antimicrobial prophylaxis for recurrent urinary tract infection. A randomized, double-blind, placebo-controlled trial. JAMA. 1990;264(6):703-706. [PubMed 2197450]
  223. Stevens DL, Bisno AL, Chambers HF, et al; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-e52. doi:10.1093/cid/ciu444 [PubMed 24973422]
  224. Stollman N, Smalley W, Hirano I; AGA Institute Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on the management of acute diverticulitis. Gastroenterology. 2015;149(7):1944-1949. doi:10.1053/j.gastro.2015.10.003 [PubMed 26453777]
  225. Strevel EL, Kuper A, Gold WL. Severe and protracted hypoglycaemia associated with co-trimoxazole use. Lancet Infect Dis. 2006;6(3):178-182. doi:10.1016/S1473-3099(06)70414-5 [PubMed 16500599]
  226. Sulfamethoxazole-Trimethoprim. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; December 5, 2017b. [PubMed 31643272]
  227. Sulfatrim tablets (sulfamethoxazole/trimethoprim) [product monograph]. Vaughan, Ontario, Canada: AA Pharma Inc; April 2021.
  228. Sulfatrim DS tablets (sulfamethoxazole/trimethoprim) [product monograph]. Vaughan, Ontario, Canada: AA Pharma Inc; April 2021.
  229. Sulfatrim Pediatric tablets (sulfamethoxazole/trimethoprim) [product monograph]. Vaughan, Ontario, Canada: AA Pharma Inc; April 2021.
  230. Sulfonamides. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; December 5, 2017a. [PubMed 31643703]
  231. Syed Q, Hendler KT, Koncilja K. The impact of aging and medical status on dysgeusia. Am J Med. 2016;129(7):753. [PubMed 26899755]
  232. Teva-Trimel and Teva-Trimel DS (sulfamethoxazole and trimethoprim) tablets and oral suspension [product monograph]. Toronto, Ontario, Canada: Teva Canada Limited; February 2018.
  233. Thies PW, Dull WL. Trimethoprim-sulfamethoxazole-induced cholestatic hepatitis. Inadvertent rechallenge. Arch Intern Med. 1984;144(8):1691-1692. doi:10.1001/archinte.144.8.1691 [PubMed 6331808]
  234. Thomas CF, Limper AH. Treatment and prevention of pneumocystis pneumonia in HIV-uninfected patients. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 6, 2019.
  235. Thyagarajan B, Deshpande SS. Cotrimoxazole and neonatal kernicterus: a review. Drug Chem Toxicol. 2014;37(2):121-129. doi:10.3109/01480545.2013.834349 [PubMed 24099411]
  236. Tomblyn M, Chiller T, Einsele H, et al; Center for International Blood and Marrow Research; National Marrow Donor program; European Blood and Marrow Transplant Group; American Society of Blood and Marrow Transplantation; Canadian Blood and Marrow Transplant Group; Infectious Diseases Society of America; Society for Healthcare Epidemiology of America; Association of Medical Microbiology and Infectious Disease Canada; Centers for Disease Control and Prevention. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective [published correction appears in Biol Blood Marrow Transplant. 2010;16(2):294]. Biol Blood Marrow Transplant. 2009;15(10):1143-1238. doi: 10.1016/j.bbmt.2009.06.019. [PubMed 19747629]
  237. Torre D, Casari S, Speranza F, et al, “Randomized Trial of Trimethoprim-Sulfamethoxazole Versus Pyrimethamine-Sulfadiazine for Therapy of Toxoplasmic Encephalitis in Patients With AIDS. Italian Collaborative Study Group,” Antimicrob Agents Chemother, 1998, 42(6):1346-9. [PubMed 9624473]
  238. Trotman RL, Williamson JC, Shoemaker DM. Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy. Clin Infect Dis. 2005;41(8):1159-1166. [PubMed 16163635]
  239. Tsapepas D, Chiles M, Babayev R, et al. Incidence of hyponatremia with high-dose trimethoprim-sulfamethoxazole exposure. Am J Med. 2016;129(12):1322-1328. doi:10.1016/j.amjmed.2016.07.012 [PubMed 27542610]
  240. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267-1284. [PubMed 15494903]
  241. Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America's clinical practice guidelines for healthcare-associated ventriculitis and meningitis [published online ahead of print February 14, 2017]. Clin Infect Dis. doi: 10.1093/cid/ciw861. [PubMed 28203777]
  242. US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. https://aidsinfo.nih.gov/guidelines. Accessed August 2020.
  243. US Department of Health and Human Services Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children. https://aidsinfo.nih.gov/contentfiles/lvguidelines/oi_guidelines_pediatrics.pdf. Accessed December 2016.
  244. US Department of Health and Human Services Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed August 28, 2017.
  245. van der Klauw MM, Wilson JH, Stricker BH. Drug-associated anaphylaxis: 20 years of reporting in The Netherlands (1974-1994) and review of the literature. Clin Exp Allergy. 1996;26(12):1355-1363. doi:10.1046/j.1365-2222.1996.d01-300.x [PubMed 9027435]
  246. van der Ven AJ, Koopmans PP, Vree TB, van der Meer JW. Adverse reactions to co-trimoxazole in HIV infection. Lancet. 1991;338(8764):431-433. doi:10.1016/0140-6736(91)91046-w [PubMed 1678095]
  247. van Dijk ST, Chabok A, Dijkgraaf MG, Boermeester MA, Smedh K. Observational versus antibiotic treatment for uncomplicated diverticulitis: an individual-patient data meta-analysis. Br J Surg. 2020;107(8):1062-1069. doi:10.1002/bjs.11465 [PubMed 32073652]
  248. Vardakas KZ, Trigkidis KK, Boukouvala E, Falagas ME. Clostridium difficile infection following systemic antibiotic administration in randomised controlled trials: a systematic review and meta-analysis. Int J Antimicrob Agents. 2016;48(1):1-10. doi:10.1016/j.ijantimicag.2016.03.008 [PubMed 27216385]
  249. Velázquez H, Perazella MA, Wright FS, Ellison DH. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med. 1993;119(4):296-301. doi:10.7326/0003-4819-119-4-199308150-00008 [PubMed 8328738]
  250. Veltri MA, Neu AM, Fivush BA, Parekh RS, Furth SL. Drug dosing during intermittent hemodialysis and continuous renal replacement therapy: special considerations in pediatric patients. Paediatr Drugs. 2004;6(1):45-65. [PubMed 14969569]
  251. Verne-Pignatelli J, Spickett GP, Dalgleish AG, Denman AM. Thrombophlebitis migrans following co-trimoxazole therapy. Postgrad Med J. 1989;65(759):51-52. doi:10.1136/pgmj.65.759.51 [PubMed 2789377]
  252. Wadsworth SJ, Suh B. In vitro displacement of bilirubin by antibiotics and 2-hydroxybenzoylglycine in newborns. Antimicrob Agents Chemother. 1988;32(10):1571-1575. doi:10.1128/AAC.32.10.1571 [PubMed 3190184]
  253. Walker SE, Paton TW, Churchill DN, Ojo B, Manuel MA, Wright N. Trimethoprim-sulfamethoxazole pharmacokinetics during continuous ambulatory peritoneal dialysis (CAPD). Perit Dial Int. 1989;9(1):51‐55. [PubMed 2488182]
  254. Wang YL, Scipione MR, Dubrovskaya Y, et al. Monotherapy with fluoroquinolone or trimethoprim-sulfamethoxazole for treatment of stenotrophomonas maltophilia infections. Antimicrob Agents Chemother. 2014;58(1):176-182. doi: 10.1128/AAC.01324-13. [PubMed 24145530]
  255. Wang HK, Sheng WH, Hung CC, et al. Clinical characteristics, microbiology, and outcomes for patients with lung and disseminated nocardiosis in a tertiary hospital. J Formos Med Assoc. 2015;114(8):742-749. doi: 10.1016/j.jfma.2013.07.017. [PubMed 24008153]
  256. Warady BA, Bakkaloglu S, Newland J, et al. Consensus guidelines for the prevention and treatment of catheter-related infections and peritonitis in pediatric patients receiving peritoneal dialysis: 2012 update. Perit Dial Int. 2012;(32 Suppl 2):S32-S86. [PubMed 22851742]
  257. Watson T, Hickok J, Fraker S, Korwek K, Poland RE, Septimus E. Evaluating the risk factors for hospital-onset Clostridium difficile infections in a large healthcare system. Clin Infect Dis. 2018;66(12):1957-1959. doi:10.1093/cid/cix1112 [PubMed 29272341]
  258. Weller PF, Leder K. Cyclospora infection. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 13, 2021.
  259. Williams MF, Doss EP, Montgomery M. Possible trimethoprim-sulfamethoxazole-induced hemolytic anemia: a case report. J Pharm Pract. 2017;30(6):653-657. doi:10.1177/0897190016683303 [PubMed 29121838]
  260. Windecker R, Steffen J, Cascorbi I, Thürmann PA. Co-trimoxazole-induced liver and renal failure. Case report. Eur J Clin Pharmacol. 2000;56(2):191-193. doi:10.1007/s002280050740 [PubMed 10877016]
  261. Wood GC, Underwood EL, Croce MA, et al, "Treatment of Recurrent Stenotrophomonas maltophilia Ventilator-Associated Pneumonia With Doxycycline and Aerosolized Colistin," Ann Pharmacother, 2010, 44(10):1665-8. [PubMed 20736426]
  262. Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137. [PubMed 26042815]
  263. World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. http://www.who.int/maternal_child_adolescent/documents/55732/en/. Published 2002.
  264. World Health Organization (WHO). Guidelines for the control of shigellosis, including epidemics due to Shigella dysenteriae type 1. Available at http://whqlibdoc.who.int/publications/2005/9241592330.pdf. Published 2005. Accessed September 20, 2017.
  265. Wulf NR, Matuszewski KA. Sulfonamide cross-reactivity: is there evidence to support broad cross-allergenicity? Am J Health Syst Pharm. 2013;70(17):1483-1494. doi:10.2146/ajhp120291 [PubMed 23943179]
  266. Ylikorkala O, Sjöstedt E, Järvinen PA, et al, "Trimethoprim-Sulfonamide Combination Administered Orally and Intravaginally in the First Trimester of Pregnancy: Its Absorption Into Serum and Transfer to Amniotic Fluid," Acta Obstet Gynecol Scand, 1973, 52(3):229-34. [PubMed 4743777]
  267. Yuzurio S, Horita N, Shiota Y, Kanehiro A, Tanimoto M. Interstitial lung disease during trimethoprim/sulfamethoxazole administration. Acta Med Okayama. 2010;64(3):181-187. doi:10.18926/AMO/40010 [PubMed 20596129]
  268. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-973.e33. http://www.jaad.org/article/S0190-9622(15)02614-6/pdf. Accessed May 17, 2016. [PubMed 26897386]
  269. Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20(3):217-219. [PubMed 17555487]
  270. Zawodniak A, Lochmatter P, Beeler A, Pichler WJ. Cross-reactivity in drug hypersensitivity reactions to sulfasalazine and sulfamethoxazole. Int Arch Allergy Immunol. 2010;153(2):152-156. doi:10.1159/000312632 [PubMed 20413982]
  271. Zhang C, Van DN, Hieu C, Craig T. Drug-induced severe cutaneous adverse reactions: Determine the cause and prevention. Ann Allergy Asthma Immunol. 2019;123(5):483-487. doi:10.1016/j.anai.2019.08.004 [PubMed 31400461]
Topic 9785 Version 444.0