The risk of severe neurotoxic reactions is sharply increased in patients with impaired renal function or prerenal azotemia. These include disturbances of vestibular and cochlear function, optic nerve dysfunction, peripheral neuritis, arachnoiditis, and encephalopathy. The incidence of clinically detectable, irreversible vestibular damage is particularly high in patients treated with streptomycin.
Renal function should be monitored carefully; patients with renal impairment and/or nitrogen retention should receive reduced doses. The peak serum concentration in individuals with kidney damage should not exceed 20 to 25 mcg/mL.
The concurrent or sequential use of other neurotoxic and/or nephrotoxic drugs with streptomycin, including neomycin, kanamycin, gentamicin, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, tobramycin, and cyclosporine should be avoided.
The neurotoxicity of streptomycin can result in respiratory paralysis from neuromuscular blockage, especially when the drug is given soon after the use of anesthesia or muscle relaxants.
The administration of streptomycin in parenteral form should be reserved for patients where adequate laboratory and audiometric testing facilities are available during therapy.
Note: Route of administration: Manufacturer’s labeling states for IM administration only; however, IV administration (off-label route) has been described (Morris 1994; Peloquin 1992; Tanoira 2014).
Aminoglycoside dosing weight: For patients who are underweight (ie, total body weight [TBW] < ideal body weight [IBW]), calculate the dose based on TBW. For patients without obesity (ie, TBW 1 to 1.25 × IBW), calculate the dose based on TBW or IBW. TBW may be preferred in patients without obesity who may have increased volume of distribution (eg, critically ill). For patients with obesity (ie, TBW > 1.25 × IBW), calculate the dose based on adjusted body weight (IBW + [0.4 × (TBW-IBW)]) (Blackburn 2015; Drew 2020). Therapeutic drug monitoring: Monitoring of serum concentrations is recommended to ensure efficacy and avoid toxicity; confirm availability of rapid streptomycin serum concentrations. Timing and frequency of concentration monitoring is individualized based on dosing and monitoring strategy (AHA [Baddour 2015]; Drew 2020; Park 2015; Zhu 2001).
Usual dosage range: IM, IV: 15 to 30 mg/kg/day or 1 to 2 g daily.
Indication-specific dosing:
Brucellosis: IM, IV: 1 g once daily in combination with doxycycline. Duration depends on extent of disease; streptomycin is usually given for the first 14 to 21 days of therapy, followed by doxycycline monotherapy (Ariza 2007; Bosilkovski 2020; Hasanjani Roushan 2006; Skalsky 2008). Note: Additional agents or other regimens are preferred for neurobrucellosis, endocarditis, and infection in pregnant women (Bosilkovski 2020).
Endocarditis (alternate agent):
Enterococcus spp. (native or prosthetic valve, susceptible to penicillin and streptomycin/resistant to gentamicin): IM, IV: 7.5 mg/kg every 12 hours in combination with ampicillin or penicillin; Duration of therapy: 4 weeks (native valve and symptoms present <3 months); ≥6 weeks (native valve and symptoms present ≥3 months or prosthetic valve). Note: For native valve endocarditis due to ampicillin-susceptible E. faecalis, a combination regimen that does not contain streptomycin is preferred (AHA [Baddour 2015]).
Mycobacterial (nontuberculous) (M. avium complex) infection (off-label use):
Pulmonary disease (severe nodular/bronchiectatic or cavitary disease) (adjunctive agent): IM, IV: 10 to 15 mg/kg once daily or 15 to 25 mg/kg 3 times weekly (ATS/ERS/ESCMID/IDSA [Daley 2020]; Peloquin 2004) or 10 to 15 mg/kg 3 times weekly (Kasperbauer 2020) or 15 mg/kg once daily (usual maximum dose: 1 g) for 1 month then 15 mg/kg 3 times weekly (BTS [Haworth 2017]). Give streptomycin as part of an appropriate combination regimen for the first 2 to 3 months of therapy (ATS/ERS/ESCMID/IDSA [Daley 2020]). Note: For older adults or patients who require >6 months of parenteral therapy, some experts recommend empiric dose reduction (BTS [Haworth 2017]).
Pulmonary disease (cavitary or severe bronchiectatic or acid-fast bacilli smear-positive respiratory samples) or systemic illness in patients with cystic fibrosis (adjunctive agent): IM, IV: 15 mg/kg once daily (maximum: 1 g daily) as part of an appropriate combination regimen (CFF/ECFS [Floto 2016]).
Disseminated disease in patients with HIV with CD4 count <50 cells/mm3, high mycobacterial loads (ie, >2 log colony-forming units/mL of blood), or in the absence of effective antiretroviral therapy (adjunctive agent): IM, IV: 1 g once daily as part of an appropriate combination regimen (HHS [OI adult 2019]).
Plague (Yersinia pestis), treatment:
Note: Consult public health officials for event-specific recommendations.
IM, IV: 1 g every 12 hours for 7 to 14 days and for at least a few days after clinical resolution (CDC [Nelson 2021]; Stout 2022).
Tuberculosis (alternative agent): IM, IV: 15 mg/kg once daily or 25 mg/kg 3 times weekly (ATS/CDC/ERS/IDSA [Nahid 2019]; ATS/CDC/IDSA [Nahid 2016]).
Tularemia (alternative agent): IM: 1 g twice daily for ≥10 days depending on severity (CDC 2019; WHO 2007).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; however, the following adjustments have been recommended:
Aronoff 2007: Note: Recommendations are based on doses of 1 to 2 g every 6 to 12 hours (1 g once daily for tuberculosis):
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl 10 to 50 mL/minute: Administer every 24 to 72 hours.
CrCl <10 mL/minute: Administer every 72 to 96 hours.
End-stage renal disease (ESRD):
Intermittent hemodialysis (IHD): One-half the recommended dose administered after hemodialysis on dialysis days. Note: Dosing dependent on the assumption of 3 times weekly complete IHD sessions.
Peritoneal dialysis (PD): Administration via PD fluid: 20 to 40 mg/L (20 to 40 mcg/mL) of PD fluid.
CRRT: Administer every 24 to 72 hours; monitor levels. Note: Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate).
ATS/CDC/IDSA [Nahid 2016]:
Tuberculosis:
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: 15 mg/kg/dose 2 to 3 times weekly.
ESRD on IHD: 15 mg/kg/dose 2 to 3 times weekly. Give after dialysis if given on day of dialysis.
There are no dosage adjustments provided in the manufacturer’s labeling.
Dose reductions are recommended by the manufacturer in patients >60 years of age.
M. avium complex disease: IM/IV: 8 to 10 mg/kg 2 to 3 times weekly (maximum dose for >50 years of age: 500 mg) (ATS/IDSA [Griffith 2007]) or 10 mg/kg once daily for the first month followed by 15 mg/kg 3 times weekly (maximum dose for >59 years of age: 750 mg) (BTS [Haworth 2017]).
(For additional information see "Streptomycin: Pediatric drug information")
Note: Initial dosing recommendations presented. Monitoring of serum concentrations is recommended to ensure efficacy and avoid toxicity.
Dosing consideration for obesity: In pediatric patients with obesity, consider use of adjusted body weight (IBW + 0.4[TBW – IBW]) to calculate initial dosage, based on experience with other aminoglycosides and in adult patients (Koshida 1989; Traynor 1995). Alternatively, adjusted body weight for aminoglycoside dosing may be calculated for patients who are obese using the equation 0.7 × TBW (Bradley 2022). With other aminoglycosides (gentamicin), fat-free mass has been used to calculate the initial dose in pediatric patients ≥2 years of age regardless of body habitus (Moffett 2018). Dosage should then be individualized based on serum concentration monitoring.
General dosing: Infants, Children, and Adolescents: IM, IV: 20 to 40 mg/kg/day in divided doses every 12 to 24 hours; maximum dose: 1,000 mg/dose (Bradley 2022; manufacturer's labeling).
Endocarditis, enterococcal (alternative agent): Note: Though not included in current pediatric endocarditis guidelines, streptomycin has been recommended for consideration in enterococcal endocarditis for gentamicin-resistant isolates (AHA [Baddour 2015]; AHA [Baltimore 2015]; Bradley 2022).
Infants, Children, and Adolescents: IM, IV: 20 to 30 mg/kg/day in divided doses every 12 hours as part of an appropriate combination regimen; maximum dose: 1,000 mg/dose (AHA [Baddour 2005]; manufacturer's labeling). Duration should be at least 4 to 6 weeks depending on whether prosthetic material is involved and which concomitant agent is used (AHA [Baltimore 2015]).
Mycobacterial infection, nontuberculous:
Buruli ulcers (Mycobacterium ulcerans infection): Limited data available: Infants, Children, and Adolescents: IM, IV: 15 mg/kg once daily; maximum dose: 1,000 mg/dose. Use as part of an appropriate combination regimen for 8 weeks (CDC 2015; WHO 2012).
Disseminated mycobacterium avium complex disease in patients with HIV (adjunctive agent): Note: May be used as the third or fourth drug in patients with CD4 count <50 cells/mm3, high mycobacterial loads (ie, >2 log colony-forming units/mL of blood), or in the absence of effective antiretroviral therapy (HHS [OI adult] 2023).
Adolescents: IM, IV: 1,000 mg once daily as part of an appropriate combination regimen (HHS [OI adult] 2023).
Pulmonary infection in patients with cystic fibrosis: Infants, Children, and Adolescents: IM, IV: 20 to 40 mg/kg/dose once daily as part of an appropriate combination regimen; maximum dose: 1,000 mg/dose. Overall treatment duration is ≥12 months after culture conversion. Note: When streptomycin is used, it is part of the initial, intensive phase of treatment; continuation phase may not include streptomycin depending on culture results (CFF/ECFS [Floto 2016]).
Pulmonary infection in patients without cystic fibrosis: Infants, Children, and Adolescents: IM: 15 mg/kg/dose once daily as part of an appropriate combination regimen; after initial period, may decrease to 15 mg/kg/dose 3 times weekly; maximum dose: 1,000 mg/dose. Overall duration is ≥12 months after culture conversion (BTS [Haworth 2017]).
Plague: Note: Consult public health officials for event-specific recommendations.
Infants, Children, and Adolescents: IM, IV: 30 mg/kg/day divided every 12 hours for 10 to 14 days; maximum dose: 1,000 mg/dose (CDC [Nelson 2021]).
Tuberculosis disease (active tuberculosis); drug-resistant (alternative agent): Note: Recommended only in patients in whom susceptibility is confirmed and when absolutely necessary (ie, a 5-drug regimen of more effective or less toxic medications is not possible); always use as part of an appropriate combination regimen. Duration should be individualized based on extent of disease, rapidity of culture conversion, clinical response, and toxicity (ATS/CDC/ERS/IDSA [Nahid 2019]; Red Book [AAP 2021]; WHO 2022).
Once-daily regimen:
Infants, Children, and Adolescents: IM, IV: 15 to 20 mg/kg/dose once daily; some experts recommend doses of 20 to 40 mg/kg/dose once daily; maximum dose: 1,000 mg/dose (ATS/CDC/ERS/IDSA [Nahid 2019]; ATS/CDC/IDSA [Nahid 2016]; Red Book [AAP 2021]; WHO 2022).
Twice-weekly regimen: Note: Once-daily therapy is typically preferred. Dosing modified from adult dosing and accounting for increased total body water (ATS/CDC/ERS/IDSA [Nahid 2019]).
Infants, Children, and Adolescents: IM, IV: 25 to 30 mg/kg/dose twice weekly (ATS/CDC/ERS/IDSA [Nahid 2019]; ATS/CDC/IDSA [Nahid 2016]).
Tuberculosis disease (active tuberculosis); meningitis (alternative agent): Note: Shorter, more intensive regimens including ethionamide may be preferred (Solomons 2022; WHO 2022).
Infants, Children, and Adolescents: IM, IV: 20 to 40 mg/kg/dose once daily; doses as low as 15 mg/kg/dose once daily have been recommended; maximum daily dose: 1,000 mg/day. Streptomycin may be discontinued once isolate is determined susceptible to first-line drugs (ATS/CDC/IDSA [Nahid 2016]; HHS [OI pediatric] 2022; Red Book [AAP 2021]).
Tularemia (alternative agent): Infants, Children, and Adolescents: IM: 30 to 40 mg/kg/day in divided doses every 12 hours for 10 days; maximum dose: 1,000 mg/dose. In mild illness, 5 to 7 days of therapy may be sufficient; longer courses may be necessary for severe disease (Red Book [AAP 2021]; WHO 2007).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no adjustments provided in the manufacturer's labeling; however, the following adjustments have been recommended (Aronoff 2007):
Infants, Children, and Adolescents: Note: Renally adjusted dose recommendations are based on doses of 20 to 40 mg/kg/day every 24 hours. Monitor serum concentrations.
GFR 30 to 50 mL/minute/1.73 m2: Administer 7.5 mg/kg/dose every 24 hours.
GFR 10 to 29 mL/minute/1.73 m2: Administer 7.5 mg/kg/dose every 48 hours.
GFR <10 mL/minute/1.73 m2: Administer 7.5 mg/kg/dose every 72 to 96 hours.
Intermittent hemodialysis (IHD): Administer 7.5 mg/kg/dose every 72 to 96 hours.
Peritoneal dialysis (PD): Administer 7.5 mg/kg/dose every 72 to 96 hours.
Continuous renal replacement therapy (CRRT): Administer every 24 hours; monitor levels. Note: Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate).
There are no adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined.
Cardiovascular: Hypotension
Central nervous system: Drug fever, facial paresthesia, headache, neurotoxicity
Dermatologic: Exfoliative dermatitis, skin rash, urticaria
Gastrointestinal: Nausea, vomiting
Genitourinary: Azotemia, nephrotoxicity
Hematologic & oncologic: Eosinophilia, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia
Hypersensitivity: Anaphylaxis, angioedema
Neuromuscular & skeletal: Arthralgia, tremor, weakness
Ophthalmic: Amblyopia
Otic: Auditory ototoxicity, vestibular ototoxicity
Respiratory: Dyspnea
<1%, postmarketing, and/or case reports: DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), toxic epidermal necrolysis
Hypersensitivity to streptomycin, other aminoglycosides, or any component of the formulation
Concerns related to adverse effects:
• Neuromuscular blockade and respiratory paralysis: [US Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants.
• Neurotoxicity: [US Boxed Warning]: May cause neurotoxicity, including disturbances of vestibular and cochlear function, optic nerve dysfunction, peripheral neuritis, arachnoiditis, and encephalopathy; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Baseline and periodic caloric stimulation and audiometric tests are recommended with prolonged therapy. Discontinue treatment if signs of ototoxicity occur.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss.
• Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis.
• Renal impairment: [US Boxed Warning]: May cause nephrotoxicity. Use with caution in patients with renal impairment; dose adjustment necessary in patients with renal impairment and/or nitrogen retention. Monitor renal function closely; peak serum concentrations should not surpass 20 to 25 mcg/mL in patients with renal impairment.
Special populations:
• Patients with genomic variants in MT-RNR1: Carriers of certain variants in the MT-RNR1 gene (eg, m.1555A>G) may be at increased risk for aminoglycoside-induced ototoxicity, including potentially significant hearing loss that may be irreversible, even when serum levels are within the normal range.
Concurrent drug therapy issues:
• Neurotoxic and/or nephrotoxic drugs: [US Boxed Warning]: Avoid concomitant or sequential use with other neurotoxic and/or nephrotoxic drugs (eg, neomycin, kanamycin, gentamicin, paromomycin, polymyxin B, colistin, tobramycin, cyclosporine).
Dosage form specific issues:
• Sulfite sensitivity: Some formulations may contain sodium metabisulfite; may cause allergic reactions including anaphylaxis or asthma exacerbations (some life-threatening) in susceptible patients.
Other warnings/precautions:
• Appropriate use: [US Boxed Warning]: Parenteral form should be used only where appropriate audiometric and laboratory testing facilities are available. IM injections should be administered in a large muscle well within the body to avoid peripheral nerve damage and local skin reactions.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intramuscular [preservative free]:
Generic: 1 g (1 ea)
Yes
Solution (reconstituted) (Streptomycin Sulfate Intramuscular)
1 g (per each): $93.75
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intramuscular:
Generic: 1 g (5 mL)
IM: Inject deep IM into large muscle mass; midlateral thigh muscle or upper outer quadrant of buttocks; rotate injection sites.
IV (off-label route): After dilution in admixture, infuse over 30 to 60 minutes (Morris 1994; Peloquin 1992; Tanoira 2014)
Parenteral:
IM: Inject deep IM into a large muscle mass appropriate for age; rotate injection sites.
IV: After further dilution, infuse over 30 to 60 minutes (Morris 1994; Peloquin 1992; Pérez Tanoira 2014).
Tuberculosis:
Treatment of tuberculosis, in combination with other appropriate antituberculosis agents, when the primary agents are contraindicated because of toxicity or intolerance.
Nontuberculosis infections:
Treatment of infections caused by susceptible bacteria that are not amenable to therapy with less potentially toxic agents, including sensitive Yersinia pestis (plague); Francisella tularensis (tularemia); Brucella; Klebsiella granulomatis (donovanosis, granuloma inguinale); Haemophilus ducreyi (chancroid); Haemophilus influenzae (in respiratory, endocardial, and meningeal infections, concomitantly with another antibacterial agent); Klebsiella pneumoniae pneumonia (concomitantly with another antibacterial agent); Escherichia coli, Proteus spp., Klebsiella aerogenes (formerly Enterobacter aerogenes), K. pneumoniae, and Enterococcus faecalis in urinary tract infections; Streptococcus viridans; E. faecalis (in endocardial infections, concomitant with penicillin); and gram-negative bacillary bacteremia (concomitant with another antibacterial agent).
Mycobacterium avium complex infection
Streptomycin may be confused with streptozocin
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoglycosides: May enhance the nephrotoxic effect of other Aminoglycosides. Aminoglycosides may enhance the neurotoxic effect of other Aminoglycosides. Risk X: Avoid combination
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Amphotericin B may enhance the neurotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Ataluren: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, an increased risk of nephrotoxicity may occur with the concomitant use of ataluren and aminoglycosides. Risk X: Avoid combination
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
Bacitracin (Systemic): Streptomycin may enhance the nephrotoxic effect of Bacitracin (Systemic). Risk X: Avoid combination
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
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Aminoglycosides may enhance the nephrotoxic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Botulinum Toxin-Containing Products: Aminoglycosides may enhance the neuromuscular-blocking effect of Botulinum Toxin-Containing Products. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: May enhance the nephrotoxic effect of Aminoglycosides. Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
Cephalosporins: May enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy
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
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. CISplatin may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Management: Avoid coadministration of colistimethate and aminoglycosides whenever possible due to the risk of nephrotoxicity and neuromuscular blockade. If coadministration cannot be avoided, monitor renal and neuromuscular function. Risk D: Consider therapy modification
Cyclizine: May enhance the ototoxic effect of Aminoglycosides. Risk C: Monitor therapy
CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Risk C: Monitor therapy
Distigmine: Aminoglycosides may diminish the therapeutic effect of Distigmine. Risk C: Monitor therapy
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Risk X: Avoid combination
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Mannitol (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Risk X: Avoid combination
Mecamylamine: Aminoglycosides may enhance the neuromuscular-blocking effect of Mecamylamine. Risk X: Avoid combination
Methoxyflurane: Aminoglycosides may enhance the nephrotoxic effect of Methoxyflurane. Risk X: Avoid combination
Netilmicin (Ophthalmic): Aminoglycosides may enhance the nephrotoxic effect of Netilmicin (Ophthalmic). Risk X: Avoid combination
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the therapeutic effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
Oxatomide: May enhance the ototoxic effect of Aminoglycosides. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
Polymyxin B: May enhance the nephrotoxic effect of Aminoglycosides. Polymyxin B may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination
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
Tacrolimus (Systemic): Aminoglycosides may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Tenofovir Products: Aminoglycosides may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. 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
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Vancomycin may enhance the neurotoxic effect of Aminoglycosides. Management: Consider avoiding coadministration of aminoglycosides and vancomycin unless clinically indicated. If coadministered, monitor closely for signs of nephrotoxicity and neurotoxicity. Risk D: Consider therapy modification
Evaluate pregnancy status prior to treatment of multidrug resistant tuberculosis in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment for multidrug resistant tuberculosis (Esmail 2018).
Streptomycin crosses the placenta.
Streptomycin may cause fetal harm if administered to a pregnant patient. There are multiple reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy.
Streptomycin is approved for the treatment of tuberculosis (TB). TB disease (active TB) is associated with adverse fetal outcomes including intrauterine growth restriction, low birth weight, preterm birth, and perinatal death (Esmail 2018; Miele 2020) as well as adverse maternal outcomes, including increased risks for anemia and cesarean delivery. Placental transmission may rarely occur with active maternal disease (Miele 2020). The treatment of multidrug resistant TB in pregnant patients should be individualized; evidence to support a specific regimen is not available (ATS/CDC/ERS/IDSA [Nahid 2019]; WHO 2020). When second-line agents are needed for the treatment of multidrug resistant TB during pregnancy, aminoglycosides should be avoided when alternative agents are effective (ATS/CDC/ERS/IDSA [Nahid 2019]). Streptomycin is not the preferred agent when an aminoglycoside is required for the treatment of TB during pregnancy (HHS [OI adult 2019]).
Untreated plague (Yersinia pestis) infection in pregnant patients may result in hemorrhage (including postpartum hemorrhage), maternal and fetal death, preterm birth, and stillbirth. Limited data suggest maternal-fetal transmission of Y. pestis can occur if not treated. Pregnant patients should be treated for Y. pestis; parenteral antibiotics are preferred for initial treatment when otherwise appropriate. Streptomycin is an alternative aminoglycoside recommended for use (in combination with a fluroquinolone) for treating pregnant patients with bubonic, pharyngeal, pneumonic, or septicemic plague (CDC [Nelson 2021]).
Streptomycin is present in breast milk.
Aminoglycosides have poor oral bioavailability (Edson 1991), which may limit systemic absorption via breast milk.
Streptomycin is considered compatible with breastfeeding. In general, antibiotics that are present in breast milk may cause non-dose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush and diarrhea (WHO 2002). Patients with multidrug resistant tuberculosis and a sputum smear-positive test should avoid breastfeeding when possible (Esmail 2018).
Baseline and periodic hearing tests (audiograms), clinical assessment for vertigo and tinnitus, BUN, creatinine, serum electrolytes; serum drug concentrations should be monitored in all patients (ATS/CDC/ERS/IDSA [Nahid 2019]).
Therapeutic:
Peak: Daily dosing: 20 to 35 mcg/mL (35 to 45 mcg/mL for mycobacterial disease); Three times weekly dosing: 65 to 80 mcg/mL (AHA [Baddour 2015]; ATS/ERS/ESCMID/IDSA [Daley 2020]; BTS [Haworth 2017]; CFF/ECFS [Floto 2016]; Edson 1991; Peloquin 2004; Zhu 2001).
Trough: <5 mcg/mL (AHA [Baddour 2015]; BTS [Haworth 2017]; CFF/ECFS [Floto 2016]; Edson 1991; Zhu 2001).
Supratherapeutic: Trough: >10 mcg/mL.
Inhibits bacterial protein synthesis by binding directly to the 30S ribosomal subunits causing faulty peptide sequence to form in the protein chain
Absorption: Oral: Poorly absorbed; IM: Well absorbed.
Distribution: Distributes into most body tissues and fluids except the brain; small amounts enter the cerebrospinal fluid only with inflamed meninges.
Vd:
Neonates (GA ≥33 weeks, PNA 4 to 20 days): 0.24 to 0.44 L/kg (Herngren 1977).
Infants ≥6 months and Children: Mean range: 0.25 ± 0.02 to 0.29 ± 0.03 L/kg (Bolme 1988).
Protein binding: 34%.
Half-life elimination:
Neonates:
Preterm, PNA 1 to 3 days: Mean: 7 hours; range: 4 to 9.1 hours (Axline 1964).
Preterm and term (GA ≥33 weeks), PNA 4 to 20 days: 1.39 to 4.64 hours (Herngren 1977).
Infants ≥6 months and Children: Mean range: 1.69 ± 0.36 to 2.58 ± 0.44 hours (Bolme 1988).
Adults: ~2 to 4.7 hours; prolonged with renal impairment.
Time to peak: IM: Within 1 to 2 hours.
Excretion: Urine (29% to 89% as unchanged drug); small amount (1%) excreted in bile, saliva, sweat, and tears.
Anti-infective considerations:
Parameters associated with efficacy: Gram-negative bacilli: Concentration dependent; associated with Cmax (peak)/minimum inhibitory concentration (MIC), goal: ≥8 to 10 (Abdul-Aziz 2020; Lacy 1998) or AUC24/MIC, goal: 30 to 50 (mild/moderate infection, patients who are immunocompetent) or 80 to 100 (severe infection) (Bland 2018; Craig 2011; Drusano 2007).
Expected drug exposure in normal renal function:
Cmax (peak): Adults:
IV: 14 mg/kg (range: 11 to 25 mg/kg) (30-minute infusion): 43.6 mg/L (range: 9 to 107 mg/L) (Zhu 2001).
IM: 18 mg/kg (range: 10 to 23 mg/kg): 42.6 mg/L (range: 2.9 to 85.2 mg/L) (Zhu 2001).
IM: 1 g: 25 to 50 mg/L (manufacturer's labeling).
AUC24: Adults:
IV: 14 mg/kg (range: 11 to 25 mg/kg) (30-minute infusion): 284 mg•hour/L (range: 124 to 680 mg•hour/L) (Zhu 2001).
IM: 18 mg/kg (range: 10 to 23 mg/kg): 264 mg•hour/L (range: 175 to 343 mg•hour/L) (Zhu 2001).
Parameters associated with toxicity: Nephrotoxicity is associated with high Cmin (trough) aminoglycoside concentrations leading to renal accumulation (Abdul-Aziz 2020; Bertino 1993; Rybak 1999; Verpooten 1989).
Postantibiotic effect: Bacterial killing continues after streptomycin concentration falls below the MIC of targeted pathogen and varies significantly based on the organism, duration of antimicrobial exposure, streptomycin concentration, and concomitant antimicrobial therapy:
E. faecalis/E. faecium (alone or in combination with ampicillin or vancomycin): ~0 to 2 hours (Fuursted 1987; Fuursted 1989).
Mycobacterium tuberculosis: 32.2 hours (range: 0.7 to 60.2 hours) (Chan 2001).
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