Note: For oral therapy, including oral step-down therapy after IV ampicillin, oral amoxicillin is usually preferred over oral ampicillin due to improved bioavailability and absorption (bioavailability 77% versus 39% to 54%, respectively) (Arancibia 1980; Bolme 1976). For ease of outpatient IV ampicillin administration, the total daily dose may be administered as a 24-hour continuous infusion (IDSA [Berbari 2015]; IDSA [Osmon 2013]; Lewis 2018; Ogawa 2014).
Bloodstream infection :
Pathogen-directed therapy for Enterococcus spp.: IV: 2 g every 4 hours; use as part of an appropriate combination regimen in the setting of suspected endocarditis or critical illness (Graninger 1992; IDSA [Mermel 2009]; Murray 2019). Duration of therapy is 7 to 14 days for uncomplicated infection (ie, fever resolution within 72 hours and absence of metastatic focus of infection or endovascular hardware) (IDSA [Mermel 2009]). Some experts recommend a duration of 5 to 7 days for uncomplicated infection with rapid blood culture clearance (within 24 hours) and in the absence of metastatic infection (Murray 2019).
Pathogen-directed therapy for Listeria monocytogenes: IV: 2 g every 4 hours; use in combination with gentamicin for nonpregnant patients. Duration should be individualized based on patient factors, source and extent of infection, and clinical response, but ampicillin is usually continued for at least 14 to 21 days (Charlier 2017; Gelfand 2020; Hof 1997).
Endocarditis, prophylaxis (dental or invasive respiratory tract procedures) (alternative agent for patients unable to take oral therapy) (off-label use): IM, IV: 2 g as a single dose 30 to 60 minutes before procedure. Note: Only recommended for patients with cardiac conditions associated with the highest risk of an adverse outcome from endocarditis and who are undergoing a procedure likely to result in bacteremia with an organism that has the potential ability to cause endocarditis (AHA [Wilson 2007]).
Enterococcus faecalis, native or prosthetic valve (penicillin-susceptible): IV: 2 g every 4 hours as part of an appropriate combination regimen (eg, with ceftriaxone or gentamicin). Duration is usually 6 weeks; for patients with native valve endocarditis and symptoms <3 months, the combination of ampicillin and gentamicin can be given for 4 weeks. Note: Ampicillin plus ceftriaxone is the preferred regimen in patients with or at risk of renal insufficiency or with gentamicin resistance (AHA [Baddour 2015]; Fernández-Hidalgo 2013; Sexton 2020), and some experts favor this combination for all patients with native valve endocarditis (Sexton 2020).
HACEK organisms, native or prosthetic valve (ampicillin-susceptible) (off-label use): IV: 2 g every 4 hours for 4 weeks (native valve) or 6 weeks (prosthetic valve) (AHA [Baddour 2015]). Note: In vitro susceptibility should be confirmed prior to use.
Viridans group streptococci and Streptococcus gallolyticus (Streptococcus bovis) (alternative agent):
Native valve: Highly penicillin-susceptible (minimum inhibitory concentration [MIC] ≤0.12 mcg/mL): IV: 2 g every 4 hours for 4 weeks (AHA [Baddour 2015]).
Native valve: Relatively penicillin-resistant (MIC >0.12 to <0.5 mcg/mL): IV: 2 g every 4 hours for 4 weeks in combination with gentamicin for the first 2 weeks (AHA [Baddour 2015]).
Native valve: Penicillin-resistant (MIC ≥0.5 mcg/mL): IV: 2 g every 4 hours in combination with gentamicin. The duration of this regimen is not well established; infectious diseases consultation recommended (AHA [Baddour 2015]).
Prosthetic valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): IV: 2 g every 4 hours for 6 weeks (with or without concomitant gentamicin for the first 2 weeks) (AHA [Baddour 2015]).
Prosthetic valve: Relatively penicillin-resistant (MIC >0.12 to <0.5 mcg/mL) or fully penicillin-resistant (MIC ≥0.5 mcg/mL): IV: 2 g every 4 hours in combination with gentamicin for 6 weeks (AHA [Baddour 2015]). For relatively resistant strains, some experts prefer a shorter duration of the gentamicin component (≥2 weeks) (Karchmer 2020).
Intra-abdominal infection, health care-associated (off-label use): Empiric or pathogen-directed therapy for Enterococcus spp. in high-risk patients (eg, postoperative infection or healthcare-associated infection in patients with prior use of antibiotics that select for Enterococcus, immunocompromising condition, valvular heart disease, or prosthetic intravascular material):
IV: 2 g every 4 hours as part of an appropriate combination regimen (Barshak 2021; SIS [Mazuski 2017]). Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Sawyer 2015; SIS [Mazuski 2017]).
Meningitis, bacterial: As a component of empiric therapy (community-acquired infections in immunocompetent patients >50 years of age and immunocompromised patients) or pathogen-directed therapy (eg, Haemophilus influenzae [beta-lactamase negative], L. monocytogenes, Neisseria meningitidis [penicillin MIC <0.1 mcg/mL], Streptococcus agalactiae, Streptococcus pneumoniae [penicillin MIC ≤0.06 mcg/mL], Enterococcus spp. [ampicillin-susceptible]):
IV: 2 g every 4 hours; for empiric therapy and for directed therapy for Enterococcus or Listeria, use as part of an appropriate combination regimen. Treatment duration is 7 to 21 days, depending on causative pathogen(s) and clinical response (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).
Osteomyelitis and/or discitis, treatment (off-label use): Pathogen-directed therapy for penicillin-susceptible Enterococcus or Streptococcus spp.: IV: 2 g every 4 hours or 12 g as a continuous infusion every 24 hours, generally for ≥6 weeks. Shorter courses are appropriate if the affected bone is completely resected (eg, by amputation) (IDSA [Berbari 2015]; Osmon 2019). For Enterococcus, some experts use with ceftriaxone in the setting of retained hardware (Osmon 2019).
Pelvic infections (off-label use):
Intra-amniotic infection (chorioamnionitis): IV: 2 g every 6 hours in combination with gentamicin. In females undergoing cesarean delivery, an anti-anaerobic agent should also be added. Continue regimen until vaginal delivery or for 1 dose after cesarean delivery (ACOG 2017). Note: Some experts recommend 1 additional dose after vaginal delivery and extension of antibiotics after cesarean delivery until patient is afebrile and asymptomatic ≥48 hours (Tita 2019).
Postpartum endometritis: Note: For patients known to be colonized with GBS (Chen 2021).
IV: 2 g every 6 hours in combination with clindamycin and gentamicin; treat until patient is clinically improved (no fundal tenderness) and afebrile for 24 to 48 hours (Brumfield 2000; Chen 2021).
Tubo-ovarian abscess: IV: 2 g every 6 hours in combination with clindamycin and gentamicin (Beigi 2020). After 24 to 48 hours of sustained clinical improvement, may transition to oral therapy to complete ≥14 days of treatment (CDC [Workowski 2015]).
Peritonitis, treatment (peritoneal dialysis patients) (off-label use): Note: Intraperitoneal administration is preferred to IV administration (ISPD [Li 2016]). Consider a 25% dose increase in patients with significant residual renal function (urine output >100 mL/day) (ISPD [Li 2010]; ISPD [Li 2016]; Mancini 2018; Szeto 2018).
Pathogen-directed therapy (eg, Enterococcus spp., Streptococcus spp.): Continuous (with every exchange): Intraperitoneal: 125 mg/L of dialysate with each exchange (ISPD [Li 2016]). Duration of therapy is ≥2 weeks for patients with adequate clinical response (Burkart 2019; ISPD [Li 2016]).
Prosthetic joint infection (off-label use): Pathogen-directed therapy (eg, penicillin-susceptible Enterococcus spp. or Streptococcus spp.): IV: 2 g every 4 hours or 12 g continuous infusion every 24 hours. Duration varies, but is generally 4 to 6 weeks; for enterococcal infections, some experts use with ceftriaxone in the setting of retained hardware (Berbari 2019; IDSA [Osmon 2013]).
Streptococcus (group B), maternal prophylaxis for prevention of neonatal disease (alternative agent) (off-label use):
Note: Prophylaxis is reserved for pregnant women with a positive group B Streptococcus (GBS) vaginal or rectal screen in late gestation; GBS bacteriuria during the current pregnancy; history of birth of an infant with early-onset GBS disease; and unknown GBS culture status with any of the following: birth <37 0/7 weeks' gestation, intrapartum fever, prolonged rupture of membranes, known GBS positive in a previous pregnancy, or intrapartum nucleic acid amplification testing positive for GBS (ACOG 2020b).
IV: 2 g as a single dose at onset of labor or prelabor rupture of membranes, then 1 g every 4 hours until delivery (ACOG 2020b).
Urinary tract infection:
Note: Uncomplicated urinary tract infection (UTI) has traditionally been defined as infection in an otherwise healthy nonpregnant female with a normal urinary tract; UTI in other patient populations has been considered complicated. Some experts instead categorize UTI as either acute simple cystitis (mild infection limited to the bladder with no signs/symptoms of upper tract or systemic infection in a nonpregnant adult) or complicated UTI (pyelonephritis or cystitis symptoms with other signs/symptoms of systemic infection) (Hooton 2019a; Hooton 2019b; Hooton 2019c). Ampicillin is not recommended for empiric therapy given decreased efficacy compared to first-line agents and high prevalence of resistance (IDSA/ESCMID [Gupta 2011]).
Acute uncomplicated or simple cystitis due to Enterococcus spp.: Oral: 500 mg every 6 hours for 5 to 7 days (Hooton 2019a; Hooton 2019b; IDSA/ESCMID [Gupta 2011]; Shah 2018).
Acute pyelonephritis or other complicated urinary tract infection due to Enterococcus spp. (off label): IV: 1 to 2 g every 4 to 6 hours; can give with an aminoglycoside for critical illness (Cole 2015; Heintz 2010; IDSA/ESCMID [Gupta 2011]). Switch to an appropriate oral regimen once patient has improvement in symptoms. Duration of therapy depends on the antimicrobial chosen to complete the regimen and ranges from 5 to 14 days (Hooton 2019c).
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.
Altered kidney function: IV:
Note: There are no dosage adjustments provided in the manufacturer's labeling and pharmacokinetic data is limited. The following recommendations are based primarily on expert opinion.
Ampicillin Dose Adjustments in Altered Kidney Function
If usual recommended dose is 1 to 2 g every 6 hoursa
If usual recommended dose is 2 g every 4 hoursb
aExpert opinion, Aronoff 2007, Blackwell 1990, Heintz 2009, Wright 1983.
bExpert opinion only.
cDialyzable (39% to 63% [Jusko 1973]); administer after hemodialysis when scheduled dose falls on dialysis days (Heintz 2009).
50 to <130
1 to 2 g every 6 hours
2 g every 4 hours
30 to <50
1 to 2 g every 8 hours
2 g every 6 hours
15 to <30
1 to 2 g every 12 hours
2 g every 8 hours
1 to 2 g every 24 hours
2 g every 12 hours
Hemodialysis, intermittent (thrice weekly)c
1 to 2 g every 24 hours
2 g every 12 hours
1 to 2 g every 24 hours
2 g every 12 hours
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at the highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010).
If usual recommended dose is 1 to 2 g every 6 hours: 2 g every 4 hours (expert opinion).
If usual recommended dose is 2 g every 4 hours: Some patients may not meet pharmacodynamic targets with 2 g every 4 hours dosing; monitor closely, consider utilizing a prolonged or continuous infusion, and if necessary, switching to an alternative agent (expert opinion).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
If usual recommended dose is 1 to 2 g every 6 hours: 2 g every 8 to 12 hours (Heintz 2009; expert opinion).
If usual recommended dose is 2 g every 4 hours: 2 g every 6 to 8 hours (Heintz 2009; expert opinion).
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) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
Note: Where possible, schedule one of the doses for after the PIRRT session (Lorenzen 2012; expert opinion).
If usual recommended dose is 1 to 2 g every 6 hours: 2 g every 8 to 12 hours (Lorenzen 2012; expert opinion).
If usual recommended dose is 2 g every 4 hours: 2 g every 8 hours (expert opinion).
There are no dosage adjustments provided in the manufacturer’s labeling.
(For additional information see "Ampicillin: Pediatric drug information")
General dosing, susceptible infection (Bradley 2021; Red Book [AAP 2021]): Infants, Children, and Adolescents:
Oral: 50 to 100 mg/kg/day divided every 6 hours; maximum daily dose: 2,000 mg/day.
IM, IV: 50 to 200 mg/kg/day divided every 6 hours; maximum daily dose: 8 g/day; higher doses (300 to 400 mg/kg/day; maximum daily dose: 12 g/day) are recommended for some infections.
Community-acquired pneumonia (CAP) (IDSA/PIDS [Bradley 2011]): Infants >3 months, Children, and Adolescents: Note: May consider addition of vancomycin or clindamycin to empiric therapy if community-acquired MRSA suspected. In children ≥5 years, a macrolide antibiotic should be added if atypical pneumonia cannot be ruled out.
Empiric treatment or S. pneumoniae (MICs for penicillin ≤2 mcg/mL) or H. influenzae (beta-lactamase negative) in fully immunized patients: IV: 150 to 200 mg/kg/day divided every 6 hours.
Group A Streptococcus: IV: 200 mg/kg/day divided every 6 hours.
S. pneumoniae (MICs for penicillin ≥4 mcg/mL): IV: 300 to 400 mg/kg/day divided every 6 hours.
Treatment: Children and Adolescents: IV: 200 to 300 mg/kg/day divided every 4 to 6 hours; maximum daily dose: 12 g/day; use in combination with other antibiotics for at least 4 weeks; some organisms may require longer duration (AHA [Baltimore 2015]).
Prophylaxis: Note: AHA guidelines (Baltimore 2015) limit the use of prophylactic antibiotics to patients at the highest risk for infective endocarditis (IE) or adverse outcomes (eg, prosthetic heart valves, patients with previous IE, unrepaired cyanotic congenital heart disease, repaired congenital heart disease with prosthetic material or device during first 6 months after procedure, repaired congenital heart disease with residual defects at the site or adjacent to site of prosthetic patch or device, and heart transplant recipients with cardiac valvulopathy):
Dental or oral procedures or respiratory tract procedures (eg, tonsillectomy, adenoidectomy): Infants, Children, and Adolescents: IV, IM: 50 mg/kg within 30 to 60 minutes before procedure; maximum dose: 2,000 mg/dose. Intravenously (IV) administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications (AHA [Wilson 2021]).
Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 200 mg/kg/day divided every 6 hours; maximum single dose: 2,000 mg; maximize doses if undrained abdominal abscesses (IDSA [Solomkin 2010]).
Meningitis (including health care-associated meningitis and ventriculitis): Infants, Children, and Adolescents: IV: 300 to 400 mg/kg/day divided every 4 to 6 hours; maximum daily dose: 12 g/day (Bradley 2021; IDSA [Tunkel 2004]; IDSA [Tunkel 2017]; Red Book [AAP 2021]).
Peritonitis (CAPD) Limited data available: Infants, Children, and Adolescents: Intraperitoneal: 125 mg per liter of dialysate for 2 weeks (ISPD [Warady 2012]).
Surgical prophylaxis: Infants, Children, and Adolescents: IV: 50 mg/kg within 60 minutes prior to surgical incision; may repeat in 2 hours if lengthy procedure or excessive blood loss; maximum dose: 2,000 mg/dose (ASHP/IDSA [Bratzler 2013]; Red Book [AAP 2021]).
Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, the following adjustments have been recommended (Aronoff 2007). Note: Renally adjusted dose recommendations are based on IM, IV doses of 100 to 200 mg/kg/day divided every 6 hours: IM, IV:
GFR 30 to 50 mL/minute/1.73 m2: 35 to 50 mg/kg/dose every 6 hours
GFR 10 to 29 mL/minute/1.73 m2: 35 to 50 mg/kg/dose every 8 to 12 hours
GFR <10 mL/minute/1.73 m2: 35 to 50 mg/kg/dose every 12 hours
Intermittent hemodialysis: 35 to 50 mg/kg/dose every 12 hours
Peritoneal dialysis (PD): 35 to 50 mg/kg/dose every 12 hours
Continuous renal replacement therapy (CRRT): 35 to 50 mg/kg/dose every 6 hours
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Generic: 500 mg
Solution Reconstituted, Injection, as sodium [strength expressed as base]:
Generic: 250 mg (1 ea [DSC]); 500 mg (1 ea [DSC]); 1 g (1 ea [DSC]); 2 g (1 ea [DSC])
Solution Reconstituted, Injection, as sodium [strength expressed as base, preservative free]:
Generic: 125 mg (1 ea); 250 mg (1 ea); 500 mg (1 ea); 1 g (1 ea); 2 g (1 ea)
Solution Reconstituted, Intravenous, as sodium [strength expressed as base, preservative free]:
Generic: 1 g (1 ea); 2 g (1 ea); 10 g (1 ea)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Generic: 250 mg, 500 mg
Solution Reconstituted, Injection, as sodium [strength expressed as base]:
Generic: 250 mg (1 ea); 500 mg (1 ea); 1 g (1 ea); 2 g (1 ea)
Suspension Reconstituted, Oral:
Generic: 125 mg/5 mL ([DSC]); 250 mg/5 mL ([DSC])
Administer around-the-clock to promote less variation in peak and trough serum levels.
Oral: Administer on an empty stomach with a full glass (8 oz) of water (ie, 30 minutes prior to or 2 hours after meals) to increase total absorption.
IM.: Inject deep IM into a large muscle mass
IV: Direct IV bolus: Administer over 3 to 5 minutes (125 to 500 mg) or over 10 to 15 minutes (1 to 2 g). More rapid infusion may cause seizures.
Infusion: Rapid infusion may cause seizures. Adjust rate of infusion so that the total dose is administered before admixture stability expires.
Oral: Administer around-the-clock to promote less variation in peak and trough serum levels. Administer on an empty stomach (ie, 1 hour prior to or 2 hours after meals) to increase total absorption; shake suspension well before using
IM: Inject deep IM into a large muscle mass
IV push: Doses ≤500 mg should be administered over 3 to 5 minutes; doses >500 mg should be administered over 10 to 15 minutes; rapid administration has been associated with seizures.
Intermittent IV infusion: Infuse over 10 to 15 minutes. Avoid infusing concomitantly with aminoglycosides if feasible; consult drug interactions database for more information.
GI tract infections: Treatment of GI tract infections caused by Shigella, Salmonella typhosa and other Salmonella, Escherichia coli, Proteus mirabilis, and enterococci. Note: Ampicillin is not recommended as a first-line agent for shigellosis, salmonellosis (nontyphoid), or Salmonella enterica species (typhoid fever) due to development of resistance (CDC 2014).
GU tract infections: Treatment of GU tract infections caused by E. coli, P. mirabilis, enterococci, Shigella, S. typhosa and other Salmonella, and nonpenicillinase-producing Neisseria gonorrhoeae. Note: Ampicillin is not recommended by the CDC as a first-line agent in the treatment of gonorrhea (CDC 2010).
Respiratory tract infections: Treatment of respiratory tract infections caused by nonpenicillinase-producing Haemophilus influenzae and staphylococci, and streptococci, including Streptococcus pneumoniae.
Bloodstream infection: Treatment of bloodstream infection caused by susceptible gram-positive organisms, including Streptococcus species, penicillin G-susceptible staphylococci, and enterococci; gram-negative bloodstream infection caused by E. coli, P. mirabilis, and Salmonella species.
Endocarditis, treatment: Treatment of endocarditis caused by susceptible gram-positive organisms, including Streptococcus species, penicillin G-susceptible staphylococci, and enterococci.
GI infections: Treatment of GI infections caused by S. typhi (typhoid fever), other Salmonella species, and Shigella species (dysentery). Note: Ampicillin is not recommended as a first-line agent for shigellosis, salmonellosis (nontyphoid), or S. enterica species (typhoid fever) due to development of resistance (CDC 2014).
Meningitis, bacterial: Treatment of bacterial meningitis caused by E. coli, group B streptococci, and other gram-negative bacteria (Neisseria meningitidis).
Respiratory tract infections: Treatment of respiratory tract infections caused by S. pneumoniae, Staphylococcus aureus (penicillinase and nonpenicillinase producing), H. influenzae, and group A beta-hemolytic streptococci.
Urinary tract infections: Treatment of urinary tract infections caused by E. coli and P. mirabilis.
Endocarditis, prophylaxis (dental or invasive respiratory tract procedures); Intra-abdominal infection, health care-associated; Intra-amniotic infection (chorioamnionitis); Osteomyelitis and/or discitis, treatment; Peritonitis, treatment (peritoneal dialysis patients); Postpartum endometritis; Prosthetic joint infection; Streptococcus (group B), maternal prophylaxis for prevention of neonatal disease; Surgical prophylaxis; Tubo-ovarian abscess
Ampicillin may be confused with aminophylline
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Central nervous system: Brain disease (penicillin-induced), glossalgia, seizure, sore mouth
Dermatologic: Erythema multiforme, exfoliative dermatitis, skin rash, urticaria
Note: Appearance of a rash should be carefully evaluated to differentiate (if possible) nonallergic ampicillin rash from hypersensitivity reaction. Incidence is higher in patients with viral infection, Salmonella infection, lymphocytic leukemia, or patients that have hyperuricemia.
Gastrointestinal: Diarrhea, enterocolitis, glossitis, melanoglossia, nausea, oral candidiasis, pseudomembranous colitis, stomatitis, vomiting
Hematologic & oncologic: Agranulocytosis, anemia, eosinophilia, hemolytic anemia, immune thrombocytopenia, leukopenia
Hepatic: Increased serum AST
Immunologic: Serum sickness-like reaction
Renal: Interstitial nephritis (rare)
<1%, postmarketing, and/or case reports: Dysgeusia (Syed 2016)
Hypersensitivity (eg, anaphylaxis) to ampicillin, any component of the formulation, or other penicillins; infections caused by penicillinase-producing organisms
Concerns related to adverse effects:
• Hypersensitivity/anaphylactoid reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity or a history of sensitivity to multiple allergens. Serious anaphylactoid reactions require emergency treatment and airway management. Appropriate treatments must be readily available.
• Rash: Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3 to 14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides difficile–associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
• Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Rash (generalized maculopapular and pruritic) usually appears 7 to 10 days after initiation and usually resolves within a week of discontinuation. It is not known whether these patients are truly allergic to ampicillin
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Ampicillin has been shown to prolong the bleeding time in neonates in 2 prospective studies. The first study found a prolonged bleeding time by an average of 60 seconds longer than baseline in neonates (n=15; GA: 33 to 41 weeks; weight: 1,760 to 3,835 g) after receiving the third and fourth doses of ampicillin (50 to 100 mg/kg/dose every 12 hours) (Sheffield 2010). The second study evaluated the effect on bleeding time in very low birth weight patients (n=20; GA: 23 to 33 weeks; weight: 400 to 1,410 g); results showed that patients receiving ampicillin for ≥10 days had a prolonged bleeding time compared to baseline; on average bleeding time was 2 minutes longer (p=0.001) (Sheffield 2011). The clinical significance of ampicillin's effect on bleeding time is unknown, but probably depends on the patient's clinical status and risk of hemorrhage.
Acemetacin: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
Atenolol: Ampicillin may decrease the bioavailability of Atenolol. 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
Chloroquine: May decrease the serum concentration of Ampicillin. Management: Separate the administration of ampicillin and chloroquine by at least 2 hours to minimize any potential negative impact of chloroquine on ampicillin bioavailability. 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
Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of Ampicillin. Management: Administer oral ampicillin at least two hours before or after lanthanum. Risk D: Consider therapy modification
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. 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
Tetracyclines: May diminish the therapeutic effect of Penicillins. 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
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Food decreases ampicillin absorption rate; may decrease ampicillin serum concentration. Management: Take at equal intervals around-the-clock, preferably on an empty stomach (30 minutes before or 2 hours after meals). Maintain adequate hydration, unless instructed to restrict fluid intake.
Ampicillin crosses the placenta.
Detectable concentrations of ampicillin are present in the cord serum and amniotic fluid following maternal IM, IV, and oral administration (Nau 1987). In a study of women treated with IV ampicillin for group B streptococcal (GBS) prophylaxis, peak concentrations in the umbilical cord were observed 30 minutes after the maternal dose and effective neonatal concentrations continued for ≥4 hours when a loading dose was given (Berardi 2018).
Due to pregnancy-induced physiologic changes, the pharmacokinetics of ampicillin may be altered; dose adjustments may be needed. Although oral absorption is not altered during pregnancy, oral ampicillin is poorly absorbed during labor (Kubacka 1983; Nau 1987).
As a class, penicillin antibiotics are widely used in pregnant women. Based on available data, penicillin antibiotics are generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Czeizel 2001; Damkier 2019; Heinonen 1977; Lamont 2014; Muanda 2017a; Muanda 2017b).
Untreated intraamniotic infection (chorioamnionitis) may lead to adverse pregnancy outcomes, including pneumonia, meningitis, and sepsis, in the newborn. Maternal complications may include postpartum uterine atony with hemorrhage, endometritis, peritonitis, sepsis, or adult respiratory distress syndrome. Ampicillin is part of the recommended regimen for the treatment of intraamniotic infection (ACOG 2017).
Untreated asymptomatic GBS disease can result in maternal urinary tract infection, intraamniotic infection, endometritis, preterm labor, and/or stillbirth. Vertical transmission from the mother can cause sepsis, pneumonia, or meningitis in the newborn. IV ampicillin is recommended as an alternative antibiotic for intrapartum prophylaxis to prevent neonatal GBS early-onset disease (ACOG 2020b).
Ampicillin is recommended for use in pregnant women for the management of preterm prelabor rupture of membranes (PROM); treatment with antibiotics is used to prolong pregnancy and decrease maternal and newborn infections (ACOG 2020a). Ampicillin may also be used in certain situations prior to vaginal delivery in women at high risk for endocarditis (ACOG 2018).
Ampicillin may be a preferred agent for the treatment of asymptomatic bacteriuria in pregnancy (IDSA [Nicolle 2019]).
Maternal Listeria monocytogenes infection varies from asymptomatic disease requiring no therapy to a febrile illness with or without additional symptoms, resulting in severe pregnancy outcomes, including fetal loss, preterm labor, neonatal sepsis, meningitis, and maternal death. Maternal treatment with IV ampicillin is recommended when fever is present, exposure is suspected, and no other cause of illness is known (ACOG 2014).
Ampicillin is present in breast milk.
Concentrations of penicillin class antibiotics are limited in breast milk (Nau 1987). Following an oral dose of ampicillin 500 mg to 2 or 3 women 5 to 7 days postpartum, breast milk concentrations ranged from trace amounts 1 hour after the dose to 0.16 mcg/mL 6 hours after the dose. In contrast, the highest maternal serum concentration (7 mcg/mL) was found 1 hour after the dose, decreasing to ≤0.4 mcg/mL 6 hours after the dose (Matsuda 1984). A second study administered oral ampicillin 500 mg 4 times a day to 10 breastfeeding women following delivery. Maternal serum and breast milk were sampled over 6 hours on days 3 and 4 of therapy. Ampicillin concentrations were 0.015 to 1.67 mcg/mL (breast milk) and 0.56 to 5.42 mcg/mL (maternal serum) (Campbell 1991).
A prospective cohort study evaluated the outcomes of breastfed infants whose mothers were taking various medications. Among 5 mother-infant pairs with reported ampicillin exposure (dose, duration, relationship to breastfeeding not provided), diarrhea was reported in 1 infant (Ito 1993). A group of 21 breastfeeding mothers taking ampicillin were given a specially designed record sheet to monitor possible ampicillin-induced side effects in their infants for 15 days postdelivery. These infants were compared to a control group of 45 breastfed infants whose mothers were not taking antibiotics. There were no significant differences between the groups (Campbell 1991). In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush or diarrhea (WHO 2002).
Although the manufacturer recommends that caution be exercised when administering ampicillin to breastfeeding women, ampicillin is considered compatible with breastfeeding when used in usual recommended doses (WHO 2002).
Take on an empty stomach 30 minutes before or 2 hours after meals. Some products may contain sodium.
With prolonged therapy, monitor renal, hepatic, and hematologic function periodically; observe signs and symptoms of anaphylaxis during first dose
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Absorption: Oral: 50%
Distribution: Into bile; penetration into CSF occurs with inflamed meninges only
Protein binding: Neonates: 10%; Adults: 15% to 18%
PNA 2 to 7 days: 4 hours
PNA 8 to 14 days: 2.8 hours
PNA 15 to 30 days: 1.7 hours
Children and Adults: 1 to 1.8 hours (Bergan 1978)
Anuric patients: 8 to 20 hours
Time to peak serum concentration: Oral: Within 1 to 2 hours
Excretion: Urine (∼90%, unchanged within 24 hours); feces
Parameters associated with efficacy:
Time-dependent; associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC), goal: ≥40% fT>MIC (bactericidal) (Craig 1998; Lacy 1999); some experts favor 100% fT>MIC in critically ill patients (Roberts 2014).
Expected drug exposure in normal renal function:
Adults, Cmax (peak):
250 mg dose (oral capsule): ~2.3 mg/L.
500 mg dose (oral capsule): ~3 mg/L.
500 mg every 6 hours (IV), steady state: 10.2 ± 0.8 mg/L (Lacy 1999).
1 g every 6 hours (IV), steady state: 40.9 ± 6.6 mg/L (Lacy 1999).
Postantibiotic effect: Generally <1 hour, varies by organism (Craig 1993; Craig 1998).
Capsules (Ampicillin Oral)
500 mg (per each): $0.65
Solution (reconstituted) (Ampicillin Sodium Injection)
1 g (per each): $1.93 - $9.00
2 g (per each): $2.80 - $16.75
125 mg (per each): $5.22
250 mg (per each): $2.58 - $4.19
500 mg (per each): $2.77 - $4.41
Solution (reconstituted) (Ampicillin Sodium Intravenous)
1 g (per each): $16.37 - $17.91
2 g (per each): $31.76 - $34.75
10 g (per each): $76.80 - $107.77
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