Principen (Bristol-Myers Squibb) — oral capsules, US; largely replaced by generics · Omnipen (Wyeth) — historical US brand; discontinued · Ampicin (various Commonwealth manufacturers) · Penbritin (UK/Commonwealth; historical brand) · Totacillin — historical brand · Ampicillin sodium for injection (multiple generic manufacturers — Pfizer, Sandoz, Fresenius Kabi, Hikma) — standard IV formulation in current use · Unasyn (ampicillin-sulbactam) — combination IV product with beta-lactamase inhibitor; distinct from ampicillin alone
Clinical safety rating: safe
Human studies have proved safety
Ampicillin is a penicillin antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidase activity, and disrupting peptidoglycan cross-linking.
| Metabolism | Ampicillin is primarily excreted unchanged in the urine via renal tubular secretion and glomerular filtration. A small portion is metabolized by hydrolysis to penicilloic acid, but hepatic metabolism is minimal. |
| Excretion | Renal: 90% unchanged via glomerular filtration and tubular secretion; biliary: 10% (small amount). |
| Half-life | Terminal elimination half-life: 1-1.8 hours in adults with normal renal function; prolonged to 7-20 hours in end-stage renal disease (CrCl <10 mL/min). |
| Protein binding | 17-20% bound to serum albumin. |
| Volume of Distribution | 0.28-0.31 L/kg (higher in neonates and critically ill patients). |
| Bioavailability | Oral: 50% (fasting); reduced by 25-50% with food. IM: ~100% (complete absorption). |
| Onset of Action | Oral: 1-2 hours (peak concentration); IM: 15-30 minutes; IV: immediate (minutes). |
| Duration of Action | Oral: 6-8 hours; IM/IV: 4-6 hours (shorter than oral due to rapid renal clearance). |
| Molecular Weight | Ampicillin anhydrous: 349.41 g/mol. Ampicillin sodium (IV formulation): 371.39 g/mol. Ampicillin trihydrate (oral formulation): 403.45 g/mol. The relatively low molecular weight facilitates placental transfer by passive diffusion. |
250-500 mg orally every 6 hours; 1-2 g IV/IM every 4-6 hours.
| Renal impairment | CrCl 10-50 mL/min: administer every 6-12 hours; CrCl <10 mL/min: administer every 12-24 hours. |
| Liver impairment | No adjustment needed for hepatic impairment; dose as in normal hepatic function. |
| Pediatric use | Neonates: 25-50 mg/kg IV/IM every 12 hours (first week), every 8 hours (1-4 weeks); Infants/Children: 25-100 mg/kg/day IV/IM divided every 6-8 hours; Oral: 50-100 mg/kg/day divided every 6-8 hours. |
| Geriatric use | CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: administer every 6-12 hours; CrCl <10 mL/min: administer every 12-24 hours; maximum 2 g/day. |
| 1st trimester | Safe. No increased risk of major congenital malformations based on the Collaborative Perinatal Project and multiple large cohort studies. Appropriate for treatment of confirmed susceptible bacterial infections including UTI, skin and soft tissue infections, and dental infections where systemic therapy is required. Oral bioavailability is limited — amoxicillin is preferred for outpatient oral therapy. GI side effects may compound first-trimester nausea. |
| 2nd trimester | Safe. Appropriate for treatment of pyelonephritis (IV), UTI, and other susceptible bacterial infections. Empiric use for UTI requires local susceptibility data — E. coli resistance to ampicillin is high (>40–60% in many regions) and urine culture with susceptibility testing should guide therapy. Standard agent in chorioamnionitis combination regimens if this complication arises at the limits of viability. Listeriosis empiric coverage should always include ampicillin regardless of trimester. |
| 3rd trimester | Safe. First-line IV antibiotic for GBS intrapartum prophylaxis when penicillin G is unavailable (2 g IV load, then 1 g IV every 4 hours until delivery). Essential component of empiric chorioamnionitis treatment (with gentamicin ± clindamycin/metronidazole). Drug of choice (with gentamicin) for listeriosis — critical given Listeria's predilection for immunocompromised states including pregnancy and its cephalosporin-resistance. Neonates born to treated mothers should be monitored for GI colonisation effects but ampicillin use does not require withholding breastfeeding. |
Clinical note
Ampicillin is a broad-spectrum aminopenicillin antibiotic with an established safety record across all trimesters of pregnancy. It is the first-line intravenous agent for Group B Streptococcus (GBS) intrapartum prophylaxis per CDC and ACOG guidelines, the drug of choice (in combination with gentamicin) for treatment of listeriosis in pregnancy, and a standard agent for urinary tract infections, chorioamnionitis regimens, and endocarditis prophylaxis in obstetric patients. No teratogenic signal has been identified in large epidemiological cohorts. It does not carry the necrotising enterocolitis (NEC) risk associated with amoxicillin-clavulanate in PPROM. Oral bioavailability is limited and erratic; the IV/IM route is standard for serious obstetric indications.
■ FDA Black Box Warning
Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients on penicillin therapy. Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents.
| Serious Effects |
Known hypersensitivity (anaphylaxis, angio-oedema, urticaria, or other IgE-mediated reactions) to ampicillin, any penicillin, or any component of the formulation.History of ampicillin/penicillin-associated serious skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis).Infectious mononucleosis (EBV infection) or cytomegalovirus (CMV) infection: ampicillin causes a characteristic, non-allergic maculopapular rash in 70–100% of these patients — the drug is not absolutely contraindicated but is contraindicated in practice given the near-universal severe rash; alternative antibiotics should be used.Concomitant use with live oral typhoid vaccine (Ty21a): antibacterial activity inactivates the vaccine strain; space by ≥3 days or use injectable Vi polysaccharide typhoid vaccine instead.Severe penicillin allergy with documented cross-reactivity risk: approximately 1–2% cross-reactivity with cephalosporins; all beta-lactams require extreme caution or avoidance in patients with prior anaphylaxis pending formal allergy evaluation.
| Precautions | Serious hypersensitivity reactions (anaphylaxis) requiring emergency treatment, Clostridium difficile-associated diarrhea (CDAD) may occur, Prolonged use may result in superinfection with non-susceptible organisms, Use with caution in patients with renal impairment (dose adjustment needed), Skin rash is common in patients with mononucleosis or concurrent allopurinol use |
Loading safety data…
| Placental transfer | Yes — ampicillin crosses the placenta readily by passive diffusion. Cord blood concentrations reach approximately 30–50% of maternal serum concentrations within 1 hour of IV administration, with cord:maternal ratios approaching 1.0 at delivery after repeated dosing. Ampicillin distributes into amniotic fluid — concentrations are lower than maternal serum but sufficient to have therapeutic effects in the fetal compartment. This transplacental transfer is the pharmacological basis for its efficacy in preventing vertical GBS transmission and treating fetal Listeria infection. Fetal tissue concentrations are therapeutically relevant for susceptible organisms in fetal lung, liver, and blood. |
| Breastfeeding | Ampicillin is excreted into breast milk in low concentrations. Reported milk levels are typically 0.1–1.2 mg/L following standard IV dosing. The relative infant dose (RID) is estimated at <1% of the maternal weight-adjusted dose, well below the 10% threshold of clinical concern. The most commonly reported adverse effects in nursing infants are GI disturbance (loose stools, diarrhoea) and candidal diaper rash due to alteration of intestinal flora. Rare allergic sensitisation is theoretically possible. Temporary interruption of breastfeeding is not warranted. Premature infants or neonates with suspected renal impairment may warrant closer observation given reduced drug clearance. |
| Lactation Rating | L1 — Safest (Hale's Lactation Risk Category). Compatible with breastfeeding. |
| Teratogenic Risk | Ampicillin is FDA Pregnancy Category B. Animal studies have not demonstrated teratogenic effects. In humans, ample data across all trimesters indicate no increased risk of major birth defects, though there is a theoretical risk of altered gut flora and maternal-fetal effects from high doses. No documented teratogenicity from controlled studies in pregnant women. |
| Fetal Monitoring | Routine prenatal monitoring. No specific fetal monitoring required. Assess maternal renal function due to ampicillin excretion. Monitor for signs of maternal infection resolution and adverse effects (rash, diarrhea, anaphylaxis). In late pregnancy, assess for neonatal jaundice risk from displacement of bilirubin from albumin at high doses. |
| Fertility Effects | No known adverse effects on male or female fertility. Ampicillin does not impair spermatogenesis or oocyte function. No impact on conception rates in animal studies. |
| Food/Dietary | Food decreases absorption of oral ampicillin; take on an empty stomach. No specific food restrictions aside from timing. Avoid alcohol as it may increase gastrointestinal irritation. |
| Clinical Pearls | Ampicillin is a bactericidal antibiotic that inhibits cell wall synthesis. It is effective against Gram-positive cocci (except penicillinase-producing staphylococci) and some Gram-negative bacilli. Use with probenecid to increase serum levels. Monitor for rash, which may indicate mononucleosis. Dose adjustment required in renal impairment (CrCl <30 mL/min). Administer IV slowly over 10-15 minutes to avoid phlebitis. |
| Patient Advice | Take ampicillin exactly as prescribed, even if you feel better. · Complete the full course of therapy to prevent resistance. · Take on an empty stomach (1 hour before or 2 hours after meals) for best absorption. · Oral suspension must be refrigerated; shake well before each use. · Discard any unused oral suspension after 14 days. · Report any skin rash, diarrhea, or difficulty breathing to your doctor immediately. · Do not use if you are allergic to penicillins or cephalosporins. · Avoid alcohol while on this medication to reduce risk of side effects. · May reduce the effectiveness of oral contraceptives; use additional birth control. |