AMPICILLIN AND SULBACTAM
Clinical safety rating: safe
Probenecid decreases renal tubular secretion of ampicillin Allopurinol may increase the incidence of skin rashes Serious and occasionally fatal hypersensitivity reactions have been reported.
Ampicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidase activity. Sulbactam is a β-lactamase inhibitor that irreversibly inhibits a broad range of β-lactamases, preventing degradation of ampicillin.
| Metabolism | Ampicillin undergoes minimal hepatic metabolism; primarily excreted unchanged in urine via renal tubular secretion. Sulbactam is primarily excreted unchanged in urine with minimal metabolism. |
| Excretion | Primarily renal (70-75% unchanged ampicillin, 75-80% unchanged sulbactam). Biliary excretion accounts for ~25% of ampicillin and ~20% of sulbactam. Fecal elimination is minor (<5%). |
| Half-life | Ampicillin: 1-1.8 hours; sulbactam: 1-1.5 hours. Prolonged in renal impairment (e.g., creatinine clearance <30 mL/min: up to 8-12 hours). |
| Protein binding | Ampicillin: 15-25% to albumin; sulbactam: 38% to albumin. |
| Volume of Distribution | Ampicillin: 0.28 L/kg; sulbactam: 0.24 L/kg. Distributes well into extracellular fluid, bile, and inflamed tissues, but limited CNS penetration unless meninges inflamed. |
| Bioavailability | IV: 100%; IM: ~80% for both components (peak serum concentrations reached 30-60 min after IM injection). Oral ampicillin alone ~30-55% but fixed combination not available orally. |
| Onset of Action | IV: immediate; IM: 15-30 minutes; oral: not available (IV/IM only). |
| Duration of Action | 6-8 hours for susceptible pathogens; dosing every 6 hours recommended due to time-dependent killing. |
| Molecular Weight | Ampicillin: 349.41 Da; Sulbactam: 255.23 Da |
1.5-3 g (ampicillin 1-2 g + sulbactam 0.5-1 g) IV/IM every 6 hours. Maximum daily dose of sulbactam is 4 g.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >30 mL/min: no adjustment. CrCl 15-30 mL/min: dose every 12 hours. CrCl 5-15 mL/min: dose every 24 hours. CrCl <5 mL/min: dose every 48 hours. Hemodialysis: administer after dialysis. |
| Liver impairment | No dose adjustment required for hepatic impairment. Monitor for toxicity in severe hepatic failure. |
| Pediatric use | Neonates <1 week: 75 mg/kg/day (ampicillin 50 mg/kg + sulbactam 25 mg/kg) IV divided every 12 hours. Neonates 1-4 weeks: 150 mg/kg/day divided every 8 hours. Infants/children: 200-400 mg/kg/day (ampicillin 150-300 mg/kg) IV divided every 6 hours; maximum sulbactam 80 mg/kg/day. |
| Geriatric use | No specific dose adjustment based on age alone; adjust per renal function. Consider lower initial doses due to age-related decline in renal function. |
| 1st trimester | Generally considered safe; use only if clearly needed. No adequate well-controlled studies in pregnant women, but animal studies have not shown fetal harm. |
| 2nd trimester | Generally considered safe; use only if clearly needed. No evidence of teratogenicity in human data. |
| 3rd trimester | Generally considered safe; use only if clearly needed. Risk of neonatal jaundice or kernicterus low with ampicillin/sulbactam. |
Clinical note
Probenecid decreases renal tubular secretion of ampicillin Allopurinol may increase the incidence of skin rashes Serious and occasionally fatal hypersensitivity reactions have been reported.
| FDA category | Human |
| Placental transfer | Both ampicillin and sulbactam cross the placenta. Ampicillin achieves fetal serum concentrations 50-100% of maternal levels; sulbactam achieves approximately 20-50%. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Diarrhea |
| Serious Effects |
Hypersensitivity to ampicillin, sulbactam, or any penicillinHistory of anaphylactic reaction to beta-lactam antibioticsInfectious mononucleosis (risk of maculopapular rash)
| Precautions | Severe hypersensitivity reactions (anaphylaxis) in penicillin-allergic patients, Clostridium difficile-associated diarrhea (CDAD), Severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome, Hepatotoxicity (elevated liver enzymes, cholestatic hepatitis), Neurologic adverse effects (seizures) with high doses or renal impairment, Superinfection with resistant organisms |
| Food/Dietary | No significant food interactions. Ampicillin-sulbactam can be taken with or without food; however, food may decrease absorption slightly but not sufficient to require separation. Avoid alcohol due to potential disulfiram-like reaction (rare with penicillins). Maintain adequate hydration. |
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| Breastfeeding | Ampicillin and sulbactam are excreted into breast milk in low concentrations. Adverse effects in the infant are unlikely. Use with caution in infants with known hypersensitivity or those at risk for diarrhea or candidiasis. |
| Lactation Rating | L1 (Compatible) |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies show no fetal harm; no adequate human studies. Crosses placenta. No known teratogenicity in first trimester; theoretical risk of kernicterus in third trimester due to bilirubin displacement at high doses is negligible with sulbactam. |
| Fetal Monitoring | Monitor maternal renal function and CBC during prolonged therapy. Fetal monitoring recommended if used for chorioamnionitis (uterine contractions, fetal heart rate). Assess neonatal jaundice if used near term. |
| Fertility Effects | No known adverse effects on fertility in animal studies; human data lacking. |
| Clinical Pearls | Ampicillin-sulbactam covers MSSA, Streptococcus spp., Enterococcus faecalis, anaerobes (including B. fragilis), and many Enterobacteriaceae. It does not cover MRSA, Pseudomonas, or ESBL-producing organisms. Sulbactam irreversibly inhibits beta-lactamases but does not restore activity against Acinetobacter due to intrinsic resistance. Dose adjustment required for CrCl <30 mL/min (extend interval to q12h). Administer within 1 hour of reconstitution due to degradation. Monitor for diarrhea, as C. difficile infection is common. |
| Patient Advice | Take this medication exactly as prescribed; do not skip doses. · Complete the full course even if you feel better. · Notify your doctor if you experience severe diarrhea, rash, or difficulty breathing. · This medication may cause diarrhea; if it is watery or bloody, contact your doctor immediately. · Inform your healthcare provider of all other medications you are taking, especially warfarin or methotrexate. |