Ampicillin Sulbactam

Ampicillin sulbactam is a parenteral aminopenicillin with a beta-lactamase inhibitor that also has intrinsic activity against Acinetobacter baumannii. It covers mixed aerobic and anaerobic infection where Pseudomonas is not expected.

Classification. Beta-lactam, aminopenicillin plus penicillanic acid sulphone inhibitor. 1.5 g contains 1 g ampicillin and 0.5 g sulbactam; 3 g contains 2 g and 1 g.

Mechanism. Ampicillin blocks penicillin-binding proteins; sulbactam inhibits many class A beta-lactamases and binds penicillin-binding protein 1 and 3 of Acinetobacter.

Spectrum. Streptococci, MSSA, Enterococcus faecalis, beta-lactamase producing Haemophilus and Moraxella, Bacteroides and oral anaerobes, many Acinetobacter (variable), and susceptible Enterobacterales. Escherichia coli and Klebsiella resistance is common. Not active against Pseudomonas, MRSA, ESBL producers or atypical organisms.

Pharmacokinetics. IV or IM. Half-life about 1 hour for both components. Mainly renal elimination. Good tissue penetration, modest CSF penetration in meningitis.

No loading dose. Maximum 12 g of the combination (8 g ampicillin and 4 g sulbactam) daily in usual indications.

Adults. 1.5 to 3 g IV or IM every 6 hours. Indications and durations: community-acquired intra-abdominal infection, skin and soft tissue infection including diabetic foot, bite wounds, pelvic inflammatory disease (with doxycycline), aspiration pneumonia and gynaecological sepsis; usual courses 5 to 14 days depending on site and source control.

Acinetobacter baumannii infection (specialist use only). Part of combination therapy, aiming for 6 to 9 g sulbactam daily in 3 to 4 divided doses, preferably as prolonged infusion over 3 to 4 hours.

Children. 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day of the combination) divided every 6 hours; maximum 8 g ampicillin daily. Neonates: use specialist paediatric dosing.

Alternatives. Amoxicillin clavulanate IV or oral, piperacillin tazobactam, cefuroxime plus metronidazole.

Contraindications. Penicillin hypersensitivity; previous jaundice or hepatic dysfunction caused by ampicillin sulbactam.

Adverse effects. Diarrhoea, pain at IM site, thrombophlebitis, rash (frequent in infectious mononucleosis and with allopurinol), Clostridioides difficile infection. Serious: anaphylaxis, cholestatic hepatitis, cytopenias, interstitial nephritis, severe skin reactions, seizures in renal failure.

Interactions. Allopurinol, methotrexate, probenecid, warfarin, oral typhoid vaccine. Aminoglycosides are inactivated if mixed.

Common prescribing errors. Assuming Pseudomonas or ESBL cover, mixing with gentamicin, using usual doses for Acinetobacter and under-dosing in renal failure.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: reduce by kidney function. - Kidney impairment: creatinine clearance 30 mL/min or more every 6 to 8 hours; 15 to 29 mL/min every 12 hours; 5 to 14 mL/min every 24 hours. Haemodialysis: dose after the session. - Liver impairment: no adjustment; monitor liver tests. - Obesity: use full doses.

Preparation. Reconstitute with water for injection or 0.9% sodium chloride. IV push over 10 to 15 minutes or infusion over 15 to 30 minutes in 50 to 100 mL. For IM use, dilute with 0.5% lidocaine. Do not mix with aminoglycosides.

Baseline and monitoring. - Baseline: allergy history, cultures, creatinine, liver tests. - During treatment: creatinine and liver tests twice weekly in prolonged courses; full blood count weekly beyond 2 weeks. - No therapeutic drug monitoring.

Stop rules. Stop for anaphylaxis, severe skin reaction, jaundice or cytopenia.

Referral and escalation. Infectious diseases for Acinetobacter infection, failure at 48 to 72 hours and bone or joint infection.