Ampicillin

Ampicillin is a parenteral aminopenicillin with the same spectrum as amoxicillin but lower oral absorption. In practice it is the intravenous drug for Listeria meningitis, enterococcal infection, neonatal sepsis and intrapartum prophylaxis against group B streptococcus.

Classification. Beta-lactam, aminopenicillin, destroyed by beta-lactamases.

Mechanism. Binds penicillin-binding proteins; bactericidal, time-dependent.

Spectrum. Enterococcus faecalis, Listeria monocytogenes, streptococci, non-beta-lactamase Haemophilus influenzae, meningococci, and susceptible Escherichia coli, Proteus and Salmonella. Not active against staphylococci that produce penicillinase, Klebsiella, Pseudomonas or ESBL producers. Resistance in Escherichia coli is common.

Pharmacokinetics. IV and IM. Oral absorption is about 30 to 55% and reduced by food, so oral use is rarely used now. Half-life about 1 hour; renal excretion about 75 to 90% unchanged. Penetrates inflamed meninges (CSF levels 5 to 10% of serum).

No loading dose except intrapartum prophylaxis. Maximum 12 g daily.

Listeria meningitis. 2 g IV every 4 hours for 21 days (with gentamicin for the first 7 days in some services). Children: 300 mg/kg/day divided every 6 hours, maximum 12 g/day.

Empirical bacterial meningitis in people over 50 years or immunocompromised. 2 g IV every 4 hours combined with a third-generation cephalosporin (and vancomycin where resistance is likely) until culture results.

Enterococcal endocarditis. 2 g IV every 4 hours for 4 to 6 weeks, with either gentamicin 3 mg/kg daily or ceftriaxone 2 g every 12 hours. Native valve with gentamicin short course is possible in selected patients.

Neonatal sepsis. 50 mg/kg every 12 hours (gestation and age under 7 days), every 8 hours thereafter; meningitis up to 100 mg/kg every 6 to 8 hours (300 mg/kg/day), always with gentamicin or a cephalosporin.

Chorioamnionitis and obstetric infection. 2 g IV every 6 hours with gentamicin 5 mg/kg once daily until delivery and at least one further dose after.

Group B streptococcus intrapartum prophylaxis. 2 g IV loading dose, then 1 g every 4 hours until delivery.

Other systemic infection. 1 to 2 g IV every 4 to 6 hours.

Alternatives. Amoxicillin has the same use with better oral options; ceftriaxone or vancomycin for resistant strains; co-trimoxazole for Listeria in penicillin allergy.

Contraindications. Penicillin hypersensitivity.

Adverse effects. Diarrhoea, rash (common and frequently non-allergic in infectious mononucleosis, CMV and lymphoma and with allopurinol), Clostridioides difficile infection. Serious: anaphylaxis, seizures at high dose or renal failure, interstitial nephritis, cytopenias, hepatitis.

Interactions. Allopurinol, methotrexate, warfarin, probenecid, oral typhoid vaccine; may antagonise the effect of bacteriostatic drugs (not usually clinically important). Aminoglycosides inactivate each other in the same syringe and bag.

Common prescribing errors. Using glucose as diluent, mixing with gentamicin, giving a full dose every 4 hours in renal failure, and assuming cover of Klebsiella.

Special groups. - Pregnancy and breastfeeding: acceptable. - Neonates: dose by gestation and postnatal age. - Older adults: reduce by renal function. - Kidney impairment: creatinine clearance 10 to 50 mL/min give 1 to 2 g every 6 to 12 hours; under 10 mL/min every 12 to 24 hours. Haemodialysis: dose after session. - Liver impairment: no adjustment. - Obesity: use actual body weight for dosing in meningitis.

Preparation. Dissolve each vial in water for injection or 0.9% sodium chloride. Give up to 500 mg by slow IV injection over 3 to 5 minutes and larger doses by infusion over 15 to 30 minutes; faster infusion risks seizures. Unstable in glucose; use within the labelled stability period. Contains about 3 mmol sodium in each gram.

Baseline and monitoring. - Baseline: cultures before first dose, creatinine, full blood count, allergy history. - During treatment: creatinine and electrolytes twice weekly; full blood count weekly beyond 2 weeks; monitor for neurotoxicity. - No therapeutic drug monitoring.

Stop rules. Stop for anaphylaxis, severe skin reaction, seizures or hepatic injury. De-escalate once susceptibility is known.

Referral and escalation. Infectious diseases for endocarditis and Listeria infection; obstetric and neonatal teams for chorioamnionitis and neonatal sepsis.