Ertapenem

Ertapenem is a once-daily carbapenem used for ESBL and AmpC Enterobacterales infection, community and mixed intra-abdominal infection, diabetic foot infection and outpatient parenteral therapy. It does not cover Pseudomonas, Acinetobacter or Enterococcus.

Classification. Beta-lactam, group 1 carbapenem.

Mechanism. Blocks penicillin-binding proteins; resists hydrolysis by ESBL and AmpC enzymes, but not carbapenemases.

Spectrum. MSSA, streptococci, pneumococci, Haemophilus, Enterobacterales including ESBL and AmpC producers, Bacteroides and other anaerobes. Not active against MRSA, Enterococcus, Pseudomonas, Acinetobacter, Stenotrophomonas or carbapenemase producers.

Pharmacokinetics. IV or IM. Half-life about 4 hours. Protein binding 85 to 95%, concentration-dependent (low albumin raises free clearance). About 80% excreted in urine.

No loading dose. Maximum 1 g daily in adults.

Adults and adolescents 13 years and over. 1 g IV or IM once daily. - Complicated intra-abdominal infection: 5 to 14 days. - Complicated skin infection including diabetic foot: 7 to 14 days. - Community-acquired pneumonia: 10 to 14 days. - Complicated urinary tract infection including pyelonephritis: 10 to 14 days (shorter courses where response is rapid). - Acute pelvic infection: 3 to 10 days. - ESBL bacteraemia (step-down after initial carbapenem): 1 g once daily. - Prophylaxis in colorectal surgery: 1 g IV once, 1 hour before incision.

Children 3 months to 12 years. 15 mg/kg every 12 hours; maximum 1 g daily.

Alternatives. Meropenem, piperacillin tazobactam for non-ESBL organisms, cefepime.

Contraindications. Hypersensitivity to carbapenems; severe hypersensitivity to other beta-lactams; IM use with amide anaesthetic hypersensitivity (lidocaine diluent).

Adverse effects. Diarrhoea, nausea, headache, infusion-site reactions, rash, raised liver enzymes. Serious: seizures (higher with renal impairment), anaphylaxis, Clostridioides difficile infection, severe skin reactions, cytopenias.

Interactions. - Valproate: carbapenems lower valproate levels by 60 to 100% within 24 hours; avoid the combination. - Probenecid raises ertapenem levels.

Common prescribing errors. Using it for Pseudomonas or Acinetobacter, giving 1 g daily in severe renal impairment, using it as sole therapy in critical illness with hypoalbuminaemia, and giving with valproate.

Special groups.

• Pregnancy and breastfeeding: limited data; use only if needed.
• Older adults: adjust by kidney function; monitor for confusion and seizures.
• Kidney impairment: creatinine clearance over 30 mL/min no change; 30 mL/min or less (including haemodialysis) 500 mg once daily. If a haemodialysis dose is given within 6 hours before the session, add 150 mg after dialysis.
• Liver impairment: no adjustment.
• Hypoalbuminaemia: albumin under 25 g/L can raise free drug clearance; in critical illness a more frequent dose or another carbapenem may be chosen on specialist advice.

Preparation. IV: reconstitute 1 g with 10 mL water for injection, dilute in 50 mL of 0.9% sodium chloride and infuse over 30 minutes; use within 6 hours. IM: reconstitute 1 g with 3.2 mL of 1% lidocaine without adrenaline; use within 1 hour; not for IV use.

Baseline and monitoring. - Baseline: allergy history, medication review (valproate), cultures, creatinine, albumin. - During treatment: creatinine and full blood count twice weekly; liver tests weekly in prolonged courses; neurological status. - No therapeutic drug monitoring.

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

Referral and escalation. Infectious diseases involvement for outpatient parenteral therapy, bacteraemia and bone infection.