4th-gen cephalosporin + beta-lactamase inhibitor Pregnancy: There are no data from the use of cefepime-enmetazobactam in pregnant women. Animal studies indicate reproductive toxicity at relevant clinical exposure of enmetazobactam but no signs of teratogenicity. Enmetazobactam should only be used during pregnancy when clearly indicated and only if the benefit for the mother outweighs the risk for the child. Breast-feeding: physico-chemical data suggest excretion in human milk and excretion in rat milk has been shown, so a risk to newborns/infants cannot be excluded — a decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy.

Cefepime with enmetazobactam

Brand names: Exblifep

A fixed intravenous combination of the fourth-generation cephalosporin cefepime with the beta-lactamase inhibitor enmetazobactam, indicated for complicated urinary tract infections including pyelonephritis and other serious Gram-negative infections.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 2 g/0.5 g cefepime/enmetazobactam (patients with normal renal function)

Route: Intravenous infusion — over 2 hours for complicated urinary tract infection, and over 4 hours for hospital-acquired pneumonia including ventilator-associated pneumonia

Frequency: Every 8 hours

Fetched UK SPC is EXBLIFEP 2 g/0.5 g powder for concentrate for solution for infusion (eMC product 15727) — the fixed combination named on this page, covering both components. Indication-specific infusion times: complicated urinary tract infections (cUTI) including pyelonephritis — 2 g/0.5 g every 8 hours as an intravenous infusion over 2 hours, with prolongation of the infusion to 4 hours recommended in patients with augmented renal clearance (eGFR > 150 mL/min); hospital-acquired pneumonia (HAP) including ventilator-associated pneumonia (VAP) — 2 g/0.5 g every 8 hours as an intravenous infusion over 4 hours, and for HAP/VAP the infusion time should be 4 hours regardless of renal impairment status. Duration: the usual duration of treatment is 7 to 10 days; in general administration should not be less than 7 days and not longer than 14 days; in patients with bacteraemia treatment up to 14 days may be required. Elderly: no dose adjustment is necessary based on age alone, but because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and renal function should be monitored. Hepatic impairment: no dose adjustment is necessary. Paediatric population: the safety and efficacy in children below 18 years of age has not yet been established and no data are available — verify any under-18 use against a children's formulary. §4.4 safety: reversible encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor and coma), myoclonus, seizures (including nonconvulsive status epilepticus) and/or renal failure have been reported with cefepime/enmetazobactam when the dose has not been reduced in patients with renal impairment, and in some cases neurotoxicity was reported despite dose adjustment. The use of cefepime-enmetazobactam in HAP/VAP is based on experience with cefepime alone plus pharmacokinetic-pharmacodynamic analyses for the combination. The fetched §4.4 text was truncated at the source-fetch limit before §4.5, so the UK interaction section was not retrieved. The openFDA fallback record fetched is cefepime alone (Apotex Corp.) — a single component of this fixed combination — and was not used.

Dose adjustments

Renal

Dose adjustment is recommended in patients with an absolute eGFR less than 60 mL/min. SPC Table 1 recommended dose of EXBLIFEP by absolute eGFR (mL/min): mild (60 – <90) cefepime 2 g and enmetazobactam 0.5 g every 8 hours; moderate (30 – <60) cefepime 1 g and enmetazobactam 0.25 g every 8 hours; severe (15 – <30) cefepime 1 g and enmetazobactam 0.25 g every 12 hours; end-stage renal disease (<15) cefepime 1 g and enmetazobactam 0.25 g every 24 hours; patients requiring haemodialysis — cefepime 1 g and enmetazobactam 0.25 g loading dose on the first day of therapy and cefepime 0.5 g and enmetazobactam 0.125 g thereafter every 24 hours, given after the haemodialysis session on haemodialysis days; patients undergoing continuous ambulatory peritoneal dialysis (CAPD) — cefepime 2 g and enmetazobactam 0.5 g every 48 hours. Patients receiving continuous renal replacement therapy (CRRT) need a higher dose than patients on haemodialysis, and the dose should be adjusted guided by the CRRT clearance (CL_CRRT in mL/min). For patients with changing renal function, serum creatinine concentrations and eGFR should be monitored at least daily and the dose adjusted accordingly. For HAP/VAP the infusion time should be 4 hours regardless of renal impairment status.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1
Hypersensitivity to any cephalosporin antibacterial agent
Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of beta-lactam antibacterial agent (e.g. penicillins, carbapenems or monobactams)

Side effects

Alanine aminotransferase increased (4.8%), aspartate aminotransferase increased (3.5%), blood bilirubin increased and alkaline phosphatase increased — common
Diarrhoea (2.9%) — common; pseudomembranous colitis, colitis, vomiting and nausea uncommon
Infusion site phlebitis (1.9%) — common
Coombs test positive — very common; prothrombin time prolonged, partial thromboplastin time prolonged, anaemia and eosinophilia common
Headache — common; dizziness uncommon; convulsion, paraesthesia and dysgeusia rare; coma, stupor, encephalopathy, altered state of consciousness and myoclonus frequency not known
Rash — common; Clostridioides difficile associated diarrhoea (CDAD) uncommon (a serious adverse reaction of C. difficile colitis occurred in 0.2%, 1/516)

Interactions

Medicinal products with nephrotoxic potential, such as aminoglycosides and potent diuretics — renal function should be monitored carefully if these are administered concomitantly (SPC §4.4; the UK §4.5 interaction section was truncated at the source-fetch limit and was not retrieved, so this is not the complete interaction list)

Clinical monograph

How it works

Cefepime inhibits cell-wall synthesis by binding penicillin-binding proteins, while enmetazobactam, a penicillanic acid sulfone inhibitor, neutralises extended-spectrum beta-lactamases and restores cefepime activity against many ESBL-producing Enterobacterales.

Prescribing in practice

Reserve for serious Gram-negative infection under specialist guidance to limit resistance, and avoid in patients with severe cephalosporin or beta-lactam hypersensitivity.
Cefepime is associated with dose-related neurotoxicity, including encephalopathy, myoclonus and non-convulsive status epilepticus, particularly in renal impairment, so renal dose adjustment is essential.
Both components are renally eliminated and require dose modification in renal impairment.

Monitoring

Monitor renal function, neurological status for signs of cefepime encephalopathy, and microbiological response.

Counselling the patient

This is a hospital intravenous antibiotic for serious infections such as kidney infection.
Report confusion, twitching, or reduced alertness, as well as any rash or breathing difficulty.

Evidence & guidelines

The ALLIUM trial supported its use in complicated urinary tract infection, including pyelonephritis.

Reference: BSAC; UKHSA AMR; NICE TA evaluation; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways