No new approvals, withdrawals or safety communications affecting infectious disease practice today.
Worth knowing about: there is currently no oral treatment for infections caused by extended-spectrum beta-lactamase-producing Enterobacterales, which is why complicated urinary tract infections in these patients mean intravenous carbapenems and, often, admission. Avibactam tomilopil is an oral prodrug of avibactam, developed with the oral cephalosporin ceftibuten.
Three phase 1 trials in healthy volunteers have now settled the dose. The prodrug is rapidly converted to active avibactam with dose-proportional exposure, both components are predominantly renally excreted with similar half-lives, and food raises avibactam exposure without materially affecting ceftibuten. A fixed-dose tablet of ceftibuten 400 mg with avibactam tomilopil 1200 mg every eight hours, taken with or without food, is proposed for phase 3.
That is a long way from a licence, and every oral beta-lactamase inhibitor before it has failed on exposure. It is worth tracking because the prize — keeping an ESBL urinary infection out of hospital — is large.
- No new approvals, recalls or safety communications for infectious disease today
- Phase 1 pharmacokinetics only; no patient efficacy data exist yet
- The unmet need is real: there is no oral option for ESBL Enterobacterales today
- Both components are renally cleared, so renal impairment dosing will need work
- Track it; do not anticipate it in a formulary discussion yet
The statistics, in plain English
Probability of target attainment simulation asks what fraction of a modelled patient population would reach a drug exposure high enough to kill the organism. It is how a dose is chosen before efficacy is known — a reasonable basis for designing a trial, and no evidence at all that patients get better.
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