Ceftazidime-Avibactam as Salvage Therapy for Carbapenem-Resistant Klebsiella pneumoniae Bacteraemia: A Narrative Review of the Stewardship Decision
DOI:
https://doi.org/10.5281/zenodo.22236518Keywords:
Carbapenem-Resistant Enterobacterales, Ceftazidime-Avibactam, Antimicrobial Stewardship, Bacteraemia, Emergent ResistanceAbstract
Stewardship usually means finding a reason not to use the newest agent. Carbapenem-resistant Klebsiella bacteraemia is the
situation where that instinct is most likely to be wrong, and where acting on it costs lives. The difficulty is that resistance to the
new agent emerges during treatment, so the drug is being spent as it is used.
Objectives: To review the published evidence on ceftazidime-avibactam for carbapenem-resistant Enterobacterales infection:
how it compares with the alternatives, how often treatment fails, how readily resistance emerges, and what that means for the
stewardship decision at the bedside.
Material and Methods: Narrative review of prospective observational cohorts, retrospective multicentre studies, randomised
trials of comparator agents, resistance surveillance and society guidance indexed in PubMed and the major infectious diseases
and microbiology journals. No new patient data were generated; every estimate quoted is one published by the original
investigators.
Results: In a prospective multicentre cohort, 38 patients treated with ceftazidime-avibactam were compared with 99 treated with
colistin. Adjusted all-cause hospital mortality 30 days after starting treatment was 9 per cent against 32 per cent (difference 23
per cent, 95% bootstrap CI 9 to 35, p = 0.001), with an adjusted probability of a better outcome of 64 per cent (95% CI 57 to 71).
In a separate series of 37 treated patients, clinical success was 59 per cent and 30-day survival 76 per cent; microbiologic failure
occurred in 27 per cent, and ceftazidime-avibactam resistance was detected in 3 of those 10 failures.
Conclusion: The comparative evidence is observational and the authors of the principal study said explicitly that it requires
confirmation in a randomised trial, which has not been done. Even so, a 23 percentage point adjusted mortality difference against
colistin is large enough that withholding the agent to preserve it is difficult to defend for an individual patient with bacteraemia.
Abbreviations: CAZ-AVI – Ceftazidime-Avibactam, CRE – Carbapenem-Resistant Enterobacterales, DOOR – Desirability of
Outcome Ranking, IPTW – Inverse Probability of Treatment Weighting, KPC – Klebsiella pneumoniae Carbapenemase, MBL –
Metallo-Beta-Lactamase.
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