Ertapenem resistance linked to higher mortality despite imipenem or meropenem susceptibility

A multicenter prospective cohort study of 374 hospitalized patients with invasive ceftriaxone-resistant Enterobacterales infections found higher 30-day mortality when isolates were ertapenem-resistant, despite susceptibility to imipenem or meropenem and treatment with one of those agents. The observational findings raise questions about whether in-vitro susceptibility alone predicts clinical outcomes in this setting.

ETP-R infections had higher 30-day mortality.
The cohort included 374 hospitalized patients.
All included isolates lacked detected carbapenemase genes.
Observational findings do not establish treatment failure causally.

The multicenter prospective cohort included hospitalized patients with invasive ceftriaxone-resistant Enterobacterales infections. Researchers compared outcomes for ertapenem-resistant (ETP-R) and ertapenem-susceptible (ETP-S) isolates. Included isolates were susceptible to imipenem or meropenem, had no detected carbapenemase genes, and patients received more than 72 hours of definitive treatment with one of those drugs. The primary outcome was 30-day mortality; analyses used inverse probability weighting to adjust for baseline differences.

Among 374 patients, 136 (36%) had ETP-R isolates and 238 (64%) had ETP-S isolates. ETP-R infection was associated with higher 30-day mortality (odds ratio 2.24, 95% CI 1.26–3.98; p=0.006). Fourteen-day and in-hospital mortality were also higher in the ETP-R group. Mortality was highest when isolates were resistant to two carbapenems. Genomic analyses found more porin alterations and non-carbapenemase β-lactamase genes in ETP-R isolates.

The findings challenge reliance on susceptibility to imipenem or meropenem alone, but do not establish that these drugs are ineffective or prove a causal mechanism. This was an observational cohort, and the authors suggest that porin loss combined with increased β-lactamase activity may contribute to reduced activity despite in-vitro susceptibility. The results warrant cautious interpretation alongside current guidance and individual clinical factors.

In practice

For hospitalized patients with invasive ceftriaxone-resistant Enterobacterales infections whose isolates are ertapenem-resistant but susceptible to imipenem or meropenem, this cohort found higher mortality with treatment including one of those higher-order carbapenems than among patients with ertapenem-susceptible isolates. The findings suggest that reported susceptibility may not fully reflect clinical outcomes in this population, but they are observational and do not show that imipenem or meropenem caused treatment failure. They do not, on their own, establish a replacement treatment approach or justify changing guidance.

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Source

Clinical Infectious Diseases: Are Higher-Order Carbapenems Effective Therapy for Patients with Ertapenem-Resistant Enterobacterales Invasive Infections? ↗

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