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Sir,

We wish to comment on the article by Amyes et al.,1 in which we are referenced2 as stating that ‘the concept that ertapenem is unlikely to increase resistance in non-fermenters is flawed’. We in fact did not state this and, on the contrary, we agree with the conclusions of Livermore et al.3 that selection (of carbapenem-resistant Pseudomonas aeruginosa in particular) is unlikely under physiologically relevant ertapenem concentrations.

In this regard, the following points are critical. First, the BSAC/EUCAST ertapenem breakpoint for susceptibility is ≤0.5 mg/L and for resistance is >2 mg/L. The former value is far below the MICs for most P. aeruginosa strains, which range between 2 and 32 mg/L with MIC50 and MIC90 values of 4–8 and ≥16 mg/L, respectively.4 Secondly, the free ertapenem plasma concentration is less than the MIC50 by 4 h post-dose.3 In critically ill patients, the protein-unbound plasma concentration after a single intravenous administration of 1 g has been documented to be 0.87 ± 0.76 mg/L 12 h after infusion and 0.24 ± 0.43 mg/L 24 h after infusion.5 In other words, relevant ertapenem concentrations are below those likely to be active against a Pseudomonas (let alone Acinetobacter), implying that selection pressure for specific resistance is minimal. Thirdly, the OASIS (Optimizing Abdominal Surgery with Invanz Study) studies indicated no significant colonization by P. aeruginosa, either with imipenem-resistant or imipenem-susceptible strains, during ertapenem therapy.6

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