JAC Advance Access originally published online on July 20, 2007
Journal of Antimicrobial Chemotherapy 2007 60(4):901; doi:10.1093/jac/dkm278
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Correspondence |
Comment on: Best in class: a good principle for antibiotic usage to limit resistance development?
1 Department of Clinical Microbiology, Ampath Laboratories, Milpark Hospital, Johannesburg, South Africa 2 Department of Pulmonology, Johannesburg Hospital, University of Witwatersrand, Johannesburg, South Africa 3 Department of Critical Care and Pulmonology, Johannesburg Hospital, University of Witwatersrand, Johannesburg, South Africa
* Corresponding author. Tel: +27-117266260; Fax: +27-114823361; E-mail: brinka{at}ampath.co.za
Keywords: ertapenem , resistance , selection , non-fermenters
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
We acknowledge that under laboratory conditions with high drug concentrations, it is possible to select for imipenem-resistant P. aeruginosa with ertapenem, but the clinical relevance seems doubtful, because in the clinical scenario adequate concentrations are not maintained for a sufficiently long duration.
It seems relevant to ask whether, using similar logic, the authors of this article would restrict the use of cefotaxime and ceftriaxone in that they might undermine ceftazidime against P. aeruginosa, or similarly levofloxacin with regard to ciprofloxacin?
We would still recommend that ertapenem be used as the preferred therapy for infections due to extended-spectrum ß-lactamase producers and, in certain specific settings as outlined in our article, for intra-abdominal sepsis, pneumonia and skin and soft tissue (including diabetic foot) infections.
A. J. B. is on the advisory board for Merck. C. F. and G. A. R. are on the advisory board for Merck and speakers bureau for Astra Zeneca.
References
1
Amyes SGB, Walsh FM, Bradley JS. Best in class: a good principle for antibiotic usage to limit resistance development? J Antimicrobial Chemother (2007) 59:825–6.
2 Brink AJ, Feldman C, Grolman DC, et al. Appropriate use of the carbapenems. S Afr Med J (2004) 94:857–61.[Medline]
3
Livermore DM, Mushtaq S, Warner M. Selectivity of ertapenem for Pseudomonas aeruginosa mutants cross-resistant to other carbapenems. J Antimicrobial Chemother (2005) 55:306–11.
4
Livermore DM, Carter MW, Bagel S, et al. In vitro activities of ertapenem (MK-0826) against recent clinical bacteria collected in Europe and Australia. Antimicrob Agents Chemother (2001) 45:1860–7.
5
Burkhardt O, Kumar V, Katterwe D, et al. Ertapenem in critically ill patients with early-onset ventilator-associated pneumonia: pharmacokinetics with special consideration of free-drug concentration. J Antimicrobial Chemother (2007) 59:277–84.
6 Nubile MJ, Friedland I, Chan CY, et al. Bowel colonization with resistant gram-negative bacilli after antimicrobial therapy for intra-abdominal infections: observations from two clinical comparative trials of ertapenem therapy. Eur J Microbiol Infect Dis (2005) 24:443–9.[CrossRef]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||