JAC Advance Access originally published online on August 30, 2007
Journal of Antimicrobial Chemotherapy 2007 60(4):901-902; doi:10.1093/jac/dkm339
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Correspondence |
Best in class: a good principle for antibiotic usage to limit resistance development?—author's response
Centre for Infectious Diseases, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK
* Tel: +44-131-242-6652; E-mail: s.g.b.amyes{at}ed.ac.uk
The point that we were emphasizing in our Leading article was that the use of weaker drugs may select for bacteria resistant to stronger members of the same class.1 In their comment, Brink et al.2 identify that the clinical use of ertapenem is likely to deliver concentrations below the MIC of ertapenem for Pseudomonas aeruginosa. This is, in fact, the point we hoped to make. However, they go on to suggest that these relatively low concentrations of ertapenem will be ineffective against this strain. It is with this issue that we are concerned. In our article, we indicate that the emergence and spread of resistance are greatly enhanced at subinhibitory concentrations; however, resistance emergence is also a dynamic process of the progressive concentration of resistant strains within the clinical population, often by the same or related strains. In the individual case that Brink et al.2 describe, ertapenem did not select carbapenem-resistant P. aeruginosa; however, we are concerned with the much broader picture for, in the face of thousands or even millions of such challenges, we maintain that selection of resistant strains is likely to occur and progressively increases their concentration in the clinical setting.
With regard to their later comment, the widespread dissemination of extended-spectrum ß-lactamases (ESBLs) and transferable ampC ß-lactamases does demonstrate that we have not used cephalosporins optimally. We do, though, have the benefit of hindsight and different strategies; in particular, the use of cephalosporins in combination with a ß-lactamase inhibitor3 might have suppressed the huge problem of cephalosporin resistance that we now face. It should be possible to learn from experience that we must not take individual treatment cases in isolation as a model for drug strategy because, unless we consider the broader potential impact of using weaker drugs, we may well face a new ‘ESBL’ problem, but this time it will be carbapenemases.
S. G. B. A. has received an educational grant from AstraZeneca.
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, Richards GA. Comment on: Best in class: a good principle for antibiotic usage to limit resistance development? J Antimicrob Chemother (2007) 60. 901.
3
Du Bois SK, Marriott MS, Amyes SGB. TEM- and SHV-derived extended-spectrum ß-lactamases: relationship between selection, structure and function. J Antimicrobial Chemother (1995) 35:7–22.
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