1 Antibiotic Resistance Monitoring and Reference Laboratory; 2 Sexually-Transmitted Bacterial Diseases Reference Laboratory; and 3 Communicable Disease Surveillance Centre, Health Protection Agency Colindale, 61 Colindale Avenue, London NW9 5HT, UK
Keywords: N. gonorrhoeae , resistance , carbapenems
Sir,
The dramatic rise in the prevalence of ciprofloxacin resistance among Neisseria gonorrhoeae isolates in the UK2% in 2000, 3% in 2001 and 10% in 20021is driving genitourinary clinics to replace fluoroquinolones with cephalosporins as standard therapy. The accepted target of curing >95% of patients with a single dose seems most likely to be achieved if a cephalosporin has low MICs and a long elimination half-life. Among available compounds these criteria are best met by ceftriaxone and cefixime, which have both proved effective in clinical trials.2 Resistance remains vanishingly rare, though a few isolates have diminished susceptibility, with MICs of 0.120.25 mg/L. New options should nevertheless be sought, because gonococci have a notorious capacity to accrue stepwise resistance to ß-lactams and because selection for cephalosporin resistance will increase with the switch to cephalosporin therapy.
Ertapenem (Merck), a new carbapenem, is potentially interesting in this context, having very low MICs for most Gram-negative bacteria and an elimination half-life of 3.8 h in healthy volunteers3who should be a better proxy for gonorrhoea patients than they are for many other patient groups! It is available for intra-muscular injection in most countries, though not those of the EU. To evaluate its possible utility, we tested ertapenem's microbiological activity against 652 gonococci collected under the ambit of the 2003 GRASP (Gonococcal Resistance to Antimicrobials Surveillance Programme). This programme is essentially as in 2002,1 with consecutive gonococci collected from 24 laboratories serving 26 clinics in England and Wales for a 3 month period (JuneAugust, inclusive). These isolates are subjected to central re-identification, and to susceptibility testing on DST agar containing 5% lysed equine blood and 0.1% Vitox. The isolates tested with ertapenem were consecutive submissions by non-London clinics in the latter 2 months of the study, and amounted to 30% of all confirmed gonococci collected. Among these 652 isolates, 10.5% required penicillin MICs 1 mg/L and 10.6% required ciprofloxacin MICs 1 mg/L, thus counting as resistant under the GRASP criteria. A further 2.5% were ciprofloxacin intermediate, with MICs of 0.120.5 mg/L (BSAC criteria, based on tests using Iso-Sensitest agar, would count 6.6%, with MICs >1 mg/L, as penicillin-resistant and 13.1%, with MICs >0.06 mg/L, as ciprofloxacin-resistant).4 The proportions resistant mirror, or slightly exceed, those for the full 2002 and 2003 GRASP collections.1
The MIC distribution of ertapenem is shown in Table 1, with that of ceftriaxone for comparison. Ertapenem MICs for the 652 isolates clustered from 0.002 to 0.06 mg/L, with fewer than 10% of values outside this range. The highest MICs found (0.25 mg/L) were for three ß-lactamase-negative isolates, two of them penicillin-resistant (MIC, 12 mg/L), and the third barely susceptible (MIC 0.5 mg/L). Ertapenem retained full activity against the 40 ß-lactamase producers represented and its MICs for ciprofloxacin-resistant isolates were no higher than for ciprofloxacin-susceptible organisms, whereas a relationship might be expected if both drugs were significantly affected by a multidrug efflux system or systems.
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In the absence of contra-indicating factors, ceftriaxone (or cefixime) remains the obvious next choice in those parts of the world, including the UK, where fluoroquinolone therapy of gonorrhoea has been undermined by resistance. Nevertheless, and contingent on the nature of whatever cephalosporin resistance emerges in the future, ertapenem may be a further option.
Acknowledgements
We are grateful to Merck & Co., for sponsoring testing of ertapenem against this sample of isolates, and to all the laboratories and clinics that have contributed to the 2003 and previous GRASP surveys.
Footnotes
* Corresponding author. Tel: +44-20-8200-4400; Fax: +44-20-8358-3292; Email: david.livermore{at}hpa.org.uk
References
1 . Fenton, K. A., Ison, C., Johnson, A. P. et al. (2003). Ciprofloxacin resistance in Neisseria gonorrhoeae in England and Wales in 2002. Lancet 361, 18679.[CrossRef][ISI][Medline]
2 . Plourde, P. J., Tyndall, M., Agoki, E. et al. (1992). Single-dose cefixime versus single-dose ceftriaxone in the treatment of antimicrobial-resistant Neisseria gonorrhoeae infection. Journal of Infectious Diseases 166, 91922.[ISI][Medline]
3
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Livermore, D. M., Sefton, A. M. & Scott, G. M. (2003). Properties and potential of ertapenem. Journal of Antimicrobial Chemotherapy 52, 33144.
4
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King, A. (2001). Recommendations for susceptibility tests on fastidious organisms and those requiring special handling. Journal of Antimicrobial Chemotherapy 48, Suppl. S1, 7780.
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