Nalidixic acid-susceptible, ciprofloxacin-resistant Neisseria gonorrhoeae strain in the UK

P. L. Ragunathan1,*, C. Ison2 and D. M. Livermore3

1 Microbiology Department, Bedford Hospital NHS Trust, Bedford, UK; 2 Sexually Transmitted Bacteria Reference Laboratory, Centre for Infections, Colindale, UK; 3 Antimicrobial Reference Laboratory, Centre for Infections, Colindale, UK


* Corresponding author. E-mail: lakshmi.ragunathan{at}bedhos.anglox.nhs.uk

Keywords: gonococcus , fluoroquinolones , susceptibility tests , resistance

Sir,

We report the first detection of a strain of Neisseria gonorrhoeae susceptible to nalidixic acid but resistant to ciprofloxacin. Although ciprofloxacin-resistant N. gonorrhoeae strains are already frequent in the UK,1 the observation is significant because disc tests with nalidixic acid are widely used to predict fluoroquinolone susceptibility for N. gonorrhoeae, being recommended, for example, by the British Society for Antimicrobial Chemotherapy (BSAC) guidelines.2 This practice is based on the fact that ciprofloxacin resistance is sometimes difficult to detect directly whereas isolates with even low-level resistance typically give no zone of inhibition to 30 µg nalidixic acid discs.2

Since May 2004, Bedford Microbiology laboratory has tested N. gonorrhoeae isolates with both nalidixic acid (30 µg) and ciprofloxacin (1 µg) discs, following technical methods given in the BSAC guidelines.2 In December 2004, we isolated N. gonorrhoeae that exhibited susceptibility to nalidixic acid but resistance to ciprofloxacin from two patients, a male and a female, both from this catchment area. Identification was confirmed by standard tests and the isolates were referred to the Sexually Transmitted Bacteria Reference Laboratory, Health Protection Agency Centre for Infections, London.

The reference laboratory confirmed the identification and found MICs of nalidixic acid and ciprofloxacin of 1.5–2 mg/L and >32 mg/L, respectively, confirming the disc diffusion results. In contrast, ciprofloxacin-resistant N. gonorrhoeae strains usually require nalidixic acid MICs ≥ 128 mg/L.3,4 Ceftriaxone and cefixime MICs were ≤0.12 mg/L and ≤0.25 mg/L, respectively, and neither isolate had ß-lactamase. Both were typed by NG–MAST5 and were assigned to type ST1218, thus belonging to a unique strain within the UK database. Epidemiological investigation revealed that this strain was probably acquired in India by the male patient who infected his female partner on return. Both patients were treated with oral cefixime, with clearance confirmed 2 weeks after treatment.

Bedford Microbiology Laboratory tested over 80 gonococcal isolates for fluoroquinolone susceptibility with both nalidixic acid and ciprofloxacin discs between May 2004 and March 2005 and detected only these two isolates with this unique resistance pattern. The prevalence of this type of resistance strain in the UK is unknown and will remain so unless both antibiotic discs are used to ascertain fluoroquinolone susceptibility in N. gonorrhoeae. The reference laboratory is carrying out more work to identify the mechanism of resistance and the extent of its dissemination. Until these investigations are complete, we advise laboratories to test gonococci with ciprofloxacin as well as nalidixic acid discs and to avoid fluoroquinolone therapy for infections due to isolates resistant to either agent.

References

1. Fenton KA, Ison C, Johnson AP et al. GRASP collaboration. Ciprofloxacin resistance in Neisseria gonorrhoeae in England and Wales in 2002. Lancet 2003; 31: 1867–9.

2. Andrews JM. BSAC standardized disc susceptibility testing method (version 3). J Antimicrob Chemother 2004; 53: 713–28.[Free Full Text]

3. Belland RJ, Morrison SG, Ison C et al. Neisseria gonorrhoeae acquires mutations in analogous regions of gyrA or parC in fluoroquinolone-resistant isolates. Mol Microbiol 1994; 14: 371–80.[ISI][Medline]

4. Ison CA, Woodford PJ, Madders H et al. Drift in susceptibility of Neisseria gonorrhoeae to ciprofloxacin and emergence of therapeutic failure. Antimicrob Agents Chemother 1998; 42: 2919–22.[Abstract/Free Full Text]

5. Martin IMC, Ison CA, Aanensen D et al. Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. J Infect Dis 2004; 189: 1499–505.





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