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• W2143425441 abstract "Sir, Ciprofloxacin is commonly prescribed as a single-dose chemoprophylactic agent for close contacts of patients with meningococcal infection. Neisseria meningitidis with reduced susceptibility to fluoroquinolones has recently emerged, with sporadic cases reported in France, Australia, Argentina, Spain, Hong Kong and Israel. Recently an outbreak of serogroup A emerged in India, and a cluster of three cases of serogroup B in the USA. To our knowledge, failure of ciprofloxacin prophylaxis due to quinolone resistance has not been reported To date, reduced susceptibility to fluoroquinolones in meningococci has remained rare, with 10 unrelated strains found in an analysis of 5300 isolates in Spain, and only 3 from .5000 isolates in France. Most mutations have arisen in GyrA. However, mutations have also been detected in GyrB and ParE, although their significance remains uncertain. In addition, in vitro changes have been induced in ParC and resistance to quinolones has also been reported through an efflux mechanism. – 4 Following the isolation of N. meningitidis with reduced susceptibility to ciprofloxacin from a 36-year-old man with meningitis in 2008, all stored viable clinical isolates from Singapore’s three largest hospitals (Tan Tock Seng, Singapore General and National University hospitals) were screened for reduced susceptibility to nalidixic acid and rifampicin by disc diffusion, using the CLSI guidelines. Ciprofloxacin MICs were determined by agar plate dilution for isolates with reduced susceptibility to nalidixic acid, using the Australian Gonococcal Surveillance Programme (AGSP) guidelines. MICs obtained with this method give identical results for identical GyrA changes in Neisseria gonorrhoeae and N. meningitidis. All isolates for which the MIC is .0.03 mg/L either have changes in the quinolone resistance determining region (QRDR) or an increased efflux of quinolones, while those for which the MIC is ,0.03 mg/L do not. In the absence of clinical correlation data, an MIC of .0.03 mg/L is taken to indicate reduced susceptibility by both the AGSP and CLSI methods. Multilocus sequence typing (MLST) was carried out using protocols available on the Neisseria MLST website. To characterize the mechanisms of resistance to ciprofloxacin, we sequenced the QRDRs of GyrA, GyrB, ParC and ParE of isolates with a ciprofloxacin MIC of .0.03 mg/L. Penicillin MICs were determined with Etests (AB BIODISK, Solna, Sweden) for all isolates, using Mueller–Hinton agar with 5% sheep blood and interpreted according to CLSI criteria for agar dilution. Of 75 isolates collected between 2000 and 2008, two (3%) were resistant to nalidixic acid, a Group C isolate from 2008 and a Group B isolate from 2002. Both isolates had a raised ciprofloxacin MIC of 0.25 mg/L. All 75 isolates were susceptible to rifampicin. There were 13 isolates (17%) intermediate and 2 (3%) resistant to penicillin (MICs of 0.38 and 0.47 mg/L). MLST confirmed that the two isolates with reduced quinolone susceptibility were unrelated. The 2008 isolate was identified as sequence type (ST)-4821. The 2002 isolate was a new ST with alleles 4, 10, 76, 71, 13, 2, 75 although the aroE allele had one nucleotide different from allele 76 (C to T at position 39). The 2008 ST-4821 isolate had the most common GyrA substitution of threonine to isoleucine at position 91. The 2002 isolate had three mutations detected in GyrA: Thr91!Val; Asn103!Asp; and Ala105!Ser. To our knowledge, the Thr91!Val substitution has not been previously described in N. meningitidis. Neither of the isolates had changes in GyrB, ParC or ParE. Similarities in the mechanism of quinolone resistance in meningococci and gonococci, have prompted concerns that resistance will climb to mirror that of gonococci. Resistance to quinolones among N. gonorrhoeae is now so common that use of ciprofloxacin for the treatment of gonorrhoea is no longer recommended by the US Centers for Disease Control and Prevention. In Singapore, ciprofloxacin resistance among gonococci reached an alarming 61.8% in 2006 (74% in 2008; A. L. Tan, unpublished data). Ciprofloxacin is a prescription-only medicine in Singapore, but is in widespread use. An outbreak of meningococcal meningitis with reduced susceptibility to quinolones has already been seen in India in 2005, a country with liberal use of ciprofloxacin. Although our data are from small numbers, as meningococcal infections are uncommon in Singapore (usually ,10 cases per year), the 3% rate of quinolone resistance in this study is remarkably high when compared with other reports. Surveillance for reduced susceptibility and judicious quinolone use is forever increasing in importance but our local resistance data for the related N. gonorrhoeae may suggest the future is already written." @default.
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• W2143425441 date "2009-12-09" @default.
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• W2143425441 title "Neisseria meningitidis with reduced susceptibility to quinolones in Singapore" @default.
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• W2143425441 doi "https://doi.org/10.1093/jac/dkp437" @default.
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