Sir, Despite our improved understanding of the epidemiological features, pathogenesis, risk factors and advances in diagnosis and treatment of meningococcal disease, the disease remains a leading cause of meningitis and sepsis. In India, meningococcal cases are reported sporadically from all parts of the country and epidemic waves occur at regular intervals affecting children and young adults. Persons in close contact with patients who have meningococcal disease are at elevated risk of contracting the disease and it has been seen that institution of chemoprophylaxis during the first few days after onset of disease in the index patient reduces the risk of secondary disease in close contacts. The high rates of morbidity and mortality associated with meningococcal disease make antimicrobial chemoprophylaxis a primary means of preventing the spread of meningococcal disease and curtailing an impending outbreak. Rifampicin, ciprofloxacin and ceftriaxone are recommended antimicrobials for chemoprophylaxis against meningococcal disease. Although rifampicin is commonly used as chemoprophylaxis to eradicate meningococcal carriage, it has been suggested to replace rifampicin with ciprofloxacin in adults, because of high rates of nasopharyngeal clearance seen with use of a single dose of ciprofloxacin compared with twice daily administration of rifampicin for 2 days. Although meningococcal resistance to the fluoroquinolones may not be a major problem, reports of emerging ciprofloxacin resistance make it essential to re-examine the use of this drug for chemoprophylaxis. First documented resistance to ciprofloxacin in Neisseria meningitidis was reported in 1992 from Greece where a single isolate with an MIC of 1 mg/L was recovered. In 1999 Kaczmarski et al. and Casin et al. from England and Wales reported meningococci with raised MICs of ciprofloxacin, but their MIC ranges were not reported. After that low-level resistance to ciprofloxacin with MICs 0.12–0.25 mg/L was reported on four more occasions from France (1999), Australia (2000), Spain (2004) and Argentina (2005). In India, as yet ciprofloxacin-resistant meningococci have not been documented but personal communications and a recent review article on meningococcal infection mention an increase in resistance to ciprofloxacin. During a recent epidemic (April 2005–April 2006) in New Delhi, 13 strains of N. meningitidis serogroup A were isolated from 249 patients clinically suspected of meningococcal infection and referred to our laboratory, which is affiliated to two teaching hospitals in Central Delhi. Bacteriological culture, isolation, identification, serogrouping and antimicrobial susceptibility testing was performed as per standard guidelines. MICs were determined for penicillin, azithromycin, ceftriaxone, chloramphenicol, ampicillin and ciprofloxacin by Etest strips using breakpoints recently recommended by NCCLS/CLSI on Mueller-Hinton agar supplemented with defibrinated sheep blood. Antimicrobial susceptibility revealed 100% susceptibility to penicillin (MIC 0.06 mg/L), azithromycin (MIC 2 mg/L), ceftriaxone (MIC 0.12 mg/L), chloramphenicol ( 2 mg/L) and ampicillin ( 0.12 mg/L). Only four isolates were found to be resistant to ciprofloxacin with MICs of 0.25 mg/L (resistance: MIC 0.12 mg/L). Two major mechanisms of fluoroquinolone resistance have been identified in meningococci. One is chromosomal mutations in the quinolone resistance determining regions (QRDRs) of the target sites for fluoroquinolones, namely the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV and the other is overexpression of endogenous efflux pumps. It has been suggested that resistance in meningococci may arise in the same manner and reach similar levels as seen in quinolone-resistant Neisseria gonorrhoeae. Oropharyngeal or nasopharyngeal cultures are not really helpful in determining the need for chemoprophylaxis and may unnecessarily delay the use of chemoprophylactic antibiotics. Thus chemoprophylaxis needs to be given empirically and knowledge of antibiotic susceptibility patterns during the previous epidemic and the current situation may help in the selection of antibiotics. Scanty data is available from India regarding antimicrobial susceptibility patterns of N. meningitidis, only sulfadiazine resistance has been previously documented. The recent encounter with meningococcal strains showing decreased susceptibility to ciprofloxacin is a cause for real concern and will have implications in chemoprophylaxis since ciprofloxacin is used to eradicate meningococci from nasopharyngeal carriers. Indiscriminate and inadequate use of this easily available (over the counter) and orally effective antibiotic in the community for a variety of infections has probably resulted in increased resistance to this valuable molecule. Continuous surveillance is necessary to monitor the emergence and spread of resistance to ciprofloxacin and other quinolones and to guide appropriate public health interventions in preventing drug-resistant meningococci. It is also another case for regulating over the counter sale of antibiotics in this and other countries.
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Jan 1, 2015
A.J Henderson + 4
Open Access