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Logo of mjafiGuide for AuthorsAbout this journalExplore this journalMedical Journal, Armed Forces India
 
Med J Armed Forces India. 2005 July; 61(3): 308.
Published online 2011 May 30. doi:  10.1016/S0377-1237(05)80200-X
PMCID: PMC4925573

Quinolones Losing Favour in Enteric Fever

Dear Editor,

Salmonella enterica serovar typhi, is endemic in India. Since 1990′s Fluoroquinolones (ciprofloxacin, ofloxacin) had been effective for multidrug resistant (MDR) strains, resistant to Ampicillin, Chloramphenical and Co-trimoxazole (ACCo). Presently however, many isolates of Salmonella, MDR and non-MDR show delayed response to ciprofloxacin [1, 2]. In UK, decreased sensitivity to ciprofloxacin increased from 2.7% in 1995 to 23% in 1999 [1]. An increase in Minimum Inhibitory Concentration (MIC) of ciprofloxacin (0.004-0.0039 mg/L in 1990 to 0.19-0.2 mg/L in 2003) has also been noted in India [2]. This is attributed to point-mutation in quinolone resistance determining region (QRDR) of topoisomerase gene, gyrA in Salmonella and leads to simultaneous resistance against nalidixic acid, a non-fluorinated narrow-spectrum quinolone [1]. Resistance to 30 μg nalidixic acid disc (zone diam < 13mm) is a simple laboratory indication of low-level susceptibility/resistance to ciprofloxacin [3]. Recent reports from India show nalidixic acid resistant salmonella (NARST) even among non-MDR salmonella strains [2, 4]. At our institute in Pune, we carried out MIC to ciprofloxacin for 21 isolates of S typhi from different parts of the country known to be resistant to nalidixic acid (MIC > 128 mg/L). Disk strengths and zone interpretations were in accordance with National Committee for Clinical Laboratory Standards (NCCLS). Out of 21 strains, 14 were known MDR isolates and 7 were sensitive strains. MIC for ciprofloxacin was raised in all, being 0.5 mg/L in 16 isolates (9MDR strains) and 1.0 mg/L in 5 isolates (all MDR strainsand all 7 sensitive strains). An MIC of >0.125 mg/L of ciprofloxacin has been associated with poor clinical response in several studies [1, 2, 4, 5]. These stains will either respond poorly or inappreciably to ciprofloxacin in-vivo, even if found sensitive invitro using 5 μg ciprofloxacin disc [3]. The current NCCLS breakpoints may have to be reevaluated for Salmonellae [3, 5]. These strains respond well to ceftriaxone or azithromycin [1, 2, 4]. Laboratories should look for nalidixic acid resistance in Salmonella isolates as a surrogate marker of decreased fluoroquinolone susceptibility and alert the physician. A blood culture is a must before starting any antibiotic in suspected enteric fever so that diagnosis is confirmed and the strain made available to the laboratory for further characterization.

References

1. Threlfall EJ, Ward LR. Decreased susceptibility to ciprofloxacin in Salmonella enterica serotype typhi, United Kingdom. Emerg Infect Dis. 2001;7:448–450. [PubMed]
2. Rodrigues C, Shenai S, Mehta A. Enteric fever in Mumbai, India: the good news and the bad news. Clin Infect Dis. 2003;36:535. [PubMed]
3. Hakanen A, Kotilainen P, Jalava J, Siitonen A, Huovinen P. Detection of decreased fluoroquinolone susceptibility in Salmonellas and validation of nalidixic acid screening test. J Clin Microbiol. 1999;37:3572–3577. [PubMed]
4. Chandel DS, Chaudhary R. Enteric fever treatment failures: a global concern. Emerg Infect Dis. 2001;7:762–763. [PubMed]
5. Joshi S, Wattal C, Sharma A, Oberoi JK, Prasad KJ. Quinolones-drug of choice for enteric fever? Ind J Med Microbiol. 2004;22(4):271–272. [PubMed]

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