Research Article

Isolated high-level ciprofloxacin resistance in Salmonella enterica subsp. enterica serotype Paratyphi A

Journal of Medical Microbiology 2004; 53(8):819 · https://doi.org/10.1099/jmm.0.05451-0

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Abstract


An isolate of Salmonella Paratyphi A from a case of enteric fever was found to have a ciprofloxacin MIC of 8 mg l1. There have been reports of increasing incidence of paratyphoid fever, along with a decrease in susceptibility to ciprofloxacin. This is the first report of Salmonella enterica serotype Paratyphi A showing resistance to ciprofloxacin.

A 23-year-old male was diagnosed as suffering from enteric fever at JIPMER, Pondicherry. Salmonella enterica subsp. enterica serotype Paratyphi A was isolated by blood culture. This strain was found to be susceptible to all antibiotics by disc diffusion, except ciprofloxacin. The MIC for ciprofloxacin as determined by both agar and broth dilution methods was found to be 8 mg l1. This exceeds the limit set for resistance by NCCLS, which is 4 mg l1 (NCCLS, 1973). Resistance to ciprofloxacin has not been reported so far in the enteric fever salmonellae; this is the first report of S. Paratyphi A with an MIC of 8 mg l1.

S. Paratyphi A causes a milder form of enteric fever than S. Typhi. Resistance to ciprofloxacin is brought about by a mutation in the target gyrase A gene. Worldwide there are reports of decreased in vitro susceptibility to ciprofloxacin in S. Paratyphi A. Threlfall et al. (2001) noted that 22 % of isolates in 2000 exhibited low level resistance to ciprofloxacin, defined as resistance at 0.125 mg l1 but susceptibility at 1 mg l1. The majority of these strains were also found to be resistant to nalidixic acid.

There have been reports of increasing incidence of paratyphoid fever in India. A study conducted in Delhi found the incidence of S. Paratyphi A in enteric fever cases to be as high as 44.9 % in 1998 (Sood et al., 1999). Additionally, multidrug resistant strains are becoming increasingly common. A study by Chandel et al., (2000) found that 45 % of S. Paratyphi A isolates were multidrug resistant. Further, they also noted a decrease in the susceptibility to ciprofloxacin. However the highest MIC recorded in that study was 2 mg l1 (Chandel et al., 2000).

This strain was found to be sensitive to all antibiotics except ciprofloxacin. This is unusual, but can be explained by the fact that resistance to other antibiotics is plasmid-mediated, and is independent of resistance to fluoroquinolones, which is chromosomally mediated. It is possible that the development of resistance to ciprofloxacin is due to exposure to the drug at concentrations near the MIC. There have been reports of multidrug resistant isolates with reduced susceptibilities to ciprofloxacin from the Indian subcontinent and elsewhere; but to the best of our knowledge, there have been no reports of high level resistance to ciprofloxacin.

The emergence of S. Paratyphi A fully resistant to ciprofloxacin is a cause for worry for both clinicians and microbiologists. Ciprofloxacin forms the mainstay of enteric fever therapy, and the rise of resistance to the same would necessitate a search for more effective antimicrobials. Of interest though, is the possibility of turning to older drugs such as chloramphenicol and cotrimoxazole for treatment, as the strain we isolated was susceptible to these. As fluoroquinolone resistance is chromosomally mediated, the chances of it spreading horizontally are reduced. However, selective pressures exerted by the overuse of these drugs may see such isolates becoming more common in the future.