Alternatives to Ciprofloxacin Use for Enteric Fever, United Kingdom

Alternatives to Ciprofloxacin Use for Enteric Fever, United Kingdom


Alternatives to Ciprofl oxacin Use for Enteric Fever, United Kingdom
To the Editor: In cases of typhoid and paratyphoid fever, it is often necessary to commence treatment before the results of laboratory sensitivity tests are available. It is therefore important to be aware of optional drug therapies available because some organisms may be resistant to key antimicrobial drugs. For typhoid and paratyphoid, ciprofl oxacin has become the fi rst-line drug of choice since the widespread emergence and spread of strains resistant to chloramphenicol, ampicillin, and trimethoprim (1).
The Laboratory of Enteric Pathogens (LEP) of the Health Protection Agency of England and Wales is the reference center for Salmonella enterica serovars Typhi and Paratyphi A for the United Kingdom; as such, this laboratory receives isolates from all cases of infection. Isolates are screened by breakpoint for resistance to antimicrobial drugs at the following levels: chloramphenicol, 8 mg/L; ampicillin, 8 mg/L; trimethoprim, 2 mg/L; ciprofl oxacin, 0.125 mg/L (decreased susceptibility); and 1.0 mg/L (high-level resistance), ceftriaxone, 1 mg/L, and cefotaxime, 1 mg/L. The levels for testing for resistance to chloramphenicol, ampicillin, trimethoprim, ceftriaxone, and cefotaxime correspond to internationally accepted therapeutic levels for these antimicrobial agents. In contrast, the levels for ciprofl oxacin (0.125 and 1.0 mg/L) have been chosen after observations of treatment failures at levels when used at below the expected recommended serum concentrations (2,3). Since 2005, a proportion of isolates exhibiting decreased susceptibility and high-level resistance to ciprofl oxacin have been tested for resistance to azithromycin by Etest (AB Biodisk, Solna, Sweden), using drug-sensitive strains of S. Typhi and S. Paratyphi A as controls.
From  (Table). The corresponding fi gures for S. Paratyphi A were 58 (25%) of 232 cases in 2001, rising to 84% in 2004, with an incidence of 73% in 2006; 9% of these were resistant to ciprofl oxacin at 1.0 mg/L (Table). Moreover, in 2006, 56 isolates of S. Typhi (23% of total) exhibited resistance to chloramphenicol, ampicillin, and trimethoprim, 54 (96%) were also resistant to ciprofl oxacin at 0.125 mg/L. When tested for resistance to ceftriaxone and cefotaxime, none of the isolates (either S. Typhi or S. Paratyphi A) were resistant at 1.0 mg/L.
Although the levels of resistance to ciprofl oxacin were for the most part below that regarded as therapeutic (MIC 0.25-1.0 mg/L), at least 21 treatment failures have been documented since 2005. These fi ndings demonstrate that the effi cacy of ciprofl oxacin for fi rst-line treatment of enteric fever in the United Kingdom has been seriously jeopardized. In cases of treatment failures, commonly used alternative antimicrobial agents have included third-generation cephalosporins such as ceftriaxone. The macrolide antimicrobial azithromycin is also being increasingly used, particularly for patients with hypersensitivity to penicillins (5). With this in mind, 50 S. Typhi and 40 S. Paratyphi A strains isolated from January 2005 through December 2006, which exhibited resistance to ciprofl oxacin at 0.125 mg/L, were tested for resistance to azithromycin by Etest. Results indicated that none of the isolates of S. Typhi exhibited MICs >8 mg/L, which corresponded to the MIC to azithromycin of a drug-sensitive control strain of S. Typhi (range 4-8 mg/L, MIC 90 6 mg/L). For S. Paratyphi A, none of the isolates exhibited MICs >12 mg/L, corresponding to that of a drugsensitive control strain of this serovar (range 6-12 mg/L, MIC 90 10 mg/L). Although there are no defi nitive data on resistance levels for azithromycin in relation to treatment of typhoid and paratyphoid, these fi ndings suggest that resistance to this antimicrobial agent in terms of treatment effi cacy has not yet been jeopardized.
These results indicate that the availability of effective antimicrobial agents for the treatment of typhoid and paratyphoid infection is becoming increasingly limited for patients in the United Kingdom. Nevertheless, despite the dramatic upsurge in the oc-currence of strains with decreased susceptibility, ciprofl oxacin still remains the drug of choice for many physicians. It is reassuring that in cases of treatment failure, third-generation cephalosporins such as ceftriaxone and macrolide antimicrobial agents such as azithromycin appear to be viable alternatives.