a Department of Microbiology, University Hospital V. Macarena, Av/Dr Fedriani s/n, Sevilla 41009; b School of Medicine, Apdo 914, Sevilla 41080, Spain
Sir,
The incidence of resistance to fluoroquinolones among aerobic Gram-negative bacilli (AGNB) has increased during the last decade.1,2 Resistance to these antibiotics was first identified as a problem in isolates of Pseudomonas aeruginosa and other non-fermenting AGNB, but more recently has become apparent among Enterobacteriaceae, particularly Escherichia coli and, to a lesser extent, Klebsiella pneumoniae, Citrobacter freundii and Salmonella spp.1,2 It has been suggested that this development is principally related to the excessive use of fluoroquinolones.2,3 To date, reports of the emergence of fluoroquinolone-resistant strains of Proteus mirabilis have been uncommon.
Recently, several novel fluoroquinolone derivatives, including clinafloxacin and trovafloxacin, have been introduced. These drugs have extended spectra of activity which encompass a broad range of Gram-negative, Gram-positive and anaerobic bacteria. The present study was undertaken to monitor the evolution of quinolone resistance in P. mirabilis clinical isolates collected during the past decade and to assess the potencies of seven quinolones against selected strains belonging to this species.
The strains of P. mirabilis included in the investigation were isolated in the Clinical Microbiology Laboratory of the University Hospital V. Macarena between April 1990 and October 1998. Identification and susceptibility testing were performed with the Pasco system (Difco, Detroit, MI, USA) between April 1990 and March 1996 and with the MicroScan Walk-Away system (Dade, Sacramento, CA, USA) between April 1996 and October 1998. The reference fluoroquinolone was ciprofloxacin and strains for which the MICs were 1 mg/L were classified as susceptible.
In order to assess the potencies of the quinolones against P. mirabilis isolates, strains with different levels of susceptibility to these drugs, as determined by the Walk-Away system, were studied. All urinary isolates recovered between May 1996 and June 1998 for which the MICs of pipemidic acid were >16 mg/L and all isolates from other sources for which the MICs of ciprofloxacin were 1 mg/L were selected; 15 strains for which the MICs of pipemidic acid were
16 mg/L were also included. In total, 74 non-replicate isolates were evaluated. After determination of the MICs of nalidixic acid (for method, see below), two groups were identified: 15 nalidixic acid-susceptible strains (MICs
16 mg/L) and 59 nalidixic acid-resistant strains (MICs
32 mg/L). The antibiotics tested were as follows: ciprofloxacin (Bayer, Leverkusen, Germany); clinafloxacin (Parke-Davis, Ann Arbor, MI, USA); nalidixic acid (Sigma, Madrid, Spain); norfloxacin (Sigma); pefloxacin (Rhône-Poulenc Rorer, Antony, France); pipemidic acid (Sigma) and trovafloxacin (Pfizer, Groton, CT, USA). MICs were determined by a microbroth dilution method recommended by the National Committee for Clinical Laboratory Standards.4 E. coli ATCC 25922 and P. aeruginosa ATCC 27853 were included as controls. The relationships between the MICs of ciprofloxacin and those of clinafloxacin and norfloxacin were investigated by regression analysis.
Altogether, 3315 isolates were evaluated in the first part of the study. The percentages of ciprofloxacin-susceptible strains during the study periods were as follows: 99.3% in 19902; 93.7% in 19934; 91.2% in 19956; and 83.8% in 19978. This trend towards reduced susceptibility is similar to those reported for E. coli and other Enterobacteriaceae,1,2 although, in our own region the percentage of E. coli strains susceptible to ciprofloxacin has been lower (<70%) than that observed in the present study for P. mirabilis isolates.5 It will be important to monitor susceptibility patterns in the future in order to determine whether the rates of resistance to the quinolones among isolates belonging to this species and other Enterobacteriaceae continue to increase.
The susceptibilities of the 15 nalidixic acid-susceptible and 59 nalidixic acid-resistant isolates of P. mirabilis to the antibiotics tested are summarized in the Table. The fluoroquinolones were consistently more potent than nalidixic acid and pipemidic acid. For the nalidixic acid-susceptible strains the MIC90s of clinafloxacin and ciprofloxacin were
10-fold lower than those of other quinolones. Against the nalidixic acid-resistant strains clinafloxacin was the most potent compound, although the MICs for these isolates were higher than those for the nalidixic acid-susceptible strains. For the ciprofloxacin-resistant strains (MICs
4 mg/L), of which there were 20, the MIC90s of all of the quinolones tested, with the exception of clinafloxacin (MIC90 4 mg/L), were
32 mg/L (data not shown). The MICs of clinafloxacin were
0.5 mg/L for 7/20 ciprofloxacin-resistant strains and
2 mg/L for 16 strains. The potential efficacy of clinafloxacin as treatment for patients with infections caused by ciprofloxacin-resistant strains remains to be evaluated.
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In summary, the percentage of clinical isolates of P. mirabilis susceptible to ciprofloxacin has decreased steadily during the past decade. Although cross-resistance is evident, clinafloxacin was the most potent of the fluoroquinolones evaluated in the present study.
Acknowledgments
We thank Patricia Hidalgo and Janet Dawson for help with preparation of the manuscript.
Notes
J Antimicrob Chemother 2000; 45: 407408
* Corresponding author. Tel: +34-95-455-7448; Fax: +34-95-437-7413; E-mail: atomas{at}cica.es
References
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