Evidence of cross-resistance between ciprofloxacin and non-fluoroquinolones in European Gram-negative clinical isolates

Sir, We report here a study that was undertaken to investigate whether ciprofloxacin resistance in Gram-negative noso-comial pathogens is a surrogate marker for cross-resistance to non-fluoroquinolones. The organisms, Escherichia coli (n = 3315), Pseudomonas aeruginosa (n = 1370), Entero-bacter aerogenes (n = 252), Enterobacter cloacae (n = 495), Proteus mirabilis (n = 379), Serratia marcescens (n = 207) and Citrobacter freundii (n = 98) were isolated from Euro-pean hospitals in 1997–1999 as part of the European SENTRY antimicrobial surveillance programme. MICs and breakpoint values of ciprofloxacin, tetracycline, gentamicin, piperacillin, piperacillin/tazobactam, cefuroxime and ceftaz-idime were determined by broth microdilution according to NCCLS guidelines. 1 The isolates were grouped as either ciprofloxacin susceptible or resistant, and the number and percentage of organisms resistant to the antimicrobials are shown in Table 1. The statistical significance of cross-resistance was calculated by Fisher's exact test and was corrected using the Bonferroni–Holm procedure. Ciprofloxacin resistance was most prevalent in E. aero-genes, with 27% of isolates resistant, followed by P. aeru-ginosa with 24%. E. cloacae and S. marcescens had the lowest incidence of ciprofloxacin resistance, at 5% and 7%, respectively. Amongst the ciprofloxacin-susceptible isolates, piperacillin/tazobactam was the most potent agent, with resistance rates of 0–9%. Piperacillin on its own was less potent with resistance levels of up to 38%. Ciprofloxacin-resistant P. aeruginosa and E. cloacae isolates show more than a six-and threefold increase in piperacillin resistance, and a seven-fold rise in resistance levels to piperacillin/ tazobactam (P < 0.01). The other organisms showed a two-to four-fold increase in resistance to these agents, and S. mar-cescens exhibited a seven-fold increase in resistance to piperacillin. Ciprofloxacin-resistant P. mirabilis remained 100% susceptible to piperacillin/tazobactam. Gentamicin resistance was also relatively low in the ciprofloxacin-susceptible group, with resistance rates of 1.6–7.1%. These rates increased two-to 14-fold in the ciprofloxacin-resistant group, with E. coli showing the largest increase. Tetracycline resistance rates increased 16-fold for cipro-floxacin-resistant E. aerogenes (P < 0.05); for the other organisms this increase was a more modest four-fold or less. P. mirabilis isolates are almost universally resistant to tetra-cycline. Nearly all P. aeruginosa isolates were cefuroxime resistant, irrespective of ciprofloxacin resistance. For the other organisms, cefuroxime resistance levels were less than or equal to seven-fold higher if ciprofloxacin resistant, and S. marcescens was 100% resistant. A similar trend was seen with ceftazidime: a two-to nine-fold increase in resistance associated with ciprofloxacin resistance. Imipenem was tested against P. aeruginosa and resistance …