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Sir, Resistance of Streptococcus pneumoniae to penicillin is now recognized as a worldwide phenomenon. Penicillinresistant strains, particularly with low-level resistance (MICs of 0.12–1.0 mg/L), are often still susceptible to some of the newer -lactams such as some third-generation cephalosporins and carbapenems, but even with these drugs their MICs are significantly higher than against penicillin-susceptible strains. Pneumococcal resistance to several nonlactam antimicrobial agents is also more common among penicillin-resistant strains than among penicillin-susceptible ones. We recently assessed the effect of multiple drug resistance on the susceptibility of pneumococci to three fluoroquinolones (ciprofloxacin, ofloxacin and levofloxacin) and report our findings here. From our collection of recent clinical isolates of S. pneumoniae from multiple US medical centres, 209 strains were selected for this study based on known antibiotic resistance patterns. These included 97 penicillin-resistant strains (MIC 2.0 mg/L), 60 penicillinintermediate strains (MIC 0.12–1.0 mg/L) and 52 penicillin-susceptible strains (MIC 0.06 mg/L). The number of drugs tested to which each strain was resistant varied from none to 11. Forty strains were susceptible to all antimicrobial agents tested. Three quinolones (ciprofloxacin, ofloxacin and levofloxacin) were tested in parallel with 12 other agents, including six -lactam and six nonlactam antimicrobial agents, and these are listed in the Table. Antimicrobial susceptibility tests were performed by broth microdilution, following the procedure outlined by the National Committee for Clinical Laboratory Standards (NCCLS). All (100% ) isolates were susceptible to vancomycin and levofloxacin. Of the other quinolones, 99% were susceptible to ofloxacin and 90% to ciprofloxacin. For the remaining antimicrobials, the proportion susceptible ranged from 25% for penicillin to 87% for clindamycin. Not unexpectedly, the susceptibility to other -lactams correlated strongly with susceptibility to penicillin. There was also a correlation between penicillin susceptibility and susceptibility to nonlactam, non-quinolone antimicrobials excluding vancomycin. This was most striking for co-trimoxazole, for which the proportion susceptible decreased from 82% of penicillin-susceptible strains to 13% of penicillin-resistant strains. There was also considerable correlation between resistance to several non-lactam agents and resistance to others. The strongest correlation occurred between chloramphenicol and tetracycline, with 100% of the 39 chloramphenicol-resistant strains being resistant to tetracycline, and between clindamycin and erythromycin, with 100% of the 27 clindamycin-resistant strains being resistant to erythromycin. The geometric mean MIC of each of the three quinolones showed no appreciable differences in relation to penicillin susceptibility (Table). Minimal variations in quinolone geometric mean MICs were observed in relation to susceptibility categories of other antibiotics singly and in combination, but there was no correlation with these categories. It is important to remember that the pneumococcal population in this study was a highly selected one and that the antimicrobial resistance described here should not be compared with other published reports describing populations of consecutive or randomly selected isolates. Most of the correlations we observed support the observations of other investigators. We also confirm studies demonstrating no correlation between ciprofloxacin resistance and penicillin resistance. Furthermore, we found no correlation between any of the quinolone MICs and MICs of clindamycin, erythromycin, chloramphenicol, tetracycline or co-trimoxazole. Thus, these three quinolone antimicrobial agents share one important characteristic that might be considered in selecting a therapeutic anti-pneumococcal agent, i.e. they are not affected by resistance to other antibiotics. The role of ciprofloxacin in pneumococcal disease is unsettled since significant rates of failure to eradicate the organism in pneumococcal lower respiratory tract infections have been reported, as have clinical failures. Levofloxacin, because of its better blood and tissue levels, may, at least theoretically, be a preferable drug in this setting.

Susceptibility of multi-resistant Streptococcus pneumoniae to ciprofloxacin, ofloxacin and levofloxacin