The rapid emergence of fluoroquinolone-methicillin-resistant Staphylococcus aureus infections in a community hospital. An in vitro look at alternative antimicrobial agents

Abstract

The introduction of ciprofloxacin on an unrestricted basis into a 900-bed community hospital resulted in the emergence of high-level fluoroquinolone resistance among methicillin-resistant Staphylococcus aureus (MRSA) during the subsequent 18 months. Susceptibility testing revealed several old and new compounds to which all the S. aureus strains were susceptible. When an MRSA strain became resistant to ciprofloxacin it also exhibited high-level resistance to ofloxacin, fleroxacin, norfloxacin, and enoxacin. Two new experimental fluoroquinolones, WIN 57273 and CI-960, exhibited good activity against all test strains. Among the glycopeptide compounds, mupirocin and teicoplanin were approximately fourfold more active than vancomycin and ramoplanin. Rifampin and trimethoprim-sulfamethoxazole (TMP/SMZ) showed good activity against most strains as did imipenem. For clindamycin, gentamicin, and tetracycline susceptibilities exhibited a bimodal distribution with at least 10% of strains having resistant MIC values. Surprisingly, the addition of sulbactam potentiated the activity of ampicillin against the ciprofloxacin-resistant MRSA strains, however, sulbactam had little effect on cefoperazone activity against these same strains. Time-kill kinetic studies of selected antimicrobials against ciprofloxacin-resistant strains indicated good killing by vancomycin, ampicillin-sulbactam, and TMP/SMZ. Teicoplanin was less bactericidal than vancomycin while these same strains rapidly developed resistance to rifampin even at concentrations 8 x MIC. These data indicate certain alternative compounds within our study warrant further investigation, especially in vivo, against multiply-resistant staphylococci.