Differing activities of quinolones against ciprofloxacin-susceptible and ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus

Abstract

The in vitro activities of nine quinolones (seven fluoroquinolones, nalidixic acid, and acrosoxacin) against methicillin-resistant Staphylococcus aureus (MRSA) were compared with those of the glycopeptides teicoplanin and vancomycin. MICs against 160 strains of ciprofloxacin-susceptible (MIC, <2.0 ,ug/ml) MRSA and 40 strains of ciprofloxacin-resistant (MIC, .2.0 tig/ml) MRSA were determined. The following MICs for 50% of the strains tested (in micrograms per milliliter) were obtained for ciprofloxacin-susceptible and -resistant strains, respectively: tosufloxacin, 0.06 and 2.0; ofloxacin, 0.25 and 16; ciprofloxacin, 0.5 and 16; pefloxacin, 0.5 and 32; acrosoxacin, 1.0 and >256; enoxacin, 1.0 and 64; fleroxacin, 1.0 and 32; norfloxacin, 2.0 and 64; nalidixic acid, 64 and 512; teicoplanin, 1.0 and 1.0; vancomycin, 2.0 and 2.0. In mutation rate studies using a range of antibiotic concentrations to reflect those achievable in vivo, resistant mutants grew only on plates containing nalidixic acid (rate of mutation to resistance, 10-7 to 10-8) and on plates containing low concentrations of ciprofloxacin, enoxacin, and norfloxacin (rate of mutation to resistance, 10-8 to 10-9). In time-kill studies, 99.9% killing was found within 8 h for all of the quinolones tested (norfloxacin and nalidixic acid were not tested). Teicoplanin and vancomycin were less rapidly bactericidal. For the clinical isolates of ciprofloxacin-resistant MRSA, different levels and patterns of quinolone resistance were found. Generally, cross-resistance among the fluoroquinolones was complete; however, incomplete cross-resistance did occur with the nonfluorinated quinolone acrosoxacin.Methicillin-resistant Staphylococcus aureus (MRSA) was first reported by Jevons in 1961 (14a). Throughout the 1960s and 1970s, these organisms were responsible for sporadic, although sometimes serious, outbreaks of hospital infections (4, 14). In the United States, few outbreaks of hospital infections due to MRSA were reported before 1980; however, since then, MRSA has caused increasing problems in hospitals in the United States (30) and worldwide (31).Resistance of MRSA to methicillin is mediated primarily by production of a unique penicillin-binding protein (PBP 2'); thus, these organisms are regarded as resistant to all P-lactam agents (11). Furthermore, many MRSA strains are resistant to a variety of other antibiotics, including gentamicin, tobramycin, erythromycin, clindamycin, tetracycline, and streptomycin (19). The choices for treatment of infections due to MRSA are few, and in the absence of susceptibility testing data or in serious infections, vancomycin is regarded as the antibiotic of choice for treatment (12). Nalidixic acid, the first quinolone agent to be developed, was active only against enterobacteria and possessed pharmacokinetics which restricted its use to treatment of urinary tract infections. In the 1980s, a new generation of quinolones, the fluoroquinolones, was introduced. These had broad-spectrum bactericidal activity, achieved satisfactory lev...

Identification of Point Mutations in Clinical Staphylococcus aureus Strains That Produce Small-Colony Variants Auxotrophic for Menadione

“…Two strains (221 SCV and 927 SCV ) produced growth revertants (designated 221 REV and 927 REV ) at rates of 1.76 ϫ 10 Ϫ6 and 1.21 ϫ 10 Ϫ6 per cell per generation, respectively, as assessed by fluctuation analysis (22). These rates are consistent with expected values for the reversion of a point mutation and are similar to other data in the literature reported for reversion of SCV strains (26,27). Sanger DNA sequencing confirmed that the revertant strains had a wild-type allele of the cognate men gene.…”

Comparative prophylactic efficacies of ciprofloxacin, ofloxacin, cefazolin, and vancomycin in experimental model of staphylococcal wound infection

“…This may just reflect the observation that the frequency of spontaneous mutation to quinolone resistance among initially quinolonesusceptible staphylococci is i0-7 to 10- (7,14,30), which is too low to have been observed with the 102 to 106 CFU used in our experiments. This does not mean, however, that a short course of perioperative treatment in humans will not select for quinolone-resistant staphylococci in niches harboring a more complex and numerous staphylococcal flora such as the nares or skin.…”

“…Cephalosporins appear to be ineffective in preventing infection by such pathogens. In contrast, the new fluoroquinolones exhibit in vitro activity against most common clean surgical wound pathogens, including many isolates of staphylococci and gram-negative species (4,15,30,43).…”

“…New fluoroquinolones such as ciprofloxacin and ofloxacin are highly active in vitro against most gram-negative wound pathogens and exhibit moderate in vitro activity against staphylococci (4,15,30,43). In animal models the fluoroquinolones have demonstrated efficacy comparable to those of traditional antistaphylococcal agents in the treatment of serious S. aureus infections (17,20).…”

Activities of newer fluoroquinolones against Shigella sonnei

“…These flasks, along with a control flask to which no test drug was added, were placed in a gyrating incubator at 37c. Quantitative bacterial counts after 0, 2, 4, 8, and 24 h of exposure to the agents were performed by spreading 0.1 ml of the appropriate dilutions onto Mueller-Hinton agar plates which were The mutation rate was considered to be the ratio of the number of the resistant colonies over the total microbial count (13). The 117 strains of S. sonnei studied showed diverse antibiograms and plasmid patterns, and there was no evidence of epidemiologic relatedness among the strains.…”