Activity of new quinolones against ciprofloxacin-resistant staphylococci

Abstract

Because of the development of newer fluoroquinolones with inproved activity against gram-positive organisms, we elected to compare the inhibitory properties of ofloxacin, temafloxacin, sparfloxacin, PD131628, PD127391, and WIN57273 against 105 ciprofloxacin-resistant staphylococci. Based on comparison of MICs for 90% of the organisms (MIC9s), WIN57273 was the most active agent against oxacillin-resistant Staphylococcus aureus; the MIC90 was 0.5 ,ig/ml. Against oxacilHin-resistant, coagulase-negative staphylococci, PD127391 and WIN57273 were the most active agents; the MIC9 was 0.5 ,ug/ml. Against isolates of staphylococci for which ciprofloxacin MICs were .32 jig/m, WVIN57273 and PD127391 still exhibited high activity, inhibiting 100 and 95% of the isolates, respectively, at 2 ,ug/ml. The spontaneous mutation rates for ciprofloxacin-susceptible staphylococci were lowest for ofloxacin. The frequency of spontaneous mutations of ciprofloxacin-resistant staphylococci was low; however, the MICs of PD127391 and WIN57273 for these mutant isolates were greater than 2 ,ug/mI. WIN57273 and PD127391 are two potent new quinolones with high levels of activity against highly ciprofloxacin-resistant staphylococci. There is, however, a major concern of selection of spontaneous mutants resistant to these newer agents.The 4-quinolone ciprofloxacin appeared to be a promising agent in the treatment of staphylococcal infections because of its activity against methicillin-resistant strains (9, 11, 16). However, reports of emerging resistance of the staphylococci to ciprofloxacin are increasing (4,7,(13)(14)(15). We observed in our 1990 clinical isolates of Staphylococcus aureus and coagulase-negative Staphylococcus spp. a 25 and 27% resistance to ciprofloxacin, respectively. Because of the development of newer fluoroquinolones with improved activity against gram-positive organisms, we elected to compare the inhibitory properties of these agents against 105 oxacillin-and ciprofloxacin-resistant staphylococci. The agents we compared were ofloxacin (2), temafloxacin (A-62254) (1), sparfloxacin (CI-978; AT-4140) (2), PD127391 Other antimicrobial agents were provided by the indicated pharmaceutical companies: ciprofloxacin, Miles Pharmaceuticals, West Haven, Conn.; temafloxacin, Abbott Laboratories, North Chicago, Ill.; ofloxacin, Ortho Pharmaceutical Corp., Raritan, N.J.The organisms used in this study were stored (-70°C) clinical isolates of oxacillin-and ciprofloxacin-resistant S. aureus and coagulase-negative Staphylococcus spp. from the Cleveland Clinic Foundation, Cleveland, Ohio. Sources of the isolates included wounds, sputum, blood, urine, and other sites. Organisms were thawed, subcultured on blood agar, and transferred on blood agar prior to testing. Organ-* Corresponding author.isms used for quality control included S. aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853.MICs were determined by microdilution according to standard procedures published by the N...

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.…”

“…In the rabbit model of endocarditis, the emergence of quinolone resistance during therapy occurs more often during therapy with ciprofloxacin than during therapy with ofloxacin (20). Similarly, the in vitro selection of quinolone-resistant mutants of S. aureus and S. epiderinidis is greater following exposure to ciprofloxacin than following exposure to ofloxacin or sparfloxacin (14,43). The majority of quinolone-resistant mutants selected by exposure to ofloxacin simultaneously lose the ability to produce coagulase, and they may be less virulent than ciprofloxacin-selected mutants (42).…”

Comparative in vitro activity of PD 127391, a new fluoroquinolone agent, against susceptible and resistant clinical isolates of gram-positive cocci

“…Our study suggests that PD 127391 as well as sparfloxacin may prove useful in infections caused by moreresistant gram-positive cocci. However, enthusiasm for these agents must be tempered with the knowledge that single-step resistant mutants, though rare, have been selected (6,9). The finding in this study of a f-lactamaseproducing, highly ciprofloxacin-resistant E. faecalis isolate requiring a disproportionately high MIC of PD 127391 is also of concern.…”

“…Because narrower-spectrum quinolones display lower levels of activity against gram-positive cocci, particularly the enterococci and streptococci, the discovery of newer quinolones with good activity against these organisms is a welcome development (1-3, 5, 8, 14, 15, 18, 19). In addition, the growing number of gram-positive bacteria which acquire resistance to commonly used antimicrobial agents, including quinolones, is of great concern and has led to a heightened interest in the evaluation of the broader-spectrum quinolones against these resistant organisms (6,8,11,17). Resistance to ciprofloxacin among methicillin-resistant S. aureus isolates, for example, is rapidly increasing, but fortunately these isolates remain susceptible, usually at higher MICs, to the newer fluoroquinolone agents, including PD 127391 (6,16,17) and sparfloxacin (9).…”

“…In addition, the growing number of gram-positive bacteria which acquire resistance to commonly used antimicrobial agents, including quinolones, is of great concern and has led to a heightened interest in the evaluation of the broader-spectrum quinolones against these resistant organisms (6,8,11,17). Resistance to ciprofloxacin among methicillin-resistant S. aureus isolates, for example, is rapidly increasing, but fortunately these isolates remain susceptible, usually at higher MICs, to the newer fluoroquinolone agents, including PD 127391 (6,16,17) and sparfloxacin (9). Bacteria which are resistant to one fluoroquinolone commonly express variable degrees of cross-resistance to other fluoroquinolone agents; however, the organisms may remain susceptible, on the basis of achievable serum drug concentrations (11,19).…”