Effect of aerobic and anaerobic environments on antistaphylococcal activities of five fluoroquinolones

Abstract

A previously established in vitro pharmacodynamic system was used to evaluate the antistaphylococcal activities of five fluoroquinolones under both aerobic and anaerobic conditions. Staphylococcus aureus ATCC 29213 was exposed to a 5-g/ml concentration of each of the following fluoroquinolones: ciprofloxacin, ofloxacin, temafloxacin, sparfloxacin, and clinafloxacin. Terminal elimination half-lives of 4, 6, 8, 8, and 13 h were simulated for the respective drugs. Each fluoroquinolone was bactericidal under both aerobic and anaerobic conditions. However, the bactericidal activity of each fluoroquinolone was delayed by anaerobiosis. This difference in fluoroquinolone activity under aerobic and anaerobic conditions could not be attributed to any particular parameter or physiochemical property but was most likely caused by a combination of factors (e.g., variations in hydrophobicity, intracellular pH, antibiotic concentration, and structure-activity relationships). Fluoroquinolone uptake studies were also performed to investigate the possibility of active, energydependent transport mechanisms in S. aureus ATCC 29213. Uptake studies indicated that active efflux does occur in S. aureus ATCC 29213.The antistaphylococcal activity of fluoroquinolones under aerobic conditions has been well established through numerous studies (13,24). However, the antistaphylococcal activity of these antimicrobial agents under anaerobic conditions has not been well studied. As staphylococci are facultative by nature, there is a distinct likelihood that some clinical infections involving these organisms occur in an anaerobic or microaerophilic environment. Hence, there exists a need to evaluate the antistaphylococcal performance of fluoroquinolones under both aerobic and anaerobic conditions. Morrissey and Smith have proposed that fluoroquinolone uptake by Staphylococcus aureus is oxygen dependent (14, 17). Further, Mitsuyama et al. have demonstrated that fluoroquinolone uptake by porin-deficient bacteria is at least partially dependent upon hydrophobicity (16). The purpose of this investigation was to evaluate the antistaphylococcal activities of five fluoroquinolones with various degrees of hydrophobicity under both aerobic and anaerobic conditions.(This report was presented as an abstract at the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Anaheim, Calif. [abstract 43].) MATERIALS AND METHODSIn vitro pharmacodynamic system. The pharmacodynamic model used in this investigation represents a modified version of that previously described by Garrison et al. (8) and has been previously described by Zabinski et al. (26). This system consisted of a 1,000-ml glass vessel with inflow and outflow ports, connective silicone tubing (Masterflex L/S thin-wall tubing; Cole-Parmer, Chicago, Ill.), a Masterflex peristaltic pump (Cole-Parmer), a fresh-medium reservoir, a stir-hot plate (Nuovo II; Barnstead/Thermolyne Corp., Dubuque, Iowa), a magnetic stir bar, and a thermometer.A 1-ml volume of a quinolone-containing solution was ...

Effects of ciprofloxacin on salt marsh sediment microbial communities

“…The lack of antibiotic activity we observed in anaerobic sediment microcosms is consistent with reports of delayed, diminished, or lack of antibiotic activity against infections involving anaerobic bacteria (Lewin et al, 1991;Zabinski et al, 1995;Morrissey and George, 2001;Stein and Goldstein, 2006). All these studies have been performed on clinical isolates and pure cultures, but there is no reason to expect that soil microbes would behave differently.…”

Evidence for a Passive Diffusion Mechanism for Sparfloxacin Uptake at the Brush-Border Membrane of the Human Intestinal Cell-linec Caco-2

“…Partition coefficients of ofloxacin and sparfloxacin, expressed as the ratio of quinolone concentration in n-octanol and 0.1 M phosphate buffer (pH 7.0) at 25°C, were 0.34 and 0.79, respectively. 18 This result means that ofloxacin is twofold more hydrophilic than sparfloxacin and therefore its uptake may partially occur through a different mechanism.…”

“…Diffusion of solutes across the intestinal epithelium depends on their lipophilicity. Sparfloxacin is one of the most hydrophobic fluoroquinolones 18 and may thus more readily cross the enterocyte membrane leaflets than other fluoroquinolones. This diffusion may be promoted by the binding of this particular fluoroquinolone to as yet unknown intracellular components, resulting in a reduction of the intracellular concentration of free sparfloxacin.…”

Comparative Pharmacodynamics of Three Newer Fluoroquinolones versus Six Strains of Staphylococci in an In Vitro Model under Aerobic and Anaerobic Conditions

“…Conversely, Wise et al found sparfloxacin and ciprofloxacin were bactericidal against E. coli under anaerobic conditions (1). Our group found five older fluoroquinolones to be bactericidal against staphylococci, regardless of whether studied in an aerobic or anaerobic environment, although the rate of kill appeared slower anaerobically (11).…”