Activity of meropenem, against Gram-positive bacteria

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...

Section: Discussionmentioning

confidence: 97%

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

Maple

Hamilton‐Miller

Brumfitt

1991

“…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.…”

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confidence: 99%

“…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.…”

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confidence: 99%

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

Zabinski

Walker

Larsson

et al. 1995

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 ...

“…Ciprofloxacin has been shown to have activity in vitro against enterococci (6,7,15) and has been used in treating enterococcal infections (3, 5). Although relatively high MICs and the existence of an inoculum effect have been noted, resistance to ciprofloxacin has been uncommon (6,7,11,15,21).In both the acute-care and long-term-care facilities of the Ann Arbor Veterans Affairs Medical Center, the majority of enterococci have high-level resistance to aminoglycosides (22,23). We determined whether resistance to ciprofloxacin among enterococcal isolates had increased from 1985 and 1986 to 1989 and 1990.…”

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confidence: 99%

“…In recent years, increasing resistance to aminoglycosides (22), penicillins (1), and.vancomycin (18) has been noted. Ciprofloxacin has been shown to have activity in vitro against enterococci (6,7,15) and has been used in treating enterococcal infections (3, 5). Although relatively high MICs and the existence of an inoculum effect have been noted, resistance to ciprofloxacin has been uncommon (6,7,11,15,21).…”

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confidence: 99%

Increasing resistance of enterococci to ciprofloxacin

Schaberg

Dillon

Terpenning

et al. 1992

We determined that resistance to ciprofloxacin has emerged in enterococci over the last 5 years in our hospital, mainly in strains demonstrating the phenotype of high-level gentamicin resistance. All high-levelgentamicin-resistant isolates from 1985 and 1986 were susceptible, whereas 24% of isolates from 1989 and 1990 were resistant to ciprofloxacin. Plasmid and genomic DNA typing showed at least six unique strains exhibiting resistance, but one type accounted for 80%o of recent resistant isolates, suggesting a role for cross infection in the emergence of resistance.Enterococci are a common cause of nosocomial infection and are notable for their resistance to many antimicrobial agents (2, 9). In recent years, increasing resistance to aminoglycosides (22), penicillins (1), and.vancomycin (18) has been noted. Ciprofloxacin has been shown to have activity in vitro against enterococci (6,7,15) and has been used in treating enterococcal infections (3, 5). Although relatively high MICs and the existence of an inoculum effect have been noted, resistance to ciprofloxacin has been uncommon (6,7,11,15,21).In both the acute-care and long-term-care facilities of the Ann Arbor Veterans Affairs Medical Center, the majority of enterococci have high-level resistance to aminoglycosides (22,23). We determined whether resistance to ciprofloxacin among enterococcal isolates had increased from 1985 and 1986 to 1989 and 1990. Additionally, we determined whether resistance was predominantly in high-level-aminoglycosideresistant strains and whether one strain or multiple strains of ciprofloxacin-resistant enterococci had emerged in our facility. Enterococci were screened for resistance to ciprofloxacin, as described previously (4), by dotting an inoculum of 104 CFU/ml of an overnight culture suspended in saline onto Mueller-Hinton agar containing 4 ,ug of ciprofloxacin per ml. Strains of enterococci causing infection in patients inMICs for infecting isolates from 1989 and 1990 were determined in the Clinical Microbiology Laboratory by the API Uniscept microdilution broth method (Analytab); the MICs for susceptible isolates were < 1.0 ,ug/ml, while those for resistant strains were >4.0 ,ug/ml. Thirty randomly chosen high-level-gentamicin-resistant, ciprofloxacin-resistant isolates from 1989 and 1990 were selected for extended susceptibility testing by microtiter broth dilution and both plasmid DNA and genomic DNA analyses. Susceptibility testing showed all these isolates to require ciprofloxacin MICs of >25 p,g/ml and gentamicin MICs of >2,000 ,g/ml. For 16 aminoglycoside-resistant isolates from 1985 and 1986, gentamicin MICs were also found to be >2,000 ,ug/ml but ciprofloxacin MICs ranged from 0.4 to 1.2 ,ug/ml. For plasmid DNA analysis, isolates were lysed and plasmid DNA was isolated according to the method described by Zervos et al. (20), with the added step that the plasmid DNA samples were incubated with 1 ,ul of 5-mg/ml RNase for 1 h at 37°C prior to electrophoresis on 0.7% agarose gels. Lambda DNA (GIBCO-BRL, Grand Island, N...