The use of antibiotics, particularly cephalosporins and TMP/SMX, is a significant risk factor for asymptomatic carriage of C. difficile in long-term care facilities. The use of H-2 blockers was also a significant risk factor for carriage; however, this finding has not been reported previously and should be confirmed by independent studies. These medications should be used judiciously in the LTCF population. When diarrheal diseases are encountered in LTCF residents, a high index of suspicion for C. difficile infection should be maintained and the appropriate diagnostic and therapeutic measures taken.

An in-vitro pharmacodynamic system was used to generate time-kill curves to demonstrate the concentration-independent pharmacodynamics of vancomycin against Staphylococcus aureus ATCC 29213. Initial vancomycin concentrations of 5, 10, 20 and 40 mg/L were studied monoexponentially while simulating a 6 h half-life. One parallel experiment was performed in duplicate using an initial peak concentration of 40 mg/L where both a distribution alpha-phase half-life of 0.66 h for 1 h and an elimination beta-phase half-life of 6 h for 11 h were simulated to determine if the transient distribution phase concentrations of vancomycin have any impact on bacterial killing beyond that provided by the elimination phase concentrations. Additionally, two monoexponential experiments with peak concentrations of 40 and 20 mg/L and a half-life of 6 h were repeated in an anaerobic chamber to determine if killing of S. aureus was affected. The time to achieve a 3 log10 kill was calculated from the linear portion of the regression line and averaged (mean +/- S.D.) 9.0 +/- 1.4 h for all aerobic monoexponential experiments and was 8.4 and 8.6 h for the aerobic biexponential experiments (P > 0.05). For the anaerobic studies, the times to reach 3 log10 kill were significantly greater averaging 18.9 +/- 1.7 h. The slopes of the bacterial kill curves were virtually identical for both monoexponential and biexponential aerobic experiments averaging -0.34 +/- 0.04, yet significantly different from the anaerobic bacterial kill curve slopes of -0.16 +/- 0.015 (P < 0.05). Time-kill curve analyses suggest that varying the concentration of vancomycin does not affect the rate or extent of bacterial killing aerobically or anaerobically against S. aureus and more efficient killing was achieved under aerobic conditions. The simulated distribution phase concentrations did not contribute to more effective killing of this strain of S. aureus.

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 ...

The greater potency of ciprofloxacin in vitro to that of ofloxacin against Pseudomonas aeruginosa may be potentially offset by the more favorable pharmacokinetic profile of the latter drug. In order to test this hypothesis, we generated time concentration kill curves for P. aeruginosa ATCC 27853 and a clinical isolate P. aeruginosa PSA 9258 using an in-vitro model to simulate the pharmacokinetic characteristics found in vivo for ciprofloxacin at a peak concentration (CPmax) of 5 mg/L and an elimination T1/2 of 4.5 h, and ofloxacin at a CPmax of 5 mg/L and a T1/2 of both 4.5 h and 6 h, and at a CPmax of 8.0 mg/L and a T1/2 of 6 h. A 3 log10 kill (T3 kill) of P. aeruginosa ATCC 27853 was achieved in 0.15 h by ciprofloxacin and of P. aeruginosa PSA 9258 in 0.09 h. Ofloxacin at a CPmax of 8 mg/L and T1/2 of 6 h achieved a T3 kill of P. aeruginosa ATCC 27853 in 0.74 h and of P. aeruginosa PSA 9258 in 0.16 h. The area under the kill curve (AUKC) was 1.10 x 10(4)and 1.96 x 10(3) mL-h/cfu for ciprofloxacin against P. aeruginosa ATCC 27853 and P. aeruginosa PSA 9258, respectively and that of ofloxacin at CPmax 8 mg/L and a T1/2 of 6 h was 9.78 x 10(4)and 2.20 x 10(4) mL-h/cfu respectively. Significant differences (P > or = 0.05) were evident between ciprofloxacin and all ofloxacin regimens against P. aeruginosa ATCC 27853 but not against P. aeruginosa PSA 9258. There was a poor correlation (r = 0.22) between the AUKC and area under the time concentration curve (AUC) for P. aeruginosa ATCC 27853 but a strong correlation (r = 0.96) between the AUKC and area under the inhibitory curve (AUIC). Similar results were obtained for P. aeruginosa PSA 9258 for which the correlation between AUKC and AUC was weak (r = 0.10) whereas that between the AUKC and AUIC was strong (r = 0.93). When the data for both P. aeruginosa were combined, a correlation coefficient of r = 0.04 for AUC and r = 0.80 for AUIC was found. These limited data suggest that fluoroquinolones can be compared using the AUIC for specific bacterial isolates. In addition, the larger AUC, higher CP, and longer T1/2 of ofloxacin in vivo did not fully compensate for the intrinsic differences in the antibiotic susceptibility against P. aeruginosa.