Comparative in vitro pharmacodynamics of imipenem and meropenem against Pseudomonas aeruginosa

Abstract

MICs are commonly used to assess the in vitro activities of antimicrobial agents; however, they provide minimal information on the pattern of bacterial activities. Time-kill studies with extensive sampling allow assessment of both the rate and extent of bacterial killing and regrowth. We compared imipenem and meropenem by both MIC-MBC testing and a time-kill study with P. aeruginosa 27853. In the time-kill study, concentration/MIC ratios ranging from 0.0625 to 32 times the MIC were studied. The kill rate, time to 99.9% kill, doubling time of regrowth, and area under the bacterial killing curve (AUKC) were evaluated. Degradation during the testing procedure was accounted for by assessing actual drug exposure as determined by the area under the concentration-time curve. Pharmacodynamic parameters were compared by using the Wilcoxon signed-rank test. The modal MIC and MBC for imipenem were 2 and 4 micrograms/ml, respectively, and those for meropenem were 0.25 and 0.5 microgram/ml, respectively. In the time-kill study, both agents displayed concentration-dependent activity over a range of 0.25 to 4 times the MIC. Initial killing (0 to 1 h) was faster with imipenem at the same concentration/MIC ratios (P = 0.0506). The time to 99.9% kill was approximately 5 h for both agents. When regrowth occurred, the doubling rate for imipenem, which was the same as that for the growth control, was twice as rapid as that for meropenem. At the same concentrations, the AUKCs over 24 h were lower for meropenem than for imipenem (P = 0.0280); however, when normalized by MIC, imipenem resulted in smaller AUKCs. Comparison of plots of area under the concentration-time curve versus AUKC, which accounted for drug degradation and actual drug exposure, revealed that meropenem was three times more active than imipenem, rather than the eightfold difference suggested by MICs. Time-kill curves with extensive sampling and measurement of actual drug exposure, rather than traditional MIC testing, may more accurately assess differences in the in vitro activities of antimicrobial agents.

Ω76: A designed antimicrobial peptide to combat carbapenem- and tigecycline-resistantAcinetobacter baumannii

“…5A). Similarly, a clinical dose of meropenem remains above MIC concentrations in the serum of human volunteers for 5 hours ( 58 ) but only displays a 100-fold CFU reduction in 4 hours ( 59 ).…”

Activity of simulated serum concentrations of daptomycin versus vancomycin during the first 24h of treatment in the presence of physiological albumin concentrations against vancomycin-susceptible, -tolerant or -intermediate-resistant Staphylococcus aureus

“…Maximal effect (E max ) was considered the maximal reduction of initial inocula. Antibacterial activity was also studied as in previous studies [21,22] by determining the area under the bacterial count-time curve (AUBC) (log 10 CFU × h/mL) as a measure of global killing along the experimental time (AUBC 0-24 ) and also along 12 h (dosing interval for vancomycin) (AUBC 0-12 ). AUBCs were calculated by the trapezoidal rule using the program GraphPad Prism 5.02 (GraphPad Software, San Diego, CA).…”

Colistin-Loaded Silk Membranes against Wound Infection with Pseudomonas aeruginosa

“…23 White et al have determined a minimum inhibitory concentration of 2 mg/liter for imipenem against P. aeruginosa (American Type Culture Collection 27853). 24 Therefore, this study used a 50-fold higher concentration of the minimum inhibitory concentration within the in vitro testing as a positive control for the colistin-covered ST-silk membranes.…”