Antimicrobial effects of continuous versus intermittent administration of carbapenem antibiotics in an in vitro dynamic model

Abstract

In an in vitro dynamic model we compared the antimicrobial effects of two carbapenems, imipenem (MIC, 1 μg/ml) and meropenem (MIC, 0.25 μg/ml) on Pseudomonas aeruginosa. The antibiotics were administered either as short- time infusions once or three times a day or as continuous infusions with steady-state levels ranging from 0.5 to 20 μg/ml. From the resulting kill curves the period of time until the onset of bacterial death (dt), the rate constant of bacterial death (ka), the maximal reduction of CFU (mr), and the period of time until bacterial regrowth occurred (tr) were determined. Additionally, the occurrence of bacterial resistance during the simulations (rq) and the postantibiotic effect (PAE) were recorded. For both investigated carbapenems no significant difference in dt, ka, mr, and PAE values between the short-time infusions and continuous infusions with steady-state levels above 2 μg/ml could be detected. The tr was longest with continuous infusions of over approximately 24 h, corresponding to steady-state levels of 3 μg/ml for imipenem and 2.5 μg/ml for meropenem. An increase in MIC was observed only during continuous infusions with steady-state levels below 2 μg/ml. Independent of the chosen method of application and despite the lower MIC of meropenem, imipenem was slightly more effective than meropenem.