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Pharmacodynamic effects of meropenem on gram-negative bacteria

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Abstract

The in vitro initial killing and post-antibiotic effect (PAE) of meropenem on five gramnegative reference strains were evaluated by bioluminescence assay of bacterial adenosine triphosphate (ATP) and viable count. Morphology studies were performed in parallel. Meropenem showed concentration-dependent long (2–5 h) PAEs onEnterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa andSerratia marcescens when assayed by bioluminescence and induced spheroplasts at almost all concentrations. The bioluminescence PAEs reached a maximum response at 4 × MIC. These PAEs of meropenem onEscherichia coli, Klebsiella pneumoniae andSerratia marcescens were longer than corresponding PAEs of imipenem shown in previous studies. The higher affinity of meropenem than imipenem for PBP 3 might explain the longer PAEs obtained with meropenem. However, there was only a very short PAE, no PAE or even a negative PAE when viable count was used as the initial value for the PAE calculation. A strong initial decrease in viability but a less pronounced change in intracellular ATP was registered. Since this initial change in cell numbers is the initial value for the PAE calculation, the length of PAE was highly method dependent. In summary, a strong initial killing and no PAE were shown using viable count as the initial value for the PAE calculation, but a weak initial killing and long PAEs were shown when bioluminescence was used throughout the experiments.

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Authors and Affiliations

  1. Departments of Infectious Diseases, University Hospital, S-581 85, Linköping, Sweden

    H. Hanberger

  2. Clinical Microbiology, University Hospital, S-581 85, Linköping, Sweden

    E. Svensson, L. E. Nilsson & M. Nilsson

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  1. H. Hanberger
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  2. E. Svensson
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  3. L. E. Nilsson
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  4. M. Nilsson
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Hanberger, H., Svensson, E., Nilsson, L.E. et al. Pharmacodynamic effects of meropenem on gram-negative bacteria. Eur. J. Clin. Microbiol. Infect. Dis. 14, 383–390 (1995). https://doi.org/10.1007/BF02114893

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