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Comparison of ertapenem, ampicillin, and meropenem against the intracellular forms of Listeria monocytogenes in human THP-1 macrophages

Abstract number: 902_p1045

Lemaire S.

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Objectives:

Ertapenem (ETP) is a new carbapenem with prolonged half-life (approximately 4 h), which could make it more suitable than meropenem (MEM) or ampicillin (AMP) for the treatment of listeriosis. However, L. monocytogenes is largely intracellular, and the activity of ETP against these forms has not been investigated. We, therefore, compared ETP to AMP and MPN in a model of human macrophages where AMP and MEM are cidal over a 24 h incubation (approximately 2 log CFU decrease; Carryn et al., J Antimicrob Chemother 2003; 51:1051–1052).

Methods:

MIC (arithmetic dilutions) and MBC (geometric dilutions) were determined in TSB by standard methods. Activity against extracellular and intracellular forms of L. monocytogenes was examined in THP-1 macrophages incubated with extracellular concentrations (ETP, 155 mg/L; AMP and MEM, 50 mg/L) equivalent to the Cmax achievable in human serum after conventional dosing. The stability of the drugs in the culture medium under our experimental conditions was checked by HPLC.

Results:

Activities in broth and in the cellular model are shown in the Table.

  BrothTHP-1 model (change log CFU over 24 h)
MIC (mg/L)MBC (mg/L)Extracellular (broth) Intracellular 
ETP0.48  ± 0.03>64-0.57 ± 0.050.96 ± 0.23
AMP0.37  ± 0.23>64-0.46± 0.03-1.81 ± 0.01
MEM0.05  ± 0.00>64-0.38± 0.05-1.82 ± 0.01
means ± SEM (n = 3 independent experiments).

Thus, whereas AMP and ETP have similar activities against L. monocytogenes in broth, AMP was cidal but ETP unable to control the growth of intracellular L. monocytogenes. Yet, assay of cell-associated ETP showed that its apparent cellular concentration exceeded the MIC. Decreasing the serum concentration in the culture medium (from 10 to 2%) did not change the results. Stability studies failed to reveal significant degradation of extracellular ETP.

Conclusions:

In this model, ETP did not eradicate intraphagocytic L. monocytogenes. Based on the results obtained MEM, ETP lack of activity is unlikely to be due to its penem structure. It is possible that intracellular conditions (e.g. binding to cytoplasmic proteins) hinder ETP intracellular activity in comparison with AMP or MEM.

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Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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