1: J Antimicrob Chemother. 2005 Jun;55(6):897-904. Epub 2005 Apr 28. 

Activity of three {beta}-lactams (ertapenem, meropenem and ampicillin) against
intraphagocytic Listeria monocytogenes and Staphylococcus aureus.

Lemaire S, Van Bambeke F, Mingeot-Leclercq MP, Tulkens PM.

Unite de Pharmacologie cellulaire et moleculaire, Universite catholique de
Louvain, Brussels, Belgium.

OBJECTIVES: Assessment of the activity of three beta-lactams [ertapenem (a
carbapenem with a prolonged half-life), meropenem and ampicillin] against
intraphagocytic Listeria monocytogenes and Staphylococcus aureus. METHODS:
Quantitative measurements of cfu changes in broth and in THP-1 macrophages
(post-phagocytosis) over time (5 and 24 h) at concentrations spanning from
sub-MICs to C(max) (maximal concentration typically observed in patients' serum
upon administration of conventional doses); morphological studies using an
electron microscope; evaluation of drug stability (HPLC), protein binding
(equilibrium dialysis) and measurement of drug cellular accumulation
(microbiological assay). RESULTS: Ertapenem was unable to control L.
monocytogenes growth in THP-1 macrophages at all concentrations and times
tested, even under conditions where ampicillin and meropenem were bactericidal.
This behaviour could not be ascribed to drug instability, protein binding or
lack of cell accumulation in comparison with ampicillin or meropenem. Ertapenem,
ampicillin and meropenem were equally effective at reducing the
post-phagocytosis inoculum of S. aureus ( approximately 1 log cfu), and caused
conspicuous changes in the morphology of intracellular bacteria consistent with
their lysis. These effects were obtained, however, only at large multiples
(100-fold or more) of the MIC maintained over 24 h. Because of the high
intrinsic antimicrobial potency of the beta-lactams studied, these
concentrations were below the C(max). CONCLUSIONS: Ertapenem will probably be
ineffective against intraphagocytic forms of L. monocytogenes for reasons that
remain to be discovered. Conversely, ertapenem could be an alternative to
ampicillin and meropenem against intraphagocytic S. aureus since its longer
half-life may allow high concentrations to be maintained for more prolonged
times.

PMID: 15860552 [PubMed - in process]