1: Antimicrob Agents Chemother. 2008 Aug; 52(8):2997-2805 [Epub 2008 Jun 2]

Restoration of susceptibility of intracellular Methicillin Resistant
Staphylococcus aureus (MRSA) to {beta}-lactams: comparison between strains,
cells, and antibiotics.

Lemaire S, Olivier A, Van Bambeke F, Tulkens PM, Appelbaum PC, Glupczynski Y.

Unité de Pharmacologie cellulaire et moléculaire, Université catholique de
Louvain, Brussels, Belgium; Department of Pathology, Penn State Milton S. Hershey
Medical Center, Hershey, PA; Laboratoire de Microbiologie, Cliniques
Universitaires UCL de Mont-Godinne, Yvoir, Belgium.

S. aureus invades eukaryotic cells. MRSA ATCC 33591 phagocytized by human THP-1
macrophages shows complete restoration of susceptibility to cloxacillin and
meropenem, becoming indistinguishable from MSSA ATCC 25923 due to the acid pH
prevailing in phagolysosomes (Lemaire et al., Antimicrob. Agents Chemother.
51:1627-32, 2007). We have examined whether this observation can be extended to
(i) strains of current clinical and epidemiological interest (3 HA-MRSA; 2
CA-MRSA; 2 HA-MRSA with VISA phenotype; 1 HA-MRSA with VRSA phenotype; 1 animal
[porcine] MRSA); (ii) activated THP-1 cells and non-professional phagocytes
(keratinocytes, CALU-3 bronchial epithelial cells); (iii) other beta-lactams
(imipenem, oxacillin, cefuroxime, cefepime). All strains showed (i) a marked
reduction of MIC in broth at pH 5.5 vs. pH 7.4; (ii) sigmoidal dose-response
curves to cloxacillin (0.01 to 100 MIC; 24 h incubation) after phagocytosis by
THP-1 macrophages, indistinguishable from each other and from that of MSSA ATCC
25923 (relative potency [E50], 6.09 x MIC; CI: 4.50 to 8.25); relative efficacy
[Emax] -0. 69 log cfu; CI: -0.79 to -0.58). Similar dose-response curves to
cloxacillin were also observed for MSSA ATCC 25923 and MRSA ATCC 33591 after
phagocytosis by activated THP-1 macrophages, keratinocytes, and Calu-3 cells. By 
contrast, there was a lesser restoration of susceptibility of MRSA ATCC 33591 to 
cefuroxime and cefepime after phagocytosis by THP-1 macrophages, even when data
were normalized for differences in MICs. We conclude that the restoration of MRSA
susceptibility to beta-lactams after phagocytosis is independent of the strain
and the type of cells, but varies between beta-lactams.

PMID: 18519727 [PubMed - as supplied by publisher]

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