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] Related Links Role of acidic pH in the susceptibility of intraphagocytic methicillin-resistant Staphylococcus aureus strains to meropenem and cloxacillin. [Antimicrob Agents Chemother. 2007] PMID:17307986 Evaluation of the extracellular and intracellular activities (human THP-1 macrophages) of telavancin versus vancomycin against methicillin-susceptible, methicillin-resistant, vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus. [J Antimicrob Chemother. 2006] PMID:17062609 Combined effect of pH and concentration on the activities of gentamicin and oxacillin against Staphylococcus aureus in pharmacodynamic models of extracellular and intracellular infections. [J Antimicrob Chemother. 2007] PMID:17220162 Effect of combination of oxacillin and non-beta-lactam antibiotics on methicillin-resistant Staphylococcus aureus. [J Antimicrob Chemother. 1994] PMID:7928809 Cell wall thickening is a common feature of vancomycin resistance in Staphylococcus aureus. [J Clin Microbiol. 2003] PMID:12517819