Restoration of susceptibility of intracellular methicillin resistant staphylococcus aureus to beta-lactams : comparison between strains, cells, and antibiotics
(2008) Antimicrobial Agents and Chemotherapy — Vol. 52, n° 8, p. 2797-2805 (2008)
Files
pdfdocument.pdf
Restricted Access - Adobe PDF
- 481.02 KB
Details
- Authors
- Abstract
- 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.
- Affiliations
Citations
Lemaire, S., Olivier, A., Van Bambeke, F., Tulkens, P. M., Appelbaum, P. C., & Glupczynski, G. (2008). Restoration of susceptibility of intracellular methicillin resistant staphylococcus aureus to beta-lactams : comparison between strains, cells, and antibiotics. Antimicrobial Agents and Chemotherapy, 52(8), 2797-2805. https://doi.org/10.1128/AAC.00123-08 (Original work published 2008)