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Restoration of susceptibility of intracellular methicillin-resistant Staphylococcus aureus to beta-lactams: comparison of strains, cells, and antibiotics.
Antimicrob Agents Chemother. 2008 Aug; 52(8):2797-805.AA

Abstract

Staphylococcus aureus invades eukaryotic cells. When methicillin-resistant S. aureus (MRSA) ATCC 33591 is phagocytized by human THP-1 macrophages, complete restoration of susceptibility to cloxacillin and meropenem is shown and the strain becomes indistinguishable from MSSA ATCC 25923 due to the acid pH prevailing in phagolysosomes (S. Lemaire et al., Antimicrob. Agents Chemother. 51:1627-1632, 2007). We examined whether this observation can be extended to (i) strains of current clinical and epidemiological interest (three hospital-acquired MRSA [HA-MRSA] strains, two community-acquired MRSA [CA-MRSA] strains, two HA-MRSA strains with the vancomycin-intermediate phenotype, one HA-MRSA strain with the vancomycin-resistant phenotype, and one animal [porcine] MRSA strain), (ii) activated THP-1 cells and nonprofessional phagocytes (keratinocytes, Calu-3 bronchial epithelial cells), and (iii) other beta-lactams (imipenem, oxacillin, cefuroxime, cefepime). All strains showed (i) a marked reduction in MICs in broth at pH 5.5 compared with the MIC at pH 7.4 and (ii) sigmoidal dose-response curves with cloxacillin (0.01x to 100x MIC, 24 h of incubation) after phagocytosis by THP-1 macrophages that were indistinguishable from each other and from the dose-response curve for methicillin-susceptible S. aureus (MSSA) ATCC 25923 (relative potency [50% effect], 6.09x MIC [95% confidence interval {CI}, 4.50 to 8.25]; relative efficacy [change in bacterial counts over the original inoculum for an infinitely large cloxacillin concentration, or maximal effect], -0.69 log CFU [95% CI, -0.79 to -0.58]). Similar dose-response curves for cloxacillin were also observed with MSSA ATCC 25923 and MRSA ATCC 33591 after phagocytosis by activated THP-1 macrophages, keratinocytes, and Calu-3 cells. By contrast, there was a lower level of restoration of susceptibility of MRSA ATCC 33591 to cefuroxime and cefepime after phagocytosis by THP-1 macrophages, even when the 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 types of cells but varies between beta-lactams.

Authors+Show Affiliations

Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, UCL 7370 Avenue E Mounier 73, Brussels B 1200, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18519727

Citation

Lemaire, Sandrine, et al. "Restoration of Susceptibility of Intracellular Methicillin-resistant Staphylococcus Aureus to Beta-lactams: Comparison of Strains, Cells, and Antibiotics." Antimicrobial Agents and Chemotherapy, vol. 52, no. 8, 2008, pp. 2797-805.
Lemaire S, Olivier A, Van Bambeke F, et al. Restoration of susceptibility of intracellular methicillin-resistant Staphylococcus aureus to beta-lactams: comparison of strains, cells, and antibiotics. Antimicrob Agents Chemother. 2008;52(8):2797-805.
Lemaire, S., Olivier, A., Van Bambeke, F., Tulkens, P. M., Appelbaum, P. C., & Glupczynski, Y. (2008). Restoration of susceptibility of intracellular methicillin-resistant Staphylococcus aureus to beta-lactams: comparison of strains, cells, and antibiotics. Antimicrobial Agents and Chemotherapy, 52(8), 2797-805. https://doi.org/10.1128/AAC.00123-08
Lemaire S, et al. Restoration of Susceptibility of Intracellular Methicillin-resistant Staphylococcus Aureus to Beta-lactams: Comparison of Strains, Cells, and Antibiotics. Antimicrob Agents Chemother. 2008;52(8):2797-805. PubMed PMID: 18519727.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Restoration of susceptibility of intracellular methicillin-resistant Staphylococcus aureus to beta-lactams: comparison of strains, cells, and antibiotics. AU - Lemaire,Sandrine, AU - Olivier,Aurélie, AU - Van Bambeke,Françoise, AU - Tulkens,Paul M, AU - Appelbaum,Peter C, AU - Glupczynski,Youri, Y1 - 2008/06/02/ PY - 2008/6/4/pubmed PY - 2009/1/31/medline PY - 2008/6/4/entrez SP - 2797 EP - 805 JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 52 IS - 8 N2 - Staphylococcus aureus invades eukaryotic cells. When methicillin-resistant S. aureus (MRSA) ATCC 33591 is phagocytized by human THP-1 macrophages, complete restoration of susceptibility to cloxacillin and meropenem is shown and the strain becomes indistinguishable from MSSA ATCC 25923 due to the acid pH prevailing in phagolysosomes (S. Lemaire et al., Antimicrob. Agents Chemother. 51:1627-1632, 2007). We examined whether this observation can be extended to (i) strains of current clinical and epidemiological interest (three hospital-acquired MRSA [HA-MRSA] strains, two community-acquired MRSA [CA-MRSA] strains, two HA-MRSA strains with the vancomycin-intermediate phenotype, one HA-MRSA strain with the vancomycin-resistant phenotype, and one animal [porcine] MRSA strain), (ii) activated THP-1 cells and nonprofessional phagocytes (keratinocytes, Calu-3 bronchial epithelial cells), and (iii) other beta-lactams (imipenem, oxacillin, cefuroxime, cefepime). All strains showed (i) a marked reduction in MICs in broth at pH 5.5 compared with the MIC at pH 7.4 and (ii) sigmoidal dose-response curves with cloxacillin (0.01x to 100x MIC, 24 h of incubation) after phagocytosis by THP-1 macrophages that were indistinguishable from each other and from the dose-response curve for methicillin-susceptible S. aureus (MSSA) ATCC 25923 (relative potency [50% effect], 6.09x MIC [95% confidence interval {CI}, 4.50 to 8.25]; relative efficacy [change in bacterial counts over the original inoculum for an infinitely large cloxacillin concentration, or maximal effect], -0.69 log CFU [95% CI, -0.79 to -0.58]). Similar dose-response curves for cloxacillin were also observed with MSSA ATCC 25923 and MRSA ATCC 33591 after phagocytosis by activated THP-1 macrophages, keratinocytes, and Calu-3 cells. By contrast, there was a lower level of restoration of susceptibility of MRSA ATCC 33591 to cefuroxime and cefepime after phagocytosis by THP-1 macrophages, even when the 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 types of cells but varies between beta-lactams. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/18519727/Restoration_of_susceptibility_of_intracellular_methicillin_resistant_Staphylococcus_aureus_to_beta_lactams:_comparison_of_strains_cells_and_antibiotics_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=18519727 DB - PRIME DP - Unbound Medicine ER -