Activity of moxifloxacin against intracellular community-acquired methicillin-resistant Staphylococcus aureus : comparison with clindamycin, linezolid and co-trimoxazole and attempt at defining an intracellular susceptibility breakpoint.

Lemaire, Sandrine;Kosowska-Shick, Klaudia;Appelbaum, Peter C.;Glupczynski, Y.;Tulkens, Paul M.;et.al.
(2011) Journal of Antimicrobial Chemotherapy — Vol. 66, n° 3, p. 596-607 (2011)

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Authors
  • Lemaire, SandrineUCLouvain
    Author
  • Kosowska-Shick, Klaudia
    Author
  • Appelbaum, Peter C.
    Author
  • Glupczynski, Y.UCLouvain
    Author
  • Van Bambeke, Françoiseorcid-logoUCLouvain
    Author
  • Tulkens, Paul M.orcid-logoUCLouvain
    Author
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Abstract
BACKGROUND: Co-trimoxazole, clindamycin and linezolid are used to treat community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, but little is known about intracellular activity. Moxifloxacin is active against intracellular methicillin-susceptible S. aureus (MSSA), but CA-MRSA has not been studied. METHODS: We used 12 clinical CA-MRSA, 1 MSSA overexpressing norA and 2 hospital-acquired MRSA (moxifloxacin MICs: 0.03 to 4 mg/L). Activity was assessed in broth and after phagocytosis by THP-1 macrophages or keratinocytes {concentration-dependent experiments [24 h of incubation] to determine relative potencies [EC(50)], static concentrations [C(s)] and maximal relative efficacies [E(max) (change in log(10) cfu compared with initial inoculum)] and time-dependent experiments [0-72 h] at human C(max)}. RESULTS: Concentration-dependent experiments: in broth, EC(50) and C(s) were correlated with the MIC for all antibiotics, but moxifloxacin achieved significantly (P < 0.01) greater killing (more negative E(max)) than the comparators; and in THP-1 cells and keratinocytes, moxifloxacin acted more slowly but still reached a near bactericidal effect (2 to 3 log(10) cfu decrease) at 24 h with unchanged EC(50) and C(s) as long as its MIC was ≤0.125 mg/L (recursive partitioning analysis). Clindamycin and linezolid were static, and co-trimoxazole was unable to suppress the intracellular growth of CA-MRSA. At human C(max) in broth, moxifloxacin killed more rapidly and more extensively (≥5 log(10) cfu decrease at 10 h) than clindamycin (4 log(10) cfu at 48 h) or co-trimoxazole and linezolid (1-2 log(10) cfu at 72 h). CONCLUSIONS: Moxifloxacin is active against both extracellular and intracellular CA-MRSA if the MIC is low, and is more effective than clindamycin, co-trimoxazole and linezolid.
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Lemaire, S., Kosowska-Shick, K., Appelbaum, P. C., Glupczynski, Y., Van Bambeke, F., & Tulkens, P. M. (2011). Activity of moxifloxacin against intracellular community-acquired methicillin-resistant Staphylococcus aureus : comparison with clindamycin, linezolid and co-trimoxazole and attempt at defining an intracellular susceptibility breakpoint. Journal of Antimicrobial Chemotherapy, 66(3), 596-607. https://doi.org/10.1093/jac/dkq478 (Original work published 2011)