1. J Antimicrob Chemother. 2011 Mar;66(3):596-607. Epub 2010 Dec 23.

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 S, Kosowska-Shick K, Appelbaum PC, Glupczynski Y, Van Bambeke F, Tulkens 

Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute,
Université catholique de Louvain, Brussels, Belgium.

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.

PMID: 21186193 [PubMed - in process]