Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 66, Issue 3, Pages 596-607Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkq478
Keywords
THP-1 macrophages; keratinocytes; Hill equation; maximal relative efficacy; relative potency; static concentration; bactericidal effect
Funding
- Belgian Fonds de la Recherche Scientifique Medicale (F.R.S.M.) [3.4.597.06]
- Senior Research Associate of the Belgian Fonds de la Recherche Scientifique (F.R.S.-FNRS)
Ask authors/readers for more resources
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. 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 [EC50], 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}. Concentration-dependent experiments: in broth, EC50 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 EC50 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). 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available