Comparative activity of moxifloxacin vs. trimethoprim-sulfamethoxazole, cloxacillin, linezolid, clindamycin, and ciprofloxacin against intracellular methicillin-sensitive and community-acquired methicillin-resistant S. aureus

Abstract number: 1733_201

Lemaire S., Van Bambeke F., Tulkens P., Glupczynski Y.

Objectives: Recurrence and persistence of S. aureus infection is often ascribed to intracellular bacterial persistence, which may also be a cause of emergence of resistance. We showed that the activity of antibiotics is always weaker when tested against intracellular bacteria in comparison to those growing in broth (AAC 2006, 50:841–851). In this context, we have examined the intraphagocytic activity of moxifloxacin (MXF; recently approved for skin and soft-tissues infections) against fully sensitive S. aureus (MSSA) and community-acquired methicillin-resistant S. aureus (CA-MRSA), in comparison with (i) antibiotics commonly used for the treatment of CA-MRSA infections (trimethoprim-sulfamethoxazole [TMP-SMX], cloxacillin [CLX], linezolid [LNZ], clindamycin [CLI]), and (ii) ciprofloxacin (CIP).

Methods: MSSA (ATCC 25923) and CA-MRSA (NRS 192) were used. MICs were determined by microdilution in MH broth according to CLSI guidelines with a 10e5 cfu/mL original inoculum. Intracellular activity was assessed on infected THP-1 macrophages (as described in details in AAC 2006, 50:841–851) after 24 h exposure to drug concentrations corresponding to their respective human Cmax (see Table). Controls cells (no antibiotic added) were incubated with gentamicin [0.5×MIC] to prevent extracellular growth (see validation in AAC 2006, 50: 841–851).

Results: The table shows the MICs of each drug, together with their corresponding intracellular activity (change in cfu from post-phagocytosis inoculum).

Conclusions: All antibiotics tested, with the exception TPM-SMX, allowed for a reduction of the intracellular inoculum, but MXF demonstrated the largest effect (~2 log decrease), but this could be due, partly, to its low MIC towards the strains examined.