JAC Advance Access published online on January 16, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh076
© 2004 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Institute for Medical Microbiology, Immunology and Hygiene,
Medical Center University of Cologne,
Goldenfelsstr. 19-21, 50935 Cologne, Germany
* Corresponding author. E-mail: Martin.Kroenke{at}medizin.uni-koeln.de.
Received 3 July 2003
; revised 17 November 2003
; accepted 17 November 2003
Objectives: After infection of non-phagocytic
cells, some Staphylococcus aureus strains
are able to survive and kill their host cells. The purpose of this
study was to determine the action of various antibiotics on the survival
of host cells and/or intracellular S. aureus. Methods: Murine keratinocyte (PAM212) and fibroblast
(mKSA) cell lines were infected with cytotoxic S. aureus and cultured in the presence of various
antibiotics at graded concentrations. The viability of host cells
was measured 24 h after infection. To determine the bacterial viability
within host cells, cellular lysates were prepared and colony forming
units were quantified using a spiral plater. Host cells infected
with fluorescein isothiocyanate (FITC)-labelled S. aureus were
analysed by flow cytometry and microscopy to determine the subcellular
localization S. aureus. Results: Oxacillin, vancomycin, gentamicin,
ciprofloxacin and trimethoprim/sulfamethoxazole did not rescue host
cells from cell death induced by intracellular S. aureus.
In contrast, linezolid, rifampicin, azithromycin, clindamycin, erythromycin
and quinupristin/dalfopristin suppressed the cytotoxic action of
S. aureus. After withdrawal
of antibiotics, intracellular S. aureus regained
cytotoxic activity and killed their host cells. Only rifampicin
was able to eliminate intracellular S. aureus completely
within 72 h. In contrast, clindamycin, azithromycin and linezolid
induced a state of intracellular persistence of viable S.
aureus. Conclusions: Antibiotics commonly used for the
management of S. aureus infections appear to create
a niche for invasive intracellular S. aureus, which
may play an important role for persistence and recurrence of infection.
Because of its unique ability to eliminate intracellular S.
aureus, rifampicin appears to be valuable for the treatment
of invasive S. aureus infections.
Keywords: anti-infective agents, staphylococcal infections,
microbial susceptibility tests, cell death
Antibiotic-induced persistence of cytotoxic Staphylococcus
aureus in non-phagocytic cells
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