1: Antimicrob Agents Chemother. 2009 Apr;53(4):1443-9. Epub 2009 Feb 2.

Intracellular activity of antibiotics in a model of human THP-1 macrophages
infected by a Staphylococcus aureus small-colony variant strain isolated from a
cystic fibrosis patient: study of antibiotic combinations.

Nguyen HA, Denis O, Vergison A, Tulkens PM, Struelens MJ, Van Bambeke F.

Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de
Louvain, Brussels, Belgium.

In a companion paper (H. A. Nguyen et al., Antimicrob. Agents Chemother.
53:1434-1442, 2009), we showed that vancomycin, oxacillin, fusidic acid,
clindamycin, linezolid, and daptomycin are poorly active against the
intracellular form of a thymidine-dependent small-colony variant (SCV) strain
isolated from a cystic fibrosis patient and that the activity of
quinupristin-dalfopristin, moxifloxacin, rifampin, and oritavancin remains
limited (2- to 3-log CFU reduction) compared to their extracellular activity.
Antibiotic combination is a well-known strategy to improve antibacterial
activity, which was examined here against an intracellular SCV strain using
combinations with either rifampin or oritavancin. Time-kill curve analysis using 
either concentrations that caused a static effect for each antibiotic
individually or concentrations corresponding to the maximum concentration in
human serum showed largely divergent effects that were favorable when antibiotics
were combined with rifampin at low concentrations only and with oritavancin at
both low and high concentrations. The nature of the interaction between rifampin,
oritavancin, and moxifloxacin was further examined using the fractional maximal
effect method, which allows categorization of the effects of combinations when
dose-effect relationships are not linear. Rifampin and oritavancin were
synergistic at all concentration ratios investigated. Oritavancin and
moxifloxacin were also synergistic but at high oritavancin concentrations only.
Rifampin and moxifloxacin were additive. This approach may help in better
assessing and improving the activity of antibiotics against intracellular SCV
strains.

PMCID: PMC2663110 [Available on 2009/10/01]
PMID: 19188397 [PubMed - in process]

Related Links

    Intracellular activity of antibiotics in a model of human THP-1 macrophages
infected by a Staphylococcus aureus small-colony variant strain isolated from a
cystic fibrosis patient: pharmacodynamic evaluation and comparison with isogenic 
normal-phenotype and revertant strains. [Antimicrob Agents Chemother. 2009]
PMID:19188393

    Pharmacodynamic evaluation of the intracellular activities of antibiotics against
Staphylococcus aureus in a model of THP-1 macrophages. [Antimicrob Agents
Chemother. 2006] PMID:16495241

    [In vitro activity of linezolid, moxifloxacin, levofloxacin, clindamycin and
rifampin, alone and in combination, against Staphylococcus aureus and
Staphylococcus epidermidis.] [Rev Esp Quimioter. 2005] PMID:16130039

    Quantitative analysis of gentamicin, azithromycin, telithromycin, ciprofloxacin, 
moxifloxacin, and oritavancin (LY333328) activities against intracellular
Staphylococcus aureus in mouse J774 macrophages. [Antimicrob Agents Chemother.
2003] PMID:12821480

    Activities of antistaphylococcal antibiotics towards the extracellular and
intraphagocytic forms of Staphylococcus aureus isolates from a patient with
persistent bacteraemia and endocarditis. [Clin Microbiol Infect. 2008]
PMID:18727801