Antimicrob Agents Chemother. 2003 Jul;47(7):2283-92.  

Quantitative analysis of gentamicin, azithromycin, telithromycin, ciprofloxacin,
moxifloxacin, and oritavancin (LY333328) activities against intracellular
Staphylococcus aureus in mouse J774 macrophages.

Seral C, Van Bambeke F, Tulkens PM.

Unite de Pharmacologie Cellulaire et Moleculaire, Universite Catholique de
Louvain, Brussels, Belgium.

Using J774 macrophages, the intracellular activities of gentamicin,
azithromycin, telithromycin, ciprofloxacin, moxifloxacin, and oritavancin
(LY333328) against Staphylococcus aureus (strain ATCC 25923) have been
quantitatively assessed in a 24-h model. S. aureus was positively localized in
phagolysosomes by confocal and electron microscopy, and extracellular growth was
prevented with 0.5 mg of gentamicin/liter (1x MIC) in controls. When tested at
extracellular concentrations equivalent to their maximum concentrations in human
serum, all antibiotics except azithromycin caused a significant reduction of the
postphagocytosis inoculum within 24 h, albeit to markedly different extents
(telithromycin [2 mg/liter], 0.60 log; ciprofloxacin [4.3 mg/liter], 0.81 log;
gentamicin [18 mg/liter], 1.21 log; moxifloxacin [4 mg/liter], 1.51 log;
oritavancin [25 mg/liter], 3.49 log). Intracellular activities were not
systematically related to drug accumulation (apparent cellular-to-extracellular
concentration ratios in infected cells: ciprofloxacin, 3.2; gentamicin, 6.8;
telithromycin, 8.7; moxifloxacin, 13.4; azithromycin, 50; oritavancin, 348).
Intracellular activity was not directly correlated to extracellular activity as
measured in broth. Conditions of pH 5 (i.e., mimicking that of phagolysosomes)
markedly reduced the activity of gentamicin, azithromycin, and telithromycin
(>or=32 x) and fairly extensively reduced that of ciprofloxacin and moxifloxacin
(>or=4 x) but did not affect oritavancin activity. We conclude that the cellular
accumulation of antibiotics is not the only parameter to take into account for
intracellular activity but that local environmental conditions (such as pH) and
other factors can also prove critical.

PMID: 12821480 [PubMed - in process]