Antimicrob Agents Chemother  2002 Jul;46(7):2095-103 

Comparative intracellular (THP-1 macrophage) and extracellular activities of
beta-lactams, azithromycin, gentamicin, and fluoroquinolones against Listeria
monocytogenes at clinically relevant concentrations.

Carryn S, Van Bambeke F, Mingeot-Leclercq MP, Tulkens PM.

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

The activities of ampicillin, meropenem, azithromycin, gentamicin,
ciprofloxacin, and moxifloxacin against intracellular hemolysin-positive
Listeria monocytogenes were measured in human THP-1 macrophages and were
compared with the extracellular activities observed in broth. All extracellular
concentrations were adjusted to explore ranges that are clinically achievable in
human serum upon conventional therapy. In broth, ampicillin, meropenem, and
azithromycin were only bacteriostatic, whereas gentamicin, ciprofloxacin, and
moxifloxacin were strongly bactericidal in a concentration-dependent manner. In
cells, ampicillin, meropenem, azithromycin, and ciprofloxacin were slightly
bactericidal (0.3- to 0.8-log CFU reductions), moxifloxacin was strongly
bactericidal (2.1-log CFU reduction), and gentamicin was virtually inactive. The
difference in the efficacies of moxifloxacin and ciprofloxacin in cells did not
result from a difference in levels of accumulation in cells (6.96 +/- 1.05
versus 7.75 +/- 1.03) and was only partially explainable by the difference in
the MICs (0.58 +/- 0.04 versus 1.40 +/- 0.17 mg/liter). Further analysis showed
that intracellular moxifloxacin expressed only approximately 1/7 of the activity
demonstrated against extracellular bacteria and ciprofloxacin expressed only
1/15 of the activity demonstrated against extracellular bacteria. Gentamicin did
not increase the intracellular activities of the other antibiotics tested. The
data suggest (i) that moxifloxacin could be of potential interest for
eradication of the intracellular forms of L. monocytogenes, (ii) that the
cellular accumulation of an antibiotic is not the only determinant of its
intracellular activity (for fluoroquinolones, it is actually a self-defeating
process as far as activity is concerned), and (iii) that pharmacodynamics
(activity-to-concentration relationships) need to be considered for the
establishment of efficacy against intracellular bacteria, just as they are for
the establishment of efficacy against extracellular infections.

PMID: 12069960 [PubMed - indexed for MEDLINE]