Journal of Antimicrobial Chemotherapy, Vol 40, 673-678, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
RP Smith, AL Baltch, M Franke, W Hioe, W Ritz and P Michelsen
Opsonophagocytic killing of some bacteria (Staphylococcus aureus,
Pseudomonas aeruginosa) by phagocytes is enhanced by previous brief
exposure of the organism to antibiotics. We studied the regrowth of
Legionella pneumophila previously pretreated with levofloxacin,
erythromycin and/or rifampicin in human monocytes. The MIC for the L.
pneumophila isolate of levofloxacin, erythromycin and rifampicin was 0.03,
0.5 and 0.001 mg/L, respectively. Growth of L. pneumophila from buffered
charcoal yeast extract (BCYE) agar for 24 h was subcultured into BYE broth
containing from 0 to 4x MIC of levofloxacin, erythromycin or rifampicin.
After incubation at 35 degrees C in 5% CO2 for 18 h, the organisms were
washed and opsonized with 20% heat inactivated pooled normal human serum.
Thereafter, L. pneumophila was exposed to human monocytes (5:1 ratio)
previously adhered to wells in tissue culture plates containing RPMI and
10% fetal calf serum. After 0, 24, 48 and 72 h of incubation, quantitative
cultures of lysed human monocytes were done on BCYE agar. Our results
indicate effective inhibition on L. pneumophila at 0 h regardless of the
antibiotic (levofloxacin, rifampicin or erythromycin) or their
concentrations (1x, 2x or 4x MIC). At 24, 48 and 72 h, recovery and
regrowth of L. pneumophila were both antibiotic- and
concentration-dependent. In comparison with controls (no antibiotic
pretreatment), peak regrowth of L. pneumophila pretreated with either 1x
MIC of levofloxacin or erythromycin was delayed (48 versus 24 h) and
reduced (30% of control peak regrowth). Regrowth of L. pneumophila
pretreated with 1x MIC of rifampicin continued beyond 72 h. Pretreatment
with levofloxacin at 4x MIC caused the greatest degree of growth inhibition
(2 log10). In contrast, at 72 h, regrowth of organisms pretreated with 4x
MIC of erythromycin or rifampicin was less than peak control (P < 0.01)
but greater than that seen with levofloxacin (P < 0.01). The rate and
degree of regrowth of L. pneumophila pretreated with combinations of
levofloxacin or erythromycin with rifampicin, or levofloxacin with
erythromycin (all at 1x MIC) was similar to that seen with single drugs.
Thus, significant delay and reduction of regrowth in this phagocytic system
occurred with levofloxacin only. Prolonged exposure of the organism at 4x
MIC levofloxacin concentrations was effective in suppressing regrowth of
pretreated L. pneumophila in human monocytes.
ORIGINAL ARTICLES
Effect of levofloxacin, erythromycin or rifampicin pretreatment on growth of Legionella pneumophila in human monocytes
Department of Medicine, Stratton VA Medical Center and Albany Medical College, NY 12208, USA.
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