Pharmacodynamic efficacy of levofloxacin against multidrug-resistant Pseudomonas aeruginosa isolated from patients with ventilator-associated pneumonia
Abstract number: P1661
Safarika A., Raftogiannis M., Baziaka F., Antonopoulou A., Koutoukas P., Giamarellos-Bourboulis E.
Objectives: Although levofloxacin (LVF) has been proposed for the treatment of ventilator-associated pneumonia (Benko R, et al. IJAA 2007; 30: 162), there is a lot of scepticism about the appropriateness of its administration in settings with high-resistance rates. The in vitro effect of LVF at concentrations close to those achieved in the epithelial lining fluid (ELF) against multidrug-resistant Pseudomonas aeruginosa (MDRPA) pathogens from patients with ventilator-associated pneumonia (VAP) was assessed.
Methods: Eleven MDRPA from patients with VAP enrolled in a prospective trial (NCT00297674) were tested. Pathogens were grown at a density greater than 1×106/ml from tracheobronchial secretions in parallel with a clinical pulmonary infection score more than 6. A log-phase inoculum of 1×106 cfu/ml of pathogens was exposed over time to 5, 10 and 25 microg/ml of LVF that corresponds to its ELF levels. They were also exposed to 18 microg/ml of meropenem (MER), to 5 microg/ml of colistin (COL) and to their interactions. The latter are concentrations equal to their mean serum levels. MER and COL were applied because these were prescribed by the attending physicians.
Results: MIC50 and MIC90 of LVF was 64 and 128 microg/ml respectively. A more than 3 log10 bactericidal effect of LVF was shown by concentrations of 5, 10 and 25 microg/ml against five, five and five isolates respectively at all times of growth. MER was bactericidal in nil isolates and COL in two isolates. Synergy defined as any more than 2 log10 decrease of bacterial growth compared with the most active single agent was shown between 5 microg/ml of LVF and MER in four, four, five and six isolates at 2, 4, 6 and 24 hours of growth respectively; between 10 microg/ml of LVF and MER in five, five, five and eight isolates respectively; and between 25 microg/ml of LVF and MER five, five, six and eight isolates respectively. Respective synergy between 5 microg/ml of LVF and COL was found in four, four, four and two isolates; between 10 microg/ml of LVF and COL in four, four, five and three isolates; and between 25 microg/ml of LVF and COL in four, five, five and three isolates.
Conclusions: Despite the great MIC values, LVF showed considerable in vitro bactericidal effect against MDRPA pathogens of VAP when applied at concentrations close to ELF. Single MER and COL were not that effective but they acted in synergy with LFV. These findings reinforce the application of LVF for VAP by MDRPA.
|Session name:||19th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Helsinki, Finland, 16 - 19 May 2009|
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