Dynamic bactericidal activity of ceftazidime in combination with glycopeptides and azithromycin against Pseudomonas aeruginosa
Abstract number: p1307
Repetto B., Palenzona A., Marchese A., Debbia E.A.
Pseudomonas aeruginosa is an opportunistic pathogen. It is intrinsically resistant to many antibiotics and evolution toward resistance is very frequently. The low permeability of the outer membrane, due to the presence of lipopolisaccaride (LPS), is considered in part responsible of this resistance. It is assumed that some agents might disorganize the structure of LPS and allow the passage of other drugs into bacteria cell. In order to verify this hypothesis, ceftazidime (CAZ) has been tested in association with glycopeptides (GLYs) and azithromycin (AZI), which is a non anti-pseudomonal agents but has been shown to interfere with some virulence factors.
A bacterial suspension of about 109 CFU/ml was seeded on plates containing increasing doses of CAZ and a fixed concentration of GLYs (300 mg/l) and AZI (16 mg/l) Results were interpreted as synergism (99%), additivity (90%), and indifference (10%) of the CFU/ml reduction found in the drugs combination in comparison to the drug alone. Time-kill experiments were performed by adding the drugs to log-phase bacterial cultures diluted to 106107 CFU/mL growing in 100 mL flasks at 37°C. Just before the compounds were added and at 2, 4, 6 and 24 hr thereafter, bacterial counts were carried out. Survivors were evaluated by determining CFU on agar plates.
CAZ in combination with GLYs reacted synergically in 35% of cases, additivity was found 52% of cases and indifference was noted in 13% of tests; the addition of AZI increased the incidence of synergisms to 42%, additivities to 49% and indifferences to 9%. The combinations that were tested through the dynamic bactericidal tests are CAZ (2xMIC)+GLYs (300 mg/l)+AZI (16 mg/l), CAZ (2xMIC)+GLYs (200 mg/l)+AZI (16 mg/l) and CAZ (2xMIC)+GLYs (300 mg/l)+AZI (32 mg/l). Preliminary results indicated that antimicrobical effect is always significant 6 hr thereafter, in particular at the presence of AZI; instead the letal effect is reduced when GLYs is used at concentration of 200 mg/l and it is increased when AZI is used at concentration of 32 mg/l (fig.1).
The present findings demonstrated that CAZ favourably reacted with GLIs at the presence of AZI. Further studies to determine the best combinations among the drugs to achieve highest rate of synergism are under way.
|Session name:||XXIst ISTH Congress|
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