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Objectives: Pseudomonas aeruginosa is an opportunistic human pathogen which is intrinsically resistant to many antibiotics and easily develops resistance towards many currently available agents. Intrisic resistance can be attributed to the low permeability of the P. aeruginosa outer membrane to a variety of antibiotics, including glycopeptides (GLYs). These drugs are active against Gram-positive bacteria and resistance is very rare, it appeared of some interest to evaluate the effect of combining these antimicrobial agents with antibiotics that might disorganize the structure of the outer membrane allowing the entry of glycopeptides into the Gram-negative cells. In order to verify this hypothesis, ceftazidime (CAZ) has been tested in association with vancomycin (VAN) or teicoplanin (TEI). The same experiments have been carried out also in the presence of azithromycin (AZI), which has been shown to interfere with some cellular synthesis in P. aeruginosa. Methods: A bacterial suspension of about 109CFU/ml was seeded on plates containing a fixed concentration of GLYs (500 mg/l) and increasing doses (2x,4x,8x,16x) of CAZ. Survivors were counted after 48 hs at 37°C. 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. The same experiments have been repeated adding AZI (16 mg/l) and using GLYs at concentrations ranging from 500 to 300 mg/l. Results: CAZ in combination with GLYs reacted synergically in 20 out of 59 cases, additivity was found in 31/59 interactions and indifference was noted in 8/59 tests. Preliminary results (12 tests performed) indicated that the addition of AZI increased the incidence of synergisms and additivities even when using GLYs concentration of 300 mg/l (figure I). Conclusions: CAZ combined with GLYs gave additive or synergistic results in the geat majority of experiments, while the simultaneous combination of AZI, CAZ and a GLY increased the incidence of additive or synergistic effect against P. aeruginosa.These data, given the high concentration of GLYs employed, could be of particular interest in clinical situations where the drugs could be topically administered.
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