Physicochemical properties and antibacterial activity of the precipitate of vancomycin and ceftazidime: implications in the management of endophthalmitis.

ABSTRACT

OBJECTIVE: To study the physicochemical properties, bioavailability, and microbicidal activity of vancomycin and ceftazidime in the precipitate formed by the drugs in mixture. METHODS: The precipitation of the drugs prepared in buffers in the pH range of 5.8 to 8.9, in normal saline, in balanced salt solution (BSS), and in Ringer lactate, was studied by light scatter analysis. Bioavailability and antibacterial activity of the precipitate and the supernatant were estimated using high-performance liquid chromatography (HPLC) and microbiologic assay respectively. RESULTS: The scatter analysis showed precipitation of vancomycin alone at pH 7.5 and in BSS. When mixed together precipitation was observed in the mixture of the two drugs within the pH range of 6.8 to 8.0 and in all solutions. HPLC of both supernatant and precipitate showed the presence of active drugs and the microbiologic assay confirmed its inhibitory activity against bacteria. The precipitate had greater activity against Gram-positive bacteria while the supernatant showed greater activity against Gram-negative bacteria. CONCLUSIONS: Vancomycin's pH dependent precipitation occurs regardless of the presence of ceftazidime. The precipitate as well as the supernatant retains significant antibacterial activity thus confirming the efficacy of combination therapy with vancomycin and ceftazidime in the management of bacterial endophthalmitis.