Comparative efficacy of successive exposure of Pseudomonas aeruginosa to gentamicin and ceftazidime.
Aminoglycoside and beta-lactam antibiotics, when used in combination, are usually given simultaneously, however, successive administration may be more efficient. The killing capacity was used to assess the effect of time intervals between low and high concentrations (2-8xMICs) of gentamicin and/or ceftazidime on Pseudomonas aeruginosa and to determine which drug is better to be administered first. The killing capacity after exposure to the antibiotic for 1 h were compared: (i) cells treated with gentamicin alone; (ii) cells treated with ceftazidime alone; and (iii) ceftazidime was added to (i) or (iv) gentamicin was added to (ii) at 0, 1 and 3 h of antibiotic removal. The bactericidal activity of gentamicin was potentiated and the viable cells decreased up to 6 h after antibiotic removal when the ceftazidime was added at O and at 1 h but the extent of bactericidal activity was reduced, when it was added at 3 h after gentamicin removal. Alternatively, treating the cells first with ceftazidime and then gentamicin was added after drug removal at O and at 1 h resulted in a marked decline in the viable cells, while addition of gentamicin after 3 h from ceftazidime removal, the extent of bactericidal activity was reduced. The non-treated cells with gentamicin started to grow heavily within 6 h of ceftazidime removal. No viable cells were detected after overnight incubation in cultures treated first with 6 or 8xMIC of gentamicin for 0.5 or 1 h. This in vitro study suggests that the optimum interval between gentamicin and ceftazidime doses, which gave the maximum bactericidal effect and the time before re-growth, appeared to be 1-2 h.
Shibl
A M
AM
College of Pharmacy, King Saud University, P. O. Box 2457, Riyodh 11 451, Saudi Arabia.
Tawfik
A F
AF
Ramadan
M A
MA