International Journal of Antimicrobial Agents 8 (1997) 257 – 261 Comparative efficacy of successive exposure of Pseudomonas aeruginosa to gentamicin and ceftazidime A.M. Shibl *, A.F. Tawfik, M.A. Ramadan College of Pharmacy, King Saud Uniersity, P. O. Box 2457, Riyodh 11 451, Saudi Arabia Accepted 27 March 1997 Abstract Aminoglycoside and  -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 – 8 ×MICs) 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 8 ×MIC 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. © 1997 Elsevier Science B.V. Keywords: Gentamicin; Ceftazidime; Killing capacity; Pseudomonas aeruginosa 1. Introduction Pseudomonas aeruginosa continues to be a major nosocomial pathogen which is leading cause of mortal- ity, particularly among patients with immunosuppres- sion, malignancy, cystic fibrosis, burns or traumatic wounds. Emergence of resistance has been reported when any of the newer anti-pseudomonal antibiotics is used alone against this organism [1]. Treatment of infections caused by this microbe is frequently compli- cated by intrinsic resistance to antimicrobial agents and by frequent development of resistance during single- agent chemotherapy. Combination demonstrates not only synergy but also a rapid killing activity [2] which contributes to its clinical efficacy. It was observed that the overall bacterial killing was greater with successive rather than simultaneous administration [3]. Because animal and human data are difficult to obtain, decisions about the selection of optimal combi- nations are based on in vitro information. Using the killing capacity, we have examined the combination of gentamicin and/or ceftazidime against standard strain of Pseudomonas aeruginosa and to determine also the spacing between doses of this combination for optimal regimen. The concentrations used were double the