Monotherapy of systematic Pseudomonas aeruginosa infections with ceftazidime. The causes of therapeutic failures

Abstract Ceftazidime, a new cephalosporin, is characterized by very good in-vitro action against P. aeruginosa. Nonetheless, clinical and (or) microbiological failure occurred in four patients with severe P. aeruginosa infections being treated with ceftazidime. Main cause infections being treated with ceftazidime. Main cause of the discrepancy between in-vitro and in-vivo results during treatment of three patients was a rapid drop in bacterial sensitivity. Superinfection with resistant microorganisms was excluded by the identity of the isolated bacteria in the different epidemiological markers before and during treatment. This rise in resistance was also demonstrated in-vitro by culturing clinically isolated material in ceftazidime-containing media: a 16-fold decrease in sensitivity was demonstrated within three subcultures. Increased beta-lactamase activity of the resistant strains makes it likely that enzymatic inactivation was part of the resistance mechanism. Good inducibility of beta-lactamases and absent resistance transfer argue for chromosomal localisation of the resistance. Because of the development of resistance, severe infections caused by P. aeruginosa should not be treated by ceftazidime alone. In order early to discover the development of resistance, microbiological samples should be taken periodically and examined for their sensitivity.