446 Current Topic: Article Vol. 6, No. 4 l-ur. J. Clin. Microbiol., August 1987, p. 446-450 0722-2211/87/04 0446-05 $3.00/0 Clinical Consequences of Development of Resistance to Third Generation Cephalosporins F. Follath l*, E. Costa 1 A. Thommen I R. Frei 1 A. Burdeska 2 J. Meyer 2 Eighteen patients are described in whom initially sensitive microorganisms were replaced by resistant isolates during administration of eeftriaxone (n = 8), cefoperazone (n = 5), moxa- lactam (n = 4), eefotaxime (n = 2) or ceftazidime (n = 1), despite combination with amino- glycosides. All patients had documented gram-negative infections; in 12 patients underlying haemaotological diseases were present. Resistant strains of Enterobacter cloacae (14), Serratia raarcescens (4), Klebsiella oxytoca ( 3 ), Pseudomonas aeruginosa (2) and Citrobacter freundii (2) emerged within 2 to 19 (mean 9) days after the beginning of treatment. In 12 patients relapse or secondary infections occurred. Seven of the patients with haematological disorders died. Resistance development was seen in 8 of 29 patients on ceftriaxone and 4 of 10 patients on moxalactam during prospective evaluations; the other drugs were used sporadically. Thus, selection of resistant bacteria is relatively frequent and may have serious clinical consequences in patients with impaired host-defense mechanisms. The introduction of new broad-spectrum cephalo- sporins has improved the possibility of effectively treating infections with gram-negative bacteria. High clinical and bacteriological success rates have been achieved with cefotaxime (1), cefoperazone (2), moxalactam (3), ceftriaxone (4) and ceftazidime (5). It soon became apparant, however, that use of these highly ~-lactamase stable antibiotics may also lead to rapid emergence of resistant bacterial strains in species such as Enterobacter cloacae, Pseudomonas aeruginosa, Serratia marcescens and Citrobacter freundii. A feature common to all these microorganisms is the presence of an inducible chromosomal/~-lactamase which pro- bably plays a major role in the development of resistance (6-8). Cross-resistance to all cephalosporins and penicillins is the rule, but in some cases suscepti- bility to aminoglycosides can also decrease (9). In contrast to the large number of microbiological studies, there are only few reports dealing with the clinical consequences of development of resistance to third generation cephalosporins. Relapse and thera- peutic failure have been most often seen in patients with Pseudomonas aeruginosa infections (3, 9-1 I). Recently, an outbreak of nosocomial cefotaxime- resistant Enterobacter cloacae infection occurred in a neonatal intensive care unit (12). 1Department of Medicine, University Hospital (Kantonspital), Basel, Switzerland. 2Department of Microbiology, Biozentrum, University of Basel, Switzerland. In this paper we describe a series of severely ill patients in whom cephalosporin-resistant gram-nega- tive bacteria emerged during treatment, resulting in life-threatening secondary infections. Materials and Methods Clinical Study. During a five year period (1980-1985) we observed a total of 18 hospitalised patients aged between eight and 74 years, in whom initially sensitive gram-negative bacteria became resistant during therapy with a third genera- tion cephalosporin. These antibiotics were only prescribed when the isolated microorganisms were insensitive to penicil- lins or first and second generation cephalosporins in vitro. The clinical indications for treatment were neutropenia with febrile episodes in seven patients, septicaemia in six, pneu- monia in three, and liver abscess and acute osteomyelitis in one patient each. The patients were seriously ill and suffered from the following underlying diseases: aplastic anaemia (n = 5), leukaemia (n = 5), lymphoma (n = 2), carcinoma (n = 2), cholangitis (n = 1), alcoholism (n = 1), chronic bronchitis (n = 1) and postoperative complications following coronary bypass (n = 1). In 16 of the 18 patients the third generation cephalosporin was substituted for a previously administered /Mactam antibiotic; 13 patients also received an aminoglycoside concomitantly. The patients developing resistance under moxalactam (n = 4) and ceftriaxone (n = 8) therapy took part in prospective clinical trials involving 10 and 29 cases respectively. Cefoperazone, cefotaxime and ceftazidime were chosen sporadically by the responsible physicians for therapy. The total number of medical patients receiving a third-generation cephalosporin during the entire observation period was between approximately 140 and 160.