In patients with severe, nonischemic dilated cardiomyopathy who were treated with ACE inhibitors and beta-blockers, the implantation of a cardioverter-defibrillator significantly reduced the risk of sudden death from arrhythmia and was associated with a nonsignificant reduction in the risk of death from any cause.

Microbial drug resistance is an inescapable consequence of the utilization of antimicrobial agents in a given environment. Nowhere is the importance of resistance more evident than among agents of the beta-lactam family. Trends toward increased resistance can be seen among fastidious gram-negative bacteria like Haemophilus influenzae, where ampicillin resistance varies from 1% to 64% globally. For Escherichia coli, ampicillin resistance has risen to > or = 50% in high-risk populations, and resistance to third-generation cephalosporins is now being seen in certain areas. Inducible beta-lactamases have been responsible for increasing multiple beta-lactam resistance among certain Enterobacteriaceae and Pseudomonas aeruginosa, and this has been associated with increased use of newer cephalosporins. Xanthomonas maltophilia with its two inducible beta-lactamases is becoming an increasingly important nosocomial pathogen, especially in areas of heavy imipenem utilization. Only through the recognition of factors associated with increasing resistance and the mechanisms responsible can strategies be designed for minimizing beta-lactam resistance.

The ability of three quinolones, two I-lactams, and one aminoglycoside to select resistant mutants was examined in tests with 30 isolates of commonly encountered nosocomial pathogens. Ciprofloxacin and norfloxacin, two new quinolone derivatives, were no more likely to select resistant mutants than amikacin, whereas nalidixic acid, an older quinolone derivative, was the most likely of the six drugs examined to select resistant mutants. Mutational frequencies of 10-7 to 10-8 were observed in most instances. In general, the mutants were 8 to 16 times less susceptible to the drug used for selection. Although most quinolone-selected mutants were cross-resistant only to other drugs within this class, certain mutants of Klebsiella pneumoniae selected by nalidixic acid, ciprofloxacin, or norfloxacin were also less susceptible to 13-lactam antibiotics. This unusual pattern of multiple drug resistance was associated with changes in outer membrane proteins of the organism. Multiple drug resistance was also observed in P-lactam-selected mutants of Enterobacter cloacae and Pseudomonas aeruginosa (,-lactams), amikacin-selected mutants of Providencia stuartii and P. aeruginosa (aminoglycosides), and I-lactam-or amikacin-selected mutants of Serratia marcescens (B-lactams plus aminoglycosides). These results underscore the need to examine carefully the frequency with which resistance to any new antibiotic develops, as well as the patterns of multiple drug resistance which may occur simultaneously.The development of resistance can significantly shorten the useful lifetime of antimicrobial agents in prophylaxis and therapy of infectious diseases and has been a major problem with nalidixic acid, a quinolone derivative, and possibly with the new cephalosporins (23, 26). Unfortunately, potential problems with the development of resistance are often not thoroughly analyzed for most antibiotics before the time the drugs become available for clinical use. The occurrence of cross-resistance to related or unrelated antibiotics is also seldom studied in depth.The recent development of new quinolone derivatives, such as norfloxacin and ciprofloxacin, has stimulated interest in these problems of resistance. New members of this class of compounds must be analyzed closely to determine whether resistance will develop as frequently as it has with nalidixic acid. Several studies have already examined this aspect (4,5,8,13,15,17,29 MIC (usually 4,8,and 16 times the MIC). The actual inoculum utilized was determined by agar dilution plate counts. After overnight incubation at 35°C in air, the apparent mutational frequencies were calculated from results obtained with the highest drug concentration on which colonies were detected. Cells selected by this procedure were considered to be resistant mutants if the MIC for the drug utilized was increased at least eightfold. For most combinations, mutants occurring at a frequency as low as 10-9 could be detected.

Knowledge of the genus Enterobacter and its role in human disease has expanded exponentially in recent years. The incidence of infection in the hospital and the community has increased. New clinical syndromes have been recognized. Enterobacter spp. have also been implicated as causes of other syndromes that traditionally have been associated almost exclusively with more easily treatable pathogens, such as group A streptococci and staphylococci. Rapid emergence of multiple-drug resistance has been documented in individual patients during therapy and in populations and environments with strong selective pressure from antimicrobial agents, especially the cephalosporins. Therapeutic options for patients infected with multiply resistant strains have become severely limited. Carbapenems or, alternatively, fluoroquinolones are the most predictively active options, although resistance to both classes has been observed on rare occasions. Enterobacter spp. appear well adapted for survival and even proliferation as the turn of the century approaches.

No abstract