Multidrug-resistant strains of Klebsiella pneumoniae are a problem in many hospitals. In 1999, the molecular epidemiology of K. pneumoniae with extended-spectrum beta-lactamases (ESBLs) was studied at 15 hospitals in Brooklyn. Of 824 unique patient isolates, 34% were presumptive ESBL producers. Of this subset, 34% were susceptible to cefoxitin, 42% to ciprofloxacin, 48% to ceftriaxone, 55% to piperacillin-tazobactam, 57% to amikacin, and 86% to cefepime. Ribotype analysis revealed 87 unique types. However, 2 clusters accounted for 35% of isolates and were present in most of the hospitals. One cluster was significantly more resistant to most antibiotics. Although there was a predominance of SHV-5, considerable heterogeneity of beta-lactamases was evident, even among isolates of the same cluster. A correlation was found between the use of cephalosporins and the prevalence of ESBL-producing strains of K. pneumoniae at each hospital. Our data suggest that there is an advanced outbreak of multidrug-resistant K. pneumonia infection that is affecting all Brooklyn hospitals.