The CTX-M-15 extended spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae isolates were identified in 36 patients hospitalized from December 2006 to September 2007 in the medical intensive care unit (ICU) of the Bicêtre hospital, South Paris, France. The incidence of colonization and/or infection was 4.8%. Eighty-nine percent of the ESBL-producing K. pneumoniae isolates were acquired in the ICU, and only 8.3% of the patients were infected. Pulsed field gel electrophoresis (PFGE) analysis of the isolates showed that 32 isolates were clonally related and contained a 160-kb plasmid carrying the bla(CTX-M-15), bla(OXA-1), bla(TEM-1), and aac6'-Ib-cr genes. CTX-M-15-producing Escherichia coli isolates collected in the ward during the same period of time contained distinct plasmids and were not clonally related. This study highlights the possible occurrence of outbreaks due to CTX-M-producing K. pneumoniae within hospital settings, whereas CTX-Ms are mostly reported in E. coli in community-acquired infections.