Nosocomial Outbreaks of Multiresistant Bacteria: Extended-Spectrum Beta-Lactamases Have Arrived in North America

The history of the antibiotic era shows that widespread use of new antibiotics fosters emergence of resistant clinical isolates, often possessing novel antimicrobial resistance mechanisms. Clinical use of oxyimino--lactams, particularly ceftazidime and cefotaxime, skyrocketed during the last 15 years. In 1983 plasmid-mediated enzymes that confer resistance to oxyimino--lactamsextended-spectrum -lactamases (ESBL)were first observed in Germany. Since then, the number and variety of these -lactamases have increased rapidly and their distribution is now worldwide.

Most of the ESBLs derive from TEM-1 or 2 and SHV-1, the common plasmid-determined -lactamases that confer resistance to penicillins and early-generation cephalosporins. Substitution of a single amino acid in the active site region of the SHV-1 molecule transforms it into the extended-spectrum -lactamase, SHV-2, that can inactivate late-generation cephalosporins. The number of derivatives of the TEM and SHV -lactamases proven to be unique by sequencing or oligotyping has now reached 26 and 5, respectively [1, 2]. Several have been found in many countries (SHV-2, SHV-4, SHV-5, TEM-6), whereas others seem to occur more commonly in one or two countries. For example, TEM-3 seems more prevalent in France and TEM-10 and TEM-12 in the United States and England [1]. Most of the isolates that produce ESBLs have come from hospitalized patients and have frequently caused nosocomial outbreaks, primarily due to Klebsiella pneumoniae strains that often have associated resistance to aminoglycosides. Recent surveys of nosocomial isolates of K. pneumoniae from Europe show that 14% to 16% produce ESBLs [3, 4]. In France the prevalence increased from less than 1% in 1985 to the current …