We initiated a worldwide collaborative study, including 455 episodes of bacteremia, to elucidate the clinical patterns of Klebsiella pneumoniae. Historically, community-acquired pneumonia has been consistently associated with K. pneumoniae. Only four cases of community-acquired bacteremic K. pneumoniae pneumonia were seen in the 2-year study period in the United States, Argentina, Europe, or Australia; none were in alcoholics. In contrast, 53 cases of bacteremic K. pneumoniae pneumonia were observed in South Africa and Taiwan, where an association with alcoholism persisted (p=0.007). Twenty-five cases of a distinctive syndrome consisting of K. pneumoniae bacteremia in conjunction with community-acquired liver abscess, meningitis, or endophthalmitis were observed. A distinctive form of K. pneumoniae infection, often causing liver abscess, was identified, almost exclusively in Taiwan.

The prevalence of extended-spectrum beta -lactamase (ESBL) production by Klebsiella pneumonia approaches 50% in some countries, with particularly high rates in eastern Europe and Latin America. No randomized trials have ever been performed on treatment of bacteremia due to ESBL-producing organisms; existing data comes only from retrospective, single-institution studies. In a prospective study of 455 consecutive episodes of Klebsiella pneumoniae bacteremia in 12 hospitals in 7 countries, 85 episodes were due to an ESBL-producing organism. Failure to use an antibiotic active against ESBL-producing K. pneumoniae was associated with extremely high mortality. Use of a carbapenem (primarily imipenem) was associated with a significantly lower 14-day mortality than was use of other antibiotics active in vitro. Multivariate analysis including other predictors of mortality showed that use of a carbapenem during the 5-day period after onset of bacteremia due to an ESBL-producing organism was independently associated with lower mortality. Antibiotic choice is particularly important in seriously ill patients with infections due to ESBL-producing K. pneumoniae.

Production of ESBLs by Klebsiella pneumoniae is a widespread nosocomial problem. Appropriate infection control and antibiotic management strategies are needed to stem the spread of this emerging form of resistance.

To evaluate the prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains among species of Enterobacteriaceae, a microdilution susceptibility test was performed with strains of Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, and Salmonella species that were isolated as part of the SENTRY project. The highest percentage of ESBL phenotype (defined as a minimum inhibitory concentration [MIC] > or =2 microg/mL for ceftazidime, ceftriaxone, or aztreonam) was detected among K. pneumoniae strains from Latin America (45%), followed by those from the Western Pacific region (25%), Europe (23%), the United States (8%), and Canada (5%). P. mirabilis and E. coli strains for which MICs of extended-spectrum cephalosporins or monobactams were elevated also were more prominent in Latin America. Testing with ceftazidime revealed more isolates with elevated MICs than did testing with ceftriaxone or aztreonam. ESBL strains showed high levels of co-resistance to aminoglycosides, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin. Imipenem remains highly effective against ESBL strains. Organisms expressing an ESBL are widely distributed worldwide, although prevalence rates are significantly higher in certain geographic regions.

Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBLproducing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs. We performed a prospective, multinational study of Klebsiella pneumoniae bacteremia and identified 10 patients who were treated for ESBL-producing K. pneumoniae bacteremia with cephalosporins and whose infecting organisms were not resistant in vitro to the utilized cephalosporin. In addition, we reviewed 26 similar cases of severe infections which had previously been reported. Of these 36 patients, 4 had to be excluded from analysis. Of the remaining 32 patients, 100% (4 of 4) patients experienced clinical failure when MICs of the cephalosporin used for treatment were in the intermediate range and 54% (15 of 28) experienced failure when MICs of the cephalosporin used for treatment were in the susceptible range. Thus, it is clinically important to detect ESBL production by klebsiellae or E. coli even when cephalosporin MICs are in the susceptible range (< 8 g/ml) and to report ESBL-producing organisms as resistant to aztreonam and all cephalosporins (with the exception of cephamycins).