Infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC) in nonhospitalized patients seem to be emerging in different countries. Their incidence, epidemiology, and clinical impact in the community have not been studied. We describe the epidemiology and clinical features of infections caused by ESBLEC in nonhospitalized patients in Spain and the results of a case-control study performed to investigate the risk factors associated with the acquisition of these organisms. The clonal relatedness of the organisms was assessed by repetitive extragenic palindromic sequence PCR. The ESBLs and the genes encoding the ESBLs were initially characterized by isoelectric focusing and PCR, respectively. Forty-nine patients (76% with urinary tract infections, 22% with asymptomatic bacteriuria, and 2% with acute cholangitis) were included. Six patients were bacteremic. Diabetes mellitus (odds ratio, 5.5; 95% confidence interval, 1.6 to 18.7), previous fluoroquinolone use (odds ratio, 7.6; 95% confidence interval, 1.9 to 30.1), recurrent urinary tract infections (odds ratio, 4.5; 95% confidence interval, 1.3 to 15.1), a previous hospital admission (odds ratio, 18.2; 95% confidence interval, 5.3 to 61.1), and older age in male patients (odds ratio per year, 1.03; 95% confidence interval, 1.03 to 1.05) were identified as risk factors by multivariate analysis. The ESBLEC isolates were not clonally related. The ESBLs were characterized as members of the CTX-M-9 group, the SHV group, and the TEM group in 64, 18, and 18% of the isolates, respectively. ESBLEC is an emergent cause of urinary tract infections in nonhospitalized patients. There was no evidence of horizontal transmission of ESBLEC strains. Avoidance of fluoroquinolone use in high-risk patients should be considered whenever possible in order to avoid the selection of these organisms.Extended-spectrum beta-lactamase (ESBL)-producing members of the family Enterobacteriaceae are resistant to penicillins, narrow-and extended-spectrum cephalosporins, and aztreonam (4). ESBL-producing organisms are also frequently resistant to aminoglycosides, trimethoprim-sulfamethoxazole, and quinolones.Until recently, most infections caused by ESBL-producing Escherichia coli (ESBLEC) or Klebsiella pneumoniae had mostly been described as nosocomially acquired (4) or nursing home related (32). However, some recent data suggest that infections due to ESBL-producing organisms might be an emergent problem in outpatients in different countries (1,8,9,11,14,15), but detailed epidemiological data were not collected in most of those studies. Moreover, the clinical relevance and the epidemiology of these infections outside nursing homes have not been studied.In a recent nationwide study of ESBL-producing organisms in Spain, 93% of ESBL-producing K. pneumoniae strains were isolated from inpatients, while 51% of ESBL-producing E. coli (ESBLEC) strains were isolated from outpatients (13) Consequently, we conducted the study described in this report, in which we describe an...

ESBL-producing E. coli is a significant cause of bloodstream infection in hospitalized and nonhospitalized patients in the context of the emergence of CTX-M enzymes. Empirical treatment of sepsis potentially caused by E. coli may need to be reconsidered in areas where such ESBL-producing isolates are present.

The epidemiology of ESBL-producing E. coli as a cause of nosocomial infection is complex. Sporadic CTX-M-producing isolates coexisted with epidemic multidrug-resistant SHV-TEM-producing isolates. These data should be taken into account for the design of control measures.

Risk-factors for bloodstream infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli were investigated using an exploratory case-double control study in which 43 cases (70% producing CTX-M enzymes) were compared with: (i) 86 patients with bacteraemia caused by non-ESBL-producing E. coli; and (ii) 86 hospitalised patients. Previous follow-up as an outpatient, urinary catheterisation and use of oxyimino-beta-lactams or fluoroquinolones were independent risk-factors for ESBL-producing E. coli among patients with E. coli bacteraemia, and previous use of oxyimino-beta-lactams or fluoroquinolones were also independent risk-factors among hospitalised patients. These findings may help in identifying patients at greater risk for bloodstream infection caused by ESBL-producing E. coli in endemic areas.

In total, 438 (1.7%) Escherichia coli and 125 (3.98%) Klebsiella pneumoniae isolates were found to be producers of extended-spectrum beta-lactamase (ESBL) during 1995-2003 in southern Spain. There was a significant increase in the frequency of ESBL-producing E. coli isolates, from < 0.36% before 1999 to 4.8% in 2003, while the frequency of ESBL-producing K. pneumoniae isolates decreased during the same period. The most common ESBLs detected in K. pneumoniae were SHV type, whereas both CTX-M and SHV types were detected in E. coli. In addition, E. coli isolates showed greater clonal diversity (84 distinct REP-PCR patterns, compared with five in K. pneumoniae), fewer enzymes per isolate, and a higher number of isolates recovered from outpatients. These differences may have implications for the control measures that should be used for these two microorganisms.