Risk Factors and Prognosis of Nosocomial Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Escherichia coli

Abstract

Extended-spectrum-␤-lactamase (ESBL)-producing Escherichia coli (ESBLEC) is an increasing cause of community and nosocomial infections worldwide. However, there is scarce clinical information about nosocomial bloodstream infections (BSIs)caused by these pathogens. We performed a study to investigate the risk factors for and prognosis of nosocomial BSIs due to ESBLEC in 13 Spanish hospitals. Risk factors were assessed by using a case-control-control study; 96 cases (2 to 16% of all nosocomial BSIs due to E. coli in the participating centers) were included; the most frequent ESBL was CTX-M-14 (48% of the isolates). We found CTX-M-15 in 10% of the isolates, which means that this enzyme is emerging as a cause of invasive infections in Spain. By repetitive extragenic palindromic sequence-PCR, most isolates were found to be clonally unrelated. By multivariate analysis, the risk factors for nosocomial BSIs due to ESBLEC were found to be organ transplant (odds ratio [OR] ‫؍‬ 4.8; 95% confidence interval [CI] ‫؍‬ 1.4 to 15.7), the previous use of oxyimino-␤-lactams (OR ‫؍‬ 6.0; 95% CI ‫؍‬ 3.0 to 11.8), and unknown BSI source (protective; OR ‫؍‬ 0.4; 95% CI ‫؍‬ 0.2 to 0.9), and duration of hospital stay (OR ‫؍‬ 1.02; 95% CI ‫؍‬ 1.00 to 1.03). The variables independently associated with mortality were a Pitt score of >1 (OR ‫؍‬ 3.9; 95% CI ‫؍‬ 1.2 to 12.9), a high-risk source (OR ‫؍‬ 5.5; 95% CI ‫؍‬ 1.4 to 21.9), and resistance to more than three antibiotics, apart from penicillins and cephalosporins (OR ‫؍‬ 6.5; 95% CI ‫؍‬ 1.4 to 30.0). Inappropriate empirical therapy was not associated with mortality. We conclude that ESBLEC is an important cause of nosocomial BSIs. The previous use of oxyimino-␤-lactams was the only modifiable risk factor found. Resistance to drugs other than penicillins and cephalosporins was associated with increased mortality.Gram-negative organisms are an important cause of nosocomial bloodstream infections (BSIs) (33), particularly when the source of the BSI is the urinary, respiratory, or gastrointestinal tract. Recently, the reemergence of Gram-negative organisms as a cause of primary BSIs has also been reported (1). In the United States, Escherichia coli is the fifth most common cause of nosocomial BSIs and is the first most common cause among Gram-negative organisms, and BSIs caused by E. coli are reported to be associated with a crude mortality rate of 22% (34); in Spain, it is the second most common cause of nosocomial BSIs (23).In recent years, extended-spectrum ß-lactamases (ESBLs), particularly those of the CTX-M family, have spread worldwide among E. coli strains inside and outside hospitals (20,26); consequently, the prevalence of BSIs caused by ESBL-producing E. coli has significantly increased (24, 28). ESBLs confer resistance to penicillins and cephalosporins and are frequently associated with resistance to fluoroquinolones, aminoglycosides, and trimethoprim-sulfamethoxazole (18); thus, ESBLproducing microorganisms are frequently truly multidrug resistant. Both antibiotic resistance a...

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