Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase- Producing Escherichia coli : Risk Factors for Inadequate Initial Antimicrobial Therapy

Abstract

Extended-spectrum-␤-lactamase (ESBL)-producing strains of Escherichia coli are a significant cause of bloodstream infections (BSI) in hospitalized and nonhospitalized patients. We previously showed that delaying effective antimicrobial therapy in BSI caused by ESBL producers significantly increases mortality. The aim of this retrospective 7-year analysis was to identify risk factors for inadequate initial antimicrobial therapy (IIAT) (i.e., empirical treatment based on a drug to which the isolate had displayed in vitro resistance) for inpatients with BSI caused by ESBL-producing E. coli. CI, 1.11 to 6.29; P ‫؍‬ 0.02). IIAT was the strongest risk factor for 21-day mortality and significantly increased the length of hospitalization after BSI onset. Our results underscore the need for a systematic approach to the management of patients with serious infections by ESBL-producing E. coli. Such an approach should be based on sound, updated knowledge of local infectious-disease epidemiology, detailed analysis of the patient's history with emphasis on recent contact with the health care system, and aggressive attempts to identify the infectious focus that has given rise to the BSI.Extended-spectrum ␤-lactamases (ESBLs) are a heterogeneous group of plasmid-mediated bacterial enzymes that confer significant resistance to oxyimino cephalosporin and monobactam antimicrobials (8,28,30). Throughout the world, increasing attention is being focused on the growing involvement of ESBL-producing strains of Escherichia coli in serious infections of hospitalized and nonhospitalized patients (3, 26, 28-30, 34, 35, 39, 45). This trend is due largely to the emergence of CTX-M type ESBLs, a rapidly expanding group of enzymes that are being encountered with increasing frequency, especially in E. coli (24,25,35,36,48). They are encoded by transferable plasmid genes captured from the chromosomes of Kluyvera spp. (6, 36). Acquisition of any ESBL determinant reduces the number of antimicrobial agents to which the microorganism is susceptible (18,25,38). This problem is compounded by the fact that ESBL producers often carry other antimicrobial resistance genes, which are located near the bla gene on the mobile DNA elements that are involved in their dissemination. In these cases, there is a substantial risk that the infecting pathogen will be resistant to the empirically prescribed antimicrobial treatment.In a previous study we found that failure to provide adequate antimicrobial therapy in the initial stages of bloodstream infections (BSI) caused by ESBL-producing Enterobacteriaceae was associated with a strong increase in the risk of 21-day mortality (45). These findings are consistent with those of other investigators (1,18,19,35,39,40). However, much less is known about the specific factors that increase the likelihood of ineffective empirical treatment in these cases (18). Identification of risk factors that are predictive of resistance to empirically prescribed antimicrobials should facilitate attempts to define more-effective managemen...

Emergence in Spain of a Multidrug-Resistant Enterobacter cloacae Clinical Isolate Producing SFO-1 Extended-Spectrum β-Lactamase

“…The multivariate analysis revealed that the prior administration of ␤-lactam antibiotics, tracheostomy, prior hospitalization, and chronic renal failure were statistically associated with SFO-1-producing E. cloacae acquisition. Most of these risk factors were previously described in the literature (17,19,28,(40)(41)(42). For patients with chronic renal failure, urinary tract pathology is increased, so chronic renal failure may indirectly favor urinary tract infection or colonization by EbSF as an important risk factor.…”

Factores asociados a infecciones urinarias producidas por enterobacterias productoras de β-lactamasas de espectro extendido: una cohorte prospectiva

“…La principal utilidad de predecir una infección por BLEE es que la cobertura antimicrobiana inapropiada durante la fase empírica en espera de los cultivos se asocia a mayor mortalidad en pacientes con infecciones graves por BLEE 11,[29][30][31][32][33] . El uso de un modelo predictor puede entregar una información útil para la toma de decisiones, más aún con variables de fácil acceso en la clínica, teniendo en cuenta el de-escalamiento terapéutico una vez obtenidos los cultivos.…”

Characterisation of extended-spectrum β-lactamases among Klebsiella pneumoniae isolates causing bacteraemia and urinary tract infection in Mozambique

“…ESBL-producing microorganisms are also often resistant to other commonly available antibiotics, such as fluoroquinolones. Knowledge of the prevalence and characterisation of ESBLs is critical for defining local empirical strategies for the treatment of infections [4]. Although in Africa the presence of ESBLs has increasingly been reported [5][6][7], data in Mozambique remain limited.…”