Predictors of Mortality in Patients with Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae : Importance of Inadequate Initial Antimicrobial Treatment

Abstract

Bloodstream infections (BSI) caused by extended-spectrum ␤-lactamase (ESBL)-producing organisms markedly increase the rates of treatment failure and death. We conducted a retrospective cohort analysis to identify risk factors for mortality in adult in-patients with BSI caused by ESBL-producing Enterobacteriaceae (ESBL-BSI). Particular attention was focused on defining the impact on the mortality of inadequate initial antimicrobial therapy (defined as the initiation of treatment with active antimicrobial agents >72 h after collection of the first positive blood culture). A total of 186 patients with ESBL-BSI caused by Escherichia coli (n ‫؍‬ 104), Klebsiella pneumoniae (n ‫؍‬ 58), or Proteus mirabilis (n ‫؍‬ 24) were identified by our microbiology laboratory from 1 January 1999 through 31 December 2004. The overall 21-day mortality rate was 38.2% (71 of 186). In multivariate analysis, significant predictors of mortality were inadequate initial antimicrobial therapy (odds ratio [OR] ‫؍‬ 6.28; 95% confidence interval [CI] ‫؍‬ 3.18 to 12.42; P < 0.001) and unidentified primary infection site (OR ‫؍‬ 2.69; 95% CI ‫؍‬ 1.38 to 5.27; P ‫؍‬ 0.004). The inadequately treated patients (89 of 186 [47.8%]) had a threefold increase in mortality compared to the adequately treated group (59.5% versus 18.5%; OR ‫؍‬ 2.38; 95% CI ‫؍‬ 1.76 to 3.22; P < 0.001). The regimens most commonly classified as inadequate were based on oxyimino cephalosporin or fluoroquinolone therapy. Prompt initiation of effective antimicrobial treatment is essential in patients with ESBL-BSI, and empirical decisions must be based on a sound knowledge of the local distribution of pathogens and their susceptibility patterns.Bloodstream infections (BSI) caused by organisms that produce extended-spectrum ␤-lactamase (ESBLs) are associated with increased rates of treatment failure and death (1, 14, 15, 19, 22, 25, 28, 30-33, 38, 39, 41, 43, 46, 47, 50, 51). ESBLs are plasmid-mediated beta-lactamases that confer resistance to oxyimino cephalosporins and monobactams (7,33). In most cases, they are the result of mutations involving the classical TEM-1/TEM-2 and SHV-1 type ␤-lactamase genes, although exceptions to this rule (e.g., CTX-M ␤-lactamases) are becoming more and more common (13,27,33,39).Patients at high risk for infection by ESBL-producing organisms are often seriously ill, with histories of lengthy hospital stays and prolonged exposure to invasive medical devices and/or procedures (3,5,13,15,25,35,41,43,49). Prior exposure to antimicrobial therapy is also a well-recognized risk factor for acquisition of an ESBL-producing organism (25,35,43,47).The presence of an ESBL determinant significantly reduces the number of antimicrobial agents to which the infecting organism is susceptible (9). In addition, because of their nosocomial origin and the frequent links between ESBL genes and other resistance genes on the mobile DNA elements that are involved in their dissemination, ESBL producers often present complex multidrug-resistant phenotypes (7,27,33,42).Inade...

Factores asociados a infecciones urinarias producidas por enterobacterias productoras de &#946;-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.…”

“…Por otro lado, las sepsis producidas por estos microorganismos presentan mayor mortalidad que las producidas por cepas no productoras de BLEE 9,10 , describiéndose el inicio tardío de un antimicrobiano adecuado como el principal factor de riesgo relacionado con la mortalidad 11 .…”

“…En sepsis donde se aíslan estos microorganismos, el foco que con mayor frecuencia se identifica es el urinario [10][11][12] generando infecciones que presentan una mayor dificultad en el tratamiento y una estadía hospitalaria más prolongada 14,15 que las infecciones del tracto urinario (ITU) producidas por patógenos no productores de BLEE. El tratamiento en estos casos se dificulta ya que estas bacterias presentan resistencia a la mayoría de los antimicrobianos que se utilizan de forma empírica en el tratamiento de las ITU, como son las cefalosporinas y quinolonas 16 .…”

EPIDEMIOLOGICAL OBSERVATORY: spreading of ESBL and carbapenemase positive strains in the period between January 2007 - June 2012, at the Hospital - University Campus - Hospital “Luigi Sacco” in Milan

“…In un ottica di prevenzione e controllo delle infezioni da ceppi positivi per ESBL e per carbapenemasi, in particolar modo nei reparti di Lungo Degenza e di Terapia Intensiva, è più che mai importante un'identificazione accurata dei casi positivi (13). Inoltre una rapida identificazione di ESBL e carbapenemasi permette l'immediata applicazione di tutte le misure di prevenzione atte al contenimento e alla diffusione dell'infezione (20) (isolamento dei pazienti, controlli programmati sui Reparti a rischio etc…), nonché la possibilità di instaurare una corretta terapia farmacologica per evitare l'insorgere di nuove e più temibili resistenze (7,23). Nell'ultimo decennio anche in Italia la prevalenza delle ESBL ed enzimi correlati ha raggiunto livelli preoccupanti, secondo numerosi studi, infatti siamo passati dalla percentuale di Enterobacteriaceae produttrici di ESBL che nel 2003 si attestava intorno al 7% con una prevalenza del tipo CTX-M di circa il 60% (dato nazionale) (15,18), a dati più recenti del 16.9% di ceppi ESBL produttori che hanno confermato la tendenza all'aumento e ad un drastico incremento del tipo CTX-M, che ha raggiunto una prevalenza del 73% (9, 22).…”

Accuracy of in vitro susceptibility tests for carbapenemase-producing Gram-negative bacteria

“…carbapenem-resistant Acinetobacter, Pseudomonas and Enterobacteriaceae) are associated with significant morbidity (Carmeli et al, 2010;Kollef et al, 2008;Sabuda et al, 2008;Souli et al, 2008;Tumbarello et al, 2007;Zavascki et al, 2006) and pose therapeutic challenges for physicians. b-Lactamase-mediated carbapenem resistance is a particular problem because these bacteria are resistant to all penicillins, cephalosporins and carbapenems.…”