Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae

Abstract

Background: Bloodstream infections (BSIs) by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) are associated with high mortality. The aim of this study is to assess the relationship between time to administration of appropriate antibiotic therapy and the outcome of patients with BSI due to KPC-Kp hospitalized in intensive care unit (ICU). Methods: An observational study was conducted in the ICUs of two academic centers in Italy. Patients with KPC-Kp bacteremia hospitalized between January 2015 to December 2018 were included. The primary outcome was the relationship between time from blood cultures (BC) collection to appropriate antibiotic therapy and 30-day mortality. The secondary outcome was to evaluate the association of different treatment regimens with 30-day mortality and a composite endpoint (30-day mortality or nephrotoxicity). A Cox regression analysis to identify factors independently associated with 30-day mortality was performed. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results: A total of 102 patients with KPC-Kp BSI were included. The most common sources of infection were intraabdominal (23.5%), urinary tract (20.6%), and skin and skin structure (17.6%). The 30-day mortality was 45%. Median time to appropriate antibiotic therapy was shorter in patients who survived (8.5 h [IQR 1-36]) versus those who died (48 h [IQR 5-108], p = 0.014). A propensity score matching showed that receipt of an in vitro active therapy within 24 h from BC collection was associated with lower 30-day mortality (HR = 0.36, 95% CI: 0.188-0.690, p = 0.0021). At Cox regression analysis, factors associated with 30-day mortality were primary bacteremia (HR 2.662 [95% CI 1.118-6.336], p = 0.027), cardiovascular disease , p = 0.029), time (24-h increments) from BC collection to appropriate therapy (HR 1.382 [95% CI 1.132-1.687], p = 0.001), SOFA score (HR 1.122 [95% CI 1.036-1.216], p = 0.005), and age (HR 1.030 [95% CI 1.006-1.054], p = 0.012). Ceftazidime-avibactam-containing regimens were associated with reduced risk of composite endpoint (30-day mortality OR nephrotoxicity) (HR 0.231 [95% CI 0.071-0.745], p = 0.014) compared to colistin-containing regimens.Conclusions: Time to appropriate antibiotic therapy is an independent predictor of 30-day mortality in patients with KPC-Kp BSI. Appropriate antibiotic therapy should begin within 24 h from the collection of BC.

Adipose tissue is a predictor of 30-days mortality in patients with bloodstream infection caused by carbapenem-resistant Klebsiella pneumoniae 

“…Based on the recommended medication and antimicrobial susceptibility test of Klebsiella pneumoniae, antibiotic treatment options were divided into polymyxin Bbased (PMB-based) or tigecycline-based (TGC-based) combination therapy or others [13]. Early appropriate antibiotic therapy was the regard of administering 48 hours or less by the prescribing physicians after the rst culture of CRKP and including at least two active drugs [14][15][16]. Forchheim, Germany.…”

Narrow-Spectrum Antibacterial Agents—Benefits and Challenges

“…While several clinical syndromes are caused by individual bacterial species, the majority can be caused by multiple species, and indeed in some cases can be polymicrobial, with the added challenge of distinguishing pathogen from colonizer. Rapid initiation of appropriate treatment correlates with reduced mortality and improved clinical outcomes, a trend most notable with bloodstream infections and sepsis [ 19 , 20 , 21 , 22 ]. This becomes especially important when considering narrow-spectrum agents, as there is a need for rapid identification of the infecting pathogen, along with the susceptibility profile, to ensure the administration of an appropriate agent in a timely fashion.…”

Caracterización clínica, epidemiológica y microbiológica de bacteriemias producidas por enterobacterias resistentes a carbapenems en un hospital universitario de Córdoba, Argentina

“…Es decir, la escasez de opciones terapéuticas trae aparejada una notoria disminución en la posibilidad de acierto de las terapias empíricas vigentes. Considerando que en este tipo de infecciones graves resulta crítica la instauración inmediata de un tratamiento empírico inicial correcto para una evolución favorable 34 , es imperioso realizar esfuerzos para adaptar las terapias empíricas a esta nueva realidad epidemiológica, lo que a su vez debería ir de la mano de una definición más acabada de los factores de riesgo asociados.…”