Epidemiology and outcomes of bloodstream infection in patients with cirrhosis Michele Bartoletti 1 , Maddalena Giannella 1 , Paolo Caraceni 1 , Marco Domenicali 1 , Simone Ambretti 2 , Sara Tedeschi 1 , Gabriella Verucchi 1 , Lorenzo Badia 1 , Russell E. Lewis 1 , Mauro Bernardi 1 , Pierluigi Viale 1,⇑ 1 Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; 2 Microbiology Unit, S. Orsola-Malpighi Hospital Bologna, Italy Background & Aims: Bloodstream infections (BSIs) in cirrhotic patients are 10-fold more common than in non-cirrhotic patients and increasingly caused by resistant pathogens. We examined 162 BSI episodes in cirrhotic patients to describe the etiology and risk factors for 30-day mortality. Methods: We retrospectively analyzed all consecutive BSIs in patients with liver cirrhosis at our 1350-bed teaching hospital (January 2008 to June 2012). Cox-proportional hazard regression was used to analyze the impact of disease and treatment-related variables on the crude 30-day mortality. Results: BSI episodes were identified in 162 patients, including 29 mixed infections. Most of episodes were classified as hospital acquired or healthcare associated (93%). Gram-negative bacteria (GNB), Gram-positive bacteria and Candida spp. caused 64%, 38%, and 10% of episodes, respectively. GNB were classified as multi-drug resistant (MDR) and extensively drug resistant (XDR) in 25% and 21% of cases, respectively. The overall crude 30-day mortality rate was 29%. Four risk factors were indepen- dently associated with 30-day crude mortality: worsening of MELD score from baseline (the last MELD score available in the 2 weeks prior BSI) to that at BSI onset (HR 1.11 per point increase, 95% CI 1.07–1.15, p <0.0001), spontaneous bacterial peritonitis as BSI source (HR 4.42, 2.04–9.54, p = 0.002), sepsis grading (HR 2.18, 1.39–3.43, p = 0.0007), and inappropriate antibiotic therapy within 24 h from blood cultures (HR 2.82, 1.50–5.41, p = 0.002). Conclusion: An increasing proportion of BSIs in cirrhotic patients are caused by resistant GNB and Candida spp. Accurate evaluation of risk factors for mortality may improve early appropriate ther- apeutic management. Ó 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Introduction Liver cirrhosis is the 10th most common cause of death in the Western world [1]. Among the complications of the End Stage Liver Disease (ESLD), infection represents the leading cause of acute decompensation [2,3] and is associated with a high mortal- ity ranging from 12% to 52% [4,5]. Bloodstream infections (BSIs) are a common complication in patients with ESLD, affecting 4–21% of patients with cirrhosis [2], making them 10 times more common than in non-cirrhotic patients [6]. Alterations in intestinal permeability induced by portal hypertension, prolonged intestinal transit, and bacterial overgrowth may facilitate a high rate of bacterial translocation from the gut into the bloodstream [7,8]. Cirrhotic patients who develop a BSI are 2.4 to 6.3 more likely to die within 30-days compared to non-cirrhotic patients with similar infections [9]. In four epidemiological studies of BSI, liver cirrhosis was a consis- tent variable independently associated with mortality [10–13]. However, few studies have examined the specific risk factors for BSI-mortality in patients with ESLD. ESLD patients are also highly prone to infections with multi- drug-resistant (MDR) microorganisms, given the frequency of hospital admissions and antibiotic prophylaxis administered for bacterial peritonitis [4]. The two largest studies on the epidemi- ology and outcome of BSI in cirrhotic patients, however, were published prior to widespread fluoroquinone and cephalosporin resistance, and currently emerging carbapenem resistance among Enterobacteriaceae. Cirrhosis may also be a unique risk factor for invasive candidiasis [14], although definitive studies establishing this link are lacking. The purpose this study was to: (i) describe the contemporary etiology of BSI in cirrhotic patients, and (ii) examine independent risk factors for all-cause patient mortality within 30-days of the positive blood cultures. Patients and methods Study design We performed a retrospective cohort study of unselected adult (P18 years) patients admitted to our hospital with diagnosis of cirrhosis who developed a Journal of Hepatology 2014 vol. xxx j xxx–xxx Keywords: Bloodstream infection; Liver cirrhosis; Multi-drug resistance; Extre- mely-drug resistance; Candidemia; Inappropriate empirical therapy; Mortality. Received 26 September 2013; received in revised form 7 March 2014; accepted 17 March 2014 ⇑ Corresponding author. Address: Infectious Disease Unit, Policlinico S. Orsola- Malpighi, Via Massarenti, 11, 40138 Bologna, Italy. E-mail address: pierluigi.viale@unibo.it (P. Viale). Research Article Please cite this article in press as: Bartoletti M et al. Epidemiology and outcomes of bloodstream infection in patients with cirrhosis. J Hepatol (2014), http://dx.doi.org/10.1016/j.jhep.2014.03.021