The Impact of Infection by Multidrug-resistant Agents in Patients With Cirrhosis

A Multicenter Prospective Study

Francesco Salerno; Mauro Borzio; Claudia Pedicino; Rosa Simonetti; Angelo Rossini; Sergio Boccia; Irene Cacciola; Andrew K. Burroughs; Matteo A. Manini; Vincenzo La Mura; Paolo Angeli; Mauro Bernardi; Daniela Dalla Gasperina; Elena Dionigi; Clara Dibenedetto; Milena Arghittu


Liver International. 2017;37(1):71-79. 

In This Article

Abstract and Introduction


Background & Aims: Bacterial strains resistant to antibiotics are a serious clinical challenge. We assessed the antibiotic susceptibility of bacteria isolated from infections in patients with cirrhosis by a multicentre investigation.

Results: Three hundred and thirteen culture-positive infections (173 community acquired [CA] and 140 hospital acquired [HA]) were identified in 308 patients. Urinary tract infections, spontaneous bacterial peritonitis and bacteremias were the most frequent. Quinolone-resistant Gram-negative isolates were 48%, 44% were extended-spectrum beta-lactamase producers and 9% carbapenem resistant. In 83/313 culture-positive infections (27%), multidrug-resistant agents (MDRA) were isolated. This prevalence did not differ between CA and HA infections. MDRA were identified in 17 of 37 patients on quinolone prophylaxis, and in 46 of 166 not on prophylaxis (45% vs 27%; P<.03). In 287 cases an empiric antibiotic therapy was undertaken, in 37 (12.9%) this therapy failed. The in-hospital mortality rate of this subset of patients was significantly higher compared to patients who received an effective broad(er)-spectrum therapy (P=.038). During a 3-month follow-up, 56/203 culture-positive patients (27.6%) died, 24/63 who have had MDRA-related infections (38%) and 32/140 who have had antibiotic-susceptible infections (22.8%) (P=.025). Multivariate analysis disclosed MDRA infection, age, hepatocellular carcinoma, bilirubin, international normalized ratio and the occurrence of portal hypertension-related complications independent predictors of death.

Conclusions: Infection by MDRA is frequent in patients with cirrhosis and the prognosis is severe, especially in patients unresponsive to empiric antibiotic therapy.


In cirrhosis bacterial infections are often associated with variceal bleeding, hepatic encephalopathy, hyponatremia and renal failure.[1–8] A meta-analysis including 11 987 cirrhotics demonstrated that bacterial infections confer a four-fold mortality increase.[9] These data underline the importance of an early diagnosis of bacterial infections to promptly undertake an effective antibiotic therapy before bacterial cultures results.[10]

Local bacterial strains sensibly influence the success of an empiric antibiotic therapy. Resistance to common antibiotics makes the empiric therapy fail and worsens the pathological process.

Recently, an increase in multidrug-resistant agents (MDRA) has been observed.[11–17] This hampers the empiric antibiotic therapy[18] and compromises prognosis. Many single-centre studies investigated this issue[11–14,17] frequently by including patients in intensive care units (ICU).[12,13] Hence, those results are representative of most severely ill patients. Other studies were retrospective,[16] with the risk of selection bias. In contrast, investigating antibiotic susceptibility deserves multicentre prospective inclusion of all patients regardless of aetiology and disease severity.[19] Moreover, ICU patients should be separated owing to the unique ICUs microbiological environment.

We made a multicentre prospective investigation on bacterial infections occurring in patients with cirrhosis by considering the in vitro susceptibilities to antibiotics, the prevalence of MDRA. Second, we evaluated the effect of different variables on the short-period clinical outcomes.