The Risk of Clostridioides difficile Infection in Cirrhotic Patients Receiving Norfloxacin for Secondary Prophylaxis of Spontaneous Bacterial Peritonitis—A Real Life Cohort

Abstract

Background and Objectives: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis. Antibiotic prophylaxis is effective but can lead to an increased incidence of Clostridioides difficile infection (CDI). The aim of this study was to evaluate the incidence of CDI and the risk factors in cirrhotic patients with a previous episode of SBP receiving norfloxacin as secondary prophylaxis. Materials and Methods: We performed a prospective, cohort study including patients with liver cirrhosis and SBP, successfully treated over a 2-year period in a tertiary university hospital. All the patients received secondary prophylaxis for SBP with norfloxacin 400 mg/day. Results: There were 122 patients with liver cirrhosis and SBP included (mean age 57.5 ± 10.8 years, 65.5% males). Alcoholic cirrhosis was the major etiology accounting for 63.1% of cases. The mean MELD score was 19.7 ± 6.1. Twenty-three (18.8%) of all patients developed CDI during follow-up, corresponding to an incidence of 24.8 cases per 10,000 person-years. The multivariate Cox regression analysis demonstrated that alcoholic LC etiology (HR 1.40, 95% CI 1.104–2.441, p = 0.029) and Child-Pugh C class (HR 2.50, 95% CI 1.257–3.850, p = 0.034) were independent risk factors for CDI development during norfloxacin secondary prophylaxis. The development of CDI did not influence the mortality rates in cirrhotic patients with SBP receiving norfloxacin. Conclusions: Cirrhotic patients with SBP and Child-Pugh C class and alcoholic liver cirrhosis had a higher risk of developing Clostridioides difficile infection during norfloxacin secondary prophylaxis. In patients with alcoholic Child-Pugh C class liver cirrhosis, alternative prophylaxis should be evaluated as SBP secondary prophylaxis.

Early Diagnosis and Prevention of Infections in Cirrhosis

“…Norfloxacin prophylaxis is reported to be associated with three major adverse outcomes: increased risk of infections by gram-positive organisms [16], increased risk of Clostridium difficile infections [105], and lastly, increased risk of development of MDROs [16,106,107].…”

Clostridioides difficile Infection in Liver Cirrhosis: A Concise Review

“…In a small prospective study conducted in Romania in 2015, among 200 Child-Pugh B and C patients hospitalized for decompensation, 9% developed CDI during their hospitalization [ 36 ]. Another prospective study, also conducted in a Romanian tertiary hospital, included 122 patients with cirrhosis and spontaneous bacterial peritonitis (SBP) who also received norfloxacin as secondary prophylaxis from 2018 to 2019, in which 18.8% of the population presented with CDI (median follow-up of 7 months) [ 37 ]. In a further over six years study, CDI incidence was 11.8% in 388 cirrhotic patients, and notably, 30.8% of the cirrhotic patients received the antibiotic rifaximin to prevent HE [ 38 ].…”

“…Age >65 years, multiple hospitalizations, inpatient stays >20 days, hypoproteinemia, Clostridioides difficile colonization (CDC), HE, antibiotic, and proton pump inhibitors (PPIs) use were found to be associated with the development of CDI in a study conducted to identify risk factors for CDI in patients with cirrhosis [ 45 ]. Furthermore, many studies have also reported risk factors for CDI development [ 22 , 23 , 30 , 32 , 35 , 37 , 39 , 46 – 49 ] although heterogeneity exists between studies. The risk factors concluded from these studies are largely in line with the previous research and can be broadly classified into several categories, namely medications (PPIs, antibiotics, etc.…”

“…Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of CDI [ 53 ] although no studies have shown that this etiology increases CDI risk in cirrhosis. A few studies suggest that alcoholic etiology is a risk factor for CDI [ 37 , 47 ]. Lastly, medication use such as rifaximin and PPIs shows conflicting results in this context.…”

“…Extensive publications have reported increased mortality of CDI in patients with cirrhosis [ 22 , 23 , 31 , 33 , 34 , 36 , 39 , 44 , 47 , 48 , 59 ]. However, one study has not established the impact of CDI development on mortality in patients with cirrhosis and SBP receiving norfloxacin as secondary prophylaxis [ 37 ]. Norfloxacin has been shown in in vitro studies as a quinolone to down-regulate inflammation, which may be a protective effect [ 60 , 61 ].…”