Clinical features and risk factors for combined Klebsiella pneumoniae infection in patients with liver cirrhosis

Abstract

This article discusses the findings presented by Zhang et al. They analyzed the risk factors and clinical characteristics associated with Klebsiella pneumoniae infection in patients with liver cirrhosis treated at a hospital in Beijing. In this article, we focus on the connection between chronic kidney disease and the intestinal microbiota, and propose microbiota transplantation as a potential treatment for this patient group. We also examine an intriguing phenomenon related to hepatic encephalopathy, and provide insights into the future research.

Key Words: Klebsiella pneumoniae; Cirrhosis; Hospital infection; Chronic kidney disease; Fecal microbiota transplantation; Hepatic encephalopathy

Core Tip: Cirrhosis complicated by Klebsiella pneumoniae infection significantly affects patient prognosis. Distinct clinical features were observed between the death and improvement groups, and understanding these differences could enhance clinical management of this disease. Fecal microbiota transplantation holds promise as a potential treatment for these patients. Further in-depth studies are essential to improve our understanding of this disease and to optimize patient outcomes.

TO THE EDITOR

We extend our warm congratulations to Zhang et al[1] on the successful publication of their research in recently. The authors retrospectively analyzed clinical and laboratory data of cirrhotic patients infected with Klebsiella pneumoniae (K. pneumoniae), outlining patient characteristics and identifying risk factors for the infection. The study found an in-hospital K. pneumoniae infection rate of 19.44%, lower than the 30% reported in earlier research. The bloodstream is the most common infection site, followed by the respiratory tract, peritoneal space, and biliary tract. Risk factors for the infection included advanced age, prolonged hospitalization, gastrointestinal hemorrhage, low serum albumin level, while prophylactic antibiotics offered protection. Other infections, chronic diseases, and invasive procedures were independent risk factors. The study also revealed a higher prevalence of chronic kidney disease (CKD) in the death group compared to the improvement group, while the incidence of hepatic encephalopathy (HE) was surprisingly lower in the death group. We here discuss these findings to offer further insights into the management of this disease, and present our perspectives as follows.

Perspective 1: Impaired renal function exacerbates the systemic inflammatory response and promotes gut-derived bacterial translocation

Numerous studies have demonstrated that the uremic environment in patients with CKD compromises intestinal barrier function and alters the structure, composition, and functionality of the gut microbiota[2-6]. These disruptions promote bacterial and endotoxin translocation, triggering systemic inflammation[2-6]. Portal hypertension in patients with cirrhosis greatly facilitates bacterial translocation, increasing the risk of infections[7]. Several clinical studies have reported a significantly higher incidence of spontaneous bacterial peritonitis, urinary tract infections, and an increased mortality risk in cirrhotic patients with concurrent CKD[8]. Our team has been working on animal research of gut microbes and liver disease, and has found an association between gut microbes and liver fibrosis[9,10]. Fecal microbiota transplantation (FMT) has shown promise in animal research, demonstrating a reduction in liver fibrosis and cirrhosis in rat models[11]. Both animal and clinical trials suggest that FMT may improve cognitive function and overall prognosis in patients with HE[12,13]. However, the optimal dosage and safety of FMT remain unclear, and multicenter randomized controlled trials are being carried out to address these uncertainties[14]. Clinical trials have also indicated the potential of FMT in treating other chronic liver diseases, such as on-alcoholic fatty liver disease and alcoholic liver disease[15]. Moreover, FMT has been reported to improve treatment success rates for Clostridium difficile co-infections in cirrhotic patients, further supporting its therapeutic potential[16-18]. Recent clinical trials have suggested that FMT may slow CKD progression[19]. Based on the above evidence, we believe that FMT may improve clinical outcomes of patients in the death group. Our team is currently conducting a study to evaluate the effectiveness of FMT in patients with cirrhosis complicated by CKD. We hope that our findings will support our hypotheses.

Perspective 2: Is HE milder in the death group?

A substantial body of evidence supports the idea that infection and inflammation are key triggers of HE[20,21]. Hepatic HE is clinically classified as overt and mild based on clinical manifestations[22]. The incidence and severity of HE correlate with the degree of infection and inflammation, and resolving infection and inflammation alleviates the symptoms of HE[23,24]. Unexpectedly, the incidence of HE in the death group was significantly lower than in the improvement group, which contradicts prior evidence[1,23,24]. Previous studies have demonstrated that dysbiosis of the gut microbiota can increase the production of harmful substances, such as ammonia, which may then enter the brain via the bloodstream, contributing to the development of HE[25]. Based on this, we speculate that the widespread use of carbapenem antibiotics in the death group may have reduced the overgrowth of harmful bacteria in the gut, thereby decreasing ammonia production, and the incidence of HE. Additionally, the authors did not specify the exact proportion of patients in each group who developed overt HE. We believe that, theoretically, the death group should have a larger proportion of overt HE due to insufficient control of infection and inflammation. We hope that future large-scale studies will address these concerns.

Perspective 3: Large-scale, multicenter prospective cohort studies are required to validate and expand the findings of Zhang et al’s research

One of the limitations of Zhang et al’s study[1], as noted by the authors, is its single-center, retrospective design, which may restrict the persuasiveness of the findings. The study revealed that the rate of hospital-acquired K. pneumoniae infection in cirrhotic patients was 19.44%, which is lower than the 30% reported previously. The study was conducted with patients from a hospital in Beijing, one of the cities with the most abundant medical resources in China, which may explain the lower in-hospital infection rate observed in their study. Therefore, we suggest that factors such as liver function classification, HE grading, antibiotics resistance should be considered, and, if possible, patients with impaired renal function should be included in their future studies. In addition, it would be valuable to assess whether interventions aimed at improving renal function could lead to better clinical outcomes. Lastly, the clinical characteristics of cirrhotic patients with and without K. pneumoniae infection should be investigated to deepen our understanding and improve the management of this disease.

CONCLUSION

The rate of K. pneumoniae infections in cirrhosis patients is on the rise. Enhancing kidney function in those with renal impairment may improve clinical outcomes of the infected patients. FMT shows promise as a potential therapeutic approach. However, additional large-scale, multicenter, prospective studies are needed to confirm and expand these findings.