Zhang Y, Zhao H, Ji SB, Xing HC. Clinical analysis of Klebsiella pneumoniae infection in patients with liver cirrhosis in Beijing. World J Hepatol 2024; 16(12): 1441-1449 [DOI: 10.4254/wjh.v16.i12.1441]
Corresponding Author of This Article
Hui-Chun Xing, PhD, Professor, Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Peking University Ditan Teaching Hospital, No. 8 Jingshun East Street, Chaoyang District, Beijing 100015, China. hchxing@sohu.com
Research Domain of This Article
Infectious Diseases
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Yu Zhang, Shi-Bo Ji, Hui-Chun Xing, Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Peking University Ditan Teaching Hospital, Beijing 100015, China
Hong Zhao, Center of Liver Diseases Division 1, Beijing Ditan Hospital, Capital Medical University, Peking University Ditan Teaching Hospital, Beijing 100015, China
Author contributions: Guarantor of the article Xing HC accepts full responsibility for the conduct of the study, has access to the data, and has control of the decision to publish; Zhang Y proposed the concept, contributed to the study design, wrote the manuscript, and performed statistical analysis; Zhao H contributed to the study design and performed statistical analysis, and data collection; Ji SB contributed to data collection.
Supported by the National Key R & D Program of China, No. 2021YFC2301800.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Beijing Ditan Hospital, No. JDLZ[2017]-001.
Informed consent statement: Written informed consent was obtained from all participants.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hui-Chun Xing, PhD, Professor, Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Peking University Ditan Teaching Hospital, No. 8 Jingshun East Street, Chaoyang District, Beijing 100015, China. hchxing@sohu.com
Received: June 4, 2024 Revised: October 7, 2024 Accepted: November 12, 2024 Published online: December 27, 2024 Processing time: 178 Days and 6.9 Hours
Abstract
BACKGROUND
The incidence of Klebsiella pneumoniae (K. pneumoniae) infection in patients with cirrhosis has been increasing over recent years, posing certain difficulties in clinical treatment.
AIM
To analyze the clinical features of patients with liver cirrhosis and identify the risk factors to help the early diagnosis and treatment of these diseases.
METHODS
Clinical data and laboratory tests were collected from 72 patients with cirrhosis confirmed by secretion or blood culture of K. pneumoniae infection at Beijing Ditan Hospital, Capital Medical University, between May 2016 and October 2018. Data from hospitalized patients with liver cirrhosis and K. pneumoniae infections, including age, sex, antimicrobial use, length of stay, site of infection, distribution of pathogenic bacteria, complications, invasive operations, laboratory indicators, treatment, and clinical regression, were extracted and retrospectively analyzed. Clinical data and biochemical values were included in the multivariate logistic regression analysis.
RESULTS
A total of 52 men and 20 women, with an age range from 29 to 85 years and an average age of 57.7 ± 12.54, were analyzed. The incidence of hospital K. pneumoniae infection in patients with cirrhosis was approximately 19.44%. The most common the infection site was the bloodstream, followed by the respiratory tract, abdominal cavity, and biliary tract. Risk factors for infection were old age, long hospital stays, gastrointestinal bleeding, and low serum albumin levels, while prophylactic antibiotics were protective factors. The multivariate analysis suggested that other infections, chronic diseases, and invasive procedures were independent factors.
CONCLUSION
In clinical practice, the length of hospital stays should be shortened as much as possible, invasive operations should be reduced, antibiotics should be rationally used, and the patients’ liver function should be timely improved. This is of great significance for reducing the incidence of hospital infection.
Core Tip: Patients with cirrhosis are susceptible to infections, particularly nosocomial infections, due to severe impairment of liver function and reduced immune function. The study profoundly expands our knowledge about the clinical feature of the Klebsiella pneumoniae (K. pneumoniae) infection with chronic liver disease. And this is the first study of its kind to be published in China on K. pneumoniae infection in individuals with liver cirrhosis. The findings of this investigation are reliable and show a considerable difference.
Citation: Zhang Y, Zhao H, Ji SB, Xing HC. Clinical analysis of Klebsiella pneumoniae infection in patients with liver cirrhosis in Beijing. World J Hepatol 2024; 16(12): 1441-1449
Cirrhosis is a late-stage liver disease. Patients with cirrhosis are susceptible to infections, particularly nosocomial infections, owing to severe impairment of liver function and reduced immune function[1]. Studies have shown that the mortality rate of patients with cirrhosis and nosocomial infections is 15%, significantly higher than the 7% mortality rate for uninfected patients[2,3]. Furthermore, nosocomial infections not only prolong the hospital stay of these patients but also significantly affect their prognosis[4]. Klebsiella pneumoniae (K. pneumoniae) is a major pathogen causing hospital-acquired infections, accounting for over 20% of all hospital-acquired infections with gram-negative bacilli[5-7]. In immunocompromised individuals, classical K. pneumoniae strains can cause serious infections, such as pneumonia, meningitis, liver abscesses, wound infections, and sepsis[8-10]. They can also increase drug resistance[11]. In 2017, the World Health Organization published a list of pathogens for which new antimicrobial treatments are urgently required. Within this list, "ESKAPE” (Enterococcus faecalis, Staphylococcus aureus, K. pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were designated as having “priority status”[12,13]. The incidence of bacteremia in patients with cirrhosis has been increasing over recent years, posing certain difficulties in clinical treatment[13,14]. The current study summarized and analyzed the clinical and laboratory examination characteristics of patients with end-stage liver disease combined with K. pneumoniae infection to help with the early diagnosis and treatment of such diseases.
MATERIALS AND METHODS
Patients
Clinical data and laboratory tests were collected from 72 patients with cirrhosis confirmed by secretion or blood culture of K. pneumoniae infection at Beijing Ditan Hospital, Capital Medical University, from May 2016 to October 2018. All patients met the diagnostic criteria for cirrhosis, as diagnosed according to the viral hepatitis control program[8]. The laboratory confirmed the pathogenic diagnosis. Alcoholic cirrhosis was diagnosed according to the guidelines for the treatment of alcoholic liver disease[9], and primary biliary cirrhosis was diagnosed according to the consensus on the diagnosis and treatment of primary biliary cirrhosis (also known as primary biliary cholangitis)[10]. Finally, 52 men and 20 women were included in the analysis (age ranged from 29 to 85 years, with an average of 57.7 ± 12.54). Additionally, 12 deaths (16.67%) were observed. This study was approved by the Ethics Committee of the Beijing Ditan Hospital, Capital Medical University, and written informed consent was obtained from all participants.
Clinical information
Clinical information, including age, sex, antimicrobial use, length of stay, site of infection, distribution of pathogenic bacteria, complications, invasive operations, laboratory indicators, treatment, and clinical regression, were collected from all patients using the hospital’s electronic medical record system.
Statistical analysis
The data were collated using Excel 2003, and the comparison of the differences in the indicators was analyzed using SPSS 22.0. The measurement data were expressed as mean ± SD or median (interquartile range), and the count data were expressed as n (%). The comparison of normally distributed measurement data between the two groups was performed using the two independent sample t-test, while the comparison of count data between the two groups was performed using the χ2 test. The analysis of influencing factors was performed using dichotomous logistics regression. A P value < 0.05 represented statistical significance.
RESULTS
Prevalence and site of nosocomial infections
Nosocomial infections occurred in 14 out of the 72 patients, with an incidence of 19.44%. The sites of infection were bloodstream in 36 cases (50.00%), respiratory tract in 13 cases (18.05%), chest in 11 cases (15.27%), abdomen in eight cases (11.11%), biliary tract in five cases (6.94%), and urinary tract in four cases (5.56%).
Single factor analysis affecting prognosis for improved discharge
The χ2 test was used to compare the differences in gender, history of hypertension, history of diabetes, history of lung disease, history of heart disease, history of chronic kidney disease, history of neurological disease, history of malignancy, history of heavy alcohol consumption, history of hospitalization within 30 days, history of antibiotic exposure within 15 days, and blood glucose > 7.8 between the death group and the group discharged in good condition. Chronic kidney disease (25% vs 3.30%; χ2 = 7.264, P = 0.007) and a history of heavy drinking (58.3% vs 23.3%; χ2 = 5.929, P = 0.015) were significantly higher in the death group than in the well-discharge group (Table 1).
Table 1 Comparison of the underlying information, n (%).
The χ2 test was used to compare differences in the site of infection between the death and discharge groups. However, no differences were found between groups (χ2 = 1.806, P = 0.771). Nevertheless, the χ2 analysis showed a higher carbapenem resistance (25% vs 1.7%; χ2 = 10.376, P = 0.001), a higher rate of co-infection with other bacteria (41.7% vs 8.3%; χ2 = 9.290, P = 0.002), and a higher incidence of liver failure (91.7% vs 18.3%; χ2 = 25.344, P < 0.001), but also lower occurrence of hepatic encephalopathy (33.3% vs 71.7%; χ2 = 22.851, P = 0.001) in the death group than in the well-discharge group (Table 2).
Table 2 Comparison of the disease information, n (%).
Moreover, the χ2 test suggested a lower rate of non-admission to the intensive care unit, a higher rate of arteriovenous placement/tracheal intubation/catheterization, higher use of carbapenems and lower use of vancomycin in the death group than in the well-discharge group (Table 3).
Table 3 Comparison of the treatment information, n (%).
A two-independent sample t-test was used to compare and analyze the differences in various measures between the death and the improved discharge groups. The results of the analysis showed significant differences in diastolic blood pressure (t = -2.385, P = 0.020), total bilirubin (TBIL) (t = 5.013, P < 0.001), direct bilirubin (t = 4.287, P < 0.001), albumin (ALB) (t = -2.144, P = 0.035), and International normalized ratio (t = 5.365, P < 0.001; Table 4).
Logistic regression analysis affecting prognosis for improved discharge
Whether or not the prognosis was improved, discharge was used as the dependent variable Y (Y = 0, death; Y = 1, improved), and each variable that was significantly different between the two groups was used as the independent variable X. Dichotomous logistics regression was used to screen the influencing factors using stepwise regression, and the final analysis showed that chronic kidney disease [B = -4.060, odds ratio (OR) = 0.017], comorbid other bacterial infections (B = -2.715, OR = 0.066), liver failure, arterial-venous placement, and TBIL were the main factors affecting the prognosis for improvement. The results of the final analysis showed that chronic kidney disease (B = -4.060, OR = 0.017), co-infection with other bacteria (B = -2.715, OR = 0.066), liver failure (B = -3.705, OR = 0.025), and higher TBIL (B = -0.008, OR = 0.992) were the main factors affecting the prognosis for discharge (Table 5).
Table 5 Logistics regression analysis of the influence on prognosis.
The number of patients with chronic liver disease in China is increasing, and many of these patients gradually progress to cirrhosis. Patients with cirrhosis are immunocompromised, and co-infection is one of the common complications in these patients, which can seriously affect their prognosis and increase the burden of medical costs. Statistical analysis shows that the most common pathogenic bacteria are gram-negative bacilli (59.7%), including Escherichia coli (E. coli) (31.09%) and K. pneumoniae (9.06%)[15]. Klebsiella spp. includes five species, among which K. pneumoniae is the most pathogenic to humans. It is 0.5-0.8 μm × 1-2 μm in size, with thick pods and hairs, without budding and flagella, and with O and K antigens. In recent years, K. pneumoniae has become a common pathogen causing hospital-acquired infections. This infection is often observed in patients with long hospital stays, severe underlying diseases, and immunocompromised patients using glucocorticoids or chemotherapy drugs. K. pneumoniae is found in the human respiratory and intestinal tracts. When the body's immunity decreases, it can cause multi-site infections, such as lung, intracranial, urinary tract, intestinal, and bloodstream infections. In severe cases, sepsis, shock, and multi-organ failure can endanger patients' lives[16,17].
In this study, 14 patients (19.44%) with K. pneumoniae sepsis had nosocomial infections. Therefore, focusing on reducing the incidence of nosocomial infections is an important preventive strategy to reduce K. pneumoniae infections. The data of the current study suggested that the incidence of nosocomial K. pneumoniae infection in patients with cirrhosis was approximately 19.44%, which is slightly lower than the approximately 30% reported in previous studies[18,19]. Patients with cirrhosis are at high risk of infection because they are at the end stage of liver disease owing to the development of hypersplenism and hypoproteinemia and reduced phagocytosis of liver macrophages, significantly reduced cellular and humoral immune function of the body, and the formation of portal hypertension, bruising, edema and increased permeability of the intestinal wall. This leads to dysbiosis of the intestinal flora and easier invasion of bacteria into the abdominal cavity through the intestinal wall[20,21]. In this study, the most common sites of complications of hospital-acquired infections in patients with cirrhosis were the bloodstream and respiratory tract, followed by the abdominal and biliary tract, which is consistent with relevant reports[22]. The study results suggest that the factors associated with hospital-acquired infections in patients with cirrhosis are complex, with older age, longer hospital stay, gastrointestinal bleeding, and low serum ALB levels being high-risk factors for infection, and prophylactic antibiotics being protective factors for infection. Longer hospital stays increase the risk of exposure to pathogenic bacteria[23-25] and cross-infection[26].
In recent years, with the extensive development of invasive procedures and with the widespread use of carbapenems, an increasing number of carbapenem-resistant K. pneumoniae have been reported worldwide, posing a serious threat to public health. The China Drug Resistance Surveillance Network showed that K. pneumoniae had the second highest isolation rate among gram-negative bacteria in 2021, making it the bloodstream infection pathogen after E. coli. Carbapenems are the last class of lactam drugs for the treatment of gram-negative bacteria and are the first-line antibiotics for treating multidrug-resistant K. pneumoniae infections[27]. Studies have shown that the resistance rate of K. pneumoniae to imipenem and meropenem has increased significantly. Its high virulence and the drug resistance have led to high morbidity and mortality, posing a serious threat to treatment and infection control. Hasan has isolated and identified gram-negative bacteria from 100 of 250 samples collected from burn patients (40%), of which 66 (66%) were carbapenem resistant[28]. Patients with decompensated cirrhosis have a higher risk of infection following the development of gastrointestinal bleeding that causes changes in pH and disrupts the micro-ecological balance in the gut, leading to an overgrowth of intestinal bacteria and dysbiosis of the intestinal flora and an increased risk of infection in patients[29]. Low serum ALB indicates poor liver function and a significantly reduced ability to fight pathogenic bacteria[29]. National and international opinions consider hypoproteinemia as a risk factor for complicating infections in cirrhosis, while prophylactic antibiotics may reduce the incidence of infection[30-32]. Multifactorial analysis suggests that co-infections, chronic diseases, and invasive operations are all independent factors. Since this research was conducted at a single center retrospectively, the external validation cohort was not accessible. Nonetheless, this is the first study of its kind to be published in China on K. pneumoniae infection in individuals with liver cirrhosis. The findings of this investigation are reliable and show a considerable difference. A multi-center prospective study with a larger sample size is now being conducted to thoroughly analyze this finding in the future.
CONCLUSION
Therefore, patients' length of stay should be shortened, invasive operations should be reduced, antibacterial drugs should be applied, and liver function should be promptly improved in clinical practice, as this could significantly reduce the incidence of nosocomial infections in patients. Currently, drug resistance in K. pneumoniae has become an important health problem that cannot be ignored and requires more attention and research. This study has several limitations. First, because this study was performed in a single center and retrospectively, an external validation cohort was not available. Second, as a retrospective study, there is a lack of drug resistance test data of the included patients. A further multicenter prospective study with a larger sample size is currently in progress to validate our study results.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade B
Novelty: Grade B
Creativity or Innovation: Grade B
Scientific Significance: Grade B
P-Reviewer: Babani SA S-Editor: Li L L-Editor: A P-Editor: Zhao YQ
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