Journal of Pharmacovigilance

Epidemiological Characteristics and Prognosis of 103 Cases of CRKP in a General Hospital in Guangzhou

Shuai Zu, Hengrui Zhao, Minghui Wen, Lei Zheng and Xiumei Hu^* Department of Laboratory Medicine, Nanfang Hospital Southern Medical University, Guangzhou, China
^*Correspondence: Xiumei Hu, Department of Laboratory Medicine, Nanfang Hospital Southern Medical University, China, Email:

Received: 10-Nov-2022, Manuscript No. JP-22-18723; Editor assigned: 14-Nov-2022, Pre QC No. JP-22-18723; Reviewed: 28-Nov-2022, QC No. JP-22-18723; Revised: 05-Dec-2022, Manuscript No. JP-22-18723; Published: 12-Dec-2022, DOI: 10.35248/2329-6887.22.10.398

INTRODUCTION

Over the past few decades, the risk of resistance due to changing mechanisms of potential resistance in Gram-negative bacteria has increased with the increase of MDR and XDR [1]. Gram-negative bacteria, dominated by carbapenem-resistant Enterobacteriaceae, have been classified by the US Centers for Disease Control and Prevention as one of the multi-resistant bacteria in the emergency threat level and Klebsiella Pneumoniae (KP) was the main carbapenem-resistant strain detected in Enterobacteriaceae [2]. The emergence of carbapenem-resistant Klebsiella pneumoniae has brought severe challenges to the clinical treatment of multi-drug-resistant bacteria. According to the data of the Chinese bacterial drug resistance monitoring network (CHINET) from 2005 to 2021, the drug resistance rate of clinically isolated Klebsiella to carbapenems showed an increasing trend, especially after 2009, the drug resistance rate of CRKP increased faster and faster [3]. The resistance rates of Klebsiella pneumoniae to meropenem and imipenem increased rapidly from 2.9% and 3.0% in 2005 to 24.4% and 23.1% in 2021, respectively. CRKP infection is common in both developed and developing countries, resulting in high patient mortality and associated high treatment costs. The distribution of CRKP in different countries is different, and the distribution of infected people and the proportion of infected CRKP are also different. According to CHINET data, there are regional differences in CRKP infection in China. For example, in 2021, the detection rate of Henan, Jiangxi, Zhejiang, and other provinces was more than 50%, while that of Guangdong, Fujian, and other provinces was less than 15%. The reasons for such differences may be related to the population base of different regions and the choice of drugs in different hospitals. In the face of the increased detection rate of CRKP in China and abroad, scholars at home and abroad have only studied the detection rate, site of infection, and molecular gene sequencing of CRKP and Klebsiella pneumoniae producing Extended-Spectrum β-Lactamase (ESBLs-KP) in terms of detection rate, infection site, and molecular gene sequencing, but there is a lack of studies on the epidemiological characteristics and prognostic status of CRKP hospital-acquired patients in different regions. Therefore, this study carried out an epidemiological investigation on "epidemiological characteristics and prognosis of clinical infection of CRKP", focusing on the analysis and summary of the prognosis of patients treated with nosocomial infection of CRKP, and providing guidance and reference suggestions for clinical treatment. The report is as follows.

Patients and Methods

Patients

A total of 103 patients with hydro Carbapenem-Resistant Klebsiella Pneumoniae (CRKP) infection admitted to a general hospital in Guangzhou from January 1, 2021, to December 31, 2021, were selected as statistical samples. The diagnostic criteria of CRKP patients are as follows: infection of various systems, such as respiratory system, urinary system, blood system, surgical site, skin, soft tissue, etc., which are in line with the clinical diagnosis of infection of this site. The pathogenic culture of samples from the related sites is KP, and the drug sensitivity results are determined as CRKP.

Clinical data collection

First of all, patients with CRKP bacterial infections, including hospital department, distribution department, primary diseases, personal history, past medical history, infection, medicine, treatment, treatment effect and whether the court, the types of samples, etc., then analyzed the characteristics and distribution. Clinical data inclusion criteria: a. complete clinical data; b. Drug sensitivity report suggests that Klebsiella pneumoniae is resistant to hydro-carbapenem drugs.

Identification of pathogenic bacteria and drug sensitivity test

The laboratory staff of the laboratory of the hospital conducted bacterial culture, separation, and identification of the samples submitted from all clinical departments. The BD Phoenix-100 automatic bacterial identification analyzer provided by American BD Company and VITEK2 Compact automatic microbial identification analyzer provided by French Bio-Meriere Company were used for bacterial identification. Drug sensitivity test (KB) paper was used to conduct a drug sensitivity test on the cultured pathogens by OXOID Company (a brand of thermo fisher scientific in the United States). The results of the drug sensitivity test were interpreted in accordance with the antimicrobial sensitivity test implementation standard M 100-S25 of the American Institute for Clinical and Laboratory Standardization in 2015 [4]. KP for any carbapenem antibiotics such as imipenem, meropenem resistant Klebsiella pneumoniae was determined as CRKP. The quality control strains (the inspection center of the health commission, PRC) were Escherichia coli ATCC 25922 and ESBLS-KPN ATCC 700603.

Statistical analysis

MS Office 2010 and SPSS 26.0 were used for statistical analysis. Due to the skewed distribution of age, median (quad) was used for statistical description. SPSS 26.0 software was used for statistical processing, and all count data were χ2 P<0.05 was considered to be statistically significant.

Results

CRKP separation rate

In 2021, a total of 7933 strains of bacteria were isolated and cultured from the specimens submitted for examination in various departments of the hospital (only the first strain was counted if the bacterial species and drug sensitivity results of the same specimen isolated from a patient were the same), among which 4668 strains of G-strain accounted for 58.8%.Among them, 2583 Enterobacteriaceae strains accounted for 55.33% of G-strains.182 strains were resistant to hydro carbapene-resistant Enterobacteriaceae, including 106 strains of CRKP (58.24% of the total). 36 carbapenem-resistant Escherichia coli (19.78% of the total number of carbapenem-resistant Enterobacteriaceae) and 15 carbapenem-resistant Enterobacteriaceae (8.24% of the total number of carbapenem-resistant Enterobacteriaceae) were the second (Table 1).

Table 1: Species, number and composition of carbapenem-resistant enterobacteriaceae bacteria in 2021.

Hospital infection rate of CRKP

In the bacterial identification of 103 patients with carbapenem-resistant Klebsiella pneumoniae nosocomial infection selected through statistics, the patients with carbapenem-resistant Enterobacter pneumoniae alone were mainly CRKP (accounting for 62.14%). CRKP+Acinetobacter baumannii (4.85%) and CRKP+Candida albicans (4.85%) were the main types of mixed infection with two or more types of bacteria, as shown in Figure 1.

Figure 1: A typical pharmacovigilance setup.

Note: Three or more microorganisms include CRKP, ESBLS-KP, MRSA, Acinetobacter baumannii, Acinetobacter baumannii/Acinetobacter calcium acetate complex, Candida peregrinum, Corynebacterium striatum, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Candida krusei, and Candida tropicalis.

Distribution of hospital infected population of CRKP

Among the 103 patients with CRKP infection, there were 74 males and 29 females, with an age distribution ranging from 1 to 90 years old, with an average of (54.82 ± 20.58) years old. Patients with Hospital infection of CRKP were mainly over 50 years old, presenting skewed distribution (Table 2).

Table 2: Summary of CRKP-infected patient’s information.

Distribution of CRKP nosocomial infection in different departments

Carbapenem-Resistant Klebsiella Pneumoniae (CRKP) was detected in 103 specimens selected from all departments of the hospital in 2021, which ranked first in the internal medicine system (accounting for 42.72%), followed by the ICU unit, as shown in Figure 2.

Figure 2: The distribution of hospital departments on 103 CRKP infected patients.

Note: Internal medicine system includes: Department of Rehabilitation physiotherapy, Hematology department ward, department of neurology, department of nephrology, department of laminar flow ward of hematology, department of gastroenterology, department of respiratory, department of vasculocardiology, department of Chinese internal medicine, department of endocrinology, department of rheumatology and immunology, department of geriatric medicine, department of oncology; Surgical systems include: General surgery, hepatobiliary surgery, neurological surgery, huiqiao surgery, thoracic surgery, burns surgery department, oral and maxillofacial surgery, trauma center wards.

Types of CRKP nosocomial infection specimens

In the whole year 2021, a total of 106 strains of CRKP were detected in the department (excluding the same bacterial species isolated from the same patient and the same drug sensitivity results). In this study, a total of 278 strains of CRKP were isolated from 103 patients with nosocomial CRKP infection (including different samples from patients with the same infection) by bacterial culture and drug sensitivity test, of which 125 strains were isolated from respiratory system specimens (sputum aspiration accounted for 20.86%, natural expectoration accounted for 17.27%). 44 strains were isolated from urinary system specimens (15.83%) and 32 strains were isolated from bloodstream specimens (11.51%), as shown in Figure 3.

Figure 3: 103 sample types of Carbapenem-Resistant Klebsiella pneumoniae.

Infection sites distribution of patients with nosocomial infection of CRKP

Among the 103 patients with CRKP infection samples selected, only 73 patients with nosocomial infection were infected at a single site, among which respiratory and pulmonary infection was the main infection site (78.08%), followed by bloodstream infection (6.85%).There were 30 patients with multiple (two or more) sites of mixed infection of CRKP, and the infection sites were mainly respiratory lung and urinary tract infections (36.67%), followed by respiratory lung and bloodstream infections (16.67%) (Figures 4 and 5).

Figure 4: 4: Infection sites distribution of 103 patients with CRKP infection (alone). Skin infections.

Figure 5: Distribution of multiple sites of infection in 103 CRKP patients. Note: urinary tract, skin soft tissue, abdominal cavity.

Prognosis of patients with nosocomial infection of CRKP

By tracing the diagnosis and treatment information of 103 patients screened from January 1, 2021 to December 31, 2021, 60 patients with CRKP infection were treated effectively, 19 patients with CRKP infection were not treated, 14 patients could not be followed up, and 10 patients with CRKP colonization were not treated, as shown in Table 3.

Table 3: Prognosis of patients with nosocomial infection of CRKP.

Table 4: Treatment of CRKP infection in 60 patients with good prognosis.

Discussion

In recent years, with the increased detection rate of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) at home and abroad, the correlation study of CRKP by scholars around the world has also increased, from the epidemiological investigation, of the cause of CRKP resistance, to the detection of CRKP resistance mechanism and resistance genes, gradually refined [5]. CRKP is a common multidrug-resistant pathogen causing hospital infection at home and abroad, which often causes pneumonia, urinary tract infection, bacteremia, and other diseases in hospital-infected patients. In this study, the epidemiological characteristics and prognosis of 103 cases of CRKP clinical infection in our hospital in 2021 were retrospectively analyzed, and the data statistics of CRKP infection sites in hospital-acquired patients (Figures 4 and 5) were found to be consistent with the results of many previous studies by domestic and foreign scholars. Research reports at home and abroad show that the detection rate and drug resistance rate of CRKP are increasing year by year, and there are related reports about the outbreak of CRKP hospital infection all over the country [6-11]. In addition, the colonization and infection rate of CRKP also showed a high trend. More than half of KP cultivated based on clinical specimens were identified as resistant to carbapenems, which limited the antimicrobial agents available to clinicians for clinical treatment and prognosis of infected patients [12]. At present, there are few relevant studies on the clinical epidemiological characteristics and prognosis of CRKP in various regions. In this study, the distribution of clinical epidemiological characteristics and prognosis of nosocomial infection of CRKP was obtained by analyzing the case data of CRKP infection in a general hospital in Guangzhou.

According to the research analysis shown, we found that CRKP nosocomial infection patients are mainly elderly men, and the infection rate of male patients is much higher than that of female patients. In clinical departments, the hospital infection rate of CRKP is different in different departments, and the infection rate of inpatients in internal medicine and ICU units is much higher than that of surgery and other departments. Internal medicine and ICU are the departments with a high incidence of multidrug-resistant bacterial infections in hospitals, which is consistent with previous reports [13-16]. Patients in these departments generally have poor health, more basic diseases, long hospital stays, frequent invasive operations, and long-term antibiotic treatment, which will undoubtedly increase the risk of infection [17,18]. In conclusion, hospital should focus on elderly male patients who live in the department of internal medicine and ICU, especially strengthening the prevention and control measures of hospital infection in the internal medicine department and ICU, so as to reduce the risk of hospital infection caused by multiple drug-resistant bacteria such as CRKP.

Through the results of this study, we found that CRKP was mainly detected in respiratory specimens, and CRKP mainly infected human lung organs. For patients with CRKP colonization or nosocomial infection, hospital departments should strengthen the disinfection of ward beds, beds should be cleaned and replaced in time and diagnostic and treatment items should be dedicated by special personnel. Once nosocomial infection such as CRKP is found, isolation work should be done in time to prevent widespread infection in the ward, and then cause serious hospital safety accidents.

According to the data in Table 3, there are still a large proportion of infected patients with little or no treatment effect after medication. Based on the prognostic status of 103 patients with nosocomial CRKP, we conducted correlation statistics on the underlying diseases of these patients, among which 59 patients without underlying diseases were infected with CRKP (57.28%). Hypertension was the central disease of CRKP infection patients with underlying diseases, with 19 patients (18.45%).Among the 60 patients with good treatment effects (medication), 36 patients without underlying diseases were infected with CRKP, accounting for 60.00%; 12 patients with underlying diseases were mainly infected with hypertension, accounting for 20.00%. Among the 19 patients with poor treatment effect (medication), 9 patients with CRKP infection without underlying diseases still accounted for the majority (47.37%).

The causes of 33 patients with poor prognosis of CRKP infection were analyzed: 1. Host factors of CRKP infection: a. The patients were in critical condition with multiple organ failures and poor vital signs; b. Long hospital stay; c. Patients have low immunity and serious cross-infection. 2. Economic factors of patients: a. Different enzyme types of CRKP: Producing KPC enzyme, NDM enzyme, OXA-48 enzyme, etc.

Currently, the 2018 China HAP/VAP Guidelines for the clinically recommended treatment of CRE indicate that: 1. Carbapenem-containing scheme: a) Carbapenems+polymyxin/tigecycline; b) Carbapenems+polymyxin+tigecycline. 2. Carbapenems-free scheme: a) Tigecycline+aminoglycoside/fosfomycin; b) Polymyxin+tigecycline/fosfomycin; c). Aminoglycoside+fosfomycin/aztreonam.

As shown in Table 4, among 79 patients with CRKP infection treated with clinical drugs, 60 patients had a good prognosis after drug treatment. In addition to carbapenems, most clinical drugs are cephalosporins inhibitor compound preparation, colistin, tigecycline, and other drugs combined therapy, namely the carbapenem-free clinical drug regimen shared in the 2018 Chinese HAP/VAP Guidelines. Among them, polycolistin B is recommended for the treatment of infection in different parts of CRE, such as bloodstream infection, ventilator-associated pneumonia, abdominal infection, central nervous system infection, etc. However, it is not recommended to use this drug alone due to its pharmacological toxicity. It is necessary for the elderly and patients with impaired renal function to monitor their renal function. Polycolistin is also recommended for the treatment of urinary tract infections in CRE due to its high concentration in urine. Tigecycline can be used in confirmed or highly suspected cases of HAP (including VAP), skin and soft tissue infections, and abdominal infections due to CRE. Two or three drugs are generally recommended for clinical treatment. Tigecycline is often used in combination with polycolistin, carbapenems, aminoglycosides and other drugs. Tigecycline is not recommended for CRE bloodstream infections and CNS infections because of its low concentration in blood and cerebrospinal fluid. Ceftaadine avibactam showed high antibacterial activity against KPC and OXA-48 serine carbapenemase strains, but not against metal β-lactamase strains.

In conclusion, we speculated that among the risk factors of 33 patients with poor prognosis, patients with underlying diseases had little correlation with CRKP infection, and patients with hypertension could be regarded as the focus of preventive treatment and related nosocomial protection after hospitalization. Among patients with a good prognosis, the combination of polymyxin B, tigecycline, and cephalosporins enzyme inhibitor compound is effective in the treatment of patients with CRKP infection, which can be used as a reference for clinicians to treat patients with nosocomial infection of CRKP. However, it is still necessary to make a comprehensive judgment and further treatment based on the actual clinical symptoms of patients and the pharmacological toxicity of drugs.

For there is still a large proportion of infected patients after drug therapy effect is invalid, even about this phenomenon reflects the limitations of this study is to diagnose the methodology and regional problems, because this research survey data from a general hospital in Guangzhou, the research results of regional factors inherent, not on behalf of the other parts of the hospital. In addition, the diagnosis method in this study is mainly pathogen biology, and problems such as long culture time, multiple interference factors and lack of high-quality diagnostic methods all lead to the lack of targeted clinical medication treatment for patients with CRKP infection, thus delaying or aggravating the condition. This phenomenon also causes us to improve and think about the clinical use of multidrug-resistant bacteria and the early diagnosis treatment plan, such as the development and clinical application of the rapid detection technology of pathogens by molecular biology PCR.

Conclusion

CRKP, as a global public health problem, deserves our pay more attention. We found through the analysis of CRKP infection data in our hospital that the hospital should focus on elderly male patients in ICU and internal medicine, and strengthen the prevention of hospital infection. CRKP often causes respiratory infection in patients, especially lung organ function damage. When patient’s etiology cultivate the results showed that infection of Klebsiella pneumoniae, can prompt clinical doctors according to the result of etiology first consider using carbapenem antibiotic and cephalosporin drugs therapy, but when the drug-sensitive test report prompts appear CRKP, according to the drug susceptibility results and symptoms in patients with consideration for Tigecycline with cephalosporins enzyme inhibitors combination of compound preparation.

Ethical Approval

This study had been reviewed and approved by the Ethics Review Committee of Nanfang Hospital of Southern Medical University.

Conflict of Interest Form

Declarations of interest: None.

The author reports no conflicts of interest in this work.

Author's Contributions

The first author Shuai Zu wrote the main manuscript text, the second author Hengrui Zhao provided the data in Table 1, the third author Minghui Wen gave comments on picture modification, the fourth author and the fifth gave some suggestions for guidance and improvement of the content of the article are proposed, especially the fifth author Xiumei Hu, as the corresponding author, plays a significant role in checking the quality of paper content.

Funding

This work was supported by grants from the National Natural Science Foundation of China (81601819) and 82272384), Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University (2016J013), Medical Science and Technology Research Foundation of Guangdong Province (A2016280).

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