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臺灣南部某醫學中心KPC-2與KPC-17產碳青黴烯酶腸桿菌菌株特性之比較

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臺灣南部某醫學中心KPC-2與KPC-17產碳青黴烯酶腸桿菌菌株特性之比較

Comparison of Characteristics of KPC-2 and KPC-17 Carbapenemase-Producing Enterobacteriaceae Strains in A Southern Taiwanese Medical Center

前言
Enterobacteriaceae can cause diseases such as pneumonia and urinary tract infections. However, with the widespread use of antibiotics, drug-resistant strains have been increasing. Even resistance to carbapenems, a class of antibiotics used as a last resort, has emerged, leading to the development of carbapenem-resistant Enterobacteriaceae (CRE). According to the Taiwan Healthcare-Associated Infection and Antimicrobial Resistance Surveillance System (THAS), the rate of CRE infections in regional and medical centers' intensive care units has risen from 9.4% in 2013 to 30.2% in the second quarter of 2023.

The mechanism leading to CRE can be classified into two types: carbapenemase-producing CRE (CP-CRE) and non-carbapenemase-producing CRE (non CP-CRE). Of particular importance is the spread of carbapenemase-producing genes, with common examples including KPC, NDM, IMP, VIM, and OXA-48. These bacteria not only pose challenges to antibiotic treatment but also contribute to increased complications and mortality rates.

KPC-producing strains have become the most common type of carbapenemase globally. From the analysis of KPC plasmids, we have learned that the KPC-17 and KPC-2 genes differ by only one amino acid (F207L). However, there are differences in the epidemiological distribution in Taiwan. In 2014, there was a cluster event of KPC-17 in southern Taiwan, while KPC-2 was the predominant type in northern hospitals. This study aims to understand whether there are differences between the two in terms of demographics, strain types, hospitalization history, drug sensitivity tests, and previous antibiotic use.

方法
This study adopts a retrospective approach, reviewing the strains of CRE at our institution from January 1, 2020, to December 31, 2022. The study population consists of individuals seeking medical care at a medical center in southern Taiwan. The criteria for CRE include strains of Enterobacteriaceae resistant to doripenem and ertapenem. The inclusion criteria involve confirmation through gene sequencing that the strain is KPC and categorizing them into two groups, KPC-2 and KPC-17.

Through retrospectively review electronic medical records, we collected information on the age, gender, medical history, length of hospital stay, mortality, hospitalization history, and previous antibiotic use of the cases. Strain analysis variables included the type of bacteria, specimen source, and drug sensitivity testing. If the bacteria type and drug sensitivity testing were the same, they were considered the same strain and excluded from strain analysis.

This study utilizes descriptive statistics to present the distribution differences in basic case data between KPC-2 and KPC-17. Additionally, logistic regression analysis is used to estimate results, presented using odds ratios and their 95% confidence intervals. A p-value less than 0.05 was considered as statistically significant.

結果
A total of 136 KPC strains were identified and grouped for analysis, which showed 102 KPC-2 and 34 KPC-17. Among the KPC-carrying pathogens, 83.8% were Klebsiella pneumoniae, and 9.6% were Escherichia coli. The most common specimen types were urine and sputum. Although this study did not find statistically significant differences between the two groups in terms of demography, bacterial species, origins, average length of hospitalization, previous antibiotic use, and mortality rate, significant differences were observed in the resistance rates to three antibiotics ─ amikacin, gentamicin, and tigecycline. Although the patients’origins from both groups mainly came from home, the previous hospitalization rates within one year were also high. Additionally, we found that among the patients who were previously hospitalized within 3 or 6 months are more likely to acquire KPC-17.

討論
Bacteria develop antibiotic resistance primarily due to the generation of resistance genes, antibiotics use, and the spread of antibiotic-resistant bacteria. Infections caused by strains carrying the KPC gene had fewer options for antibiotic treatment, and the optimal therapeutic approach is currently inconclusive. Therefore, understanding the site of infection, and the application of pharmacokinetic/pharmacodynamics principles of drugs is crucial in antibiotic selection.
This study reveals that, although both groups of patients primarily come from home, there is a high rate of recurrent hospitalization within one year. Considering the relatively high rate of hospitalization history in this study, it might be speculated that there is a potential transmission of these antibiotic-resistant strains between hospitals and communities.
This study has four limitations: Firstly, the data source relies on electronic medical records from our institution. Information from other medical facilities is unavailable. Secondly, the strains included in the study were not identified using pulsed-field gel electrophoresis to confirm whether they are the same strain, leading to the possibility of repeated inclusion. Thirdly, we did not perform resistance gene sequencing for aminoglycosides and tigecycline. Fourthly, this retrospective analysis is limited to a single hospital in southern Taiwan. Future studies should collect a larger number of cases and integrate data from other medical institutions to further validate the findings of this study.

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