Carbapenem resistance in critically important human pathogens isolated from companion animals: a systematic literature review

Angie Alexandra Rincón-Real,Martha Cecilia Suárez-Alfonso 질병관리본부 2022 Osong Public Health and Research Persptectives Vol.13 No.6

This study aimed to describe the presence and geographical distribution of Gram-negative bacteria considered critical on the priority list of antibiotic-resistant pathogens published by the World Health Organization, including carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Acinetobacter spp., and carbapenem-resistant Pseudomonas aeruginosa. A systematic review of original studies published in 5 databases between 2010 and 2021 was conducted, including genotypically confirmed carbapenem-resistant isolates obtained from canines, felines, and their settings. Fifty-one articles met the search criteria. Carbapenem-resistant isolates were found in domestic canines and felines, pet food, and on veterinary-medical and household surfaces. The review found that the so-called “big five”—that is, the 5 major carbapenemases identified worldwide in Enterobacterales (New Delhi metallo-β-lactamase, active-on-imipenem, Verona integron-encoded metallo-β-lactamase, Klebsiella pneumoniae carbapenemase, and oxacillin [OXA]-48-like)—and the 3 most important carbapenemases from Acinetobacter spp. (OXA-23-like, OXA-40-like, and OXA-58-like) had been detected in 8 species in the Enterobacteriaceae family and 5 species of glucose non-fermenting bacilli on 5 continents. Two publications used molecular analysis to confirm carbapenem-resistant bacteria transmission between owners and dogs. Isolating critically important human carbapenem-resistant Gram-negative bacteria from domestic canines and felines highlights the importance of including these animal species in surveillance programs and antimicrobial resistance containment plans as part of the One Health approach.

Molecular Analysis of Carbapenem-Resistant Enterobacteriaceae at a South Korean Hospital

( Miyoung Lee ),( Tae-jin Choi ) 한국미생물생명공학회 2020 한국미생물·생명공학회지 Vol.48 No.3

The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is increasing globally, resulting in high mortality rates. Although CRE is a relatively recent problem in Korea (the first case was not diagnosed until 2010), it is responsible for serious morbidities at an alarming rate. In this study, we carried out a molecular genetic analysis to determine the incidence of CRE and carbapenemase-producing Enterobacteriaceae (CPE) at a general hospital in Korea between August 2017 and August 2019. Forty strains of CPE were isolated from various clinical specimens and analyzed via antimicrobial susceptibility testing, polymerase chain reaction to detect β-lactamase genes, deoxyribonucleic acid sequencing, multilocus sequence typing, curing testing, and conjugal transfer of plasmids. The results demonstrated that all 40 isolates were multidrug- resistant. The fluoroquinolone susceptibility test showed that 75% of the Enterobacteriaceae isolates were resistant to ciprofloxacin, whereas 72.5% were resistant to trimethoprim-sulfamethoxazole. Further, conjugation accounted for 57.5% of all resistant plasmid transfer events, which is 4.3-fold higher than that observed in 2010 by Frost et al. Finally, the high detection rate of transposon Tn4401 was associated with the rapid diffusion and evolution of CPE. Our results highlight the rapid emergence of extensively drugresistant strains in Korea and emphasize the need for employing urgent control measures and protocols at the national level.

Efficacy of Lactobacillus fermentum Isolated from the Vagina of a Healthy Woman against Carbapenem-Resistant Klebsiella Infections In Vivo

( Hanieh Tajdozian ),( Hoonhee Seo ),( Sukyung Kim ),( Md Abdur Rahim ),( Saebim Lee ),( Ho-yeon Song ) 한국미생물생명공학회 2021 Journal of Microbiology and Biotechnology Vol.31 No.10

Carbapenem-resistant Enterobacteriaceae (CRE) that produce Klebsiella pneumoniae carbapenemase are increasingly reported worldwide and have become more and more resistant to nearly all antibiotics during the past decade. The emergence of K. pneumoniae strains with decreased susceptibility to carbapenems, which are used as a last resort treatment option, is a significant threat to hospitalized patients worldwide as K. pneumoniae infection is responsible for a high mortality rate in the elderly and immunodeficient individuals. This study used Lactobacillus fermentum as a candidate probiotic for treating CRE-related infections and investigated its effectiveness. We treated mice with L. fermentum originating from the vaginal fluid of a healthy Korean woman and evaluated the Lactobacilli’s efficacy in preventive, treatment, nonestablishment, and colonization mouse model experiments. Compared to the control, pre-treatment with L. fermentum significantly reduced body weight loss in the mouse models, and all mice survived until the end of the study. The oral administration of L. fermentum after carbapenemresistant Klebsiella (CRK) infection decreased mortality and illness severity during a 2-week observation period and showed that it affects other strains of CRK bacteria. Also, the number of Klebsiella bacteria was decreased to below 5.5 log10 CFU/ml following oral administration of L. fermentum in the colonization model. These findings demonstrate L. fermentum’s antibacterial activity and its potential to treat CRE infection in the future.

Carbapenem-resistant Enterobacteriaceae: Prevalence and Risk Factors in a Single Community-Based Hospital in Korea

이효진,최재기,조성연,김시현,박선희,최수미,이동건,최정현,유진홍 대한감염학회 2016 Infection and Chemotherapy Vol.48 No.3

Background: Carbapenemase-producing Enterobacteriaceae (CPE) are Gram-negative bacteria with increasing prevalence of infection worldwide. In Korea, 25 cases of CPE isolates were reported by the Korea Centers for Disease Control and Prevention in 2011. Most CPE cases were detected mainly at tertiary referral hospitals. We analyzed the prevalence and risk factors for carbapenem- resistant Enterobacteriaceae (CRE) in a mid-sized community-based hospital in Korea. Materials and Methods: We retrospectively analyzed all consecutive episodes of Enterobacteriaceae in a mid-sized community- based hospital from January 2013 to February 2014. CRE was defined as organisms of Enterobacteriaceae showing decreased susceptibility to carbapenems. Risk factors for CRE were evaluated by a case–double control design. Carbapenemase was confirmed for CRE using a combined disc test. Results: During 229,710 patient-days, 2,510 Enterobacteriaceae isolates were obtained. A total of 41 (1.6%) CRE isolates were enrolled in the study period. Thirteen species (31.7%) were Enterobacter aerogenes, 8 (19.5%) Klebsiella pneumoniae, 5 (12.2%) Enterobacter cloacae, and 15 other species of Enterobacteriaceae, respectively. Among the 41 isolates, only one (2.4%) E. aerogenes isolate belonged to CPE. For evaluation of risk factors, a total of 111 patients were enrolled and this included 37 patients in the CRE group, 37 in control group I (identical species), and 37 in control group II (different species). Based on multivariate analysis, regularly visiting the outpatient clinic was a risk factor for CRE acquisition in the control group I (P = 0.003), while vascular catheter and Charlson comorbidity index score ≥3 were risk factors in control group II (P = 0.010 and 0.011, each). Patients with CRE were more likely to experience a reduced level of consciousness, use a vasopressor, be under intensive care, and suffer from acute kidney injury. However, CRE was not an independent predictor of mortality compared with both control groups. Conclusion: In conclusion, the prevalence of CRE was higher than expected in a mid-sized community-based hospital in Korea. CRE should be considered when patients have a vascular catheter, high comorbidity score, and regular visits to the outpatient clinic. This study suggests the need for appropriate prevention efforts and constant attention to CRE infection control in a midsized community-based hospital.

Study on the Distribution of Carbapenem-Resistant Enterobacteriaceae (CRE) in Busan, 2022

Kyeong-A Kim,Hye-sook Heo,Hye-jun Kim,Su-Jin Shin,Young-Ran Na 대한미생물학회 2023 Journal of Bacteriology and Virology Vol.53 No.2

This study was conducted on the incidence of as carbapenemase-resistant Entero-bacteriaceae (CRE) infection and carbapenemase-producing Enterobacteriaceae(CPE) gene distribution in Busan to prepare basic data for preventing the spreadof CRE infection by confirming the regional characteristics of CRE infection. Thetotal of 2,429 strains from 92 clinics were obtained from rectal swab, sputum,stool, urine, blood, wound, bile, transtracheal aspiration, pus, ascetic fluid, bronchialwashing, catheter tip, genital, skin, sore, tissue, from January to December 2022. The CRE infection was tested by the method tested by the Korea Disease Controland Prevention Agency (KDCA). Species identification was confirmed by VITEK 2. Klebsiella pneumoniae which was detected in 1,698 (70.2%), was the mostcommon isolated CRE, followed by Escherichia coli in 430 (17.8%), Enterobactercloacae 90 (3.7%) and Citrobacter freundii 44 (1.8%). Among the identifiedCREs, 2,029 (83.5%) strains were identified as CPE. More than half of the detectedCPE types were 1,680 (69.2%) of KPC-2 (Klebsiella pneumonia carbapenases-2),followed by 166 (6.8%) of NDM-1 (New Delhi metallo-β-lactamase-1), 58 (2.4%)of KPC-3, and 51 (2.4%) of NDM-5. These findings provide good basic data forcomprehensive surveillance of CREs, suggesting that KPC and NDM are widespreadin Busan. In the analyzed CRE samples, Ertapenem resistance was the most com-mon at 99.5%, imipenem resistance 72.3%, meropenem resistance 67.9%, anddoripenem resistance 48.7%. It is expected that this study can be used as basicdata for preparing suitable countermeasures against CRE infection in the com-munity in the future.

Epidemiological Characteristics of Carbapenemase Producing Carbapenem-Resistant Enterobacteriaceae Colonization

정인숙,Song Ju Yeoun 한국간호과학회 2022 Asian Nursing Research Vol.16 No.3

Purpose: This study identified the epidemiological characteristics, including the size and major strains, of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) and CP-CRE-related factors by comparing the characteristics of patients in the CP-CRE and non-CP-CRE groups and the CP-CRE and non-CRE groups. Methods: This secondary data analysis study included 24 patients in the CP-CRE group, 113 patients in the non-CP-CRE group, and 113 in the non-CRE group. The size and type of CP-CRE were analyzed in terms of frequency and percentage, and CP-CRE risk factors were identified using multiple logistic regression analysis. Results: The rate of CP-CRE positivity among patients with CRE was 17.5%, and the most common causative organism in the CP-CRE group was Klebsiella pneumoniae (81.8%). There were no significant differences between patients in the CP-CRE and non-CP-CRE groups. When compared with the non-CRE group, the isolation of multidrug-resistant organisms except for CRE, particularly vancomycin-resistant Enterococcus, was confirmed as a major risk factor. Conclusion: To prevent CP-CRE acquisition, patients with multidrug-resistant organisms require treatment with more thorough adherence to CRE prevention and management guidelines.

Clinical Laboratory Aspect of Carbapenem-Resistant Enterobacteriaceae

Chang-Eun Park 대한임상검사과학회 2020 대한임상검사과학회지(KJCLS) Vol.52 No.1

The correct distinction of carbapenem-resistant Enterobacteriaceae (CRE) and ccarbapenemase producing Enterobacteriaceae (CPE) and the rapid detection of CPE are important for instituting the correct treatment and management of clinical infections. Screening protocols are mainly based on cultures of rectal swab specimens on selective media followed by phenotypic tests to confirm a carbapenem-hydrolyzing activity, the rapid carbapenem inactivation method, lateral flow immunoassay, the matrix-assisted laser desorption ionization–time-of-flight test and molecular methods. The CPE is accurate for detection, and is essential for the clinical treatment and prevention of infections. A variety of phenotypic methods and gene-based methods are available for the rapid detection of carbapenemases, and these are expected to be routinely used in clinical microbiology laboratories. Therefore, to control the spread of carbapenemase, many laboratories around the world will need to use reliable, fast, high efficiency, simple and low cost methods. Optimal effects in patient applications would require rapid testing of CRE to provide reproducible support for antimicrobial management interventions or the treatment by various types of clinicians. For the optimal test method, it is necessary to combine complementary test methods to discriminate between various resistant bacterial species and to discover the genetic diversity of various types of carbapenemase for arriving at the best infection control strategy.

카바페넴 내성 장내세균: 최신지견과 치료전략

이효진,이동건 대한의사협회 2018 대한의사협회지 Vol.61 No.4

The emergence of carbapenem-resistant Enterobacteriaceae (CRE) has become a major problem within the field of healthcare-associated infections worldwide in the last decade. The treatment of infections caused by CRE is challenging, and a consensus strategy has not been established. This article reviews old and new antibiotics for the treatment of CRE, and summarizes the overall mechanisms of resistance, epidemiology, diagnosis, and infection control of CRE. For CRE treatment, combination therapies may be preferred. Carbapenem still plays an important role in CRE treatment. Other existing treatment options against CRE include colistin, tigecycline, fosfomycin, and aminoglycosides. New therapeutic options include ceftazidime-avibactam, aztreonam-avibactam, plazomicin, eravacycline, meropenem-vaborbactam, and imipenem-cilastatin-relebactam. Few randomized controlled trials have been conducted, so more studies of new agents against CRE are needed. Because there are relatively few therapeutic options for CRE, adequate infection prevention measures and antimicrobial stewardship are required. Moreover, both personal and national preventive efforts are needed.

Improving the Rapidity and Accuracy of Carbapenem-Resistant Enterobacteriaceae Detection by Shortening the Enrichment Duration

Lee Miyoung 한국미생물·생명공학회 2022 한국미생물·생명공학회지 Vol.50 No.4

Identifying carbapenem-resistant Enterobacteriaceae (CRE) is necessary to prevent nosocomial CRE infection outbreaks. Here, a rapid identification method with reduced enrichment time was developed without compromising accuracy. A total of 49 rectal swabs requested for CRE screening at the Department of Diagnostic Medicine at Hospital B in Busan, Korea, were included in this study. Specimens were inoculated on MacConkey and CHROMID Carba media either directly or following enrichment for 3, 6, and 24 h in 100 μl trypticase soy broth containing an ertapenem disk. The enriched cultures were further inoculated on CHROMID Carba or MacConkey media containing an ertapenem disk. In total, 19 CRE and 5 carbapenemintermediate Enterobacteriaceae isolates were obtained from the 49 swabs. Among the 19 CRE isolates, carbapenemase-producing Enterobacteriaceae constituted 13 strains. Moreover, of the 19 CRE isolates, 16 (81.25%) and 17 (88.24%) were identified from the direct cultures on MacConkey and CHROMID Carba media, respectively. After 3 h of enrichment, the proportions of the CRE identified in the media were: MacConkey medium, 16/19 (81.25%); CHROMID Carba medium, 17/19 (88.24%); and MacConkey medium containing an ertapenem disk, 17/19 (88.24%). The detection rates after 6 h of enrichment were the same for all three media (19/19 strains, 100%), whereas those after 24 h of enrichment were 21, 22, and 24 strains, respectively, but included false positives. These findings suggest that a 6-h enrichment before inoculation on the CHROMID Carba medium is optimal for the rapid and accurate detection of CRE in clinical samples.

카바페넴분해효소 생성 장내세균 검출을 위한 Multiplex PCR의 개발 및 평가

김시현,배일권,김나영,송새암,김선주,Joseph Jeong,신정환 대한임상미생물학회 2019 Annals of clinical microbiology Vol.22 No.1

Background: The isolation of carbapenemase-producing Enterobacteriaceae (CPE) has become increasingly common. Continuous surveillance for these organisms is essential because their infections are closely related to outbreaks of illness and are associated with high mortality rates. The aim of this study was to develop and evaluate multiplex PCR as a means of detecting several important CPE genes simultaneously. Methods: We aimed to develop a multiplex PCR that could detect seven CPE genes simultaneously. The multiplex PCR was composed of seven primer sets for the detection of KPC, IMP, VIM, NDM-1, GES, OXA-23, and OXA-48. We designed different PCR product sizes of at least 100 bp. We evaluated the performance of this new test using 69 CPE-positive clinical isolates. Also, we confirmed the specificity to rule out false-positive reactions by using 71 carbapenem-susceptible clinical strains. Results: A total of 69 CPE clinical isolates showed positive results and were correctly identified as KPC (N=14), IMP (N=13), OXA-23 (N=12), OXA-48 (N=11), VIM (N=9), GES (N=5), and NDM (N=5) by the multiplex PCR. All 71 carbapenem-susceptible clinical isolates, including Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, showed negative results. Conclusion: This multiplex PCR can detect seven CPE genes at a time and will be useful in clinical laboratories. (Ann Clin Microbiol 2019;22:-13)