High frequency of extended-spectrum beta-lactamase-producing Enterobacteriaceae carriers at a Japanese long-term care hospital

IntroductionLong-term care hospitals (LTCHs) are at a high risk for the inflow and spread of antimicrobial resistance (AMR) pathogens. However, owing to limited laboratory resources, little is known about the extent to which AMR organisms are endemic.MethodsWe performed active surveillance for carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in newly admitted patients at Marugame Medical Center, a nearly 200-bedded LTCH located in Kagawa, Japan. From August to December 2021, we tested stool samples from patients wearing diapers and confirmed the genetic variants using specific PCR assays. We also collected clinical variables and compared them between AMR carriers and non-carriers.ResultsStool samples were collected from 75 patients, with a median age of 84 years. CRE strain was not detected, but 37 strains of ESBL-E were isolated from 32 patients (42.7%). During the study period, 4.9% of in-hospital patients (37 per 756 patients) were identified to be ESBL-E carriers in the routine microbiological processing, suggesting that active surveillance detected approximately 9-fold more ESBL-E carriers. The bla_CTX-M-9 group was the most common (38.5%), followed by the bla_TEM (26.9%). The clinical backgrounds of the ESBL-E non-carriers and carriers were not significantly different.ConclusionOur active screening demonstrated that nearly half of the patients hospitalized or transferred to a Japanese LTCH were colonized with ESBL-E. We highlight the enforcement of universal basic infection prevention techniques at LTCHs where patients carrying AMR pathogens gather.     

ICU患者发生产ESBLs革兰阴性杆菌 感染的危险因素分析及预测模型的建立

[摘要]　目的　探讨ICU患者发生产超广谱β-内酰胺酶（extended spectrum beta-lactamases, ESBLs）革兰阴性杆菌感染的危险因素，并构建相关预测模型。方法　选取2017年5月—2021年4月我院ICU发生大肠埃希菌或肺炎克雷伯菌感染的189例患者作为研究对象，收集患者的临床资料，使用单因素分析、LASSO回归和多因素Logistic回归分析ICU患者30 d内发生产ESBLs革兰阴性杆菌感染的危险因素，并据此建立列线图预测模型。结果　急性生理与慢性健康评分≥16分、留置尿管时长≥7 d、抑酸剂使用时长≥3 d、第三代头孢菌素使用时长≥3 d、抗菌药物联用时长≥3 d和ICU住院时间≥15 d是ICU患者30 d内发生产ESBLs革兰阴性杆菌感染的危险因素（P均＜0.05）。依此建立预测ICU患者30 d内发生产ESBLs革兰阴性杆菌感染的列线图风险模型，模型验证结果显示C-index为0.795，校正曲线趋近于理想曲线，AUC为0.807（95%CI：0.775～0.839），在2%～81%预测范围内，列线图净获益。结论　ICU患者30 d内发生产ESBLs革兰阴性杆菌感染的危险因素包括APACHEⅡ评分≥16分、留置尿管时长≥7 d、抑酸剂使用时长≥3 d、第三代头孢菌素使用时长≥3 d、抗菌药物联用时长≥3 d和ICU住院时间≥15 d，据此构建的列线图模型能有效预测ICU患者30 d内发生产ESBLs革兰阴性杆菌感染的风险概率，具有一定的临床价值。     

Performance of the new FilmArray Blood Culture Identification 2 panel and its potential impact on clinical use in patients with Gram-negative bacteremia

IntroductionRapid diagnostic tests have been developed recently for rapid species or resistance genes identification, offering the potential to improve the selection of appropriate antibiotics. The newly developed FilmArray Blood Culture Identification 2 (BCID2) panel, which can identify more species and resistance genes, such as extended-spectrum beta-lactamase, is expected to make an impact on antimicrobial practice.MethodsThe consecutive 50 inpatients with Gram-negative bacilli bacteremia were enrolled to this retrospective single-center study. In addition to the existing FilmArray Blood Culture Identification (BCID) panel, we have implemented BCID2 panel for positive blood culture. The sensitivity and specificity of BCID and BCID2 panel were respectively calculated, and a simulation study of time to effective, optimal and de-escalation therapy was performed based on BCID or BCID2 result.ResultsA total of 52 Gram-negative organisms in 50 patients were identified from blood cultures. Of these, 45 (87%) organisms were detected by BCID2 panel, which was more than BCID panel (41 organisms, 79%). BCID2 panel detected 5 CTX-M genes, which were concordant with conventional method. The time to effective therapy did not differ between BCID arm and BCID2 arm; however, the median time to optimal therapy (34 h in BCID arm and 26 h in BCID2 arm, P = 0.0007) and the median time to de-escalation therapy (42 h in BCID arm and 22 h in BCID2 arm, P = 0.0005) were significantly shortened.ConclusionsThis simulation study of BCID2 panel showed high sensitivity and specificity, and the potential impact on shortening the time to optimal and de-escalation therapy.     

Phylogenetic groups and antimicrobial resistance characteristics of Escherichia coli strains isolated from clinical samples in North Iran

Background and study aimExtraintestinal pathogenic Escherichia coli (ExPEC) is one of the most common bacterial pathogens, which causes a remarkable amount of morbidity and mortality. This study was designed to determine the antibiotic resistance profiles, phylogenetic groups, and subgroup analyses among the ExPEC strains isolated from hospitalized patients in north Iran.Patients and MethodsThis cross-sectional investigation was conducted at five educational hospitals in Rasht in north Iran. Using standard microbiological tests, 150 E. coli isolates were identified. The antibiotic susceptibility pattern of all isolates was determined using the disk diffusion method. The double disk phenotypic confirmatory test was performed to detect extended-spectrum β-lactamase (ESBL)-producing isolates. A triplex polymerase chain reaction (PCR) was performed to determine the phylogenetic group of each strain.ResultsThe results of antibiogram pattern showed that E. coli isolates were mostly non-susceptible to ampicillin (79.3%), followed by nalidixic acid (75.3%) and cephalothin (70%), whereas nitrofurantoin (94.7%) was the most effective agent, followed by imipenem (92.7%). The rate of ESBL-producing isolates was 53.3% (80/150). Multiplex PCR screening revealed that the most common phylogroup was the B2 group (97 isolates; 64.6%), followed by the D group (34, 22.7%). In contrast, phylogroup analyses showed that B2₃ (50.7%) and D₂ (16.4%) were the most common subgroups.ConclusionsOur findings indicated a considerable rate of antibiotic resistance and ESBL-producing isolates among E. coli strains isolated from clinical samples. Moreover, we reported a tendency that most isolates belonged to the B2 and D phylogroups. As a result, the detection of genotypic identical or similar isolates indicated that these isolates have an endurance capability in the hospital environment and could be transmitted among patients.     

Estimating the association between antibiotic exposure and colonization with extended-spectrum β-lactamase-producing Gram-negative bacteria using machine learning methods: a multicentre,prospective cohort study

ObjectivesThe aim of the study was to measure the impact of antibiotic exposure on the acquisition of colonization with extended-spectrum β-lactamase-producing Gram-negative bacteria (ESBL-GNB) accounting for individual- and group-level confounding using machine-learning methods.MethodsPatients hospitalized between September 2010 and June 2013 at six medical and six surgical wards in Italy, Serbia and Romania were screened for ESBL-GNB at hospital admission, discharge, antibiotic start, and after 3, 7, 15 and 30 days. Primary outcomes were the incidence rate and predictive factors of new ESBL-GNB colonization. Random forest algorithm was used to rank antibiotics according to the risk of selection of ESBL-GNB colonization in patients not colonized before starting antibiotics.ResultsWe screened 10 034 patients collecting 28 322 rectal swab samples. New ESBL-GNB colonization incidence with and without antibiotic treatment was 22/1000 and 9/1000 exposure-days, respectively. In the adjusted regression analyses, antibiotic exposure (hazard ratio (HR) 2.38; 95% CI 1.29–4.40), age 60–69 years (HR 1.19; 95% CI 1.05–1.34), and spring season (HR 1.25; 95% CI 1.14–1.38) were independently associated with new colonization. Monotherapy ranked higher als combination therapy in promoting ESBL-GNB colonization. Among monotherapy, cephalosporins ranked first followed by tetracycline (second), macrolide (fourth) and cotrimoxazole (seventh). Overall the ranking of cephalosporins was lower when used in combination. Among combinations not including cephalosporins, quinolones plus carbapenems ranked highest (eighth). Among sequential therapies, quinolones ranked highest (tenth) when prescribed within 30 days of therapy with cephalosporins.ConclusionsImpact of antibiotics on selecting ESBL-GNB at intestinal level varies if used in monotherapy or combination and according to previous antibiotic exposure. These finding should be explored in future clinical trials on antibiotic stewardship interventions.Clinical Trial registrationNCT01208519.     

Infections caused by extended-spectrum β-lactamase-producing Enterobacterales after rectal colonization with ESBL-producing Escherichia coli or Klebsiella pneumoniae

ObjectivesInfections as a result of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) are considered infections with a high public health burden. In this study, we aimed to identify incidences of and risk factors for healthcare-associated infections (HAIs) after rectal colonization with ESBL-producing Escherichia coli (ESBL-EC) or Klebsiella pneumoniae (ESBL-KP).MethodsThis prospective cohort study was performed in 2014 and 2015. Patients colonized with ESBL-EC or ESBL-KP were monitored for subsequent HAI with ESBL-E and other pathogens. In the case of an ESBL-E infection, rectal and clinical isolates were compared using pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS) for ESBL-KP isolates. Proportional hazard models were applied to identify risk factors for HAIs, and to analyse competing risks.ResultsAmong all patients admitted to the hospital during the study period, 13.6% were rectally screened for third-generation cephalosporin-resistant Enterobacterales (3GCREB). A total of 2386 rectal carriers of ESBL-EC and 585 of ESBL-KP were included in the study. Incidence density (ID) for HAI with ESBL-E was 2.74 per 1000 patient days at risk (95% confidence interval (CI) 2.16–3.43) among carriers of ESBL-EC, while it was 4.44 per 1000 patient days at risk (95% CI 3.17–6.04) among carriers of ESBL-KP. In contrast, ID for HAI with other pathogens was 4.36 per 1000 patient days at risk (95% CI 3.62–5.21) among carriers of ESBL-EC, and 5.00 per 1000 patient days at risk (95% CI 3.64–6.69) among carriers of ESBL-KP. Cox proportional hazard regression analyses identified colonization with ESBL-KP (HR = 1.58, 95% CI 1.068–2.325) compared with ESBL-EC as independent risk factor for HAI with ESBL-E. The results were consistent over all competing risk analyses.ConclusionsClinicians should be aware of the increased risk of ESBL-E infections among patients colonized with ESBL-KP compared with ESBL-EC that might be caused by underlying diseases, higher pathogenicity of ESBL-KP and other factors.     

产ESBLs肺炎克雷伯菌ESBLs基因与可移动遗传元件相关性分析

目的 了解产超广谱β-内酰胺酶(extended spectrum beta-lactamases, ESBLs)肺炎克雷伯菌(Klebsiella pneumoniae, Kpn)ESBLs基因与可移动遗传元件(mobile genetic elements, MGEs)标记基因的携带情况及其相关性。方法 收集从住院患者标本中分离出的产与非产ESBLs Kpn非重复菌株各100株，采用PCR检测细菌中4种ESBLs基因与8种MGEs标记基因，并作指标聚类分析。结果 产ESBLs Kpn中，ESBLs基因阳性率高达100%；MGEs标记基因以IS26、ISEcp1、traA、trbC和intI1基因为主，阳性率高于非产ESBLs Kpn(P<0.05)；ESBLs基因与MGEs标记基因的同时检出率明显高于非产ESBLs Kpn (P<0.05)；基因blaSHV-12、blaOXA-1与MGEs基因tnpU、tnp513、merA、intI1相关联，基因blaTEM-1、blaCTX-M-125与MGEs基因ISEcp1、IS26、traA相关联。产与非产ESBLs Kpn均没有只检出MGEs标记基因的菌株。结论 产ESBLs Kpn ESBLs基因和MGEs标记基因携带率高，两者存在相关性，可能是产ESBLs Kpn出现多重耐药的重要原因；MGEs标记基因在Kpn中可能不是单独存在的。     

Extended-spectrum β-lactamase-producing Enterobacteriaceae,national study of antimicrobial treatment for pediatric urinary tract infection

Objective

To evaluate clinical practices for ESBL-producing urinary tract infection (UTI) in France.

革兰阴性杆菌β-内酰胺酶表型和基因型研究

目的了解铜陵地区临床分离的革兰阴性杆菌产生超广谱β-内酰胺酶(ESBLs)、头孢菌素酶(AmpC酶)和金属β-内酰胺酶(MBL)的分布情况,并检测产ESBLs大肠埃希菌和肺炎克雷伯菌的ESBLs基因型鉴定。方法采用三维试验检测革兰阴性杆菌产ESBLs和AmpC酶,纸片协同法检测MBL,用聚合酶链反应(PCR)对ESBLs表型阳性的大肠埃希菌和肺炎克雷伯菌进行TEM型、SHV型、CTX-M型三种耐药基因检测并克隆测序。结果356株革兰阴性杆菌检出产酶株90株,检出率25.3%。单产ESBLs革兰阴性杆菌57株,检出率16.0%,以肺炎克雷伯(31.6%)、大肠埃希菌(31.0%)检出率高;单产AmpC酶4株,检出率1.1%,其中阴沟肠杆菌3株;同时产ESBLs和AmpC酶16株,检出率4.5%,以鲍曼不动杆菌(12.5%)检出率最高;产MBL细菌13株,均为非发酵菌,以嗜麦芽窄食单胞菌检出率最高,为71.4%。17株ESBLs表型阳性的大肠埃希菌和肺炎克雷伯菌有16株检出ESBLs耐药基因,其中CTX-M型15株(88.2%),TME型13株(76.1%),SHV型2株(11.8%),有11株细菌同时带有两种ESBLs基因,1株带有3种ESBLs基因。结论革兰阴性杆菌产生ESBLs、AmpC酶和MBL多种β内酰胺酶,铜陵地区大肠埃希菌和肺炎克雷伯菌ESBLs基因型以CTX-M型为主。     

ESCMID-EUCIC clinical guidelines on decolonization of multidrug-resistant Gram-negative bacteria carriers

ScopeThe aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings.MethodsThese evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations.RecommendationsThe panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints.