Comparison of multiple-locus variable-number tandem repeat analysis and pulsed-field gel electrophoresis in a setting of polyclonal endemicity of vancomycin-resistant Enterococcus faecium.

In order to assess whether multiple-locus-variable number tandem repeat analysis (MLVA) could replace pulsed-field gel electrophoresis (PFGE) for genotyping vancomycin-resistant isolates of Enterococcus faecium (VREF), this study compared the typeability, discriminatory power, concordance and costs of these methods for VREF isolates obtained from patients, environmental samples and the hands of healthcare workers (HCWs) in a medical intensive care unit (ICU) where VREF was endemic. Over a 58-day period, 393 VREF isolates (373 vanA, one vanA/B, 19 vanB) were cultured from patient rectal swabs (n = 76), the environment (n = 270) and the hands of HCWs (n = 47). PFGE was able to divide 358 (91.1%) isolates into 19 PFGE types (>six bands different) and 24 subtypes (one to three bands different). MLVA was able to type 391 (99.5%) isolates into 11 genotypes. The discriminatory power of PFGE subtypes was 83%, as compared to 68% for MLVA. Concordance between the two methods, based on matched or mismatched MLVA types and PFGE types or subtypes, was 67.5% and 82.8%, respectively. Using PFGE, 13 isolates could be genotyped in 3 days; MLVA genotyped 94 isolates in 2 days. For both methods, the estimated costs were Euro 7 ($10)/isolate. PFGE and MLVA produced highly concordant results when assigning genotypes to nosocomial VREF isolates. MLVA was faster, but PFGE subtyping was more discriminatory.     

Mechanisms of antibiotic resistance in enterococci

Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches.     

Linezolid in the treatment of vancomycin-resistant Enterococcus faecium in solid organ transplant recipients: report of a multicenter compassionate-use trial

Abstract: Vancomycin‐resistant Enterococcus faecium (VRE) is increasing in incidence in solid organ transplant recipients and has a high (up to 83%) associated mortality rate. Until recently, there have been no consistently effective antimicrobial therapies for VRE infection. Linezolid is a new antibiotic that belongs to the class of oxazolidinones approved by the FDA for the treatment of VRE infections, including those with bacteremia. Here, we report the experience with linezolid in an open‐label, compassionate‐use trial at 53 US centers for the treatment of documented VRE infections in patients with solid organ transplants. Eighty‐five patients with solid organ transplants and documented VRE infections were studied. Blood cultures were positive for VRE in 43 patients, while 42 patients had other, non‐rectal, sites of infection. Fifty‐three patients responded well to treatment, with clinical resolution of the infection (62.4% survival rate). Of these, 47 had documented negative cultures post therapy. The mean duration of therapy for cured patients was 23.5 days. Thirty‐two (37.6%) patients died, 28 due to sepsis and organ failure (32.9% failure rate), and 4 due to unrelated causes. Mortality rates for patients with bacteremia were comparable to mortality rates observed with patients who had positive cultures from other sites. Adverse reactions to linezolid included thrombocytopenia (4.7%), decreased leukocyte count (3.5%), and an increase in blood pressure (1.2%), none of which led to discontinuation of therapy. Linezolid appears to be a safe and effective treatment option for VRE, even in the presence of bacteremia, and may lead to decreased mortality in solid organ transplant recipients with VRE infection.     

Vancomycin-resistant enterococci colonization in a neonatal intensive care unit: who will be infected?

Objective: To determine the incidence of vancomycin-resistant enterococcus (VRE) colonization in our neonatal intensive care unit (NICU) over five-year period, rate of progression to VRE infection and associated risk factors.

Methods: A retrospective analysis of a prospective surveillance for VRE colonization and health care-associated infections was made. Contact precautions were taken against colonization, although the application varied over the years due to repairs in the unit.

Results: VRE rectal colonization was detected in 200/1671 neonates (12%) admitted to NICU. It showed great interannual variability from 1.9% to 30.3%. Sytemic VRE infection developed in 6/200 VRE-colonized patients (3%) within a median of 9 days (range: 3–58 days). The risk factors for VRE infection development identified in the univariate analysis were long hospital stay (≥30 days), necrotizing enterocolitis, surgical procedure, extraventricular drainage, receipt of amphotericin B and receipt of glycopeptides after detection of VRE colonization. Crude in-hospital mortality was higher in neonates who developed a systemic VRE infection (p?<?0.001).

Conclusion: Maintaining physical conditions in the unit favorable for infection control and rational use of antibiotics are essential in the control of VRE colonization and resultant infections. Special attention should be directed to VRE-colonized babies carrying the risk factors.     

Impact of single-room contact precautions on acquisition and transmission of vancomycin-resistant enterococci on haematological and oncological wards,multicentre cohort-study,Germany, January−December 2016

BackgroundEvidence supporting the effectiveness of single-room contact precautions (SCP) in preventing in-hospital acquisition of vancomycin-resistant enterococci (haVRE) is limited.AimWe assessed the impact of SCP on haVRE and their transmission.MethodsWe conducted a prospective, multicentre cohort study in German haematological/oncological departments during 2016. Two sites performed SCP for VRE patients and two did not (NCP). We defined a 5% haVRE-risk difference as non-inferiority margin, screened patients for VRE, and characterised isolates by whole genome sequencing and core genome MLST (cgMLST). Potential confounders were assessed by competing risk regression analysis.ResultsWe included 1,397 patients at NCP and 1,531 patients at SCP sites. Not performing SCP was associated with a significantly higher proportion of haVRE; 12.2% (170/1,397) patients at NCP and 7.4% (113/1,531) patients at SCP sites (relative risk (RR) 1.74; 95% confidence interval (CI): 1.35–2.23). The difference (4.8%) was below the non-inferiority margin. Competing risk regression analysis indicated a stronger impact of antimicrobial exposure (subdistribution hazard ratio (SHR) 7.46; 95% CI: 4.59–12.12) and underlying disease (SHR for acute leukaemia 2.34; 95% CI: 1.46–3.75) on haVRE than NCP (SHR 1.60; 95% CI: 1.14–2.25). Based on cgMLST and patient movement data, we observed 131 patient-to-patient VRE transmissions at NCP and 85 at SCP sites (RR 1.76; 95% CI: 1.33–2.34).ConclusionsWe show a positive impact of SCP on haVRE in a high-risk population, although the observed difference was below the pre-specified non-inferiority margin. Importantly, other factors including antimicrobial exposure seem to be more influential.     

Outbreak of vancomycin-resistant Enterococcus spp. in an Italian general intensive care unit

Following the identification of two clinical isolates of vancomycin-resistant enterococci (VRE) from intensive care unit (ICU) patients, a surveillance programme detected that six of eight ICU patients were colonised by VRE. Standard epidemic control measures were instituted in the ICU. During a 16-month period, 13 (2.5%) of 509 ICU patients had VRE-positive swabs upon admission, and 43 (8.7%) of 496 VRE-negative patients were colonised by VRE in the ICU. Patients who acquired VRE in the ICU had a longer ICU stay (p < 0.0001). No other statistically significant differences were demonstrated. Two patients had documented infection (infection/colonisation index, 3.6%; overall VRE infection frequency, 0.4%), but both recovered and were discharged. VRE colonisation did not increase the mortality rate. Automated ribotyping identified three clusters containing, respectively, the first 52 Enterococcus faecium isolates, two Enterococcus faecalis isolates, and two further isolates of E. faecium. Multilocus sequence typing demonstrated that two E. faecium isolates representative of the two ribotypes belonged to sequence types 78 and 18, and that these two isolates belonged to the epidemic lineage C1, which includes isolates with a wide circulation in northern Italy. The outbreak was controlled by continuous implementation of the infection control programme, and by the opening of a new unit with an improved structural design and hand-washing facilities.     

万古霉素衍生物的合成与活性研究进展

万古霉素是临床上治疗革兰氏阳性细菌感染的最后一道防线，但其耐药菌的出现使寻找抗该耐药菌的万古霉素衍生物具有重要意义。本文综合近十年来该领域的工作成果，介绍了万古霉素的抗菌机制，并按照万古霉素单体修饰、二聚体及万古霉素模拟物等三个方面对万古霉素衍生物进行介绍，并总结了衍生位点及基团与化合物抗菌活性之间的关系。     

万古霉素耐药肠球菌的同源性及耐药机制分析

目的探讨万古霉素耐药肠球菌(VRE)的同源性及主要耐药机制。方法收集我院临床分离的9株VRE,采用E-test法检测其对万古霉素等10种抗菌药物的最低抑菌浓度值,脉冲场凝胶电泳技术进行同源性分析,多重PCR技术扩增万古霉素耐药基因并测序。结果9株VRE均为屎肠球菌,共分为6个克隆,耐药表型和基因型均为vanA型。结论本院VRE为vanA基因型,VRE的增加与局部克隆传播、耐药基因的水平转移以及抗菌药物的选择压力有关。