Fecal microbiota transplantation to eradicate vancomycin-resistant enterococci colonization in case of an outbreak

Objective

A rapid and worrying emergence of vancomycin-resistant enterococci (VRE) gut colonization is occurring worldwide and may be responsible for outbreaks, especially in healthcare facilities. While no efficient decolonization strategies are recommended, we assessed fecal microbiota transplantation (FMT) to eradicate VRE colonization.

Molecular analysis of streptogramin resistance in enterococci

The new semi-synthetic streptogramin antibiotic combination quinupristin/dalfopristin (Synercid) is a promising alternative for a treatment of infections with multiple resistant gram-positive pathogens, e.g. glycopeptide- and multi-resistant Enterococcus faecium. Streptogramins consist of two unrelated compounds, a streptogramin A and B, which act synergistically when given in combination. Mechanisms conferring resistance against both components are essential for resistance against the combination in E. faecium. In this species resistance to streptogramin A compounds is mediated via related acetyltransferases VatD and VatE. Resistance against streptogramins B is either encoded by the widespread ermB gene cluster conferring resistance to macrolide-lincosamide-streptogramin B antibiotics or via expression of the vgbA gene, which encodes a staphylococcal-type lactonase. E. faecalis is intrinsically resistant to streptogramins. Due to a wide use of streptogramins (virginiamycins S/M) in commercial animal farming a reservoir of streptogramin-resistant E. faecium isolates had already been selected. Determinants for streptogramin resistance are localized on plasmids that can be transferred into an E. faecium recipient both in vitro in filter-matings and in vivo in the digestive tracts of rats. Hybridization and sequencing experiments revealed a linkage of resistance determinants for streptogramins A and B on definite plasmid fragments.     

Detection of vancomycin variable enterococci (VVE) among clinical isolates of Enterococcus faecium collected across India-first report from the subcontinent

PurposeEmergence of vancomycin variable enterococci (VVE) poses a challenge to empiric vancomycin therapy. Vancomycin-variable enterococci (VVE) are vanA-positive, yet phenotypically vancomycin-susceptible enterococci that can switch to a vancomycin-resistant phenotype when exposed to vancomycin. The aim of the present study was to determine the prevalence of VVE in India.MethodsIsolates of phenotypically vancomycin susceptible Enterococcus faecium from 20 tertiary care hospitals across India were collected and tested for the presence of vanA, vanR, vanS, vanB and vanC genes by conventional PCR using previously published primers. Isolates positive for vanA gene were considered as VVE.ResultsThe prevalence of VVE was 1.5% (5/340). Only one VVE isolate was positive for vanR and vanS, and all the isolates were negative for vanB and vanC.ConclusionsAlthough the prevalence is low, our finding emphasizes the importance of routinely screening for van genes in enterococci that are phenotypically susceptible. Silenced vanA able to escape detection and revert to resistance during vancomycin therapy represents a new challenge in clinical settings.     

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.     

肠球菌医院感染特征及新型抗菌药物耐药性研究

目的探讨肠球菌属细菌分布及耐药性特征,为指导临床合理用药及控制医院感染提供依据。方法对该院2011年1月至2013年12月年临床送检标本进行细菌分离培养、鉴定和药敏试验。结果共检出肠球菌属细菌140株,屎肠球菌71株(50.7%),粪肠球菌60株(42.9%),其他肠球菌9株(6.4%),其中尿液99株(70.7%);粪肠球菌对青霉素、氨苄西林、红霉素的耐药率为15.0%、12.5%和75.0%,屎肠球菌对青霉素、氨苄西林、左氧氟沙星、环丙沙星、红霉素耐药率大于80.0%,粪肠球菌和屎肠球菌对万古霉素(5.0%、4.2%)、利奈唑胺(8.4%、1.4%)极度敏感,喹奴普丁/达福普丁对粪肠球菌耐药率(100.0%)高于屎肠球菌(26.7%),达托霉素无耐药菌株。结论肠球菌属以泌尿系统感染为主,屎肠球菌检出率略大于粪肠球菌,屎肠球菌对大多数抗菌药物耐药率高于粪肠球菌,喹奴普丁/达福普丁仅对屎肠球菌有较高敏感性,万古霉素、利奈唑胺、达托霉素对肠球菌属细菌保持极高敏感性。     

A composite bacteriophage alters colonization by an intestinal commensal bacterium

The mammalian intestine is home to a dense community of bacteria and its associated bacteriophage (phage). Virtually nothing is known about how phages impact the establishment and maintenance of resident bacterial communities in the intestine. Here, we examine the phages harbored by Enterococcus faecalis, a commensal of the human intestine. We show that E. faecalis strain V583 produces a composite phage (ϕV1/7) derived from two distinct chromosomally encoded prophage elements. One prophage, prophage 1 (ϕV1), encodes the structural genes necessary for phage particle production. Another prophage, prophage 7 (ϕV7), is required for phage infection of susceptible host bacteria. Production of ϕV1/7 is controlled, in part, by nutrient availability, because ϕV1/7 particle numbers are elevated by free amino acids in culture and during growth in the mouse intestine. ϕV1/7 confers an advantage to E. faecalis V583 during competition with other E. faecalis strains in vitro and in vivo. Thus, we propose that E. faecalis V583 uses phage particles to establish and maintain dominance of its intestinal niche in the presence of closely related competing strains. Our findings indicate that bacteriophages can impact the dynamics of bacterial colonization in the mammalian intestinal ecosystem.     

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.