Glycopeptide-resistant Enterococci Research Articles

The survival of multi-drug resistant bacteria on raw Douglas fir material

In today’s age of ecological transition, the use of materials such as renewable wood in construction is particularly relevant, but also a challenge in the healthcare sector where the hygiene dimension also comes into play. In this study we have investigated the survival of multi-resistant bacteria commonly responsible for healthcare-associated infections (HAIs) (ESBL-positive Klebsiella pneumoniae and glycopeptide-resistant Enterococcus faecalis) on two different types of wood (Douglas fir : Pseudotsuga menziesii and Maritime Pine : Pinus pinaster) compared to other materials (smooth: stainless steel and rough: pumice stone) and the effect of a disinfection protocol on the bacterial survival on Pseudotsuga menziesii. Approximately 108 bacteria were inoculated on each material and bacterial survival was observed over several days (D0, D1, D2, D3, D6, D7 and D15). Each analysis was performed in triplicate for each time and material. The results show an important reduction of the bacterial inoculum for Klebsiella pneumoniae and Enterococcus faecalis on Douglas fir, in contrast with the results obtained on maritime pine, stainless steel and pumice stone. No bacterial survival was detected on Douglas fir after application of a hospital disinfection protocol. These different results show that wood may have a place in the future of healthcare construction. Further studies would be interesting to better understand the different properties of wood.

Platanosides from Platanus × acerifolia: New molecules, SAR, and target validation of a strong lead for drug-resistant bacterial infections and the associated sepsis

Three undescribed (1–3) and nine known (4–12) platanosides were isolated and characterized from a bioactive extract of the May leaves of Platanus × acerifolia that initially showed inhibition against Staphylococcus aureus. Targeted compound mining was guided by an LC-MS/MS-based molecular ion networking (MoIN) strategy combined with conventional isolation procedures from a unique geographic location. The novel structures were mainly determined by 2D NMR and computational (NMR/ECD calculations) methods. Compound 1 is a rare acylated kaempferol rhamnoside possessing a truxinate unit. 6 (Z,E-platanoside) and 7 (E,E-platanoside) were confirmed to have remarkable inhibitory effects against both methicillin-resistant S. aureus (MIC: ≤ 16 μg/mL) and glycopeptide-resistant Enterococcus faecium (MIC: ≤ 1 μg/mL). These platanosides were subjected to docking analyses against FabI (enoyl-ACP reductase) and PBP1/2 (penicillin binding protein), both of which are pivotal enzymes governing bacterial growth but not found in the human host. The results showed that 6 and 7 displayed superior binding affinities towards FabI and PBP2. Moreover, surface plasmon resonance studies on the interaction of 1/7 and FabI revealed that 7 has a higher affinity (KD = 1.72 μM), which further supports the above in vitro data and is thus expected to be a novel anti-antibacterial drug lead.

Antibiogram Pattern and Virulence Trait Characterization of Enterococcus Species Clinical Isolates in Eastern India: A Recent Analysis.

Objective We aimed to evaluate the current antimicrobial susceptibility pattern and characterize putative virulence traits among Enterococcus species isolates from various clinical specimens in view of their increased isolation rates in both community-related and serious nosocomial infections, as well as resistance to many antibiotics. Methods Study (April 2017–March 2018) included consecutive, nonrepeated, discrete, and clinically significant isolates of enterococci. Susceptibility testing included detection of high-level aminoglycoside-resistant (HLAR) and glycopeptide-resistant enterococci (GRE). All screen-positive GRE isolates were investigated by polymerase chain reaction for species confirmation and presence of vanA/vanB genes. Virulence genes ace , asa1 , cyt , efa , esp , gelE , and hyl were investigated by molecular methods. Hemolysin and biofilm production were studied using phenotypic methods. Results Of 111 isolates, 89 (80.1%), 16 (14.4%), and 6 (5.4%) were from urine, pus, and blood, respectively, consisting predominantly of E. faecalis (67, 60.4%) and E. faecium (32, 28.8%). E. hirae (5, 4.5%) was the predominant non- E. faecalis non- E. faecium isolate. Other species were E. durans (4, 3.6%), E. avium (2, 1.8%), and E. mundtii (1, 0.9%). Seven (6.3%) out of the 111 isolates were GRE, all vanA genotype. HLAR was observed in 70 (63.1%) isolates, significantly higher in E. faecium than E. faecalis (81.2 vs. 58.2%; p < 0.05). All were susceptible to daptomycin. Hemolysin activity and biofilm production were observed in 38 (34.2%) and 36 (32.4%) isolates. Most frequent virulence genes were efa (77, 69.4%), ace (71, 63.9%), asa1 (67, 60.3%), and gelE (66, 59.4%). There was a predominant association of esp and hyl genes with E. faecium and that of the other genes with E. faecalis . Conclusion The study will contribute to the existing limited data on virulence trait characterization of clinical E. spp. isolates in India. At the same time, it will help to serve as a guide in the choice of empirical therapy in enterococcal infections leading to favorable clinical outcomes by decreasing the clinical failure, microbiological persistence, and associated mortality, and will lead to future studies on controlling the spread of virulent and multiresistant isolates.

Antimicrobial resistance and antibiotic consumption in intensive care units, Switzerland, 2009 to 2018.

BackgroundIntensive care units (ICU) constitute a high-risk setting for antimicrobial resistance (AMR).AimWe aimed to describe secular AMR trends including meticillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci (GRE), extended-spectrum cephalosporin-resistant Escherichia coli (ESCR-EC) and Klebsiella pneumoniae (ESCR-KP), carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) from Swiss ICU. We assessed time trends of antibiotic consumption and identified factors associated with CRE and CRPA.MethodsWe analysed patient isolate and antibiotic consumption data of Swiss ICU sent to the Swiss Centre for Antibiotic Resistance (2009–2018). Time trends were assessed using linear logistic regression; a mixed-effects logistic regression was used to identify factors associated with CRE and CRPA.ResultsAmong 52 ICU, MRSA decreased from 14% to 6% (p = 0.005; n = 6,465); GRE increased from 1% to 3% (p = 0.011; n = 4,776). ESCR-EC and ESCR-KP increased from 7% to 15% (p < 0.001, n = 10,648) and 5% to 11% (p = 0.002; n = 4,052), respectively. CRE, mostly Enterobacter spp., increased from 1% to 5% (p = 0.008; n = 17,987); CRPA remained stable at 27% (p = 0.759; n = 4,185). Antibiotic consumption in 58 ICU increased from 2009 to 2013 (82.5 to 97.4 defined daily doses (DDD)/100 bed-days) and declined until 2018 (78.3 DDD/100 bed-days). Total institutional antibiotic consumption was associated with detection of CRE in multivariable analysis (odds ratio per DDD: 1.01; 95% confidence interval: 1.0–1.02; p = 0.004).DiscussionIn Swiss ICU, antibiotic-resistant Enterobacterales have been steadily increasing over the last decade. The emergence of CRE, associated with institutional antibiotic consumption, is of particular concern and calls for reinforced surveillance and antibiotic stewardship in this setting.

Emergence of Drug Resistant Enterococcus Species from Patients with Urinary Tract Infections in a Tertiary Care Centre- A Retrospective Analysis

Introduction: Urinary Tract Infection (UTI) is one of the most common infections, among patients who are hospitalised. Enterococci are one of the frequent isolates among UTI patients, gaining considerable clinical importance, due to their escalating drug resistance, affecting debilitated patients or patients with prolonged hospital stay. Among Multi-Drug Resistant (MDR) enterococci, glycopeptide-resistant enterococci are being increasingly reported. The intrinsic resistance of enterococci and their ability to acquire and disseminate antibiotic resistant genes to other organisms pose a challenge in the treatment of enterococcal infections with MDR. Aim: To investigate the prevalence of MDR, Extensively-Drug Resistant (XDR) and Pan-Drug Resistant (PDR) Enterococci spp. isolated from urine samples in a tertiary care centre. Materials and Methods: The present retrospective study was conducted to find the burden of drug resistant Enterococcus spp. in urine samples, analyse their antibiogram and patients’ socio-demographic information from January to December 2019. Records of microscopic observations to antibiogram of each isolate was noted down from the register for urine samples, and further analysed. The data was coded, verified, entered and analysed using Statistical Package for Social Sciences (SPSS) version 18.0. Results: The majority of patients 127 (20%) belonged to the age group of 21-30 years of age. Among 10,535 urine samples received, 635 culture isolates were identified as Enterococcus spp., of which 17.95%, 3.30% and 0.62% were identified as MDR, XDR and PDR enterococci, respectively. The antimicrobial susceptibility was found to be least for High Level Gentamicin (HLG) (66.14%), and penicillin (68.81%), followed by ampicillin (81.10%) and nitrofurantoin (86.40%). Twenty eight isolates (7.9%) were identified as Vancomycin Resistant Enterococci (VRE), 9 (2.5%) as linezolid resistant and 12 (3.4%) as linezolid intermediate enterococci. Conclusion: Identification and prevention of the alarming increase in MDR, XDR and PDR enterococci spp. is cardinal to prevent morbidity and mortality of affected patients. Analysis of antibiogram periodically, is important in selection of appropriate drugs to prevent the incoherent use of antibiotics.

N-Terminal guanidine derivatives of teicoplanin antibiotics strongly active against glycopeptide resistant Enterococcus faecium.

Antibiotic resistance is one of the major challenges in healthcare of our time. To meet this challenge, we designed and prepared guanidine and lipophilic guanidine derivatives of the glycopeptide antibiotic teicoplanin to armed them with activity against the most threatening nosocomial bacteria, multiresistant enterococci. From teicoplanin and its pseudoaglycone, a series of N-terminal guanidine derivatives have been prepared with free and amide C-terminal parts. Six aliphatic and aromatic lipophilic carbodiimides were prepared and used for the synthesis of lipophilic guanidine teicoplanin conjugates. All new N-terminal guanidine antibiotics showed high activity against a standard panel of Gram-positive bacteria. Four selected derivatives displayed excellent antibacterial activity against a series of nosocomial VanA Enterococcus faecium strains.

Phosphonopeptides Revisited, in an Era of Increasing Antimicrobial Resistance.

Given the increase in resistance to antibacterial agents, there is an urgent need for the development of new agents with novel modes of action. As an interim solution, it is also prudent to reinvestigate old or abandoned antibacterial compounds to assess their efficacy in the context of widespread resistance to conventional agents. In the 1970s, much work was performed on the development of peptide mimetics, exemplified by the phosphonopeptide, alafosfalin. We investigated the activity of alafosfalin, di-alanyl fosfalin and β-chloro-L-alanyl-β-chloro-L-alanine against 297 bacterial isolates, including carbapenemase-producing Enterobacterales (CPE) (n = 128), methicillin-resistant Staphylococcus aureus (MRSA) (n = 37) and glycopeptide-resistant enterococci (GRE) (n = 43). The interaction of alafosfalin with meropenem was also examined against 20 isolates of CPE. The MIC50 and MIC90 of alafosfalin for CPE were 1 mg/L and 4 mg/L, respectively and alafosfalin acted synergistically when combined with meropenem against 16 of 20 isolates of CPE. Di-alanyl fosfalin showed potent activity against glycopeptide-resistant isolates of Enterococcus faecalis (MIC90; 0.5 mg/L) and Enterococcus faecium (MIC90; 2 mg/L). Alafosfalin was only moderately active against MRSA (MIC90; 8 mg/L), whereas β-chloro-L-alanyl-β-chloro-L-alanine was slightly more active (MIC90; 4 mg/L). This study shows that phosphonopeptides, including alafosfalin, may have a therapeutic role to play in an era of increasing antibacterial resistance.

Emerging extensively drug-resistant bacteria (eXDR) in France in 2018

ObjectiveThis 2018 report of Healthcare-Associated Infections Early Warning and Response System (HAI-EWRS) notifications of carbapenemase-producing Enterobacteriaceae (CPE) or glycopeptide-resistant Enterococcus faecium (GRE), and of strains analysed by the National Reference Center for anti-microbial resistance (NRC) aimed to describe the epidemiology of emerging extensively drug-resistant bacteria (eXDR) in France and control measures implemented in hospital settings. Patients and methodsAll HAI-EWRS notifications of eXDR received at the national level and all eXDR strains received at the NRC between January 1, 2018 and January 31, 2018 were analysed. Variables analysed were number of cases, number of strains, resistance mechanism, sample type, link with a foreign country, and control measures implemented. ResultsIn 2018, 1704 CPE notifications and 315 GRE notifications were reported in France, with an increasing trend since 2012 (×6 for CPE, ×3 for GRE), from respectively 364 and 155 hospitals (+66% for CPE, +57% for GRE since 2012). eXDR strains were mainly isolated from rectal screening swabs. Notifications with patients receiving standard precautions were more often associated with outbreaks than notifications with patients receiving contact precautions at admission. NRC received 2674 CPE strains and 775 GRE strains in 2018 (×8.3 and ×2.8 compared with 2012). ConclusionThe increasing annual number of eXDR notifications and eXDR strains received by the NRC is multifactorial but reflects a worrying spread of eXDR in France. The number of infections remains low, but this article shows that existing recommendations are not fully implemented.

Methicillin-resistant Staphylococcus aureus and glycopeptide-resistant enterococci in fecal samples of birds from South-Eastern Poland

BackgroundThe incidence of human infection and colonization with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) has increased in the recent years. Environmental sources, including bird droppings, might play an important role as resistance reservoirs.ResultsFresh fecal samples were collected from rooks and wild-living birds during the autumn-winter period of 2016/2017, and tested for the presence of bacteria associated with human diseases. Besides bacteria representing the genera Enterococcus, Campylobacter, Escherichia, and Staphylococcus, Enterobacter, Citrobacter, Proteus, Hafnia, and Pseudomonas were also identified. The susceptibility of S. aureus and Enterococcus spp. isolates to methicillin, and vancomycin and teicoplanin, respectively, was analyzed to assess the avian wildlife as a reservoir of MRSA and VRE strains. Twenty-two percent of all S. aureus isolates were methicillin-resistant. These strains were screened by polymerase chain reaction (PCR), using the most widely used primer sets specific for the mecA gene. Twenty percent of all Enterococcus strains were phenotypically vancomycin-resistant. The presence of van resistance genes in these strains was investigated by PCR using vanA and vanB gene-specific primers. A good correlation between mecA gene detection and disc diffusion data was observed, while some discrepancy was noted between the PCR data and the vancomycin/teicoplanin phenotypic resistance pattern. The incidence of strains resistant to methicillin and glycopeptide antibiotics in wild-living birds was twice that in rooks.ConclusionsThe study suggests that rooks from urban areas and passerine birds from the natural habitat carry antibiotic-resistant Enterococcus spp. and S. aureus strains, probably reflecting the presence of such isolates in the environmental food sources.

Once-daily tigecycline for outpatient parenteral antibiotic therapy: a single-centre observational study.

BackgroundTigecycline has potential utility in the treatment of complex polymicrobial infections or those caused by MDR organisms in the ambulatory care setting owing to its breadth of antimicrobial coverage. Whilst licensed for twice-daily IV administration, its long half-life permits once-daily administration, which may facilitate successful outpatient parenteral antibiotic therapy (OPAT).MethodsA retrospective case series of patients receiving once-daily tigecycline under OPAT was analysed at a single-centre NHS acute hospital (January 2016–June 2018). Patient demographics, including comorbidities, antimicrobial indication, concurrent antimicrobial therapies, treatment duration and adverse events related to treatment were recorded using medical records. Treatment outcomes were defined using the BSAC National Outcomes Registry System (NORS).ResultsA total of 25 treatment episodes (24 individual patients) were analysed. The most common indications were bone and joint infections (n = 8) and intra-abdominal infections (n = 7). MDR organisms were common, including ESBL-producing Enterobacterales (n = 13) and glycopeptide-resistant enterococci (n = 4). Median treatment duration was 18 days. Nineteen of 25 (76%) cases had complete cure of treatment, 3 patients experienced treatment-related adverse reactions necessitating cessation of therapy and 3 experienced failure due to disease progression. Eight patients experienced non-limiting adverse effects, such as nausea, vomiting and rash, and one patient had a transient rise in amylase 3 times the upper normal limit (with no evidence of pancreatitis).ConclusionsOnce-daily tigecycline can be successfully used for management of complex infections in the OPAT setting, with predominantly mild adverse effects, which can be managed with antiemetics or slow administration.

Identification, antimicrobial susceptibility and virulence factors of Enterococcus species isolated from clinical specimens at an Indian tertiary care hospital

Purpose: Enterococcus species have increasingly emerged as important pathogens in serious nosocomial and community acquired infections. The objective was to determine species identification, evaluate current susceptibility pattern and characterize various virulence determinants among clinical isolates of enterococci at an Indian hospital. Methods & Materials: Consecutive isolates from clinical specimens (April to September 2017) were included. Species identification was performed by conventional biochemical tests. Antimicrobial susceptibility testing was as per CLSI guidelines, including detection of high-level gentamicin resistance (HLGR), high-level streptomycin resistance (HLSR) and glycopeptide resistant enterococci (GRE). All screen-positive GRE isolates were investigated by PCR for species confirmation and presence of vanA/ vanB genes. Virulence genes asa1, esp, hyl, cyl, and gelE were investigated by molecular methods. Haemolysin and biofilm production were studied phenotypically. Results: Of 71 strains isolated, 57 (80.3%), 9 (12.7%) and 5 (7.0%) were from urine, pus and blood respectively consisting of E. faecalis (45, 63.4%), E. faecium (20, 28.2%), E. durans (3, 4.2%), and E. avium, E. hirae, E. mundtii (1, 1.4%). Six (8.4%) were GRE (5 E. faecium, 1 E. faecalis), all vanA phenotypically and genotypically. HLGR and HLSR was observed in 41 (57.7%) and 23 (32.4%) isolates respectively, higher in E. faecium compared to E. faecalis (85.0% and 40.0% vs 46.6% and 28.8%). Resistance to other antibiotics was also higher in E. faecium. All were susceptible to daptomycin. Hemolysin activity was significantly higher in E. faecalis compared to E. faecium (55.5% vs 0%). Biofilm production was observed in 23 (32.4%) isolates. Virulence genes detected were asa1 (9, 45%), gel (9, 45%), esp (7, 35%), cyt (6, 30%) and hyl (1, 5%). Frequency of asa, gel, and cyl was higher in E. faecalis than E. faecium (7, 7, 5 vs 2, 2, 1), whereas esp and hyl was more in E. faecium compared to E. faecalis (5, 1 vs 0, 0). Conclusion: Prevalence of a wide variety of Enterococcus species in clinical samples together with their variable antimicrobial susceptibility pattern and virulence traits emphasizes the need for their routine speciation and susceptibility testing which may help control the spread of multidrug resistant Enterococcus species.

Factors associated with acquisition of glycopeptide-resistant enterococci during a single-strain outbreak.

The aim of our study was to describe and to investigate the factors associated with glycopeptide-resistant enterococci (GRE) acquisition during a single-strain outbreak which occurred in several wards of hospital from September 2013 to January 2014. We designed a case-control study. Analyses were performed using Bayesian methods. Univariate logistic regressions with informative priors from published studies were conducted. A multivariate model was build including variables with a probability of odd-ratio exceeding one (Pr) &gt;85% or &lt;15%. Thirteen cases and 52 controls were recruited. The description of this outbreak highlighted the importance to quickly detect patients at risk of GRE carriage in order to implement the isolation measures and to transfer to dedicated department if they are effectively carriers. Following multivariate analysis, antibiotics during hospitalisation (Pr = 0.968), number of hospitalisation days in the year (Pr = 0.964), antacids intake (Pr = 0.878) (with a risk increase), immunosuppression (Pr = 0.026) and isolation measures (Pr = 0.003) (both with protective effect) were associated with GRE acquisition. The use of Bayesian statistics was useful because of our study's small population size and prior information availability.

Epidemiology of invasive infections caused by vancomycin sensitive and resistant enterococcal strains among oncology patients at the National Cancer Institute of Sri Lanka from 1st of July 2012 to 31st of July 2013

Introduction and Objectives: Enterococci have traditionally been regarded as low grade pathogens but have emerged as an increasingly important cause of nosocomial infections in the last decade. While the Enterococcus faecalis remains the predominate species in clinical infection, Enterococcus faecium isolates are increasing in proportion. This study was carried out to describe the epidemiology of invasive enterococcal infections among oncology patients at the National Cancer Institute of Sri Lanka (NCISL). Methods: 60 patients with invasive enterococcal infections, who were treated as inward patients at the National Cancer Institute of Sri Lanka from 1.7.2012 to 31.7 21013 whose samples were sent for microbiological investigation were included in this study. Speciation of the isolates was done by using a rapid manual analytic system (RapID STR panel-Oxoid). Vancomycin sensitivity was assessed in all enterococcal isolates by disc diffusion method, agar dilution screening method (CLSI guideline 2013)16 and detection of minimum inhibitory concentration (MIC) by using Vancomycin gradient strips. Teicoplanin MIC was assessed only in vancomycin resistant isolates using teicoplanin gradient strips. Associated factors for getting an infection with vancomycin resistant strains were assessed using a data extraction sheet. Results: The incidence of invasive enterococcal infections among oncology patients was 1.1 per 1000 admissions. The incidence of invasive enterococcal infection caused by vancomycin resistant species was 0.16 per 1000 admissions. E. faecium was the dominant species causing invasive enterococcal infections (55%). Using the gradient strip method for determination of vancomycin MIC as the gold standard, the screening agar dilution method had 100% sensitivity and specificity and the disc diffusion test had a low specificity (77.8%). Almost all the participants (96.6%) had acquired the enterococcal infection from the hospital. Vancomycin resistant infections were more common in patients who had haematological malignancies, who were treated with 3rd generation cephalosporins and cytotoxic chemotherapy drugs. Conclusions: E. faecium is the dominant species causing invasive enterococcal infections in oncology patients (55%) and phenotypically compatible with the VanA phenotype of glycopeptide resistant enterococci.

Antibiotic resistance in Swiss nursing homes: analysis of National Surveillance Data over an 11-year period between 2007 and 2017

BackgroundWe evaluated data from isolates of nursing home (NH) patients sent to the Swiss centre for antibiotic resistance (ANRESIS). We focussed on carbapenem-resistance (CR) among Gram-negative pathogens, extended-spectrum cephalosporin-resistant (ESC-R) Escherichia coli/Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and glycopeptide-resistant enterococci (GRE).MethodsNH patient isolates from 01/2007 to 10/2017 were extracted. Temporal trends in resistance were described and risk factors associated with ESC-R and MRSA were assessed. For every administrative subdivision in Switzerland (i.e. canton), we calculated a coverage rate, defined as number of beds of governmentally-supported nursing homes, which sent ≥1 isolate in each 2014, 2015, and 2016, divided by the total number of supported beds.ResultsWe identified 16′804 samples from 9′940 patients. A majority of samples (12′040; 71.6%) originated from the French/Italian speaking part of Switzerland. ESC-R E. coli increased from 5% (16/299) in 2007 to 22% (191/884) in 2017 (P < 0.01), whereas MRSA decreased from 34% (35/102) to 26% (21/81) (P < 0.01). Provenience from the German (vs. French/Italian) speaking part of Switzerland was associated with decreased risk for ESC-R (OR 0.5, 95% CI 0.4–0.7) and for MRSA (OR 0.1, 95% CI 0.1–0.2). CR among Pseudomonas aeruginosa was 10% (105/1096) and showed an increasing trend over time; CR among Enterobacteriaceae (37/12′423, 0.3%) and GRE (5/1′273, 0.4%) were uncommon. Overall coverage rate was 9% (range 0–58% per canton). There was a significant difference between the French/Italian (median 13%, interquartile range [IQR] 4–43%) and the German speaking cantons (median 0%, IQR 0–5%) (P = 0.02).ConclusionsESC-R among E. coli is emerging in Swiss NHs, whereas MRSA show a declining trend over time. A minority of NHs are represented in ANRESIS, with a preponderance of institutions from the French/Italian speaking regions. Efforts should be undertaken to improve resistance surveillance in this high-risk setting.

The use of high-throughput sequencing to investigate an outbreak of glycopeptide-resistant Enterococcus faecium with a novel quinupristin-dalfopristin resistance mechanism

High-throughput sequencing (HTS) has successfully identified novel resistance genes in enterococci and determined clonal relatedness in outbreak analysis. We report the use of HTS to investigate two concurrent outbreaks of glycopeptide-resistant Enterococcus faecium (GRE) with an uncharacterised resistance mechanism to quinupristin-dalfopristin (QD). Seven QD-resistant and five QD-susceptible GRE isolates from a two-centre outbreak were studied. HTS was performed to identify genes or predicted proteins that were associated with the QD-resistant phenotype. MLST and SNP typing on HTS data was used to determine clonal relatedness. Comparative genomic analysis confirmed this GRE outbreak involved two distinct clones (ST80 and ST192). HTS confirmed the absence of known QD resistance genes, suggesting a novel mechanism was conferring resistance. Genomic analysis identified two significant genetic determinants with explanatory power for the high level of QD resistance in the ST80 QD-resistant clone: an additional 56aa leader sequence at the N-terminus of the lsaE gene and a transposon containing seven genes encoding proteins with possible drug or drug-target modification activities. However, HTS was unable to conclusively determine the QD resistance mechanism and did not reveal any genetic basis for QD resistance in the ST192 clone. This study highlights the usefulness of HTS in deciphering the degree of relatedness in two concurrent GRE outbreaks. Although HTS was able to reveal some genetic candidates for uncharacterised QD resistance, this study demonstrates the limitations of HTS as a tool for identifying putative determinants of resistance to QD.

Efficiency of different control measures for preventing carbapenemase-producing enterobacteria and glycopeptide-resistant Enterococcus faecium outbreaks: a 6-year prospective study in a French multihospital institution, January 2010 to December 2015.

An infection control programme was implemented in a 21,000-bed multihospital institution for controlling the spread of carbapenemase-producing Enterobacteriaceae (CPE) and glycopeptide-resistant Enterococcus faecium (GRE), classified as ‘emergent extensively drug-resistant bacteria’ (eXDR) in France. We evaluated factors associated with outbreaks occurrence (n = 103), which followed 901 eXDR introductions (index case followed or not by secondary cases) from 2010 to 2015. In univariate analysis, knowing that patients had been hospitalised abroad, bacterial species (GRE vs CPE, as well as the CPE Klebsiella pneumoniae compared with the other Enterobacteriaceae species) and type of measures implemented within the first 2 days of hospitalisation were associated with outbreaks occurrence, but not the type of wards where carriers were hospitalised, nor the eXDR colonisation or infection status. In multivariate analysis, occurrence of outbreaks was significantly lower when contact precautions (odds ratio (OR): 0.34; 95% confidence interval (CI): 0.22–0.54) and even more when dedicated nursing staff (OR: 0.09; 95% CI: 0.02–0.39) were implemented around eXDR index cases within the first 2 days of hospitalisation (p < 10 − 3). GRE introductions were more frequently associated with occurrence of outbreaks than CPE (OR: 3.58; 95% CI: 2.32–5.51, p < 10 − 3). A sustained and coordinated strategy is efficient to limit the spread of eXDR at the scale of a large health institution.

VanA Mediated Glycopeptide Resistant Enterococcus faecium (GRE) Infection in an Elderly Patient with Chronic Kidney Disease – A Case Report

VanA Mediated Glycopeptide Resistant Enterococcus faecium (GRE) Infection in an Elderly Patient with Chronic Kidney Disease – A Case Report

First outbreak of colonization by linezolid- and glycopeptide-resistant Enterococcus faecium harbouring the cfr gene in a UK nephrology unit

To describe an outbreak of colonization by linezolid- and glycopeptide-resistant Enterococcus faecium harbouring the cfr gene in a UK nephrology unit. Isolates of linezolid-resistant E.faecium were typed by pulsed-field gel electrophoresis (PFGE), and examined by polymerase chain reaction (PCR) and sequencing for the transmissible cfr gene that confers resistance to linezolid. Enhanced environmental cleaning, initial and weekly screening of all patients, and monitoring of adherence to standard infection control precautions were implemented. Five patients with pre-existing renal disease were found to have rectal colonization with linezolid-resistant E.faecium over a two-week period. The index case was a 57-year-old male from India who had travelled to the UK. One patient also had a linezolid-resistant E.faecium of a different PFGE profile isolated from a heel wound. All isolates were confirmed to harbour the cfr gene by PCR and Sanger sequencing, and all were resistant to glycopeptides (VanA phenotype). This article describes the first UK outbreak with a single strain of linezolid- and glycopeptide-resistant E.faecium harbouring the cfr gene, affecting five patients in a nephrology unit. Following the implementation of aggressive infection control measures, no further cases were detected beyond a two-week period.

Evaluation of Susceptibility of Glycopeptide-resistant and Glycopeptide-sensitive Enterococci to Commonly Used Biocides in a Super-speciality Hospital: A Pilot Study.

Context:Although existence of a probable association between glycopeptide and biocide resistance among enterococci has often been hypothesized, all studies conducted so far on this subject have been inconclusive.Aims:The aim of this study was to explore the possibility of the existence of an association between glycopeptide resistance and reduced susceptibility to biocides among Enterococcus spp.Settings and Design:This was a pilot study conducted in a super-speciality hospital situated in New Delhi, India, between June and November, 2015.Patients and Methods:Fourteen isolates of Enterococcus spp. obtained from various clinical samples of inpatients were subjected to susceptibility testing by modified Kirby-Bauer disk diffusion method to the following antibiotics: ampicillin (30 μg), gentamicin (120 μg), linezolid (30 μg), teicoplanin (30 μg), and vancomycin (30 μg). Based on the preliminary glycopeptide susceptibility results, all the isolates were classified into glycopeptide-sensitive and glycopeptide-resistant groups, respectively. Isolates belonging to both of these groups were subjected to tube dilution method for determining minimum inhibitory concentration of three biocides, namely, sodium hypochlorite, povidone-iodine, and absolute ethanol, respectively. Minimum bactericidal concentration of these disinfectants was also determined as per standard guidelines.Statistical Analysis Used:Not applicable.Results:More number of glycopeptide-sensitive strains exhibited reduced susceptibility to sodium hypochlorite than glycopeptide-resistant strains of enterococci. However, more number of glycopeptide-resistant isolates exhibited lower susceptibility to povidone-iodine than glycopeptide-sensitive isolates of enterococci. Both glycopeptide-sensitive and glycopeptide-resistant enterococci were equally susceptible to absolute ethanol.Conclusions:It seems that biocide resistance is an important issue and may have links with antibiotic resistance. This study points towards a possible association between glycopeptide resistance and reduced susceptibility to povidone iodine among enterococci. More studies should be conducted in order to further explore this supposedly enigmatic issue.

Bacterial spectrum and antimicrobial-resistance pattern of bloodstream infections in neutropenic and non-neutropenic adult cancer patients

Background: Bloodstream infections (BSI) in cancer patients remain associated with significant morbidity and mortality. The choice of an empirical antibiotic regimen is usually based on the local epidemiology of the microorganisms and their antimicrobial susceptibility profile. We present the spectrum and the antimicrobial susceptibility of the causative agents of BSI in adult cancer patients in East Sussex Healthcare Trust (ESHT), UK. Materials and Methods: This retrospective study was conducted at ESHT from January 2006 to December 2015. Demographic and laboratory data were collected from the pathology information system. Results: A total of 640 episodes of BSI occurred in 297 patients (159 male). Of the 297 patients, 239 (80%) had haematology malignancies, whereas 54 (18%) had solid organ tumours. Four patients had both. Majority of BSI (383, 60% episode) occurred in neutropenic patients. A total of 802 organisms (477 [59%] and 325 [41%] organisms from neutropenic and non-neutropenic patients, respectively) were isolated. Of 802, 406 (51%) Gram-positive and 386 (49%) Gram-negative organisms were isolated. Seven Mycobacterium species and three Candida species were isolated. Most common organisms in neutropenic patients were coagulase-negative Staphylococcus (CoNS) (22%), Klebsiella species (14%), Escherichia coli (13%), Streptococcus species (10%) and Pseudomonas species (10%). In non-neutropenic patients, CoNS (29%), E. coli (11%), Pseudomonas species (8%), Streptococcus species (7%) and Klebsiella species (5%) were isolated. Twelve glycopeptide-resistant Enterococci (26% of total 47 Enterococcus species) were isolated. Four methicillin-resistant Staphylococcus aureus (14% of total 28 S. aureus) were isolated. Furthermore, 15 extended-spectrum β-lactamase producing Gram-negative bacilli were isolated. Among Gram-negative organisms, more than 91% isolates were sensitive to piperacillin/tazobactam, ceftazidime and ciprofloxacin and higher sensitivity rates (>95%) were recorded in gentamicin, polymyxin B and meropenem. Conclusion: This study highlights an ongoing trend towards Gram-positive organisms causing BSI in cancer patients. The antimicrobial regimens used in our institution are highly effective against commonly isolated organisms. The identification and the antimicrobial susceptibility of the microorganisms causing BSI in cancer patients remain important to develop antimicrobial treatment strategies including antimicrobial guidelines as well as infection control and to prevent the spread of antimicrobial resistance.