Vancomycin-susceptible Enterococcus Faecalis Research Articles

Prevalence and predictors of multidrug-resistant bacteremia in liver cirrhosis.

Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24-9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.

Prevalence and Molecular Characterization of Vancomycin Variable Enterococcus faecium Isolated From Clinical Specimens.

Vancomycin variable Enterococcus (VVE) bacteria are phenotypically susceptible to vancomycin, but they harbor the vanA gene. We aimed to ascertain the prevalence of VVE among clinically isolated vancomycin-susceptible Enterococcus faecium (VSE) isolates, as well as elucidate the molecular characteristics of the vanA gene cluster within these isolates. Notably, we investigated the prevalence and structure of the vanA gene cluster of VVE. Between June 2021 and May 2022, we collected consecutive, non-duplicated vancomycin-susceptible Enterococcus faecium (VSE) samples. Real-time PCR was performed to detect the presence of vanA, vanB, and vanC. Overlapping PCR with sequencing and whole-genome sequencing were performed for structural analysis. Sequence types (STs) were determined by multilocus sequence typing. Exposure testing was performed to assess the ability of the isolates to acquire vancomycin resistance. Among 282 VSE isolates tested, 20 isolates (7.1%) were VVE. Among them, 17 isolates had partial deletions in the IS1216 or IS1542 sequences in vanS (N=10), vanR (N=5), or vanH (N=2). All VVE isolates belonged to the CC17 complex and comprised five STs, namely ST17 (40.0%), ST1421 (25.0%), ST80 (25.0%), ST787 (5.0%), and ST981 (5.0%). Most isolates were related to three hospital-associated clones (ST17, ST1421, and ST80). After vancomycin exposure, 18 of the 20 VVEs acquired vancomycin resistance. Considering the high reversion rate, detecting VVE by screening VSE for vanA is critical for appropriate treatment and infection control.

Genetic analysis of vancomycin-variable Enterococcus faecium clinical isolates in Italy

PurposeTo investigate the occurrence of vancomycin-variable enterococci (VVE) in a hospital in central Italy.MethodsvanA positive but vancomycin-susceptible Enterococcus faecium isolates (VVE-S) were characterized by antibiotic susceptibility tests, molecular typing (PFGE and MLST), and WGS approach. The reversion of VVE-S to a resistant phenotype was assessed by exposure to increasing vancomycin concentrations, and the revertant isolates were used in filter mating experiments. qPCR was used to analyze the plasmid copy number.ResultsEleven putative VVE-S were selected. WGS revealed two categories of vanA cluster plasmid located: the first type showed the lack of vanR, the deletion of vanS, and an intact vanH/vanA/vanX cluster; the second type was devoid of both vanR and vanS and showed a deletion of 544-bp at the 5′-end of the vanH. Strains (n = 7) carrying the first type of vanA cluster were considered VVE-S and were able to regain a resistance phenotype (VVE-R) in the presence of vancomycin, due to a 44-bp deletion in the promoter region of vanH/vanA/vanX, causing its constitutive expression. VVE-R strains were not able to transfer resistance by conjugation, and the resistance phenotype was unstable: after 11 days of growth without selective pressure, the revertants were still resistant but showed a lower vancomycin MIC. A higher plasmid copy number in the revertant strains was probably related to the resistance phenotype.ConclusionWe highlight the importance of VVE transition to VRE under vancomycin therapy resulting in a potential failure treatment. We also report the first-time identification of VVE-S isolates pstS-null belonging to ST1478.

Role of membrane vesicles in the transmission of vancomycin resistance in Enterococcus faecium

Clonal transmission and horizontal gene transfer (HGT) contribute to the spread of vancomycin-resistant enterococci (VRE) in global healthcare. Our study investigated vesiduction, a HGT mechanism via membrane vesicles (MVs), for vanA and vanB genes that determine vancomycin resistance. We isolated MVs for VRE of different sequence types (STs) and analysed them by nanoparticle tracking analysis. Selected MV samples were subjected to DNA sequence analysis. In resistance transfer experiments, vancomycin-susceptible enterococci were exposed to MVs and bacterial supernatants of VRE. Compared to bacteria grown in lysogeny broth (MVs/LB), cultivation under vancomycin stress (MVs/VAN) resulted in increased particle concentrations of up to 139-fold (ST80). As a key finding, we could show that VRE isolates of ST80 and ST117 produced remarkably more vesicles at subinhibitory antibiotic concentrations (approx. 9.2 × 1011 particles/ml for ST80 and 2.4 × 1011 particles/ml for ST117) than enterococci of other STs (range between 1.8 × 1010 and 5.3 × 1010 particles/ml). In those MV samples, the respective resistance genes vanA and vanB were completely verifiable using sequence analysis. Nevertheless, no vancomycin resistance transfer via MVs to vancomycin-susceptible Enterococcus faecium was phenotypically detectable. However, our results outline the potential of future research on ST-specific MV properties, promising new insights into VRE mechanisms.

Assessing Clinical Outcomes of Vancomycin Treatment in Adult Patients with Vancomycin-Susceptible Enterococcus faecium Bacteremia.

Enterococcal bacteremia is associated with high mortality and long-term hospitalization. Here, we aimed to investigate the clinical outcomes and evaluate the risk factors for mortality in adult patients treated with vancomycin (VCM) for vancomycin-susceptible Enterococcus faecium (E. faecium) bacteremia. This is a retrospective, record-based study. The data were collected from inpatients at a single university hospital between January 2009 and December 2020. The area under the curve (AUC) of VCM was calculated using the Bayesian approach. The primary outcome was a 30-day in-hospital mortality. A univariate analysis showed significant differences in the concomitant use of vasopressors, history of the use of no clinically relevant activity antimicrobial agents against E. faecium, VCM plasma trough concentration, and renal dysfunction during VCM administration between the 30-day in-hospital mortality and survival groups. However, the groups' AUC/minimum inhibitory concentration (MIC) were not significantly different. A multivariate analysis suggested that concomitant vasopressors may be an independent risk factor for 30-day in-hospital mortality (odds ratio, 7.81; 95% confidence interval, 1.16-52.9; p = 0.035). The VCM plasma trough concentrations and the AUC/MIC in the mortality group were higher than those in the surviving group. No association between the AUC/MIC and the treatment effect in E. faecium bacteremia was assumed, because the known, target AUC/MIC were sufficiently achieved in the mortality group. There may be no association between the AUC/MIC and the treatment effect in E. faecium bacteremia. When an immunocompromised host develops E. faecium bacteremia with septic shock, especially when a vasopressor is used in a patient with unstable hemodynamics, it may be difficult to treat it, despite efforts to ensure the appropriate AUC/MIC and therapeutic vancomycin concentration levels.

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.

1038. In Vitro Activity of Tebipenem, an Orally Available Carbapenem Agent, Against a Collection of Surveillance Gram-Positive Clinical Isolates

BackgroundTebipenem, an orally bioavailable carbapenem administered as a pro-drug, completed a phase 3 clinical trial for evaluating its safety and efficacy for the treatment of complicated urinary tract infection and acute pyelonephritis. The purpose of this study was to investigate the in vitro activity of tebipenem and comparator agents, including ertapenem and meropenem, against a recent collection of Gram-positive isolates associated with clinical infections.MethodsThe susceptibility of 580 Gram-positive organisms were tested, including: methicillin-susceptible Staphylococcus aureus (MSSA, 489 isolates), methicillin-susceptible Staphylococcus epidermidis (MSSE, 31), other methicillin-susceptible coagulase-negative staphylococci (MSCoNS, 29), and vancomycin-susceptible Enterococcus faecalis (31). The isolates were collected primarily from pneumonia in hospitalized patients (498 isolates; 85.9%), urinary tract infections (42 isolates; 7.2%), and bloodstream infections (38 isolates; 6.6%). Organisms were tested using reference broth microdilution methods in a central laboratory. ResultsTebipenem had an MIC90 value of 0.03 mg/L against MSSA and 0.015 mg/L against MSSE isolates. Ertapenem MIC90 values were 8-fold higher against MSSA (MIC90, 0.25 mg/L) and 32-fold higher against MSSE (MIC90, 0.5 mg/L). Tebipenem displayed an MIC90 value of 0.03 mg/L against MSCoNS species other than S. epidermidis. This result was 8- and 32-fold lower than those of meropenem (MIC90, 0.25 mg/L) and ertapenem (MIC90, 1 mg/L), respectively. Tebipenem inhibited all E. faecalis isolates at ≤1 mg/L (MIC90, 1 mg/L), with an MIC90 value at least 2-fold lower than meropenem (MIC90, >1 mg/L) and 16-fold lower than ertapenem (MIC90, >8 mg/L).ConclusionTebipenem displayed potent activity against methicillin susceptible staphylococci, including MSSA, MSSE, and other MSCoNS. Tebipenem in vitro activity was greater than meropenem and ertapenem when tested against E. faecalis. These data indicate that tebipenem may be an option for treating urinary tract infections caused by these organisms or as an empiric option to provide broader coverage against Gram-negative and -positive organisms. Disclosures S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Abby L. Klauer, n/a, Cidara Therapeutics, Inc. (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Nicole Cotroneo, Spero Therapeutics (Employee, Shareholder) Ian A. Critchley, Ph.D., Spero Therapeutics (Employee, Shareholder) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)

1260. In Vitro Activity of Eravacycline Against Clinically Significant Bacteria Isolated from Patients with Cancer

Abstract Background Bacterial infections are common in patients with cancer (PWC). Many bacteria have developed resistance to currently used antibiotics, posing therapeutic challenges. we evaluated the in vitro activity of eravacycline (a novel fluorocycline) against clinical bacteria recently (2018-2019) isolated from PWC. Methods All 565 isolates tested were from blood cultures. CLSI approved broth microdilution method was used. Appropriate ATCC controls were included. MIC50, MIC90, MIC ranges and percent susceptibility calculations were made using FDA breakpoints when available. Eravacycline susceptibility breakpoint for most Gram-positive organisms (GPO) is ≤ 0.06 mg/L and for Enterobacterales is ≤ 0.5 mg/L. Results Eravacycline had potent activity against Staphylococcus aureus (methicillin-susceptible and resistant strains), oxacillin-susceptible coagulase-negative staphylococci (CoNS) including Staphylococcus lugdunensis, viridans group streptococci, beta-hemolytic streptococci. Streptococcus pneumoniae. Bacillus spp., Corynebacterium spp., and Micrococcus spp. It was slightly less active against oxacillin-resistant CoNS, and vancomycin-susceptible Enterococcus faecalis (MIC90 0,125 mg/L respectively) and was moderately active against vancomycin-resistant Enterococcus faecium (MIC50, 0.06, and MIC90. 0.25 mg/L). Eravacycline had potent activity against Escherichia coli (including ESBL producing strains), Citrobacter spp., and non-ESBL Klebsiella spp. Eravacycline inhibited 83% of ESBL positive K. pneumoniae, 83% of Enterobacter cloacae, and 80% of carbapenem-resistant Enterobacteriaceae (CRE) isolates at ≤ 0.5 mg/L. The presence of ESBLs increased MIC90 value no more than 2 fold. Eravacycline was also active against many non-fermentative GNB (Achromobacter spp., Acinetobacter spp., Sphingomonas paucimobilis, and Stenotrophomonas maltophilia). Table 1. Percent Susceptibility of Gram-negative isolates to Eravacycline Table 2. Percent Susceptibility of Gram-positive isolates to Eravacycline Conclusion Our data demonstrate that eravacycline has promising activity against clinically significant bacterial pathogens isolated from PWC including many drug resistant strains such as CRE and non--fermentative GNB. it might play an important role in the treatment of bacterial infections in PWC and warrants clinical evolution in this setting. Disclosures Samuel L. Aitken, PharmD, MPH, BCIDP, Melinta Therapeutoics (Individual(s) Involved: Self): Consultant, Grant/Research Support Kenneth Rolston, MD, Tetraphase Pharmaceuticals (Grant/Research Support)

Association of vancomycin trough concentration on the treatment outcome of patients with bacteremia caused by Enterococcus species

BackgroundPharmacokinetic-pharmacodynamic (PK/PD) targets of vancomycin therapy have been recognized for methicillin-resistant Staphylococcus aureus infections but not for other gram-positive bacterial infections. Therefore, we investigated whether vancomycin concentration targets such as the trough level and ratio of the area under the curve to minimum inhibitory concentration (AUC/MIC) are associated with the treatment outcome in enterococcal bacteremia.MethodsA retrospective cohort analysis enrolled patients with bacteremia caused by vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis who were treated with vancomycin from January 2007 to December 2017 at a tertiary hospital located in Seoul, South Korea. Patients without vancomycin concentrations were excluded from the study. The primary outcome was 28-day all-cause mortality.ResultsA total of 37 patients were enrolled—26 with E. faecium infection and 11 with E. faecalis infection. The 28-day all-cause mortality rate was 21.6 %. In univariate analysis, vancomycin trough level (≤ 15 µg/mL; p = 0.042), age (p = 0.044), and septic shock (p = 0.049) were associated with 28-day mortality but not AUC24/MIC (> 389; p = 0.479). In multivariate analysis, vancomycin trough concentration (≤ 15 µg/mL; p = 0.041) and younger age (p = 0.031) were associated with 28-day mortality in patients with enterococcal bacteremia.ConclusionsIn this study, a vancomycin trough level of 15 µg/mL or lower was associated with 28-day mortality in enterococcal bacteremia. However, relatively large prospective studies are needed to examine the efficacy of vancomycin PK/PD parameters in patients with enterococcal bacteremia.

A nosocomial cluster of vancomycin resistant enterococci among COVID-19 patients in an intensive care unit

BackgroundCurrently, hospitals have been forced to divert substantial resources to cope with the ongoing coronavirus disease 2019 (COVID-19) pandemic. It is unclear if this situation will affect long-standing infection prevention practices and impact on healthcare associated infections. Here, we report a nosocomial cluster of vancomycin-resistant enterococci (VRE) that occurred on a COVID-19 dedicated intensive care unit (ICU) despite intensified contact precautions during the current pandemic. Whole genome sequence-based typing (WGS) was used to investigate genetic relatedness of VRE isolates collected from COVID-19 and non-COVID-19 patients during the outbreak and to compare them to environmental VRE samples.MethodsFive VRE isolated from patients (three clinical and two screening samples) as well as 11 VRE and six vancomycin susceptible Enterococcus faecium (E. faecium) samples from environmental sites underwent WGS during the outbreak investigation. Isolate relatedness was determined using core genome multilocus sequence typing (cgMLST).ResultsWGS revealed two genotypic distinct VRE clusters with genetically closely related patient and environmental isolates. The cluster was terminated by enhanced infection control bundle strategies.ConclusionsOur results illustrate the importance of continued adherence to infection prevention and control measures during the COVID-19 pandemic to prevent VRE transmission and healthcare associated infections.

Update on the in vitro activity of dalbavancin against indicated species (Staphylococcus aureus, Enterococcus faecalis, β-hemolytic streptococci, and Streptococcus anginosus group) collected from United States hospitals in 2017–2019

This study updates dalbavancin activity against contemporary (2017–2019) isolates of indicated species/groups (n = 16,451). Isolates from 71 hospitals were tested by broth microdilution method. All isolates were susceptible to dalbavancin. Dalbavancin MIC50/90 values remained stable for Staphylococcus aureus, vancomycin-susceptible Enterococcus faecalis, β-hemolytic streptococci, and Streptococcus anginosus group since its clinical approval.

Antimicrobial Activity of Telavancin Tested In Vitro Against a Global Collection of Gram-Positive Pathogens, Including Multidrug-Resistant Isolates (2015-2017).

This study evaluated the in vitro antimicrobial activity of telavancin against a large collection of Gram-positive pathogens of clinical importance, which were collected worldwide from 2015 through 2017, including methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, Enterococcus spp., β-hemolytic streptococci (BHS), Streptococcus pneumoniae, and viridans group streptococci (VGS). This report completes 7 years of continuous surveillance data for telavancin using the approved reference method for in vitro testing methodology that includes the addition of polysorbate 80. For isolates collected from 2015 through 2017, telavancin exhibited potent activity against the following species and groups that have Clinical and Laboratory Standards Institute (CLSI)-approved interpretive criteria: MRSA (MIC90 value, 0.06 μg/mL; 100% susceptible), vancomycin-susceptible Enterococcus faecalis (MIC90 value, 0.25 μg/mL; 99.9% susceptible), BHS (MIC90 value, 0.03 μg/mL; 100% susceptible), and VGS (MIC90 value, 0.03 μg/mL; 99.0% susceptible). Importantly, telavancin maintained excellent antimicrobial activity against multidrug-resistant subsets of these pathogen groups and against ceftaroline-nonsusceptible (telavancin MIC90 value, 0.06 μg/mL; 100% susceptible) and ceftaroline-resistant (telavancin MIC90 value, 0.12 μg/mL; 100% susceptible) S. aureus isolates.

Does vancomycin resistance increase mortality in Enterococcus faecium bacteraemia after orthotopic liver transplantation? A retrospective study

BackgroundThe relevance of vancomycin resistance in enterococcal blood stream infections (BSI) is still controversial. Aim of this study was to outline the effect of vancomycin resistance of Enterococcus faecium on the outcome of patients with BSI after orthotopic liver transplantation (OLT).MethodsThe outcome of OLT recipients developing BSI with vancomycin-resistant (VRE) versus vancomycin-susceptible Enterococcus faecium (VSE) was compared based on data extraction from medical records. Multivariate regression analyses identified risk factors for mortality and unfavourable outcomes (defined as death or prolonged intensive care stay) after 30 and 90 days.ResultsMortality was similar between VRE- (n = 39) and VSE- (n = 138) group after 30 (p = 0.44) or 90 days (p = 0.39). Comparable results occurred regarding unfavourable outcomes. Mean SOFANon-GCS score during the 7-day-period before BSI onset was the independent predictor for mortality at both timepoints (HR 1.32; CI 1.14–1.53; and HR 1.18; CI 1.08–1.28). Timely appropriate antibiotic therapy, recent ICU stay and vancomycin resistance did not affect outcome after adjusting for confounders.ConclusionVancomycin resistance did not influence outcome among patients with Enterococcus faecium bacteraemia after OLT. Only underlying severity of disease predicted poor outcome among this homogenous patient population.Trial registrationThis study was registered at the German clinical trials register (DRKS-ID: DRKS00013285).

Risk factors and outcome associated with the acquisition of linezolid-resistant Enterococcus faecalis

ObjectivesLinezolid is a synthetic oxazolidinone antibiotic frequently used to treat vancomycin-resistant enterococcal infections. Vancomycin-susceptible Enterococcus faecalis can develop resistance to linezolid in environments with excessive linezolid use. The aim of this study was to define risk factors and outcome associated with the acquisition of linezolid-resistant E. faecalis (LREfs). MethodsA retrospective case–control study was designed including patients hospitalised from January 2014 to October 2017 at Hospital Civil de Guadalajara ‘Fray Antonio Alcalde’ in Guadalajara, Mexico. A total of 50 patients culture-positive for LREfs and 100 control patients hospitalised in the same room and time as the cases were included. Clinical and demographic data were collected and analysed. ResultsRisk factors for the presence of LREfs included prior linezolid use [odds ratio (OR) = 6.74], prior clindamycin use (OR = 6.72) and previous surgery (OR = 5.79). The mortality rate was 18% for LREfs cases versus 9% for controls. ConclusionLREfs has emerged and spread in our hospital, an environment in which linezolid use is considerable. Risk factors for LREfs are prior antibiotic use, including linezolid, and previous surgery.

Do pneumatic tube transport systems transmit potential pathogens? A hygienic risk assessment in a university hospital

Prompted by an outbreak of vancomycin-resistant enterococci (VRE) in a medical facility, this study examined a pneumatic tube transport system (PTS) as a potential transmission channel. Samples from the receiving station and entry racks were gathered via smear technique. Sponges used for PTS decontamination were soaked with 0.89% NaCl and transported through the channel. Micro-organisms were recovered from the tubes and cleaning sponges using a wash-away technique. Air sampling was performed at the receiving station in order to detect any airborne contamination. Tubes were artificially inoculated with Escherichia coli K12 NCTC 10538 and Staphylococcus epidermidis DSM 20044 and sent through the PTS to investigate channel contamination. No pathogens were detected in effluent air from the PTS or in tubes during routine operation. Entry racks for the test tubes were contaminated with coagulase-negative staphylococci (CNS), aerobic bacilli, moulds and vancomycin-susceptible Enterococcus faecium. E.coli proved to be unsuitable for detecting bacterial transmission by the PTS due to low persistence, but S.epidermidis was more resilient. After sending contaminated test tubes through the PTS, levels of S.epidermidis only decreased marginally. Subsequently, sponges soaked with disinfectant solution were put through the system and these eliminated S.epidermidis completely from the first attempt. Routine hygienic maintenance of the PTS makes pathogen transmission highly unlikely, although entry racks should be disinfected regularly. Any involvement of the PTS in the VRE outbreak at the study institution was unlikely.

736. The Use of Bacteriophages to Inhibit Different Strains of Vancomycin-Resistant or Susceptible Enterococci

BackgroundVancomycin-resistant Enterococci (VRE) is a well-known infectious complication among immunocompromised patients, especially hematopoietic cell transplant (HCT) recipients. VRE colonization of the gastrointestinal tract could be associated with VRE bacteremia and worse outcomes in HCT recipients. The use of systemic antibiotics to eradicate VRE colonization is highly discouraged because of the lack of efficacy, the rapid onset of antibiotic resistance, and the disruption of the normal microbiota. Bacteriophages (phages) may constitute a good alternative to antibiotics to eliminate specific pathogens without disrupting the patient’s normal microbiota.MethodsSewage samples were collected from the City of Houston for phages isolation. Samples were centrifuged, filtered and exposed to several targeted VRE host strains. After several amplification, the final filtrate was titrated and checked for the presence of VRE-specific phages. Isolated phages were observed under electron microscopy and were tested against multiple VRE strains isolated from different sources including patients’ stool samples, patients’ room environment, sewage samples, clinical isolates of daptomycin-resistant VRE strains or vancomycin-susceptible Enterococcus faecium (VSEF) and Enterococcus faecalis (VSEf) strains.ResultsFour VRE-specific phages were isolated from sewage samples (MDA1, MDA2, MDA3, and MDA4). All phages belong to the Caudovirales order. Phage MDA1 belongs to the Podoviridae family, phage MDA2 is a Siphoviridae, whereas MDA3 and MDA4 belong to the Myoviridae family (Figure 1A). All phages were lytic and were able to inhibit at least four VRE strains and only MDA1 had activity against VSEF and MDA4 against VSEf. The efficacy of these lytic phages complemented one another as the combination of these four phages inhibited all different VRE strains (Figure 1B).ConclusionOur results highlight the feasibility and the potential success of these phages in inhibiting VRE in vitro. These VRE-specific phage cocktails may be used in future studies to reduce VRE colonization and subsequent infections in HCT recipients. DisclosuresRoy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix: Advisory Board, Research Grant; Clinigen: Advisory Board; Merck: Advisory Board, Consultant, Grant/Research Support, Research Grant, Speaker’s Bureau; Oxford immunotec: Consultant, Grant/Research Support; Shire: Research Grant, Speaker’s Bureau; Viracor: Grant/Research Support.

Association between vancomycin pharmacokinetic/pharmacodynamic parameters, patient characteristics, and mortality in patients with bacteremia caused by vancomycin-susceptible Enterococcus faecium: a single-center retrospective study

BackgroundVancomycin is commonly used to treat Enterococcus faecium (E. faecium) bacteremia. However, there are very few studies on the association between the trough concentration, area under the curve from 0 to 24 h /minimum inhibitory concentration (AUC24/MIC) ratio, and the therapeutic effect of vancomycin on E. faecium bacteremia. This study aimed to investigate the associations between vancomycin pharmacokinetic/pharmacodynamic parameters, patient characteristics, and mortality in patients with E. faecium bacteremia.MethodsThis retrospective study included patients with E. faecium bacteremia who received vancomycin between April 2012 and February 2018 at a single acute care hospital in Japan. Patients who received renal replacement therapy (hemodialysis or continuous hemodiafiltration), had an unmeasured serum vancomycin concentration, with unmeasured laboratory values, or received other antibiotics for treating E. faecium bacteremia were excluded from the study. The bivariate associations between 30-day all-cause mortality and patient characteristics were assessed.ResultsAmong 87 patients diagnosed with E. faecium bacteremia, 45 were included in the final analysis. Of these, 12 (26.7%) died within 30 days of the diagnosis. The vancomycin trough concentration was higher in the 30-day all-cause mortality patients than in the survival patients (20.5 vs. 14.6 μg/mL; P = 0.022). There was no significant difference in the proportion of patients with a vancomycin AUC24/MIC ≤389 between the groups. The 30-day all-cause mortality patients showed a higher Charlson Comorbidity Index (CCI) and Sequential Organ Failure Assessment score at the first measurement of the vancomycin trough concentration than the survival patients. The same finding was observed among patients with a high CCI score (≥5 points).ConclusionsWhereas the vancomycin trough concentration and AUC24/MIC ratio were not associated with mortality in patients with E. faecium bacteremia, disease severity was associated with mortality in these patients.

A Retrospective Cohort Study of Risk Factors for Surgical Site Infection Following Liver Transplantation.

Surgical site infection is an important complication in the postoperative period among liver transplant recipients. However, little is known about the risk factors in this patient group. Therefore, the objective of this study was to analyze the incidence and risk factors for surgical site infections among adult liver transplant recipients. Medical records of adult liver transplant recipients from January 1, 2009, to December 31, 2015, were analyzed in this retrospective cohort study. We enrolled 156 recipients' medical records. Forty-two (26.9%) cases of surgical site infections were identified. The main isolated microorganisms were methicillin-resistant Staphylococcus species, extended spectrum β-lactamase-producing Klebsiella species, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Acinetobacter baumannii, and vancomycin-susceptible Enterococcus faecalis. We found that long operative times (≥487 minutes) and differences in body mass index between donor and recipient (≥1.3 kg/m2) increased the risk for surgical site infections by approximately 5 times (odds ratio [OR], 5.5; 95% confidence interval [CI], 2.5-11.8), and capillary glycemia ≥175 mg/dL in the first 96 postoperative hours increased the risk by approximately 3 times (OR, 2.97; 95% CI, 1.43-6.17). There was a high incidence of surgical site infections among the studied population and that some risk factors identified differ from those reported in the scientific literature.

In vitro activity of oritavancin alone or in combination against vancomycin-susceptible and -resistant enterococci.

The optimal treatment for serious infections due to Enterococcus spp. is unknown although combination antimicrobial therapy is often recommended for invasive infections to achieve bactericidal activity and improve clinical outcomes. Oritavancin is a novel lipoglycopeptide agent with in vitro activity against enterococci, including vancomycin-resistant VanA-type Enterococcus faecium. Data on its activity in combination with other antibacterials are limited. The objective of this study was to evaluate the activity of oritavancin alone and in combination with ceftriaxone, daptomycin, gentamicin, linezolid and rifampicin against vancomycin-susceptible and -resistant enterococci in in vitro time-kill analyses. Five enterococcal strains were used for all experiments: three vancomycin-resistant VanA-type E. faecium clinical bloodstream isolates, vancomycin-resistant VanA-type E. faecium ATCC 700221 and vancomycin-susceptible Enterococcus faecalis ATCC 29212. Individual drugs were tested at ¼, ½, 1, 2 and 4× MIC. Oritavancin combination experiments were performed with each agent at ¼× MIC. Daptomycin was the most active single agent and was bactericidal against all strains at 4× MIC, followed by oritavancin, which was bactericidal against all three clinical VRE strains at ≥2× MIC. In combination experiments at ¼× MIC, oritavancin was synergistic with gentamicin against strains not displaying high-level aminoglycoside resistance. No other synergy against VRE strains was observed in any experiment. Strain- and drug-dependent antagonism was observed for many combinations. These in vitro data do not support the routine use of combination therapy with oritavancin in the treatment of infections due to VRE.

Comparison of antibiotic resistance and virulence in vancomycin-susceptible and vancomycin-resistant Enterococcus faecium strains

Aim. Today, infections caused by vancomycin-resistant Enterococcus faecium (VRE) are a major problem in the healthcare system. The aim of this study was to compare the antibiotic resistance and virulence traits between vancomycin-susceptible E. faecium (VSE) and VRE clinical isolates.Material and Methods. Studies were performed on 66 E. faecium (32 VRE and 34 VSE) strains. Susceptibility testing and identification were performed, and strains were examined for ß-lactamase, hemolysin and biofilm production. Isolates were tested for the presence of 5 van genes, 8 virulence genes and 6 aminoglycoside-modifying enzyme (AME) genes. Obtained amplicons were subjected to electrophoretical separation and DNA sequencing.Results. Among 32 VRE isolates, 28 were found to have the VanA phenotype, and 4 the VanB. The most frequent resistance and virulence profile among VRE strains was resistance to ampicillin, imipenem, gentamicin, streptomycin, teicoplanin, and vancomycin with enterococcal surface protein (esp), endocarditis antigen (efaA), collagen adhesin (acm), and hialuronidase (hyl) genes; among VSE: resistance to ampicillin, imipenem, gentamicin, streptomycin with esp, efaA, acm, and hyl genes. Conclusions. Our findings prove that both VRE and VSE strains were well equipped with virulence and resistance genes, although VRE strains were characterized by a greater variety and a higher number of these genes. However, statistical analysis revealed no significant differences between VSE and VRE strains (p > 0.05). Nevertheless, our results suggest that VRE strains may slowly acquire and incorporate resistance and virulence genes, due to their ability to survive in a hospital environment for a long time.