Vancomycin-resistant Enterococcus Species Research Articles

Antimicrobial activity of eravacycline and other comparative agents on aerobic and anaerobic bacterial pathogens in Taiwan: A clinical microbiological study

ObjectivesEravacycline, a new tetracycline derivative, exhibits broad-spectrum antimicrobial susceptibility. This study aimed to comprehensively investigate in vitro activities of eravacycline, tigecycline, and ertapenem against various Gram-positive, Gram-negative, and anaerobic bacteria. MethodsMinimum inhibitory concentrations (MICs) were determined using the broth microdilution method. The following bacterial species were collected: vancomycin-sensitive (VS) Enterococci species, vancomycin-resistant Enterococci species (VRE), Staphylococcus aureus, Streptococcus anginosus, Bacteroides species, Clostridioides difficile, Clostridium innocuum, Clostridium perfringens, Parabacteroides distasonis, and Stenotrophomonas maltophilia. ResultsWe found that eravacycline exhibited superior in vitro activity compared to tigecycline and ertapenem. Notably, it exhibited the lowest MIC90 for several bacterial species, including VS E. faecalis (0.12 µg/mL), VS E. faecium (0.12 µg/mL), and others. Besides, VRE was susceptible to eravacycline (MIC90:0.12 µg/mL) and tigecycline (MIC90:0.12 µg/mL), but was all resistant to ertapenem (MIC90 > 64 µg/mL). S. aureus was also susceptible to eravacycline (MIC90:0.5 µg/mL) as well as tigecycline (MIC90:1.0 µg/mL). Furthermore, S. anginosus showed higher susceptibility to eravacycline (MIC90:2.0 µg/mL) and tigecycline (MIC90:4.0 µg/mL), but lower to ertapenem (MIC90:32.0 µg/mL). Eravacycline and tigecycline also demonstrated good susceptibility to anaerobes, including Bacteroides species (susceptibility rate: 100%), P. distasonis (100%), C. difficile (94.1‒100%), C. innocuum (94.1‒96.1%), and C. perfringens (88.9‒96.3%). For S. maltophilia, both tigecycline and eravacycline showed an MIC90 of 2 µg/mL. A moderate-to-strong correlation (rho = 0.608–0.804, P < 0.001) was noted between the MIC values of eravacycline and tigecycline against various bacterial species. ConclusionsOur study highlights the potential of eravacycline as an effective treatment option for multidrug-resistant bacterial infections.

Bacterial Resistance in Nephrology

Bacterial resistance to antibiotics (ABR) is a major threat to public health, particularly in nephrology, with far-reaching consequences, including longer hospital stays, higher healthcare costs and increased mortality. Indeed, patients with chronic kidney disease (CKD) are a population at risk of developing infections caused by antibiotic-resistant bacteria (ARBs), given their overexposure to healthcare facilities and the quality of their gut microbiota already damaged by CKD. It is a population with very high rates of colonization and ARB infection worldwide. The mechanisms deployed by these AROs to counteract the effect of antibiotics are multiple. This may include the production of antibiotic-inhibiting enzyme (ATB), waterproofing of the bacterial membrane, or modification of the antibiotic target. They include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) species, and several multidrug-resistant Gram-negative organisms. The emergence and global spread of these ARBs is facilitated by ATB selection pressure, inter-agency transmission of resistance determinants, suboptimal infection control practices, and frequency of international travel, among other factors. The spread of this veritable pandemic highlights the urgent need for new treatment options, the implementation of awareness campaigns to properly prescribe antibiotics and improve infection prevention practices, particularly at hemodialysis centers.

Green-synthesis, characterization, and antibacterial activity of Azanza garckeana seed extract silver nanoparticles against vancomycin-resistant Enterococci

The need for alternative treatment of infections caused by vancomycin-resistant Enterococci (VRE) is of global concern. This study used Azanza garckeana (AG) seeds to synthesize silver nanoparticles (AgNPs) with anti-VRE activity. The nanoparticles were characterized using UV-Vis, FTIR, SEM, and EDXRF. Antimicrobial activities, MIC, and MBC were evaluated by agar well and microtiter dilution, respectively. UV-spectroscopy confirmed the presence of peaks at 435 nm for spherical AgNPs. FTIR spectrum showed sharp peaks at 3441, 2936, 2859, 1640, and 1385 cm−1, indicating the presence of hydroxyl, methyl, methylene, alkenyl, and alkyl groups in the AgNPs. SEM and EDXRF results revealed particles with clustered crystalline patterns and silver as the highest element present, with nickel also present in very minute amounts. The AgNPs exhibited inhibitory activity against the VRE species at both 50 and 100 µg/ml. Also, MIC values varied between 12.5 µg/ml and 25 µg/ml, while MBC values were 50 µg/ml and 25 µg/ml respectively. Conclusively, A. garckeana AgNPs demonstrated potent antimicrobial activity, suggesting their antimicrobial properties could be utilized in a variety of biomedical applications.

Antimicrobial Resistance Patterns of Staphylococcus aureus and Enterococcus Species at the Ethiopian Public Health Institute, Ethiopia: A Five-Year Retrospective Analysis.

The study aimed to investigate the antimicrobial resistance patterns of Staphylococcus aureus and Enterococcus species isolated from clinical specimens over a period of five years, including resistance to methicillin and vancomycin. Bacterial identification and antimicrobial susceptibility testing reports from 2017 to 2021 at the Ethiopian Public Health Institute were used for this retrospective study. The organisms were identified using either BD Phoenix M50, Vitek 2 compact, or conventional biochemical methods, whichever was available at the time of testing. The antimicrobial susceptibility profiles of the isolates were determined using either Kirby-Bauer disc diffusion, BD phoenix M50, or Vitek 2 compact. WHONET software was used to analyze the antimicrobial resistance patterns of both organisms. The p-values of ≤0.05 were considered statistically significant. During the study period, a total of 315 Staphylococcus aureus and 92 Enterococcus species were isolated. Out of 315 Staphylococcus aureus isolates, 27% and 5.1% were methicillin and vancomycin resistant, respectively. Staphylococcus aureus showed very high resistance to Penicillin G (86.7%). Out of 92 Enterococcus species recovered, 8.7% were vancomycin-resistant. Enterococcus species showed very high resistance to Penicillin G (71.4%) and tetracyclines (83.3%). Methicillin-resistant Staphylococcus aureus shows 100% resistance to penicillin followed by ciprofloxacin (50%), erythromycin (45.6%), and tetracycline (44.2%) and lower resistance to vancomycin (18.8%). All vancomycin-resistant isolates of both organisms were fully resistant (100%) to all antibiotics tested, except for linezolid and daptomycin, to which they were susceptible. This study found a high prevalence of methicillin and vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus species between 2017 and 2021. However, there were no statistically significant changes in the prevalence of these organisms during the study period. This suggests that larger and more representative nationwide data is needed to show trends of these pathogens.

Culture-dependent and molecular characterization of Vancomycin-Resistant Enterococci from clinical, food, and water samples across Osun State, Southwest Nigeria

The emergence and continuous rise in the prevalence of vancomycin-resistant Enterococci (VRE) are alarming and pose a public health threat. The factors responsible for this include intrinsic resistance, acquired resistance, and horizontal gene transfer among Enterococci. This study aimed to evaluate the current prevalence rate, phenotypic and genotypic identification of VRE strains isolated from clinical (in and out-patients), ready-to-eat (RTE) food, and water samples across three geopolitical regions of Osun State in southwestern Nigeria. A total of 466 clinical, RTE food and water samples were analyzed using conventional microbiological techniques, molecular identification of isolates, and detection of van genes using specific primers by polymerase chain reaction (PCR). Phenotypic identification revealed 69 VRE isolates; 64 of which were confirmed VRE with molecular techniques. The overall VRE prevalence rate was 13.7% (64/466), while the proportion of Enterococci that was VRE was 34.6% (64/185). The prevalence of clinical, food, and water samples from the individual sample types was 15.7% (26/166); 14.0% (21/150,) and 11.3% (17/150) respectively.The occurrence of VRE species was 45.3% for E. faecalis, 12.5% for E. hirae, 4.7% each for E. gallinarum, and E. durans; 3.1% each for E. faecium and E. casseliflavus and 1.6% for E. avium. Other unidentified species were 16 (25.0%). Additionally, 47 (73.4%) had either the vanA, vanB, or vanC genes; as detected in 10 (15.6%), 8 (12.5%), and 29 (45.3%) isolates respectively across the different sample types and species respectively. Hence, a high occurrence of vanC carriage in the recovered VRE isolates was recorded. This information is vital as continued monitoring and surveillance is crucial to provide data to clinicians and public health workers. It could serve as a key factor in managing and curtailing the spread of VRE strains, to control its growth and infections caused in hospital and community settings.

Association of Appropriate Empirical Antimicrobial Therapy With In-Hospital Mortality in Patients With Bloodstream Infections in the US

Bloodstream infections (BSIs) are a major public health problem associated with high morbidity. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy. To estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality. This retrospective cross-sectional study used data from the Premier Healthcare database from 2016 to 2020. The analysis included 32 100 adult patients (aged ≥18 years) with BSIs from 183 US hospitals who received at least 1 new systemic antimicrobial agent within 2 days after blood samples were collected during the hospitalization. Patients with polymicrobial infections were excluded from the analysis. Appropriate empirical therapy was defined as initiation of at least 1 new empirical antimicrobial agent to which the pathogen isolated from blood culture was susceptible either on the day of or the day after the blood sample was collected. Multilevel logistic regression models were used to estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality for patients infected with gram-negative rods (GNRs), gram-positive cocci (GPC), and Candida species. Among 32 100 patients who had BSIs and received new empirical antimicrobial agents, the mean (SD) age was 64 (16) years; 54.8% were male, 69.9% were non-Hispanic White, and in-hospital mortality was 14.3%. The most common pathogens were Escherichia coli (58.4%) and Staphylococcus aureus (31.8%). Among patients infected with S aureus, methicillin-resistant S aureus was isolated in 43.6%. The crude proportions of appropriate empirical therapy use were 94.4% for GNR, 97.0% for GPC, and 65.1% for Candida species. The proportions of appropriate therapy use for resistant organisms were 55.3% for carbapenem-resistant Enterobacterales species and 60.4% for vancomycin-resistant Enterococcus species. Compared with inappropriate empirical therapy, receipt of appropriate empirical antimicrobial therapy was associated with lower in-hospital risk of death for 3 pathogen groups (GNR: adjusted odds ratio [aOR], 0.52 [95% CI, 0.42-0.64]; GPC: aOR, 0.60 [95% CI, 0.47-0.78]; Candida species: aOR, 0.43 [95% CI, 0.21-0.87]). In this cross-sectional study of patients hospitalized with BSIs, receipt of appropriate initial empirical antimicrobial therapy was associated with lower in-hospital mortality. It is important for clinicians to carefully choose empirical antimicrobial agents to improve outcomes in patients with BSIs.

Evolutionary conservation of motifs within vanA and vanB of vancomycin-resistant enterococci.

Global Health is threatened by the rapid emergence of multidrug-resistant bacteria. Antibiotic resistomes rapidly evolve, yet conserved motifs elucidated in our study have the potential for future drug targets for precision medicine. This study aimed to identify conserved genetic sequences and their evolutionary pathways among vancomycin-resistant Enterococcus species such as Enterococcus faecium and Enterococcus faecalis. We retrieved a total of 26 complete amino acid and nucleotide sequences of resistance determinant genes against vancomycin (vanA and vanB), streptomycin (aac-aah), and penicillin (pbp5) from the publicly available genetic sequence database, GenBank. The sequences were comprised of bacteria classified under the genera of Enterococcus, Staphylococcus, Amycolatopsis, Ruminococcus, and Clostridium. Sequences were aligned with Clustal Omega Multiple Sequence Alignment program and Percent Identity Matrices were derived. Phylogenetic analyses to elucidate evolutionary relationships between sequences were conducted with the neighbor-end joining method through the Molecular Evolutionary Genetics Analysis (MEGAX) software, developed by the Institute of Molecular Evolutionary Genetics at Pennsylvania State University. Subsequent network analyses of the resistance gene, vanB, within E. faecium were derived from ScanProsite and InterPro. We observed the highest nucleotide sequence similarity of vanA regions within strains of E. faecium (100%) and E. faecalis (100%). Between Enterococcus genera, we continued to observe high sequence conservation for vanA and vanB, up to 99.9% similarity. Phylogenetic tree analyses suggest rapid acquisition of these determinants between strains within vanA and vanB, particularly between strains of Enterococcus genera, which may be indicative of horizontal gene transfer. Within E. faecium, Adenosine 5'-Triphosphate (ATP)-Grasp and D-ala-D-ala ligase (Ddl) were found as conserved domains of vanA and vanB. We additionally found that there is notable sequence conservation, up to 66.67%, between resistomes against vancomycin and streptomycin among E. faecium. Resistance genes against vancomycin have highly conserved sequences between strains of Enterococcus bacteria. These conserved sequences within vanA and vanB encode for ATP-Grasp and Ddl motifs, which have functional properties for maintaining cell wall integrity. High sequence conservation is also observed among resistance genes against penicillin and streptomycin, which can inform future drug targets for broader spectrum therapies.

Molecular screening the emergence of vancomycin and gentamycin resistant enterococcus species in burn' patients in basrah government, Iraq

Emergence of multidrug resistance bacteria (MDR) in burn infections including Enterococcus yet to be managed and highlighted in most of hospitals in our region. This study included 200 clinical samples collected from wound, urine, stool and blood of 75 burn patients in Al-Faiha Teaching Hospital in Basrah, Iraq, between 2020 -2021. Based on Enterococci chromo agar, biochemical test and PCR for 16S rRNA gene, 50 isolates were identified as Enterococcus spp., involving 20 (40%) E. faecium, 14 (28%) E. faecalis, 7 (14%) E. gallinarum, 6 (12%) E. gilvus, 2 (4%) E. casseliflavus and 1 (2%) E. avium. All detected Enterococci were reported worldly as pathogenic bacteria to human. Six new local strains of Enterococcus were recorded in NCBI and the Gene bank as follow; Enterococcus gallinarum strain IraqYaHa5 and IraqYaHa19, Enterococcus faecium strain IraqYaHa23, IraqYaHa48 and IraqYaHa60, Enterococcus gilvus strain IraqYaHa50. Phylogenetic tree was constructed to all isolated Enterococci. The clinical isolates showed resistance up to nine antibiotics. However, enterococci isolated from healthy people during this study were 100% sensitive to six of those antibiotics. Duplex PCR was applied to detect vancomycin and gentamicin resistance genes. All resistant Enterococcus to gentamicin had harboured aph (3’).

Epidemiology, resistant pathogens, and causes of early death in cases of bloodstream infection in patients with hematological malignancies from 2012–2019

PurposeTo investigate the epidemiology, causative pathogen antibiotic susceptibility, and mortality risk factors of bloodstream infection (BSI) in patients with hematological malignancies (HMs). MethodsSingle-center retrospective analysis of BSI cases in patients with HMs in a Chinese tertiary hospital from 2012–2019. ResultsAmong 17,796 analyzed admissions, 508 BSI episodes (2.9%; 95% confidence interval: 2.6%–3.2%) were identified. Of 522 resulting isolates, 326 (62.5%) were Gram-negative, 173 (33.1%) were Gram-positive. The BSI incidence among patients with different HMs (severe aplastic anemia: 6.7%; acute leukemia: 6.2%; myelodysplastic syndrome: 3.2%; multiple myeloma: 1.3%; and lymphoma: 1.0%) differed significantly (p < 0.001). The BSI incidence was significantly higher in the hematopoietic stem cell transplantation (HSCT) group (10.2%) than in the non-HSCT group (2.5%; p < 0.001). Escherichia coli (30.7%, 160/522) was the most common pathogen, followed by Coagulase-negative staphylococci (19.4%, 101/522) and Klebsiella pneumoniae (10.0%, 52/522)., The rates of imipenem resistance for E. coli, K. pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii were 6.4%, 15.0%, 27.8%, and 79.0%, respectively. All the Gram-positive pathogens were linezolid susceptible. Three vancomycin-resistant Enterococcus species were isolated. The overall 14-day mortality was 9.8% (95% confidence interval: 7.2%–12.4%). A multivariate analysis showed that HM subtype severe aplastic anemia, A. baumannii, and malignancy non-remission were independent 14-day mortality risk factors. ConclusionsGram-negative bacteria were the most common pathogens, with E. coli as the predominant strain, causing BSIs in HM patients. A carbapenem-resistant A. baumanni with a high mortality rate in HM patients made empirical antimicrobial choice a highly challenging issue.

Colonization with Multidrug-resistant Organisms in Patients with Ventricular Assist Devices.

Infection is a leading cause of morbidity and mortality in patients with ventricular assist devices (VAD). The impact of colonization with multidrug-resistant organisms (MDRO) on outcomes in this cohort is unknown. Patients on VAD support from July 2008 to September 2018 at a single site were evaluated for MDRO colonization after implantation. MDROs included methicillin-resistant Staphylococcus aureus , vancomycin-resistant Enterococcus species, and extended-spectrum beta-lactamase producing gram-negative bacteria. 378 patients with 433 VADs were included. 42.6% (n = 161) of patients were colonized with an MDRO throughout the duration of VAD support. Eighty-two VAD infections occurred, 74.4% (n = 61) of whom were MDRO colonized before infection. MDRO colonization was associated with an increased risk of a subsequent VAD infection (hazard ratio 3.704, p < 0.001). MDRO colonization is common after VAD implantation and is associated with future VAD infections. Further study is needed to determine best management strategies for VAD recipients with MDRO colonization given this increased risk.

Prevalence of high-level aminoglycoside and vancomycin-resistant enterococcus species at a tertiary care hospital in greater noida, u.p

Prevalence of high-level aminoglycoside and vancomycin-resistant enterococcus species at a tertiary care hospital in greater noida, u.p

Prevalence of high-level aminoglycoside and vancomycin-resistant enterococcus species at a tertiary care hospital in greater noida, u.p

Prevalence of high-level aminoglycoside and vancomycin-resistant enterococcus species at a tertiary care hospital in greater noida, u.p

The Kinocidin Interleukin-26 Shows Immediate Antimicrobial Effects Even to Multi-resistant Isolates.

The cationic proinflammatory cytokine Interleukin 26 (IL-26) shows antibacterial activity and inhibits the replication of cytomegalovirus and hepatitis C virus. This study evaluates the early microbicidal activities of IL-26 against major bacterial species including multi-resistant variants and Candida albicans. Recombinant IL-26 was bacterially expressed and studied for its microbicidal effects in culture. We show that IL-26 has strong 90% bactericidal activities against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, and Acinetobacter baumannii. Similarly, IL-26 sensitivity was also detectable in vancomycin-resistant Enterococcus species, methicillin-resistant S. aureus, and carbapenem-resistant A. baumannii clinical isolates. Additionally, a significant, albeit weak fungicidal effect against Candida albicans was observed. Activities against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were not detectable. The proinflammatory cytokine and kinocidin IL-26 shows strong bactericidal activities against A. baumannii and, almost selectively, against Gram-positive bacteria.

Antimicrobial properties of Pediococcus acidilactici and Pediococcus pentosaceus isolated from silage.

The objective of this study was to isolate multifunctional bacteriocin-producing strains; to characterize the expressed bacteriocin for the control of Listeria monocytogenes and vancomycin-resistant Enterococcus; to evaluate the safety of studied strains; and to explore their antifungal activity. Two Pediococcus strains were isolated from silage samples obtained from an organic farm in Belogradchik, Bulgaria. The strains were identified by 16S rRNA sequencing analysis and characterized as bacteriocins producers. Strong antimicrobial activity was detected against more than 74 different strains of Listeria monocytogenes, 27 different vancomycin-resistant Enterococcus strains. In addition, studied strains were able to inhibit the growth of strains of Alternaria alternate, Aspergillus flavus, Aspergillus niger, Cladosporium sphaerospermum, Penicillium chrysogenum and Penicillium expansum. Some aspects of the antimicrobial mode of action were evaluated, including killing curves and aggregation properties. Both strains generated positive PCR results for the presence of pediocin PA-1, but not for other bacteriocins evaluated in this screening process. Metabolomic analysis of the cell-free supernatants from both strains was performed in order to explain the observed antifungal activity against different moulds. According to PCA and PLS-DA score plot, P. acidilactici ST3522BG and P. pentosaceus ST3633BG were clearly clustered from control (MRS). Increases in the production of benzoic acid, 2-hydroxyisocaproic acid, β-phenyl-lactic acid, α-hydroxybutyric acid and 1,3-butanediol were recorded, these metabolites were previously described as antifungal. Pediococcus acidilactici ST3522BG and P. pentosaceus ST3633BG were evaluated as producing bacteriocin strains with high specificity against Listeria and vancomycin-resistant Enterococcus species. In addition, both investigated Pediococcus strains were evaluated as producer of effective antifungal metabolites with potential for the inhibition of mycotoxin-producing moulds. To the best of our knowledge, this report is a pioneer in the evaluation of Pediococcus strains isolated from silage with highly specific bacteriocinogenic antimicrobial activity against Listeria spp. and vancomycin-resistant Enterococcus spp., and antifungal activity against mycotoxin-producing moulds.

Comparative Analysis of Prevalence and Antibiotic Resistance in Vancomycin-Resistant Enterococcus from Clinical Samples – Demographics and Phenotypes

Background: Of all enterococci species, the most renowned clinically as multidrug-resistant pathogens are Enterococcus faecium and Enterococcus faecalis. Vancomycin-resistant Enterococcus (VRE) species are the principal cause of opportunistic hospital-acquired infections, due to numerous resistance mechanisms. Methods: In this study, the prevalence and antibiotic resistance profiles of VRE according to clinical sources from three selected hospitals in Southwest-Nigeria were investigated. Altogether, 431 samples (urine, rectal, and wound swabs - caesarian section (CS), automobile accidents, and other skin lesions and abrasions) were collected from three selected hospitals in Osun State, Nigeria. Established techniques were employed for the recovery of enterococci and screening for VRE while antibiotic susceptibility tests were carried out by disc diffusion technique. Results: Altogether, 208 (48.3%) enterococci strains were recovered from which 85 (40.9%) were VRE. E. faecium predominated at 71.8% (61/85) and E. faecalis at 28.2% (24/85) as determined by phenotypic characterization. VRE isolates exhibited 100%, 97.6%, and 92.9% resistance to ampicillin, clindamycin, and quinupristin-dalfopristin (Q/D) respectively. The least resistance in-vitro was to tigecycline (27.1%). None of the antibiotics exhibited 100% activity against all the isolates. vanA resistant phenotype was prevalent at 65.9%. E. faecium from all study locations displayed higher levels of resistance than E. faecalis. Multiple antibiotic resistance (MAR) indices in all VRE isolates were ≥0.2, all being multidrug-resistant. Conclusions: The high prevalence rate along with the high level of multidrug resistance observed in the present study is worrisome and poses a continuous threat in the therapy of illnesses triggered by VRE as vancomycin was perceived as a drug of choice to curb enterococcal infections.

Quantification and Multidrug Resistance Profiles of Vancomycin-Resistant Enterococci Isolated from Two Wastewater Treatment Plants in the Same Municipality.

Wastewater treatment plants (WWTPs) are points of control for the environmental dissemination of antimicrobial resistant bacteria. Vancomycin-resistant enterococci (VRE) were used as indicators of antimicrobial resistance (AMR) in two WWTPs (biologically aerated filter (BAF) and conventional activated sludge (CAS)) in the same municipality. The removal and abundance of enterococci and VRE as well as the species and antimicrobial resistance profiles of VRE were assessed. Enterococci and VRE from the primary and final effluents were enumerated. Results were assessed from an ecological context. VRE was not selected for by either WWTP but the BAF system outperformed the CAS system for the removal of enterococci/VRE. Enterococcus faecalis (n = 151), E. faecium (n = 94) and E. casseliflavus/E. gallinarum (n = 59) were the dominant VRE species isolated. A decrease in levofloxacin resistance in enterococci was observed in the BAF WWTP. An increase in nitrofurantoin resistant (p < 0.001) and a decrease in quinupristin/dalfopristin (p = 0.003) and streptomycin (p = 0.022) resistant enterococci were observed in the CAS WWTP, corresponding to a shift of VRE from E. faecalis to E. faecium. Wastewater treatment processes can be managed to limit the dissemination of antimicrobial resistance determinants into the surrounding environment.

2412. Oral Vancomycin Prophylaxis Against Recurrent Clostridioides difficile Infection: Efficacy and Side-effects: Two Hospitals Experience

Background Clostridioides difficile is the most common hospital-acquired pathogen with an unchanged infection prevalence between 2011–2015. The data regarding the effectiveness of chemical prophylaxis to prevent recurrent C. difficile infection (CDI) are conflicting.MethodsWe conducted a retrospective study of hospitalized patients with CDI history in 2 New York academic hospitals over a 4.5-year period to determine the effectiveness of vancomycin prophylaxis for CDI prevention. The participating hospitals implemented an automated alert to providers recommending oral vancomycin 125 mg twice daily in patients with a history of CDI scheduled to receive any systemic antimicrobials for the duration of therapy and 5 days thereafter. Measured outcomes included the rate of breakthrough and recurrent CDI, defined as CDI during and in the one-month following prophylaxis, respectively. A self-controlled, before and after study design was employed to examine whether the use of oral vancomycin was associated with an increase in the prevalence of vancomycin-resistant Enterococcus species (VRE) both in absolute numbers and in comparison to vancomycin-sensitive Enterococcus species (VSE) in the period following vancomycin prophylaxis.Results264 patients were included in the final analysis. Breakthrough CDI was identified in 17 (6.4%; 95% CIs 3.8%–10.1%) and recurrent CDI in 22 (8.3%; 95% CIs 5.3%–12.3%) patients. Of the 102 patients with a history of CDI within the 3 months preceding the administration of prophylaxis 4 (3.9%, 95% CIs 1.1%-9.7%) had breakthrough CDI and 9 had recurrent disease (8.3%, 95% CIs 5.3%–12.3%). In the 3 months following vancomycin prophylaxis there was an increase in both the absolute number of VRE and the ratio of VRE to VSE isolates compared with the combined period of 1.5 months preceding and the 3–4.5 months following the administration of prophylaxis. The increase in the absolute number of VRE colonized patients remained in the extended period of 6 months following prophylaxis.ConclusionProphylactic vancomycin is an effective strategy to prevent CDI recurrence, but is associated with an increase in VRE colonization in the immediate period after administration. The risk of VRE infection should lead to careful selection of patients at the highest risk for CDI recurrence.Disclosures All authors: No reported disclosures.

Structural basis for the substrate recognition of peptidoglycan pentapeptides by Enterococcus faecalis VanYB

Vancomycin resistance in Enterococci and its transfer to methicillin-resistant Staphylococcus aureus are challenging problems in health care institutions worldwide. High-level vancomycin resistance is conferred by acquiring either transposable elements of the VanA or VanB type. Enterococcus faecalis VanYB in the VanB-type operon is a d,d-carboxypeptidase that recognizes the peptidyl-d-Ala4-d-Ala5 extremity of peptidoglycan and hydrolyses the terminal d-Ala on the extracellular side of the cell wall, thereby increasing the level of glycopeptide antibiotics resistance. However, at the molecular level, it remains unclear how VanYB manipulates peptidoglycan peptides for vancomycin resistance. In this study, we have determined the crystal structures of E. faecalis VanYB in the d-Ala-d-Ala-bound, d-Ala-bound, and -unbound states. The interactions between VanYB and d-Ala-d-Ala observed in the crystal provide the molecular basis for the recognition of peptidoglycan substrates by VanYB. Moreover, comparisons with the related VanX and VanXY enzymes reveal distinct structural features of E. faecalis VanYB around the active-site cleft, thus shedding light on its unique substrate specificity. Our results could serve as the foundation for unravelling the molecular mechanism of vancomycin resistance and for developing novel antibiotics against the vancomycin-resistant Enterococcus species.

Biosynthetic Potential of Bioactive Streptomycetes Isolated From Arid Region of the Thar Desert, Rajasthan (India).

Acquisition of Actinobacteria, especially Streptomyces from previously underexplored habitats and the exploration of their biosynthetic potential have gained much attention in the rejuvenated antibiotics search programs. Herein, we isolated some Streptomyces strains, from an arid region of the Great Indian Thar Desert, which possess an ability to produce novel bioactive compounds. Twenty-one morphologically distinctive strains differing in their aerial and substrate mycelium were isolated by employing a stamping method. Among them, 12 strains were identified by a two-level antimicrobial screening method, exerting antimicrobial effects against a panel of indicator strains including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus species. Based on their potent antimicrobial activity, four isolates were further explored by 16S rRNA gene-based identification, genetic screening, and metabolomic analysis; and it was found that these strains belong to the genus Streptomyces. The selected strains were found to have polyketide synthase and non-ribosomal peptide synthetase systems. In addition, extracellular metabolomic screening revealed that the isolates produced analogs of doxorubicinol, pyrromycin, erythromycin, and 6-13 other putative novel metabolites. These results demonstrate the significance of Streptomyces inhabiting the arid region of Thar Desert, suggesting that similar arid environments can be considered as the reservoirs of novel Streptomyces strains that could have biotechnological significance.

Allied Commensal Forces against Vancomycin-Resistant Enterococci

In this issue of Cell Host & Microbe, Caballero etal. (2017) define a precise, limited consortium of commensal bacteria that restores resistance to colonization by clinically vexing vancomycin-resistant Enterococcus species.