scholarly journals Exploring the Therapeutic Potenital of the Leaderless Enterocins K1 and EJ97 in the Treatment of Vancomycin-Resistant Enterococcal Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Ingvild Reinseth ◽  
Hanne H. Tønnesen ◽  
Harald Carlsen ◽  
Dzung B. Diep
Keyword(s):  
Therapeutic Potential ◽  
Stress Conditions ◽  
Antibiotic Resistant ◽  
Enterococcal Infection ◽  
Vancomycin Resistant Enterococci ◽  
Niche Adaptation ◽  
Important Virulence Factor ◽  
Membrane Bound ◽  
Vancomycin Resistant ◽  
Enterococcal Infections

The membrane-bound protease Eep is an important virulence factor in pathogenic enterococci. The protein is involved in stress response via the RIP pathway which is crucial for pathogenic enterococci to evade host immune attacks during infection. Eep serves also as a receptor for the bacteriocins enterocin K1 and enterocin EJ97. The bacteriocins kill Enterococcus faecium and E. faecalis, respectively, and their antibiotic resistant derivatives including vancomycin resistant enterococci (VRE). This functional duality of Eep makes these two enterocins very promising as options in the prospective treatment of enterococcal infections because wildtype enterococcal cells (with an intact Eep) are sensitive to the bacteriocins while bacteriocin-resistant-mutants (without a functional Eep) become less virulent. As a first step to explore their therapeutic potential in the treatment of systemic enterococcal infections, we investigated the compatibility of the bacteriocins with human blood, and the phenotypic changes of eep-mutants toward different stress conditions. We found that the bacteriocins were compatible with blood, as they did not cause haemolysis and that the bacteriocins retained most of their antibacterial effect when incubated in blood. The bacteriocins were autoclavable which is a crucial criterium for the development of parenteral administration. Eep-mutants, which became resistant to the bacteriocin were, as expected, less capable to withstand stress conditions such as exposure to lysozyme and desiccation. Further, their ability to chain, a trait implicated in niche adaptation as well as being necessary for genetic transfer via conjugation, was also severely affected. Together, these results indicate that the bacteriocins are promising for treatment of VRE infection.

scholarly journals Quantifying the Exposure to Antibiotic-Resistant Pathogens Among Patients Discharged From a Single Hospital Across All California Healthcare Facilities

2015 ◽  
Vol 36 (11) ◽  
pp. 1275-1282 ◽  
Author(s):  
Rupak Datta ◽  
Shawn Brown ◽  
Vinh Q. Nguyen ◽  
Chenghua Cao ◽  
John Billimek ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Nursing Homes ◽  
Hospital Readmissions ◽  
Time Dependent ◽  
Antibiotic Resistant ◽  
Total Exposure ◽  
Healthcare Facilities ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant

OBJECTIVETo assess the time-dependent exposure of California healthcare facilities to patients harboring methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase (ESBL)–producing Escherichia coli and Klebsiella pneumoniae, and Clostridium difficile infection (CDI) upon discharge from 1 hospital.METHODSRetrospective multiple-cohort study of adults discharged from 1 hospital in 2005–2009, counting hospitals, nursing homes, cities, and counties in which carriers were readmitted, and comparing the number and length of stay of readmissions and the number of distinct readmission facilities among carriers versus noncarriers.RESULTSWe evaluated 45,772 inpatients including those with MRSA (N=1,198), VRE (N=547), ESBL (N=121), and CDI (N=300). Within 1 year of discharge, MRSA, VRE, and ESBL carriers exposed 137, 117, and 45 hospitals and 103, 83, and 37 nursing homes, generating 58,804, 33,486, and 15,508 total exposure-days, respectively. Within 90 days of discharge, CDI patients exposed 36 hospitals and 35 nursing homes, generating 7,318 total exposure-days. Compared with noncarriers, carriers had more readmissions to hospitals (MRSA:1.8 vs 0.9/patient; VRE: 2.6 vs 0.9; ESBL: 2.3 vs 0.9; CDI: 0.8 vs 0.4; all P<.001) and nursing homes (MRSA: 0.4 vs 0.1/patient; VRE: 0.7 vs 0.1; ESBL: 0.7 vs 0.1; CDI: 0.3 vs 0.1; all P<.001) and longer hospital readmissions (MRSA: 8.9 vs 7.3 days; VRE: 8.9 vs 7.4; ESBL: 9.6 vs 7.5; CDI: 12.3 vs 8.2; all P<.01).CONCLUSIONSPatients harboring antibiotic-resistant pathogens rapidly expose numerous facilities during readmissions; regional containment strategies are needed.Infect. Control Hosp. Epidemiol. 2015;36(11):1275–1282

scholarly journals ddcP, pstB, and excess D-lactate impact synergism between vancomycin and chlorhexidine against Enterococcus faecium 1,231,410

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249631
Author(s):  
Pooja Bhardwaj ◽  
Moutusee Z. Islam ◽  
Christi Kim ◽  
Uyen Thy Nguyen ◽  
Kelli L. Palmer
Keyword(s):  
Enterococcus Faecium ◽  
Whole Genome ◽  
Vancomycin Resistant Enterococci ◽  
Control Hospital ◽  
Skin Antisepsis ◽  
Life Threatening ◽  
Membrane Bound ◽  
Vancomycin Resistant ◽  
Hospital Associated Infections

Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens that cause life-threatening infections. To control hospital-associated infections, skin antisepsis and bathing utilizing chlorhexidine is recommended for VRE patients in acute care hospitals. Previously, we reported that exposure to inhibitory chlorhexidine levels induced the expression of vancomycin resistance genes in VanA-type Enterococcus faecium. However, vancomycin susceptibility actually increased for VanA-type E. faecium in the presence of chlorhexidine. Hence, a synergistic effect of the two antimicrobials was observed. In this study, we used multiple approaches to investigate the mechanism of synergism between chlorhexidine and vancomycin in the VanA-type VRE strain E. faecium 1,231,410. We generated clean deletions of 7 of 11 pbp, transpeptidase, and carboxypeptidase genes in this strain (ponA, pbpF, pbpZ, pbpA, ddcP, ldtfm, and vanY). Deletion of ddcP, encoding a membrane-bound carboxypeptidase, altered the synergism phenotype. Furthermore, using in vitro evolution, we isolated a spontaneous synergy escaper mutant and utilized whole genome sequencing to determine that a mutation in pstB, encoding an ATPase of phosphate-specific transporters, also altered synergism. Finally, addition of excess D-lactate, but not D-alanine, enhanced synergism to reduce vancomycin MIC levels. Overall, our work identified factors that alter chlorhexidine and vancomycin synergism in a model VanA-type VRE strain.

scholarly journals Not too close! impact of roommate status on MRSA and VRE colonization and contamination in Nursing Homes

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Marco Cassone ◽  
Meghan Linder ◽  
Cheon Jee Shin ◽  
Julia Mantey ◽  
Kristen Gibson ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Relative Risk ◽  
Nursing Homes ◽  
Infection Prevention ◽  
Index Patient ◽  
Antibiotic Resistant ◽  
Future Studies ◽  
Vancomycin Resistant Enterococci ◽  
Specific Index ◽  
Vancomycin Resistant

AbstractMultiple room occupancy is common in Nursing Homes (NHs), and its role in transmission of antibiotic-resistant pathogens is unclear. We investigated prevalence of patient colonization and environmental contamination with vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) in NH roommates, compared it with expected prevalence, and determined specific body and environmental sites that may act as sources of roommate colonization. Roommate contamination was associated with index patient’s colonization (relative risk (RR): 2.57 (95% CI 1.04–6.37)) for MRSA, and index patient’s immediate environment contamination for VRE (RR: 3.60 (95% CI 1.59–8.12)). When specific index patient sites associated with roommate colonization were investigated, the side table (Fisher’s p = 0.029 and 0.047 for VRE and MRSA, respectively) and the nurse call button (p = 0.001 and 0.052) stood out, together with patient hands in the case of VRE (p = 0.026). Future studies should be carried out to establish whether these sites should be a specific target of infection prevention campaigns in NHs with multiple occupancy rooms.

scholarly journals Occurrence of vancomycin resistant enterococci (VRE) in two Durban wastewater treatment plants for effluent reuse

2019 ◽  
Author(s):  
◽  
Chibuzor Ezinne Madu
Keyword(s):  
Efflux Pump ◽  
Antibiotic Resistance Genes ◽  
World Health ◽  
Treated Wastewater ◽  
Seasonal Effects ◽  
Multidrug Efflux Pump ◽  
Antibiotic Resistant ◽  
Vancomycin Resistant Enterococci ◽  
Resistant Strains ◽  
Vancomycin Resistant

The presence of enterococci in improperly treated wastewater leads to pollution of the recipient water bodies which directly or indirectly affects the humans especially when antibiotic resistant strains are involved. In 2017 the World Health Organization listed vancomycin resistant enterococci (VRE) among those with highest priority for further surveillance and research, both among humans and in the receiving aquatic environment. The purpose of this study is to determine how efficient the WWTPs are in removing both vancomycin-resistant enterococci (VRE) and vancomycin-sensitive enterococci (VSE) from wastewater. One hundred (60 wastewater and 40 river) samples were collected from July 2016 to June 2017 which covered the warm and cold seasons of South Africa. Primary isolation and enumeration were carried out on Slanetz and Bartley agar supplemented with and without vancomycin (6 µg/mL) for vancomycin resistant enterococci (VRE) and total enterococci (TE) respectively. Presumptive enterococci were selected using Gram staining, growth on bile aesculin agar, catalase and pyrase tests. The presumptive enterococci isolates (202 VRE and 67 VSE) were confirmed and speciated using polymerase chain reaction (PCR). The identified Enterococcus isolates were subjected to antibiotic susceptibility testing (AST) to examine their resistance profile against fifteen antibiotics including vancomycin. Antibiotic resistance genes (van, tet and emeA) were detected by PCR. The TE and VRE counts of the two WWTPs influents ranged from 6.1 to 7.2 log10 CFU/100 mL (for TE) and 4.3 to 6.7 log10 CFU/100 mL (for VRE) while the effluent concentration of Plant II contained 1.5 to 4.4 log10 CFU/100 mL and 0.9 to 3.4 log10 CFU/100 mL for TE and VRE respectively. Neither TE nor VRE was detected in Plant I effluent. The TE and VRE counts of the recipient river samples were higher than the effluents. There were no visible seasonal effects based on the counts. The removal efficiencies in the two plants ranged from 95 to 100%, where chlorination played a major role. Two hundred and sixty- nine (202 VRE and 67 VSE) isolates were identified by PCR as Enterococcus. The most abundant species was E. faecium followed by E. faecalis while other species include E. hirae, E. gallinarum, E. durans, E. casseliflavus and E. cecorium. MALDI-TOF and PCR were used in parallel for the identification of the isolates, which resulted in 80.1% agreement for genus identification. The AST results showed that a large percentage (39 to 98%) were resistantto all other antibiotics except amoxicillin/clavulanic acid and imipenem to which the isolates showed high sensitivity. Four van genes (vanA, vanB, vanC1, vanC2/3) and 4 tet genes (tetK, tetL, tetM, tetO), and also the multidrug efflux pump gene, emeA were detected among the 269 enterococci isolates with vanA and tetL being the most prevalent. At least one virulence gene (ace, asa1, cylA, efaA, esp, gelE and hyl) occurred in 74% (67/88) of the isolates. The result showed that the two WWTPs are efficient in removing both enterococci and VRE from their influents. Thus these effluents had little or no effect to enterococci count of their interlinked recipients. Also, a majority of the isolates are not only antibiotic resistant strains but are also virulent. They therefore pose risk to public health.

scholarly journals Systematic Review of Measurement and Adjustment for Colonization Pressure in Studies of Methicillin-ResistantStaphylococcus aureus, Vancomycin-Resistant Enterococci, andClostridium difficileAcquisition

2011 ◽  
Vol 32 (5) ◽  
pp. 481-489 ◽  
Author(s):  
Adebola O. Ajao ◽  
Anthony D. Harris ◽  
Mary-Claire Roghmann ◽  
J. Kristie Johnson ◽  
Min Zhan ◽  
...  
Keyword(s):  
Clinical Care ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Medline Search ◽  
Colonization Pressure ◽  
Vancomycin Resistant Enterococci ◽  
Control Metric ◽  
Cross Transmission ◽  
Vancomycin Resistant ◽  
Definition Of

Objective.Colonization pressure is an important infection control metric. The aim of this study was to describe the definition and measurement of and adjustment for colonization pressure in nosocomial-acquisition risk factor studies of methicillin-resistantStaphylococcus aureus(MRSA), vancomycin-resistant enterococci (VRE), andClostridium difficile.Methods.We performed a computerized search of studies of nosocomial MRSA, VRE, andC. difficileacquisition published before July 1, 2009, through MEDLINE. Studies were included if a study outcome was MRSA, VRE, orC. difficileacquisition; the authors identified risk factors associated with MRSA, VRE, orC. difficileacquisition; and the study measured colonization pressure.Results.The initial MEDLINE search yielded 505 articles. Sixty-six of these were identified as studies of nosocomial MRSA, VRE, orC. difficileacquisition; of these, 18 (27%) measured colonization pressure and were included in the final review. The definition of colonization pressure varied considerably between studies: the proportion of MRSA- or VRE-positive patients (5 studies), the proportion of MRSA- or VRE-positive patient-days (6 studies), or the total or mean number of MRSA-, VRE-, orC. difficile-positive patients or patient-days (7 studies) in the unit over periods of varying length. In 10 of 13 studies, colonization pressure was independently associated with MRSA, VRE, orC. difficileacquisition.Conclusion.There is a need for a simple and consistent method to quantify colonization pressure in both research and routine clinical care to accurately assess the effect of colonization pressure on cross-transmission of antibiotic-resistant bacteria.

scholarly journals Genetic Basis for Vancomycin-Enhanced Cephalosporin Susceptibility in Vancomycin-Resistant Enterococci Revealed Using Counterselection with Dominant-Negative Thymidylate Synthase

2013 ◽  
Vol 58 (3) ◽  
pp. 1556-1564 ◽  
Author(s):  
Christopher J. Kristich ◽  
Dušanka Djorić ◽  
Jaime L. Little
Keyword(s):  
Thymidylate Synthase ◽  
Genetic Basis ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant

ABSTRACTAntibiotic-resistant enterococci are major causes of hospital-acquired infections. All enterococci are intrinsically resistant to most cephalosporins, antibiotics in the beta-lactam family that impair peptidoglycan synthesis by inactivating the transpeptidases responsible for cross-linking. In addition, clinical isolates of enterococci often possess acquired resistance to vancomycin, a glycopeptide antibiotic that impairs peptidoglycan biosynthesis by a mechanism distinct from that of the beta-lactams, namely, by binding to thed-Ala-d-Ala termini found in peptidoglycan precursors to prevent their utilization by biosynthetic transglycosylases. Antimicrobial synergism between vancomycin and beta-lactams against vancomycin-resistant enterococci was originally described decades ago, but the genetic basis for synergy has remained unknown. Because a complete understanding of the mechanism underlying synergy between vancomycin and beta-lactams might suggest new targets or strategies for therapeutic intervention against antibiotic-resistant enterococci, we explored the genetic basis for synergy between vancomycin and cephalosporins inEnterococcus faecalis. To do so, we developed a counterselection strategy based on a dominant-negative mutant of thymidylate synthase and implemented this approach to create a panel of mutants in vancomycin-resistantE. faecalis. Our results confirm that vancomycin promotes synergy by inducing expression of thevanresistance genes, as a mutant in which thevangenes are expressed in the absence of vancomycin exhibits susceptibility to cephalosporins. Further, we show that peptidoglycan precursors substituted withd-Ala-d-Lac are not required for vancomycin-enhanced cephalosporin sensitivity. Instead, production of thed,d-carboxypeptidase VanYBis both necessary and sufficient to dramatically sensitizeE. faecalisto cephalosporins.

Risk factors for enterococcal infection and colonization by vancomycin-resistant enterococci in critically ill patients

Infection ◽  
2014 ◽  
Vol 42 (6) ◽  
pp. 1013-1022 ◽  
Author(s):  
M. Papadimitriou-Olivgeris ◽  
E. Drougka ◽  
F. Fligou ◽  
F. Kolonitsiou ◽  
A. Liakopoulos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Enterococcal Infection ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant

Nosocomial Infection Caused by Antibiotic-Resistant Organisms in the Intensive-Care Unit

1996 ◽  
Vol 17 (4) ◽  
pp. 236-248 ◽  
Author(s):  
John P. Flaherty ◽  
Robert A. Weinstein
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Antimicrobial Agents ◽  
Selective Pressure ◽  
Antibiotic Use ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Vancomycin Resistant Enterococci ◽  
Close Proximity ◽  
Vancomycin Resistant

AbstractResistance to antimicrobial agents is an evolving process, driven by the selective pressure of heavy antibiotic use in individuals living in close proximity to others. The intensive care unit (ICU), crowded with debilitated patients who are receiving broad-spectrum antibiotics and being cared for by busy physicians, nurses, and technicians, serves as an ideal environment for the emergence of antibiotic resistance. Problem pathogens presently include multiply resistant gram-negative bacilli, methicillin-resistantStaphylococcus aureus, and the recently emerged vancomycin-resistant enterococci. The prevention of antimicrobial resistance in ICUs should focus on recognition via routine unit-based sur veillance, improved compliance with handwashing and barrier precautions, and antibiotic-use policies tailored to individual units within hospitals.

scholarly journals Chloride-Inducible Expression Vector for Delivery of Antimicrobial Peptides Targeting Antibiotic-Resistant Enterococcus faecium

2015 ◽  
Vol 81 (11) ◽  
pp. 3889-3897 ◽  
Author(s):  
Kathryn Geldart ◽  
Juan Borrero ◽  
Yiannis N. Kaznessis
Keyword(s):  
Antimicrobial Peptides ◽  
Protein Expression ◽  
Enterococcus Faecium ◽  
Inducible Promoter ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Enterococcal Infections

ABSTRACTAntibiotic-resistant enterococcal infections are a major concern in hospitals where patients with compromised immunity are readily infected.Enterococcus faeciumbacteria are of particular interest as these pathogens account for over 80% of vancomycin-resistant enterococcal infections. Antimicrobial peptides (AMPs) produced at the site of infection by engineered bacteria may offer a potential alternative to traditional antibiotics for the treatment of resistant bacteria such asE. faecium. For this mode of delivery to be effective, it is essential to identify a suitable protein expression system that can be used in the desired delivery bacterium. In this study, we describe a promising chloride-inducible promoter and its application in the bacterial delivery of AMPs fromLactococcus lactisto reduce counts ofE. faeciumbacteriain vitro. Reporter gene studies show that at chloride concentrations found within the human intestines, the chloride-inducible promoter exhibits high levels of protein expression compared to those of the commonly used nisin-inducible promoter. These results indicate that this system is powerful and would not require the exogenous administration of an inducer molecule. In its application for AMP production againstE. faeciumin vitro,L. lactisproducing AMPs under the chloride promoter rapidly decreasedE. faeciumcounts by nearly 10,000-fold. As an extension of this application, we also demonstrate the potential in using this type of delivery system in combination with traditional antibiotics to slow the development of resistance. Collectively, this study shows the promise of using a chloride-inducible promoter for the bacterial delivery of AMPs in the body for the treatment of vancomycin-resistant enterococci (VRE) and other antibiotic-resistant bacteria.

scholarly journals ddcP, pstB, and excess D-lactate impact synergism between vancomycin and chlorhexidine against Enterococcus faecium 1,231,410

2018 ◽  
Author(s):  
Pooja Bhardwaj ◽  
Moutusee Z. Islam ◽  
Christi Kim ◽  
Uyen Thy Nguyen ◽  
Kelli L. Palmer
Keyword(s):  
Enterococcus Faecium ◽  
Whole Genome ◽  
Vancomycin Resistant Enterococci ◽  
Control Hospital ◽  
Skin Antisepsis ◽  
Life Threatening ◽  
Membrane Bound ◽  
Vancomycin Resistant ◽  
Hospital Associated Infections

AbstractVancomycin-resistant enterococci (VRE) are important nosocomial pathogens that cause life-threatening infections. To control hospital-associated infections, skin antisepsis and bathing utilizing chlorhexidine is recommended for VRE patients in acute care hospitals. Previously, we reported that exposure to inhibitory chlorhexidine levels induced the expression of vancomycin resistance genes in VanA-type Enterococcus faecium. However, vancomycin susceptibility actually increased for VanA-type E. faecium in the presence of chlorhexidine. Hence, a synergistic effect of the two antimicrobials was observed. In this study, we used multiple approaches to investigate the mechanism of synergism between chlorhexidine and vancomycin in the VanA-type VRE strain E. faecium 1,231,410. We generated clean deletions of 7 of 11 pbp, transpeptidase, and carboxypeptidase genes in this strain (ponA, pbpF, pbpZ, pbpA, ddcP, ldtfm, and vanY). Deletion of ddcP, encoding a membrane-bound carboxypeptidase, altered the synergism phenotype. Furthermore, using in vitro evolution, we isolated a spontaneous synergy escaper mutant and utilized whole genome sequencing to determine that a mutation in pstB, encoding an ATPase of phosphate-specific transporters, also altered synergism. Finally, addition of excess D-lactate, but not D-alanine, enhanced synergism. Overall, our work identified factors that alter chlorhexidine-induced vancomycin resensitization in a model VanA-type VRE strain.

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