Vancomycin resistant enterococci

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Vancomycin resistant enterococci

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Vancomycin resistant enterococci

  1. 1. Dr.T.V.Rao. MD Dr.T.V.Rao MD 1
  2. 2. Introduction to EnterococciEnterococci are gram-positivecocci which often occur in pairs(diplococci)Two species are commoncommensal organisms in theintestines of humans:E. faecalis and E. faeciumEnterococci occur almosteverywhere, including soil, food,water, plants, animals, birds, andinsects they inhabit in humans andother animals gastrointestinaltract and the female genital tract Dr.T.V.Rao MD 2
  3. 3. Characters of EnterococciGram(+) , Catalase(-)CocciCan grow in media :6.5% sodium chlorideE. faecalis and E. faecium(90%)Part of the normalbowel flora. theprominent cause ofnosocomial infections. Dr.T.V.Rao MD 3
  4. 4. Habitat of Enterococci Enterococci normally inhabit the bowel. They are found in the intestine of nearly all animals, from cockroaches to humans. Enterococci are readily recovered outdoors from vegetation and surface water, probably because of contamination by animal excrement or untreated sewage . In humans, typical concentrations of enterococci in stool are up to 108 CFU per gram . Dr.T.V.Rao MD 4
  5. 5. Growing Importance of EnterococciEnterococcus species are normal flora of the intestinaltract. Enterococcus faecalis frequently causes infectionswithin the peritoneal cavity, especially followingpenetrating trauma such as gunshot wounds, andsurgical wounds, urinary tract infections, prostateinfections, and infections of damaged or compromisedskin, such as diabetic or decubitus ulcers, burns, andsurgical wounds. Other opportunistic fecal streptococciinclude E. faecium and E. durans. Dr.T.V.Rao MD 5
  6. 6. Prominent Cause of Nosocomial InfectionsThe enterococci have becomethe second most commonbacterium isolated fromnosocomial urinary andwound infections, and thethird most common cause ofnosocomial bacteremia.Furthermore, the enterococciare among the mostantibiotic resistant of allbacteria, with some isolatesresistant to all knownantibiotics Dr.T.V.Rao MD 6
  7. 7. Clinical ManifestationInfections with VRE do notdiffer from other enterococcalinfections other than in theirtherapy.The most common sites ofinfection :The urinary tract andbloodstream.In addition, enterococci maycause endocarditis due to theirability to adhere to heartvalves.They rarely cause respiratorytract infections. Dr.T.V.Rao MD 7
  8. 8. Glycopeptides Mechanism of ActionVancomycin and teicoplanininhibit cell wall synthesis byforming complexes withpeptidyl-D-alanyl-D-alanineterminivanA and vanB resistancephenotypes are associatedwith the acquisition of geneclusters that lead to theproduction of peptidoglycanending in D-alanyl-D-lactate Dr.T.V.Rao MD 8
  9. 9. Vancomycin Resistance Increases Morbidity and MortalityVancomycin-resistant enterococci (VRE), first reported inEurope in 1988, are emerging as a global threat to publichealth . The incidence of VRE infection and colonizationamong hospitalized patients has increased rapidly in thelast 7 years. From 1989, the year VRE was first identifiedin the United States, through 1993. Infection with VREmay be associated with increased mortality , and noeffective antimicrobial therapy is available for many VRE. Dr.T.V.Rao MD 9
  10. 10. VRE EpidemiologyFound world-wide, but rates vary greatlyHospital outbreaks often involve clonal spreadAlso seen in nursing homes and long term care facilitiesIn Europe, animals may be a source due to the use of theglycopeptide, avoparcinFirst described in EuropePrimarily a nosocomial pathogenAlarming increase from 1989 to 1993intensive care unitsteaching hospitalshospitals with more than 500 beds. Dr.T.V.Rao MD 10
  11. 11. Vancomycin and Development of VRE StrainsMechanism of action: Inhibits bacterial cell wall synthesisSpectrum of action: Gram positive organisms Including: Listeria, Rhodococcus, Peptostreptococcus Bacteriostatic against enterococcusMechanism of resistance: Enterococcus: Van A – E Peptidoglycan precursor has decreased affinity for vancomycin – D-ala-D-ala replaced by D-ala-D-lac Dr.T.V.Rao MD 11
  12. 12. Vancomycin-Resistant Enterococci(VRE), are bacterial strains of the genusEnterococcus that are resistant to the antibioticvancomycin. Enterococci are gram-positivecoccoid-shaped bacteria found in the digestivetract of some humans. To become VRE,vancomycin-sensitive enterococci typicallyobtain new DNA in the form of plasmids ortransposons which encode genes that confervancomycin resistance.Dr.T.V.Rao MD 12
  13. 13. vanA and vanB Phenotypes vanA vanBVancomycin MIC >64 4-1024Teicoplanin MIC 16-512 ≤ 0.5Usual species faecium, faecalis faecium, faecalisAcquired Yes YesTransferable Yes Yes
  14. 14. MOLECULAR BASIS OFVANCOMYCIN RESISTNACE
  15. 15. vanC, vanD, and vanE Phenotypes vanC vanD vanEVancomycin 2-32 128 16MICTeicoplanin ≤ 0.5 4.0 0.5MICUsual species gallinarum, faecium faecalis casseliflavis, flavescensAcquired No Yes YesTransferable No No No
  16. 16. Glycopeptide-Resistance TransposonsIn E. faecium, vanA andrelated genes are located ona transposon (Tn1546)which resides on a plasmidResistance is associatedwith a number of genes(vanHAX gene cluster,vanS, vanR, vanX andvanZ)vanB phenotype isassociated with Tn5382 Dr.T.V.Rao MD 16
  17. 17. vanA Genes and Their Enzymatic Products (I)vanA protein is a ligase produces D-ala-D-lac rather than D-ala-D-ala (vanA alone does not lead to resistance)vanH protein is a dehydrogenase converts pyruvate to D-lactic acid (the source of lactate for the above reaction)vanX protein is D,D-dipeptidase cleaves D-ala-D-ala (Cetinkaya et al. 2000. Clin Micro Rev. 13: 686-707) Dr.T.V.Rao MD 17
  18. 18. vanA Genes and Their Enzymatic Products (II) vanS is a sensor detects the presence of vancomycin or some effect of it vanR is a regulator may turn on vanHAX vanY is a carboxypeptidase cleaves terminal D-Ala vanZ increases the MIC of teicoplanin mechanism is unknownCetinkaya et al. 2000. Clin Micro Rev. 13: 686-707 Dr.T.V.Rao MD 18
  19. 19. vanB Genes and Resistance vanB is also a ligase involved with D-ala-D-lac production vanXB has dipeptidase activity associated with high level vancomycin resistance vanHB, vanYbB, vanSB and vanRB genes similar to their vanA counterparts Teicoplanin does not induce the synthesis of vanB proteins and cells are still susceptibleCetinkaya et al. 2000. Clin Micro Rev. 13: 686-707 Dr.T.V.Rao MD 19
  20. 20. vanC, vanD and vanE ResistancevanC ligases result in D-ala-D-ser net result is reduced vancomycin bindingvanD ligase has some homology with other van ligasesvanE ligase rare more closely related to vanC than the other van ligases Dr.T.V.Rao MD 20
  21. 21. Result Spreading ResistanceEnterococci that acquirethe vanA phenotype arehighly resistant tovancomycin and toteicoplaninEnterococci can pass thevanA gene cluster to S.aureus E. faecalis rather tan E. faecium (so far) Dr.T.V.Rao MD 21
  22. 22. Infections Caused by Vancomycin Resistant EnterococciUrinary tract infection (most common)Intra-abdominal and pelvic infection (also common)Surgical wound infectionBacteremia—bacteria in the bloodEndocarditis —infection of the inner surface of the heartmuscles and valvesNeonatal sepsis —bacteria in the blood, occurring ininfantsMeningitis —infection of the membranes that surroundthe brain and spinal cord Dr.T.V.Rao MD 22
  23. 23. Dr.T.V.Rao MD 23
  24. 24. Diagnosis of VRESpecimens can proceeded as per clinical NeedsDiagnosis requires culturing the organism. VREis easily grown on culture plates in a laboratory.To get material to culture, a sample of theinfected tissue is taken. For a wound infection, aswab is usually rubbed over the surface to getinfected material. Blood is drawn and cultured todetect sepsis or endocarditis. Urine samples aretaken to identify urinary infections . Dr.T.V.Rao MD 24
  25. 25. Enterococci are Bile Esculin Test PositiveEnterococci are able to growin the presence of bile andhydrolyze the esculin; theliberateddiphydroxycourmarincomplexes with ferric citratepresent in the media to forma dark brown/black solublecompound. Dr.T.V.Rao MD 25
  26. 26. Bile Esculin Test Positive for group D streptococci and enterococci Dr.T.V.Rao MD 26
  27. 27. Detection of Vancomycin ResistanceSusceptibility to vancomycinwas performed by Kirby-Bauer Disc DiffusionMethod on Mueller HintonAgar by using 30 gvancomycin disc .Vancomycin resistance wasalso determined byVancomycin agar screenmethod using 6 g/ml ofvancomycin incorporated inBrain Heart Infusion (BHI)agar. Dr.T.V.Rao MD 27
  28. 28. Detection of Vancomycin ResistanceMinimum InhibitoryConcentration (MIC) of allthe isolates were done byMacro broth dilutionmethod, using dilutionsof vancomycin rangingfrom 2 g/ml to 512 g/ml. Dr.T.V.Rao MD 28
  29. 29. Drug Resistance can beEstablished by E-Test Dr.T.V.Rao MD 29
  30. 30. *Chromogenic Methods in Diagnosis of VREChromogenic mediumfor the detection ofVancomycin ResistantEnterococcus (VRE) E.faecalis and E. faecium* Colorex™ PreparedChromogenic Media by BioMedDiagnostics Dr.T.V.Rao MD 30
  31. 31. Genotypic Detection of VRERapid detection ofvancomycin resistanceby polymerase chainreaction (PCR). usefulin epidemiologicstudiesPCR cant be performeddirectly on clinicalspecimens. Dr.T.V.Rao MD 31
  32. 32. Control and Prevention Limiting the use of certain broad spectrum antibiotics may also lead to a decrease in the rates of VRE colonization and infection. One study suggested that reduction of third- generation cephalosporins with the substitution of piperacillin/tazobactam could reduce the incidence of VRE in an intensive care unit settingHospital Infection Control Practices Advisory Committee (HICPAC). Recommendations for preventing the spread ofvancomycin resistance. Infect Control Hosp Epidemiol 1995; 16:105 Dr.T.V.Rao MD 32
  33. 33. Control and Prevention The CDC has recently published recommendations for preventing the spread of vancomycin resistance Prudent use of vancomycin Education of hospital staff regarding the problem Rapid and accurate identification of VRE in the microbiology laboratory Aggressive infection control measures utilizing contact isolation and cohorting where necessary to prevent person-to-person transmissionHospital Infection Control Practices Advisory Committee (HICPAC). Recommendations for preventing the spread of vancomycinresistance. Infect Control Hosp Epidemiol 1995; 16:105 Dr.T.V.Rao MD 33
  34. 34. Hand Washing can Reduce the Spread of VRE Dr.T.V.Rao MD 34
  35. 35. Created by Dr.T.V.Rao MD for ‘ e ‘Learning Resources for Medical and Paramedical Professionals in Developing World Email doctortvrao@gmail.com Dr.T.V.Rao MD 35

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