ESKAPE Pathogens Antibacterial Stewardship


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ESKAPE Pathogens Antibacterial Stewardship

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ESKAPE Pathogens Antibacterial Stewardship

  1. 1. Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  2. 2. Antibiotics Advanced MedicineThe discovery of potentand safe antimicrobialagents is arguably thesingle greatest health careadvance in history. Theavailability of theseagents rapidly reducedthe morbidity andmortality associated witha host of formerly fataldiseases. Dr.T.V.Rao MD 2
  3. 3. Microbes follow the Darwins TheoryThe widespread use ofantibiotics has beenassociated with what wenow know to be thepredictable emergence ofresistance.Early confidence thatinfections would eventuallybe conquered has given wayto a greater appreciation ofthe genetic flexibility ofcommon human pathogens Dr.T.V.Rao MD 3
  4. 4. ESKAPE AND CDCAccording to the latestdata from the Centersfor Disease Controland Prevention(CDC), the sixESKAPE bacteria areresponsible for twothirds of all healthcare-associatedinfections (HAIs) Dr.T.V.Rao MD 4
  5. 5. ESKAPEPathogens of Highest Concern The most serious, life- threatening infections are caused by a group of drug- resistant bacteria that the Infectious Diseases Society of America (IDSA) has labeled the "ESKAPE" pathogens, because they effectively escape the effects of antibacterial drugs Dr.T.V.Rao MD 5
  6. 6. ESKAPE - BacteriaESKAPE bacteria—Enterococcus faecium,Staphylococcus aureus,Klebsiella species,Acinetobacter baumannii,Pseudomonas aeruginosa,andEnterobacter species—areamong the biggest threat ofinfectious diseasesphysicians face today, Dr.T.V.Rao MD 6
  7. 7. Bad Bugs, No Drugs: No New Drugs Enterococcus faecium(E), Staphylococcus aureus(S), Klebsiella pneumoniae(K), Acinetobacter baumannii(A), Pseudomonas aeruginosa(P), and Enterobacter spp. (also E. coli) (E) The late-stage clinical development pipeline remains unacceptably lean Some important molecules for problematic pathogens such as MRSA and E. faecium Few novel prospects for other ESKAPE pathogens, especially multidrug-resistant gram-negative bacilli, such as A. baumannii and P. aeruginosa) Dr.T.V.Rao MD 7
  8. 8. Why ESKAPE ARE THREATThe ESKAPE pathogens(Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa, andEnterobacter species) areresponsible for a substantialpercentage of nosocomialinfections in the modernhospital and represent the vastmajority of isolates whoseresistance to antimicrobialagents presents serioustherapeutic dilemmas forphysician Dr.T.V.Rao MD 8
  9. 9. Why ESKAPE Microbes are a Global ConcernThe ESKAPE MICROBESare extraordinarilyimportant, not only becausethey cause the lion’s share ofnosocomial infections butalso because they representparadigms of pathogenesis,transmission, and resistance. Dr.T.V.Rao MD 9
  10. 10. Dr.T.V.Rao MD 10
  11. 11. ESKAPE Bacteria are Major Nosocomial AgentsAccording to the latestdata from the Centers forDisease Control andPrevention (CDC), the sixESKAPE bacteria areresponsible for two thirds ofall health care-associated infections(HAIs). Dr.T.V.Rao MD 11
  12. 12. Enterococcus speciesEnterococci were responsible for one out of eight HAIs in2006-2007. A 2004 study found about two thirds of E.faecium bloodstream infections were resistant tovancomycin, one of the most commonly used antibioticsto treat enterococcal infections. Some physicians aretreating vancomycin-resistant E. faecium with the newantibiotics linezolid, daptomycin, and tigecycline, butthese drugs have not been studied extensively for useagainst these infections. Furthermore, many patientscannot tolerate them. Dr.T.V.Rao MD 12
  13. 13. Enterococcus faecium (and faecalis)With the advent of vancomycin-resistant E.faecium, which are intrinsically resistant toampicillin and carbapenems, in the mid-1990s weencountered virtually untreatable organisms–However, enterococci have relatively lowvirulence, and treatment is not always required inmixed infections, unless also in blood;IV catheter infections may clear if the catheter isremoved. Dr.T.V.Rao MD 13
  14. 14. Newer Drugs Active Against VRE (and MRSA)Synercid (synergistic combination of two streptogramins)Bactericidal–Active against E. faecium but not E. faecalis–Side-effect of total-body tenderness–Rarely used•Linezolid (oxazolidinone)–Bacteriostatic Both po and IV–Occasional thrombocytopenia, esp. after 14 days (need tocheck plt counts at least weekly)–Emergence of resistant isolates–Increasingly important for MRSA Dr.T.V.Rao MD 14
  15. 15. Newer Drugs Active Against VRE (and MRSA)Daptomycin (lipopeptide)–Rapidly bactericidal (important for bacteremias)–IV only–Binds to surfactant, so not effective in pneumonia–Occasional elevations of creatine phosphokinase (CPK) andassociated muscle aches; seems not to be a serious problem–Increasingly important for MRSA•Tigecycline (glycylcycline; derivative of minocycline)–Bacteriostatic–IV only–Active not only against Staph, Strep, and Enterococcus, butalso against Enterobacteriaceae Dr.T.V.Rao MD 15
  16. 16. Staphylococcus aureusThe prominent name among the ESKAPEbacteria, methicillin-resistant Staphylococcusaureus (MRSA) outbreaks have been reportedamong otherwise-healthy athletes, militaryrecruits, school children, and others. MRSAcaused an estimated 94,000 invasive infections—more than 19,000 of them fatal—in 2005,according to a recent study by CDC. MRSA is aserious and growing threat in hospitals andother health care facilities, Dr.T.V.Rao MD 16
  17. 17. MRSAMRSA has drawnmore attention fromthe pharmaceuticalindustry than any ofthe other ESKAPEbugs. Several newdrugs are effectiveagainst theseinfections. Dr.T.V.Rao MD 17
  18. 18. Problems with MRSA in Treatments60-65% of SA are MR (both ICU and non-ICU) (DMC 2009) (forpresumptive treatment, must assume MR)Vancomycin MIC –MICs have been generally risingFor vanco MIC >1 µg/ml, efficacy reduced, and even higher MICsmay be selected (hVISA)Therefore, for MIC >1 (>50%), we use daptomycin (esp. forbacteremia) (but not for pneumonia, in which case we use linezolid)Other alternatives to vancomycinTMP/SMX: IV/po; cidal; ~90% are S–Clindamycin: IV/po; not reliably cidal; must check D-test; ~50%Sensitive•We are losing vancomycin, but we have alternatives Dr.T.V.Rao MD 18
  19. 19. Klebsiella speciesThese gram-negative bacteria causeinfections in the urinary, biliary, andgastrointestinal tracts, and in traumawounds. Klebsiella species and theirgram-negative cousin E. coli togetheraccounted for 18 percent of all HAIs in2006-2007, and a growing proportion ofthese two carry resistance to a remarkablespectrum of antibiotics. Dr.T.V.Rao MD 19
  20. 20. Problems with Enterobacteriaceae ESBL –Klebsiella pneumonia and E. coli(~8-10%) –>90% Sensitive to carbapenems,Cefotetan/cefoxitin, tigecycline KPC ß-lactamases (~1-3% Klebpneumonia Resistant to carbapenems,as well as other ß-lactams) Dr.T.V.Rao MD 20
  21. 21. KPC’sMight appear susceptible to imipenem or meropenem,but with borderline MICs Usually ertapenem-resistant–Modified Hodge test to confirm•Usually susceptible only to colistin, tigecycline, selectaminoglycosides, and possibly TMP/SMX•Easily spread in hospitals (often requires cohorting ofstaff and patients to control) Dr.T.V.Rao MD 21
  22. 22. Acinetobacter baumanniiTraditionally infectspatients in ICU and BurnUnits•Now being seen ingeneral hospitalpopulation and nursinghomes•Antimicrobialresistance is a majorconcern Dr.T.V.Rao MD 22
  23. 23. Acinetobacter baumannii:Drug resistance is a majorproblem in Acinetobacterinfections, which areresponsible for about 3 percentof all HAIs,. Soldiers arereturning from Iraq andAfghanistan with cases ofhighly resistant Acinetobacterwound infections. Strains haveemerged that are resistant to allbut the most toxic newgeneration of Antibiotics Dr.T.V.Rao MD 23
  24. 24. Pseudomonas aeruginosaThe most commonlyencountered multiresistantgram-negative pathogenRelatively low pathogenicity:mainly a problem in ICUs BurnUnit Patents from long-termcare facilities Additional riskfactors:Immunocompromised,debilitated, priorhospitalizations, priorantibiotic therapy,trauma outdoors withexposure to water/soil Dr.T.V.Rao MD 24
  25. 25. Pseudomonas aeruginosa:Pseudomonas is aparticular problem forpatients on respirators andthose with cystic fibrosis.Eight percent of all HAIs arecaused by P. aeruginosa, andone quarter of these areresistant to carbapenems, aclass of antibioticscommonly used for theseinfections. There are no newdrugs in development forthese highly resistantinfections. Dr.T.V.Rao MD 25
  26. 26. Enterobacter species:One in 20 HAIs is caused bythis group of bacteria. LikeKlebsiella, E. coli, and the othergram-negatives, Enterobacterspecies have developed broad-spectrum resistance to multipleclasses of antibiotics. One drug,tigecycline, might work againstthese infections. There is nonew antibiotics in the pipeline. Dr.T.V.Rao MD 26
  27. 27. The Challenge:Global Antibiotic ResistanceClinical and media reports have documented therapid rise of antibiotic-resistant and MDRbacterial infections, now a major global publichealth concern. Most hospital-acquiredinfections are resistant to at least one drug, andthe incidence of multi-drug resistance is rising.The inability to rapidly get these infections undercontrol results in nearly 100,000 deaths every yearin the United States, many more in DevelopingWorld Dr.T.V.Rao MD 27
  28. 28. Dr.T.V.Rao MD 28
  29. 29. Antimicrobial Stewardship.Antimicrobial stewardship is a key component of amultifaceted approach to preventing emergence ofantimicrobial resistance. Good antimicrobialstewardship involves selecting an appropriate drug andoptimizing its dose and duration to cure an infectionwhile minimizing toxicity and conditions for selectionof resistant bacterial strains. Studies conducted over theyears indicate that antibiotic use is unnecessary orinappropriate in as many as 50% of cases. Dr.T.V.Rao MD 29
  30. 30. Other Aspects of Antimicrobial StewardshipThe appropriate use of antimicrobials is an essential partof patient safety. The frequency of inappropriate antimicrobial use is oftenused as a surrogate marker for the avoidable impact onantimicrobial resistance. The combination of antimicrobial stewardship andcomprehensive infection control has been shown to limitthe emergence and transmission of antimicrobial resistantbacteria. Dr.T.V.Rao MD 30
  31. 31. ANTIMICROBIAL STEWARDSHIP GUIDELINESCurrent efforts to thwart thesiege of MDROs and to addressthe lack of development ofantimicrobial agents center onantimicrobial stewardship. In2007, The Infectious DiseasesSociety of America (IDSA)published guidelines inconjunction with the Society forHealthcare Epidemiology ofAmerica to outlineantimicrobial stewardshippractices. Dr.T.V.Rao MD 31
  32. 32. Developing Antibiotic Stewardship -Committee Membership and LeadershipMedical Staff- Active participation is critical to successIncludes Chief Medical Officer support, ID , Hospitalists,Intensivists, Pulmonary, ED, Community MDs and others aswillingPharmacy- Coordinates the efforts of the team, guidelinedevelopment, education and tracking reportsInfection Prevention & Control- Prevention Strategies, handhygiene, precautions, medical staff-nursing laison Microbiology- Data trends, special testing expertiseQuality & Organizational Development- PerformanceImprovement guidance; meeting guidance Dr.T.V.Rao MD 32
  33. 33. Core Members of the Antimicrobial Stewardship Team Infectious disease physician (Director or Co-director) Clinical pharmacist with infectious disease training (Co-director or core member) Other members of the team – Microbiologist – Information system specialist – Infection control professional – Hospital epidemiologist Dr.T.V.Rao MD 33
  34. 34. Goals of CommitteeAssist providers in appropriate use ofantimicrobial therapy with improved patientoutcomesSlow the development of antimicrobial resistanceDevelop evidence- based appropriate useguidelinesEducate providers and staff regarding guidelinesTrack resistance patterns and report back to medical andhospital staff Dr.T.V.Rao MD 34
  35. 35. Need to Develop AntibioticStewardship in Developing NationsAntimicrobial stewardship is one method manyinstitutions are implementing to achieve this balance.Antimicrobial stewardship encompasses a wide range ofservices aimed at improving patient outcomes andminimizing the untoward effects of antimicrobial agentsincluding side effects as well as induction of resistance.These programs have been shown to decrease both thedevelopment of resistance as well as expenditures onantimicrobial agents. Dr.T.V.Rao MD 35
  36. 36. Antimicrobial Stewardship: Plan the programme to the Needs of your Hospital on ……Restriction of theoximinocephalosporins– VRE– C. difficile– ESBLs– AmpC hyperproduction• Use vancomycin according toHICPACguidelines– VRE– VISA– VRSA Dr.T.V.Rao MD 36
  37. 37. Should Plan Matter onJudicious Use of Antibiotics Fluoroquinolones – judicious use – Elimination of ciprofloxacin • Association with MRSA • Association with C. difficile • Cost benefit with a single fluoroquinoloneformulary • Carbapenems – restriction – Metallo-beta-lactamases – Other carbapenemases (KPC 1 – 3, OXA) Dr.T.V.Rao MD 37
  38. 38. Why Participate in Stewardship?The primary goal ofstewardship is to…Optimizeclinical outcomes whileminimizing unintendedconsequences ofantimicrobial use, includingtoxicity, the selection ofpathogenic organisms, andemergence of resistance.Secondary goals…Reducehealthcare costs withoutadversely impacting qualityof care. Dr.T.V.Rao MD 38
  39. 39. Modifying Empiric Therapy“Empiric therapy”: treatment prescribed before culture data andother testing results are availableIn most cases, empiric therapy should be narrowed at day 3-4 orearlier–If cultures are negative, try to narrow regimen–If cultures are positive, usually can focus regimenOften, empiric antibiotics are continued due to inertia, complicatedclinical pictureNeed automated reminders at day 3-4 for regimens includingmultiple antibiotics –aggressive efforts to decrease number andduration of antibioticsSuccess might be stopping one agent out of 3, or limiting durations to7 days instead of 14 Dr.T.V.Rao MD 39
  40. 40. Supplemental Elements to a Stewardship ProgramEducation –e.g., Antibioticrounds in the ICUGuidelines and clinicalpathwaysAntimicrobial cyclingAntimicrobial order forms orcomputer order entryCombination therapyStreamlining and de-escalationof therapyDose optimization•Parenteral to oralconversion Dr.T.V.Rao MD 40
  41. 41. Alliance for the Prudent Use of AntibioticsThe Alliance for the Prudent Use of Antibiotics(APUA) is a non profit organization founded in 1981by Dr. Stuart B. Levy, Professor of Medicine atTufts University and headquartered in Boston,Massachusetts APUA’s mission is to strengthensociety’s defenses against infectious disease bypromoting appropriate access and use toantimicrobial agents (antibiotics, antivirals,antimalarial etc.) and controlling antimicrobialresistance on a worldwide basis. Dr.T.V.Rao MD 41
  42. 42. Become a Member of Alliance for the Prudent Use of Antibiotics (APUA) An international organization dedicated to curbing antibiotic resistance Chapters exist currently in several Asian countries: Australia, China, India, Nepal, Pakistan, Philippines, South Korea, Taiwan, Vietnam Dr.T.V.Rao MD 42
  43. 43. Research on Newer Antibiotics is a Priority"The difficulty in identifyingnovel antimicrobial agentswith reliable activity againstthese pathogens argues foran augmentation of researchin the basic and populationscience of resistance, as wellas careful studies to identifyoptimal strategies forinfection control andantimicrobial use. Dr.T.V.Rao MD 43
  44. 44. Infectious Diseases Society of America supports Issues on antibiotic use IDSA support strengthening current approaches to antimicrobial resistance, to protect effectiveness of the drugs currently available. We must maximize hospital infection- control practices, to limit the spread of resistance Dr.T.V.Rao MD 44
  45. 45. ReferencesNo ESKAPE! New Drugs Against MRSA, OtherSuperbugs Still Lacking IDAClinical Impact of Resistance and Control of Antibiotic UsageStephen A. Lerner, M.D. Professor of Medicine Division of InfectiousDiseases Wayne State University School of Medicine Detroit,Michigan, USA Dr.T.V.Rao MD 45
  46. 46. Programme Created by Dr.T.V.Rao MD for ‘ e ‘ learning resources forMedical and Paramedical Students in the Developing World Email Dr.T.V.Rao MD 46
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