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Prevention, Diagnosis, & Management of Hospital-Associated Infections IM R-1 Orientation Paul Pottinger, MD, DTM&H June 27, 2013 Slide 2 Hospital-Associated Infections OBJECTIVE Increase your confidence in preventing, diagnosing, treating HAIs Increase your confidence in preventing, diagnosing, treating HAIs Understand your role in Antimicrobial Stewardship Understand your role in Antimicrobial StewardshipFORMAT Case-based & interactive Case-based & interactiveCONTENT Common infections you will see PGY 1 Common infections you will see PGY 1SLIDES Available on the web Available on the web Slide 3 Oh the Humanity! MDR Infections: More Toxic Drugs Necessary More Toxic Drugs Necessary Longer Admissions Longer Admissions More Complications More Complications Increased Morbidity Increased Morbidity Increased Mortality Increased Mortality Magnitude of the Problem Slide 4 Money Its a Drag Annual Cost of MDR Infections: $30B Our Reality: Fee for Performance (carrot) Denial for Nosocomial Infections (stick) Slide 5 Ever heard this term? Come from a center with a program? Our Drugs vs. Their Genes Antimicrobial Stewardship Slide 6 Patient Care The primary goal of antimicrobial stewardship is to optimize clinical outcomes while minimizing unintended consequences of antimicrobial use, including toxicity, the selection of pathogenic organisms (such as Clostridium difficile), and the emergence of resistance. Financial Effective antimicrobial stewardship programs can be financially self-supporting and improve patient care. Comprehensive programs have consistently demonstrated a decrease in antimicrobial use (22% 36%), with annual savings of $200,000$900,000 in both larger academic hospitals and smaller community hospitals. Dellit TH et al. Clin Infect Dis. 2007;44:159-77. Stewardship Goals Slide 7 Infection Control Micro Lab Providers AbxStewardship QI/QA Pharmacy Patients Slide 8 Jeannie Chan, PharmD HMC Rupali Jain, PharmD UWMC Slide 9 Slide 10 Stewardship Teams at UWMC & HMCStewardship Teams at UWMC & HMC OCCAM (in your pocket, on your phone, online)OCCAM (in your pocket, on your phone, online) Service PharmacistsService Pharmacists ID Consult ServiceID Consult Service Stewardship Resources Slide 11 Slide 12 A 27 y/o man on the heme-onc service develops a fever to 40.2 o C 6 days following initiation of induction chemo Rx for AML. A Hickman catheter is present in the R subclavian vein. No localizing sxs on exam, Hickman entry site looks clean. Vitals fine. His WBC = 0.9, with an ANC = 100. Possible sources of fever? Increased risk of infection? What type? Diagnostic W/U? Empiric antibiotics? Case Slide 13 Case Possible sources of fever? Increased risk of infection? What type? Diagnostic W/U? Empiric antibiotics? Non-Infectious: Chemo, DVT / PE, CANon-Infectious: Chemo, DVT / PE, CA Infectious: CABSI, typhlitis, HAP, UTIInfectious: CABSI, typhlitis, HAP, UTI ANC StaphANC Staph (fungal risk over time) (fungal risk over time) H&P!H&P! CXR, U/A + micro, BCx x 2, sputum GS / C&S, Dopplers or CT-A, abd imagingCXR, U/A + micro, BCx x 2, sputum GS / C&S, Dopplers or CT-A, abd imaging Cover PsA with Ceftaz; Cover MRSA in sepsis, suspect CABSI, or if febrile in 3 days.Cover PsA with Ceftaz; Cover MRSA in sepsis, suspect CABSI, or if febrile in 3 days. Slide 14 Case BCX x 2 drawn via Hickman: Both grow GPCs in clusters after 24 hours incubationBCX x 2 drawn via Hickman: Both grow GPCs in clusters after 24 hours incubation Catheter-Associated Bloodstream Infection (CABSI) Working Diagnosis Slide 15 CABSI Confirm Diagnosis? Look for alternative sourcesLook for alternative sources Send quantitative BCx from line & peripheralSend quantitative BCx from line & peripheral CFU 2-3 X > peripheral CFU 2-3 X > peripheral Line Cx + > 2 hours sooner Line Cx + > 2 hours sooner Likely Bugs Coagulase-negative staphCoagulase-negative staph MSSA or MRSAMSSA or MRSA Line likely source Slide 16 CABSI Empiric Abx Add Vancomycin until ID / sensitivities are backAdd Vancomycin until ID / sensitivities are back Maintain Ceftazidime for PsA coverage until ANC > 500Maintain Ceftazidime for PsA coverage until ANC > 500 Other Management Central Lines: To Keep or Not to Keep?Central Lines: To Keep or Not to Keep? Slide 17 CABSI Line Management Pull line if:Pull line if: Patient is septic (once new access in) Non-Tunneled Line (PICC) Line is not needed or not working Pocket or track infection proximal to the cuff S.aureus, Pseudomonas, NTM, or fungus Valvular heart disease Still febrile after 48 hours of salvage attempt. Slide 18 CABSI Line Management Salvage Strategy: Abx LockSalvage Strategy: Abx Lock Vanco + Heparin soak the lumen Pros: 50% success rate50% success rate Cons : Lumen inaccessible during therapyLumen inaccessible during therapy Risk of heparin bolusRisk of heparin bolus Wont treat extra-lumenal infectionWont treat extra-lumenal infection EDTA + Abx or EtOH other options. via ID Consult Slide 19 CABSI Line Management Salvage Strategy: Guidewire ExchangeSalvage Strategy: Guidewire Exchange Save the Site, not the Line! Pros: Avoid complications of temporary accessAvoid complications of temporary access Cons : May fail if extra-lumenal infectionMay fail if extra-lumenal infection Consider exchange in HD Line infections. via ID Consult Slide 20 CABSI Line Management Salvage Strategy: Pull ItSalvage Strategy: Pull It Save the Patient, not the Site! Pros: Most likely to cure the infection whether bugs in lumen or on surfaceMost likely to cure the infection whether bugs in lumen or on surface Cons : Subjects pt to temporary accessSubjects pt to temporary access Slide 21 CABSI: Prevention Central Line Bundle Hand HygieneHand Hygiene Maximal Barrier Precautions Upon InsertionMaximal Barrier Precautions Upon Insertion Chlorhexidine Skin AntisepsisChlorhexidine Skin Antisepsis Optimal Catheter Site Selection, with Subclavian Vein as the Preferred Site for Non-Tunneled CathetersOptimal Catheter Site Selection, with Subclavian Vein as the Preferred Site for Non-Tunneled Catheters Daily Review of Line Necessity with Prompt Removal of Unnecessary LinesDaily Review of Line Necessity with Prompt Removal of Unnecessary Lines Slide 22 Slide 23 A 68 y/o woman with type-2 DM & HTN recently Rxd for CAP with cefotaximeA 68 y/o woman with type-2 DM & HTN recently Rxd for CAP with cefotaxime Now admitted for major CVANow admitted for major CVA Febrile Ceftazidime startedFebrile Ceftazidime started BCx & foley cath urine grew K.pneumoniaeBCx & foley cath urine grew K.pneumoniae Two days later: Fever persists, and she becomes less responsive.Two days later: Fever persists, and she becomes less responsive. 1) Switch to Levo or Cipro 2) Switch to Ceftriaxone 3) Switch to Cefepime 4) Switch to Meropenem 5) Everythings groovy, make no change 1) Switch to Levo or Cipro 2) Switch to Ceftriaxone 3) Switch to Cefepime 4) Switch to Meropenem 5) Everythings groovy, make no change Case Slide 24 Catheter-Associated UTI: CAUTI Pathogenesis Colonization: Endogenous flora ascends peri-catheter space or lumenColonization: Endogenous flora ascends peri-catheter space or lumen Infection: Inflammatory response to adherent or invasive bugs (common)Infection: Inflammatory response to adherent or invasive bugs (common) Confirm Diagnosis U/A and Quantitative UcxU/A and Quantitative Ucx Slide 25 Slide 26 Slide 27 Treatment Options: CAUTI Empiric coverage depends on gram stain: GNRs: Ceftazidime vs. Mero if MDRO hx GPCs: add Vancomycin (cover Staph) Total Length of Therapy: Usually 7 days; longer may be needed pyelo Definitive Treatment: Focus spectrum based on C&S results Slide 28 Emerging Resistance: ESBL Extended Spectrum -Lactamases Mutant TEM-1, SHV-1, CTX-M, or OXA -lactamaseMutant TEM-1, SHV-1, CTX-M, or OXA -lactamase Enzymes hydrolyze oxyimino--lactams (includes 3 rd Gen Cephalosporins)Enzymes hydrolyze oxyimino--lactams (includes 3 rd Gen Cephalosporins) Usually in Klebsiella spp. and E.coliUsually in Klebsiella spp. and E.coli Consider in all nosocomial infections with these organismsConsider in all nosocomial infections with these organisms Risk Factor = Previous -lactam use Overall prevalence may > 10% Slide 29 ESBL Worry if resistance skips a generationWorry if resistance skips a generation Confirm with 3-fold decrease in MIC with lacatmase inhibitorConfirm with 3-fold decrease in MIC with lacatmase inhibitor Rx of choice:Rx of choice: Carbapenem Carbapenem Variable success: Variable success: FQ FQ Aminoglycoside Aminoglycoside TMP/SMX, Nitro, Fosfo TMP/SMX, Nitro, Fosfo Slide 30 CRE Doomsday GNRs David Ricci Consider empiric contact precautions in pts recently admitted overseas Slide 31 CAUTI Other Management Change or remove the catheter if UTI detectedChange or remove the catheter if UTI detected Colonization virtually universal No need for routine surveillance cultures!Colonization virtually universal No need for routine surveillance cultures! Appreciate difference between asymptomatic bacteriuria and UTI!Appreciate difference between asymptomatic bacteriuria and UTI! Slide 32 CAUTIPrevention Use foley only when necessary!Use foley only when necessary! Aseptic insertion techniqueAseptic insertion technique Maintain securely, proper bag placementMaintain securely, proper bag placement Know who has a FoleyKnow who has a Foley Condom caths when feasibleCondom caths when feasible Pull them ASAP can always put one back if pt failsPull them ASAP can always put one back if pt fails Slide 33 Slide 34 Slide 35 Slide 36 Case: VAP ATS/IDSA Guidelines MDR Pathogen Risks Hospitalized 5 days Hospitalized 5 days Abx in last 90 days Abx in last 90 days High ward MDR prevalence High ward MDR prevalence SNF resident SNF resident Contact with MDR patient Contact with MDR patient Chronic Dialysis Chronic Dialysis Chronic Infusions Chronic Infusions Immunosuppressed Immunosuppressed Slide 37 Anti-Pseudomonal cephalosporin Anti-Pseudomonal cephalosporin (Ceftaz, Cefepime) or Anti-Pseudomonal carbapenem Anti-Pseudomonal carbapenem (Meropenem, Imipenem) or -lactam with lactamase inhibitor -lactam with lactamase inhibitor(Piperacillin/tazobactam)+ Anti-Pseudomonal FQ Anti-Pseudomonal FQ (Cipro, Levo) or Aminoglycoside Aminoglycoside (Gent, tobra) +/- Linezolid or Vancomycin Linezolid or Vancomycin Case: VAP MDR Pathogen Risks Hospitalized 5 days Hospitalized 5 days Abx in last 90 days Abx in last 90 days High ward MDR prevalence High ward MDR prevalence SNF resident SNF resident Contact with MDR patient Contact with MDR patient Chronic Dialysis Chronic Dialysis Chronic Infusions Chronic Infusions Immunosuppressed Immunosuppressed Pseudomonas aeruginosa Pseudomonas aeruginosa Burkholderia Burkholderia Stenotrophomonas Stenotrophomonas Klebsiella Klebsiella Citrobacter Citrobacter Acinetobacter Acinetobacter MRSA MRSA ATS/IDSA Guidelines Slide 38 Slide 39 Slide 40 Methods - Retrospective analysis 1999-2005 - University Hospital (Washington U) - N =102 Adults - Nosocomial MRSA pneumonia - MRSA established by BAL - Monotherapy with vancomycin > 72 hrs Measurements - Vancomycin trough levels - Clinical outcome Study Design Patient Outcomes From: Isakow W, et al. ICAAC 2006. DHS/PP MRSA VAP: Vancomycin Levels? Case: VAP Slide 41 MRSA: Van comycin MIC Creep? Soriano CID 2008 Not all VSSA created alike.Not all VSSA created alike. Published reports of rising vanco MICs in last 5 years.Published reports of rising vanco MICs in last 5 years. Presumed MOR: increased cell wall thickness.Presumed MOR: increased cell wall thickness. Retrospective case series: higher MICs associated with higher liklihood of clinical failure on vanco.Retrospective case series: higher MICs associated with higher liklihood of clinical failure on vanco. Slide 42 MRSA: Vancomycin MIC Creep? MIC 2 still considered susceptible (VSSA) Concern: clinical failures with vanco.MIC 2 still considered susceptible (VSSA) Concern: clinical failures with vanco. Recommend you routinely check vanco MIC, certainly if pt fails to clear bacteremia or clinically improve after 7 days of therapy.Recommend you routinely check vanco MIC, certainly if pt fails to clear bacteremia or clinically improve after 7 days of therapy. Consider switch to alternative agent if MIC = 2, and if pt is failing vanco.Consider switch to alternative agent if MIC = 2, and if pt is failing vanco. Slide 43 MRSA: Vancomycin MIC Creep? Consider switch to alternative agent if MIC = 2, and if pt is failing vanco.Consider switch to alternative agent if MIC = 2, and if pt is failing vanco. What, pray tell, shall I use instead of Vitamin V? Slide 44 Slide 45 Study Design Methods - Retrospective analysis of 2 prospective, randomized, case-control studies - N =1019 Adults - Nosocomial pneumonia - Suspected gram-positive pneumonia - 339 with documented S. aureus - 160 with documented MRSA Regimens - Vancomycin + Aztreonam - Linezolid + Aztreonam Clinical Cure From: Wunderink RG, et al. Chest 2003;124:1789-97. DHS/PP P = 0.009 P = 0.182 Vancomycin vs. Linezolid Round One: VAP Wunderink et al. CHEST / 124 (5) 2003 Slide 46 Slide 47 Methods - Blinded, Randomized prospective non-inferiority trial of pneumonia - Nosocomial pneumonia - N =1225 Adults Randomized - 339 with documented MRSA - Well-matched except 9% more ventilated pts in vanco arm Regimens - Vancomycin 15mg/kg IV Q 12 H - Linezolid 600mg IV Q 12 H - Both arms treated 7-14 days Study Design Outcomes From: Chastre J et al, 2010 IDSA Conference and CID January 2012 Not significantly different P = 0.042 CI = 0.5-21.6 Vancomycin vs. Linezolid Round Two: VAP Slide 48 Newer, Fancier, Pricier Better! LinezolidVancomycin For empiric MRSA VAP coverage Slide 49 Round Two: VAP Vancomycin vs. Linezolid Jury Still Out.. At least for meJury Still Out.. At least for me Trend to survival benefit with Linezolid in meta-analysis Trend to survival benefit with Linezolid in meta-analysis Trend to better clinical response in large prospective trial sponsored by industry no mortality difference Trend to better clinical response in large prospective trial sponsored by industry no mortality difference Adverse events comparable Adverse events comparable Many intensivists now favor linezolid for MRSA VAP at UW we start with vanco Many intensivists now favor linezolid for MRSA VAP at UW we start with vanco Slide 50 Methods (N = 401) - Microbiologically-Proven VAP* - Received initial appropriate therapy - Randomized, double-blinded - Performed 1999-2002 Methods (N = 401) - Microbiologically-Proven VAP* - Received initial appropriate therapy - Randomized, double-blinded - Performed 1999-2002 Regimens* - 8 days of therapy - 15 days of therapy Regimens* - 8 days of therapy - 15 days of therapy Methods (N = 401) - Microbiologically-Proven VAP* - Received initial appropriate therapy - Randomized, double-blinded - Performed 1999-2002 Methods (N = 401) - Microbiologically-Proven VAP* - Received initial appropriate therapy - Randomized, double-blinded - Performed 1999-2002 Regimens* - 8 days of therapy - 15 days of therapy Regimens* - 8 days of therapy - 15 days of therapy Study Design ResultsResults From: Chastre J, et al. JAMA 2003;290:2588-98. * All patients had quantitative cultures from bronchoscopy DHS/PP Case: VAP How Long to Treat? (Less is More) Slide 51 Slide 52 Slide 53 Abx Stewardship: Ceftaroline Anti-MRSA Cephalosporin FDA-Approved forFDA-Approved for Acute Skin & Soft Tissue Infxn due to susceptible MSSA & MRSA, GAS, GBS, E.coli, Klebsiella Acute Skin & Soft Tissue Infxn due to susceptible MSSA & MRSA, GAS, GBS, E.coli, Klebsiella CAP due to susceptible S.pneumo, MSSA, H.flu, Klebsiella, E.coli CAP due to susceptible S.pneumo, MSSA, H.flu, Klebsiella, E.coli Slide 54 Abx Stewardship: Ceftaroline Anti-MRSA Cephalosporin Toxicities: minimal, but frequent + coombs DAT.Toxicities: minimal, but frequent + coombs DAT. Dose: 600mg I VQ 12 H. No levels!Dose: 600mg I VQ 12 H. No levels! Cost: ~ $82 / day (vs. ~$12 / day for vanco)Cost: ~ $82 / day (vs. ~$12 / day for vanco) Consider: Consider in proven MRSA failing vanco, ONLY with ID approval.Consider: Consider in proven MRSA failing vanco, ONLY with ID approval. Slide 55 Prevention: VAP What Works? VAP Bundle! Elevate head of bed to 30Elevate head of bed to 30 Sterile technique with hand hygiene & ETT suctioning. Oral care.Sterile technique with hand hygiene & ETT suctioning. Oral care. Daily sedation holidayDaily sedation holiday Get the tube out ASAP!!Get the tube out ASAP!! Small added benefit: Silver-coated tubes or continuous suctionSmall added benefit: Silver-coated tubes or continuous suction Slide 56 POP QUIZ Antimicrobial Stewardship Slide 57 Slide 58 Slide 59 Ignac Philipp Semmelweis (1818-65) 1) Clean Your *&^%@! Hands Hand Hygiene Remains Cornerstone of ICHand Hygiene Remains Cornerstone of IC Biggest Cost:Benefit Ratio AroundBiggest Cost:Benefit Ratio Around Patients Will Thank (or Chastise) You!Patients Will Thank (or Chastise) You! Obey Precaution PlacardsObey Precaution Placards Prevent Infection Slide 60 P2P2P2P2 I WANT YOU To bring MDR bugs under control! Slide 61 Slide 62 1656 2008 Slide 63 VAP CABSI CAUTI Time + Tube = Trouble Slide 64 2) Dis-Invade ASAP Big 3 Associated with Indwelling Tubes VAPVAP CABSICABSI CAUTICAUTI Prevent Infection Daily or twice daily checklist: Is Tube Necessary? Is Tube Necessary? Is Site Care Appropriate? Is Site Care Appropriate? Slide 65 3) Less is More Coverage: Use only what you need. Coverage: Use only what you need. Trend: Reduce duration of abx Trend: Reduce duration of abx Caveat: Lack of RCTs in many syndromes some still need long course (hardware-assocd osteo, etc) Caveat: Lack of RCTs in many syndromes some still need long course (hardware-assocd osteo, etc) Advice: Limit duration & spectrum in consultation with ID service Advice: Limit duration & spectrum in consultation with ID service Limit Drug Exposure Slide 66 4) De-Escalate ASAP Example: VAP Fact: VAP pts usually critically ill, little physiological tolerance for error Fact: VAP pts usually critically ill, little physiological tolerance for error Fact: Mortality worse if initial abx dont cover pathogen Fact: Mortality worse if initial abx dont cover pathogen Fact: ATS / IDSA Guidelines call for broad, empiric coverage Fact: ATS / IDSA Guidelines call for broad, empiric coverage Limit Drug Exposure Slide 67 4) De-Escalate ASAP Example: VAP Fact: VAP pts usually critically ill, little physiological tolerance for error Fact: VAP pts usually critically ill, little physiological tolerance for error Fact: Mortality worse if initial abx dont cover pathogen Fact: Mortality worse if initial abx dont cover pathogen Fact: ATS / IDSA Guidelines call for broad, empiric coverage Fact: ATS / IDSA Guidelines call for broad, empiric coverage Limit Drug Exposure FACT: Targeting the Pathogen Should: Decrease Emergence of Drug Resistance Decrease Emergence of Drug Resistance Decrease Costs Decrease Costs Decrease Toxicity Decrease Toxicity Slide 68 5) Sometimes You Need a Hummer Reality: Nosocomial MDR pathogens are here. Reality: Nosocomial MDR pathogens are here. Impact: Devastating for individuals, high outbreak potential. Impact: Devastating for individuals, high outbreak potential. Approach: Diagnose & treat aggressively... With help from ID. Approach: Diagnose & treat aggressively... With help from ID. Treat MDROs Aggressively Slide 69 Abx Stewardship: Conclusion Our vs. Their Genes Be a Microbiota Champion!Be a Microbiota Champion! Few new abx comingFew new abx coming Abx resistance is our faultAbx resistance is our fault Fixing this is our responsibilityFixing this is our responsibility Together, we can do it!Together, we can do it! OCCAM your Friend!OCCAM your Friend!abx@uw.edu Brains Slide 70 abx@uw.eduabx@uw.edu Feedback?