New and rapid detection of antimicrobial resistance: CLINICAL IMPLICATIONS OF RAPID RESULTS OF ANTIMICROBIAL SUSCEPTIBILITY TESTING Esther Calbo ESCMIDInfectious DiseaseseLibraryUnit Hospital Universitari MútuaTerrassa, Barcelona, Spain by author DISCLOSURES I have accepted grants, speaking engagements and conference invitations from Astellas AstraZeneca Novartis Pfizer MSDESCMID eLibrary by author OUTLINE • THE PROBLEM • THE EVIDENCE • MY (biased and clinical) OPINION. •ESCMIDNo comments on the different rapid diagnoseseLibrary techniques will be made. by author THE PROBLEM ESCMID eLibrary by author THE DILEMMA 50% ESCMID eLibrary Gottesman et al. CID 2009 by authorKumar Crit Care 2006 BALANCE EARLY ACTIVE UNNECESARY USE UNNECESARY BROAD ESCMIDSPECTRUM eLibrary by author THE PERFECT TREATMENT APPROPRIATE FAST ESCMID eLibrary by author GOLD HOUR OR GOLD FEVER ESCMID eLibrary by author RAPID 2005-2010 40% 165 ICUs 18.000 pts 28% Am & Eu ESCMID eLibrary by authorFerrer et al. Crit Care Med 2014 CREDIT GOES TO THE BUNDLE EL MÉRITO ES DEL BUNDLE ESCMID eLibrary by authorPuskarich et al. Crit Care Med 2011 CAUSES OF INAPPROPRIATE THERAPY IN BSI AT HUTM 2015 APPROPRIATE NO DIAGNOSIS MULTIDRUG RESISTANCE 11% Rapid diagnosis 9% 80% ESCMID eLibrary by authorBoix L, Calbo E et al SEIMC 2016 EFFICENCY OF MICROBIOLOGICAL SAMPLES ESCMID eLibrary Boix L, Calbo E. ECCMID 2016 Vincent Crit Care Med 2015 by author Interest of the clinicians for microbiological reports Acctions to be taken Sampling 1. Adequate clinical evolution … 2. Inadequate clinical evolution, modification of clinical decisions and therapeutic modification … 3. Revitalized interest: protocol, clinical trials, publications, congresses, reports, … interest 2 MULTIRESISTANCE AND COST 3 HIGH MORTALITY 1 SENSITIVITY 24 h 48 h 72 h 3-5 days time ? ESCMIDEARLY eLibrary DIAGNOSES Edwards et al. Arch Intern Med 1973; 132:678-82 Spencely et al. J Infect 1979; 1:23-26 Cunney et al. Int J Antimicrob Chemother 2000; 14:13-9 by authorR. Cantón (personal experience) REAL LIFE ESCMIDIN EDeLibrary by author RISK OF INAPPROPRIATE THERAPY Clinical Basal MDR Basal DDD diagnosis rates rates DIRECTED Empiric therapy Empiric therapy Directed therapy THERAPY according to according to acoording to local local guidelines senior expert susceptibility and syndrome opinion pattern 20:00 pm 08:00 am 19:00 pm TO 12h 18 h 72 h Blood BC Gram Final Culture results ESCMIDSamples eLibrarystain RAPID DIAGNOSTIC by authorMETHODS EVIDENCE I ESCMIDOBSERVATIONAL eLibrary STUDIES by author OBSERVATIONAL STUDIES • >900 patients wit suspected infections (BSI) . 9 ICUs in Europe. • PCR/ MALDITOF >800 species / mecA, vanA/vanB, KPC NPV • TIME to results= 6 h 97% ESCMID57% eLibrary by authorVincent . CCM 2015 EVIDENCE II ESCMIDQUASI-EXPERIMENTAL eLibrary STUDIES by author Studies published 1994-2010 Rapid molecular techniques + direct communication ESCMID eLibrary by authorBuehler CMR 2016 QUASI EXPERIMENTAL AUTHOR SAMPLES TEST MORTALITY COST LOS Pardo BSI FilmArray = Diag Micr Infect 84 cases Gram positive+ Dis 2015 252 controls AST* Huang BSI MALDI-TOF + CID 246 cases AST* NA = 2015 256 controls Box BSI Verigen Gram Pharmacother 64 cases Positive Blood = 2015 103 controls culture Suzuki BSI Verigen Gram JIC 88 cases +&- Blood 2015 147 controls culture Perez BSI MALDI-TOF Arch Pathol Lab 107 cases +AST* = Med 2013 112 controls GalarESCMIDBact infections Vitek +on time eLibrary Eur J Clin 290 cases Microbiol 2012 284 controls = by authorAST= Antimicrobial Stewardship Team Impact of rapid organism identification via MALDI-TOF combined with antimicrobial stewardship team intervention in adult patients with bacteriemia and candidemia Lab working time: 6:00-23:30. Only BSI Antimicrobial Stewardship Team : 2 ID+3 ID pharmacist+1 resident INTERVENTION PERIOD : Real time alerts were paged 6:00-23.30 and mailed daily MICRO DATA FOR INTERVENTION Gram stain 26% Susceptibility results 38% MALDI-TOF identification results 35% ESCMIDAntimicrobial eLibrary Stewardship Team INTERVENTION: 25% intiated or broadened coverage 73 % Gram stain by author Huang CID 2013 EVIDENCE III ESCMIDRANDOMIZED eLibrary CLINICAL TRIALS by author Randomized Trial on Rapid Multiplex Polymerase Chain Reaction- Based Blood Culture Identification and susceptibility Testing. Rapid multiplex PCR (24h/ 7 d) >20 species mecA, vaA/B, blaKPC Shorter time to MO identification Lower use of broad spectrum Less treatment of contaminants No differences in time to 1.3h 22 h appropriate AB (70%), mortality, LOS or cost Shorter time to de-scalation only in theESCMID PCR+AST group eLibrary In complex clinical scenarios ph may prefer discussion with ID prior to modifying therapy by author Banerjee CID 2015 Impact of same-day antibiotic susceptibility testing on time to appropriate antibiotic treatment of patients with bacteraemia: a RCT • 750 bed hospital. Micro Lab 24 h/ 7 days+ (S. aureus mecA) • FAST: multiplex PCR identification + semi-molecular method for AST • Microbiologist advised the optimal therapy by phone. • Empiric atb therapy was inadequate in 26%. Outcome FAST SOC p Value N=114 N=109 Mean time to results (h) 50.7 66.3 <0.001 Mean time to appropriate therapy (h) 28.2 26.9 0.9 LOS (days) 11 11 0.8 ESCMIDMortality (%) eLibrary12.3 7.3 0.2 by authorBeuving Eur J Clin Microbiol Infect Dis 2015 ESCMIDMY (biased and clinical) eLibrary OPINION by author SOME FINAL REFLEXIONS THE THEORY THE REALITY of early identification and antibiogram in Micro Lab and clinical practice . Early empirical appropriate AB • Implementation on the Lab .Early descalation workflow: 24/7 .Better clinical outcomes: • Impact on mortality is .LOS multifactorial • .Mortality Benefit is conditioned by basal rates: .Lower ecological impact: – MDR/ inappropriate use/ DDD .Lower CD rates • Stewardship teams are crucial 24/7 .Lower MDR rates ESCMID eLibrary• Cost by author …………..OPINION 1) EARLY administration (<1 h) of the appropriate antibiotic therapy in patients with septic shock and severe sepsis saves lives. Although the integration of antibiotic treatment in a bundle resuscitation is probably the most important. 2) The existence of INSTITUTIONAL RECOMMENDATIONS for empirical treatment adapted to local epidemiology may favor that> 90% of patients with infection receive appropriate therapy. 3) The benefit of an EARLY identification and detection of resistance mechanisms is conditioned by: Baseline rates of inadequate treatment (MDR +/- prescribers clinical expertise) ESCMIDThe structure (AST team, Microbiologist eLibrary availability to implement 24/7) 4) Treatment recommendations are better accepted when they come from an ID by author THANKS FOR YOUR ATENTION ESCMID eLibrary by author Back up slides ESCMID eLibrary by author RCT 2 years, 1200 bed, 1498 patients INTERVENTION: Vitek2 + BC tested directly 24h / 7 d + phone call to ID Vs CONTROL: Vitek 1+ overnight ESCMID< 20 h eLibrary Lower use of AB 24 vs 28 DDD No differences in mortality by authorKarremans JAC 2008 TIME TO START OF TREATMENT MORTALITY BY SITE OF INFECTION Global 27% 13% 0.015 ESCMID eLibrary by authorHranjec et al. Lancet Infect Dis 2012 I have a dream • SENSIBILITY AND NEGATIVE PREDICTIVE VALUE • RAPIDITY To reduce mortality To decrease MDR To decrease DDD ESCMIDCost-effectiveness eLibrary by author.