NUOVE IPOTESI e MODELLI di STEWARDSHIP

Esperienze di successo di antimicrobial stewardship Bologna, 18 novembre 2014 NUOVE IPOTESI e MODELLI di STEWARDSHIP Pierluigi Viale Clinica di Malattie Infettive Policlinico S. Orsola Malpighi

Interventions to improve antibiotic prescribing practices for hospital inpatients Types of interventions v Restrictive: selective reporting of laboratory susceptibilities, formulary restriction, requiring prior authorization of prescriptions by infectious diseases physicians, microbiologists, pharmacists etc, therapeutic substitutions, automatic stop orders and antibiotic policy change strategies including cycling, rotation and cross-over studies. vpersuasive: distribution of educational materials; educational meetings; local consensus processes; educational outreach visits; local opinion leaders; reminders provided verbally, on paper or on computer; audit and feedback. v Structural: changing from paper to computerized records, rapid laboratory testing, computerized decision support systems and the introduction or organization of quality monitoring mechanisms. Cochrane Database of Systematic Reviews 30 APR 2013 DOI: 10.1002/14651858.CD003543.pub3 http://onlinelibrary.wiley.com/doi/10.1002/14651858.cd003543.pub3/full#cd003543-fig-0003

THE HISTORICAL PERIODS of ANTIMICROBIAL STEWARDSHIP The PRESENT PUSH COMPULSORY PROGRAMS PULL POST PRESCRIPTION REVIEWS (semi-compulsory programs) The NEXT FUTURE SHARED NEW PARADIGMS for MANAGEMENT PROBLEM-DRIVEN PROTOCOLS and PROGRAMS PULL The dream of the outcome-directed stewardship

Antimicrobial stewardship programs: the devil is in the details Cunha CB et al, Virulence 2013; 4: 147 149 Antimicrobial stewardship is a developing field, and every program must be tailored to its respective institution / unit and each article has a distinctive focus and perspective.

How to lay out a stewardship program? -Hospital wide -Drug directed -Setting directed -Disease directed

Structural: changing from paper to computerized records, rapid laboratory testing, computerized decision support systems and the introduction or organization of quality monitoring mechanisms COULD THE RENAISSANCE OF THE MICROBIOLOGICAL DIAGNOSIS REPRESENT AN OPPORTUNITY FOR NEW STEWARDSHIP PARADIGMS?

MALDI-TOF and ASP Study Population Antibiotic use Patient outcome Perez 2013 Huang 2013 Clerc 2013 Wenzler 2014 Perez 2014 Carreno 2014 201 pts with BSI (100 pre-intervention, 101 intervention) 501 pts with BSI (256 pre-intervention, 245 intervention) Time to antibiotic optimization 46-h reduction (P =.004); Reduced time to active treatment (P <.001) Time to effective therapy of 30.1 vs 20.4 h (P =.021) Optimal antibiotic therapy (90.3 vs 47.3 h; P <.001) 202 pts with BSI Greater percentage of patients with ID consultation compared with Gram stain results alone (35.1% vs 20.8%; P = NR) 109 pts with BSI and/or pneumonia (66 preintervention, 53 intervention) 265 pts with BSI (112 pre-intervention, 153 intervention) 104 pts with BSI (78 pre and 26 post test) LOS (11.9 d vs 9.3 d; P =.01) Hospital costs per pt (P =.009) 2.8-day decrease in mean LOS (P =.07) Reduced mortality (20.3% vs 14.5%; P=.02) NR Time to effective therapy (77.7 Increase in clinical cure h vs 36.6 h; P <.0001) (15% vs 34%; P =.016) Time to optimal antibiotic therapy (80.9 h vs 23 h; P <.001) Reduced mortality (21% vs 8.9%; P =.01) NR Time to sepsis resolution 4 vs. 3 days (P=0.08)

Impact of Rapid Organism Identification via Matrix-Assisted Laser Desorption / Ionization Time-of-Flight Combined With Antimicrobial Stewardship Team Intervention in Adult Patients With Bacteremia and Candidemia. Huang AM et al Clin Infect Dis 2013; 57: 1237-45 A pre post quasi-experimental study was conducted to analyze the impact of MALDI-TOF with AST intervention in patients with bloodstream infections. The AST provided evidence based antibiotic recommendations after receiving real-time notification following blood culture Gram stain, organism identification, and antimicrobial susceptibilities. Outcomes were compared to a historic control group. A total of 501 patients with bacteremia or candidemia were included in the final analysis: 245 patients in the intervention group and 256 patients in the preintervention group

AMS team intervention

Impact of Antimicrobial Stewardship Intervention on Coagulase- Negative Staphylococcus Blood Cultures in Conjunction with Rapid Diagnostic Testing. Nagel JL et al, J. Clin. Microbiol. 2014, 52:2849 single-center, quasi-experimental study. Adult patients with a CoNS blood culture identified via MALDI-TOF over a 3-month period were compared to a historical control group with CoNS identified by conventional methods. Patients were divided into 4 categories: Pts with CoNS BSI before/after implementation of MADLI-TOF plus AST intervention Pts with CoNS contamination before/after MADLI-TOF plus AST intervention During the preintervention study period, prescribers were immediately notified of positive Gram stain results from blood cultures. The AST did not intervene for positive bacterial cultures in real time but AST reviewed daily reports from Monday through Friday for all patients receiving restricted antimicrobials and recommended therapy changes on the basis of institutional guidelines and clinical judgment. All stewardship activities, except for the addition of real-time alerts for positive blood cultures during the intervention period, remained unchanged during the study time frame.

Impact of Antimicrobial Stewardship Intervention on Coagulase- Negative Staphylococcus Blood Cultures in Conjunction with Rapid Diagnostic Testing. Nagel JL et al, J. Clin. Microbiol. 2014, 52:2849

Doripenem, Gentamicin, and Colistin, Alone and in Combinations, against Gentamicin- Susceptible, KPC-Producing K. pneumoniae Strains with Various ompk36 Genotypes Clancy CJ et al, Antimicrob Ag Chemother 2014; 58:3521 Proposed algorithm for predicting active antimicrobial regimens DORIPENEM MIC < 8mg/L DORIPENEM MIC > 8mg/L

Impact of infectious diseases service consultation on diagnosis of infective endocarditis. Yamamoto S et al Scand J Infect Dis 2012;44:270-5 Routine consultation with an ID service for cases of positive blood culture was implemented at Kameda Medical Center in November 2004. In addition, ID service doctors started to give lectures on ID to doctors and also provided local guidelines on ID incidence of IE BEFORE 48.7 per 100,000 patients discharged from the hospital AFTER 84.8 per 100,000 patients (p = 0.01). Relapse rate of IE within 6 months BEFORE 22,2% AFTER 2,2% (p = 0.02).

Effect of a 3-Step Critical Pathway to Reduce Duration of Intravenous Antibiotic Therapy and Length of Stay in CAP. Carratalà J et al, Arch Intern Med. 2012;172:922-928. Prospective, randomized trial. Enrolled patients (401 adults who required hospitalization for CAP) were randomly assigned to follow a 3-step critical pathway including early mobilization and use of objective criteria for switching to oral antibiotic therapy and for deciding on hospital discharge or usual care. Primary End Point: LOS. The 3-steps of the critical pathway were (1) early mobilization of patients; (2) use of objective criteria for switching to oral antibiotic therapy; and (3) use of predefined criteria for deciding on hospital discharge. Early mobilization was defined as movement out of bed with a change from the horizontal to the upright position for at least 20 minutes during the first 24 hours of hospitalization, with progressive movement each subsequent day during hospitalization, as described elsewhere. Criteria for switching were ability to maintain oral intake; stable vital signs (considered as temperature 37.8 C, respiratory rate <24 breaths/min, systolic blood pressure > 90 mm Hg without vasopressor support for at least 8 hours); and absence of exacerbated major comorbidities (ie, heart failure, COPD) and/or septic metastases. Predefined criteria for hospital discharge were meeting criteria for switching to oral antibiotic, baseline mental status, and adequate oxygenation on room air (PaO2 60 mm Hg or pulse oximetry >90%).

Effect of a 3-Step Critical Pathway to Reduce Duration of Intravenous Antibiotic Therapy and Length of Stay in CAP. Carratalà J et al, Arch Intern Med. 2012;172:922-928.

A cost savings for each day of reduction in length of stay for CAP is between 2,273 and 2,473 USD Economic benefit of a 1- day reduction in hospital stay for CAP Kozma CM, et al. J Med Econ. 2010;13:719 27 One day of reduction of LOS for every CAP Means, for 100 CAP cases, 227,300 USD saved

The epidemiology of adults with severe sepsis and septic shock in Scottish emergency departments. Gray A et al, Emerg Med J 2012 Jun 29

The epidemiology of adults with severe sepsis and septic shock in Scottish emergency departments. Gray A et al, Emerg Med J 2012 Jun 29 % Sepsis resuscitation bundle compliance MORTALITY 28.3% 55 66 48 29 LACTATE MEASUREMENT BLOOD CULTURE TAKEN ATB WITHIN 3 H FLUID RESUSCITATION WHEN SBP < 90 mmhg

Short- and long-term mortality in severe sepsis/septic shock in a setting with low antibiotic resistance: a prospective observational study in a Swedish university hospital. Linnér A, et al, Front Public Health. 2013;1:51. The day 28, hospital, and 1-year mortality rates were 19, 29, and 34%, respectively. 93% of the patients received adequate antibiotics from the beginning. Multi-resistant bacteria were only found in three cases (out of 101 patients). Among the 43 patients admitted to the ICU through the ED, the median time to antibiotics was 86 min (interquartile range 52 165), and overall 77% received appropriate antibiotics within 2 h. The results demonstrate relatively low mortality rates among ICU patients with severe sepsis/septic shock, as compared to reports from outside Scandinavia. Early adequate antibiotic treatment and the low incidence of resistant isolates may partly explain these findings.