The International Collaborative Conference in Clinical Microbiology & Infectious Diseases PLUS: Antimicrobial stewardship in hospitals: Improving outcomes through better education and implementation of effective interventions 24 26 February 2015 Gulf Hotel, Kingdom of Bahrain How to Optimize Antibiotic Stewardship in ICU Tariq Al-Musawi, MD, MS, ABIM Consultant Infectious Disease & Critical Care Medicine Deputy Chief, Critical Care Services Co-Chair, Infection Control Committee Saad Specialist Hospital, Al-Khobar, Saudi Arabia
ESKAPE Pathogens E S K A P E Enterococcus faecium (VRE) Staphylococcus aureus (MRSA) Klebsiella & Escherichia coli (ESBL+) Acinetobacter baumannii Pseudomonas aeruginosa Enterobacter species
Alvarez 1996 Rello 1997 Luna 1997 Kollef 1998 Kollef 1999 Ibrahim 2000 Mortality (%) Mortality Associated With Initial Inadequate Antibiotic Therapy among ICU Patients with Serious Infections 100 80 60 40 20 0 Alvarez. Int Care Med. 1996;22:387. Ibrahim. Chest. 2000;118:146. Kollef. Chest. 1999; 115:462. Kollef MH. Chest. 1998;113:412. Luna. Chest. 1997;111:676. Rello. AJRCCM. 1997;156:196. Appropriate Inappropriate
Interventions Vs Outcomes
Policies & Interventions Policies that support optimal antibiotic use: Document dose, duration, and indication Develop and implement facility specific treatment recommendations
Policies & Interventions Interventions: Broad interventions: antibiotic Time outs, prior authorization, etc. Pharmacy-driven interventions: automatic change from IV to oral, dose adjustment and optimization, etc. Infection and syndrome specific intervention
Antibiotic Stewardship Interventions in ICU Antibiotic restriction or pre-approval Formal infectious diseases physician consultation Implementation of guidelines or protocols for de-escalation Formal reassessment of antibiotics on a pre-specified day of therapy Guidelines for antibiotic prophylaxis or treatment in ICU Implementation of computer-assisted decision support
Antibiotic Stewardship Interventions in ICU Antibiotic restriction or pre-approval Formal infectious diseases physician consultation Implementation of guidelines or protocols for de-escalation Formal reassessment of antibiotics on a pre-specified day of therapy Guidelines for antibiotic prophylaxis or treatment in ICU Implementation of computer-assisted decision support
Implementation of computer-assisted decision support Antibiotic Stewardship Interventions in ICU Antibiotic restriction or pre-approval Formal infectious diseases physician consultation Implementation of guidelines or protocols for deescalation Formal reassessment of antibiotics on a pre-specified day of therapy Guidelines for antibiotic prophylaxis or treatment in ICU
Antibiotic Stewardship Interventions in ICU Antibiotic restriction or pre-approval Formal infectious diseases physician consultation Implementation of guidelines or protocols for de-escalation Formal reassessment of antibiotics on a pre-specified day of therapy Guidelines for antibiotic prophylaxis or treatment in ICU Implementation of computer-assisted decision support
Antibiotic Stewardship Interventions in ICU Antibiotic restriction or pre-approval Formal infectious diseases physician consultation Implementation of guidelines or protocols for de-escalation Formal reassessment of antibiotics on a pre-specified day of therapy Guidelines for antibiotic prophylaxis or treatment in ICU Implementation of computer-assisted decision support
Implementation of computer-assisted decision support Antibiotic Stewardship Interventions in ICU Antibiotic restriction or pre-approval Formal infectious diseases physician consultation Implementation of guidelines or protocols for de-escalation Formal reassessment of antibiotics on a pre-specified day of therapy Guidelines for antibiotic prophylaxis or treatment in ICU
Outcome of Antibiotic Stewardship in ICUs Amount of targeted or overall antibiotic use Study Marra Sintchenko Meyer Geissler Unit of Measurement DDD/1000 ptdays DDD/1000 ptdays DDD/1000 ptdays DOT/1000 ptdays Antibiotic use in non-intervention period or group Antibiotic use in intervention period or group Difference 1265 1112-12% 0.61 1925 1606-17% 0.04 1059 888.6-14% 0.05 P value 940 610-35% <0.01 Du g/day 346.3 310.9-10% 0.25 Brahmi No. of prescriptions 1.8/pt 1.5/pt -17% 0.02 Mullett Does/pt 19.8 22 +11% NS Am J Infect Control 2009; 37: 204 9 J Am Med Inform Assoc 2005; 12: 398 402 Infection 2010; 38: 19 24 Intensive Care Med 2003; 29: 49 54 Crit Care Med 2003; 31:1088 93 Med Mal Infect 2006; 36: 460 5 Pediatrics 2001; 108: E75
Outcome of Antibiotic Stewardship in ICUs Amount of targeted or overall antibiotic use Most studies of restriction reported significant reduction in use of targeted Abx All showed a compensatory increase by ~ 200-300% in the use of other agents with a similar spectrum of use
Outcome of Antibiotic Stewardship in ICUs Amount of targeted or overall antibiotic use Studies of fluoroquinolone restriction resulted in the increased use of: Cefepime Int J Antimicrob Agents 2007; 30: 360 5 aminoglycosides/macrolides J Hosp Infect 2005; 59: 83 9 Other studies led to increased use of piperacillin/tazobactam when restricting: ceftazidime cefepime J Infect Chemother 2006; 12: 190 4 Braz J Infect Dis 2007; 11: 277 80
Outcome of Antibiotic Stewardship in ICUs Appropriateness of antibiotics Use of antibiotic management support programs resulted in: fewer susceptibility mismatch alerts (12 Vs 103 cases/ year, P<0.01) excessive drug-dosage alerts (87 Vs 202 cases/ year, P<0.01) mean days of excessive anti-infective doses (2.7 Vs 5.9 days/ patient, P<0.002) N Engl J Med 1998; 338: 232 8
Outcome of Antibiotic Stewardship in ICUs Duration of therapy Introduction of formal feedback on day 14 resulted in doctors discontinuing antibiotic therapy in 90% as compared with 48% of patients without such feedback (P<0.001) Intensive Care Med 2003; 29: 49 54 A formal daily guideline for reassessment of VAP treatment led to a shorter duration of treatment (6.0 ± 4.9 days vs 8.0 ± 5.6 days, P=0.001) Chest 2004; 125: 1791 9
Outcome of Antibiotic Stewardship in ICUs Duration of therapy Re-evaluation guideline at day 3 for patients with pulmonary infiltrates led to: far fewer patients being treated beyond this time point (28% vs 93%, P=0.0001) much shorter mean duration of antibiotic treatment (3 vs 9.8 days, P=0.0001) Am J Respir Crit Care Med 2000; 162: 505 11 Broad day 3 reassessment protocol for all antibiotic recipients reduced average treatment durations in the ICU from 14.1 ± 2.9 days to 11.9 ± 1.2 days (P<0.001) Med Mal Infect 2006; 36: 460 5
Outcome of Antibiotic Stewardship in ICUs Rates of antibiotic resistance Cirpofloxacin restriction: Reduction in cipro-resistant P. aeruginosa Also reduction in cipro-resistant A. baumannii and K. pneumonia Int J Antimicrob Agents 2007; 30: 360 5 In another study by Aubert et al, no reduction of cipro-resistant Enterobacteriaceae J Hosp Infect 2005; 59: 83 9
Outcome of Antibiotic Stewardship in ICUs Rates of antibiotic resistance Ceftazidime-restriction led to reduced ceftazidime-resistant: A. baumannii & ESBL-producing K. pneumoniae J Infect Chemother 2006; 12: 190 4 P. aeruginosa E. coli & K. pneumoniae Pharm World Sci 2008; 30:787 93 Int J Antimicrob Agents 2007; 30: 360 5 Crit Care Med 2003; 31:1088 93
Outcome of Antibiotic Stewardship in ICUs Rates of antibiotic resistance A day 3 reassessment protocol performed over 2 years was associated with reductions in: ESBL Klebsiella (68% to 44%, P<0.001) and carbapenem-resistant Pseudomonas (61% to 41%, P<0.05) Med Mal Infect 2006; 36: 460 5 A day 3, day 7 and day 10 antibiotic reassessment intervention performed over 3 years demonstrated reduction in: Antimicrobial-resistant bacteria of nosocomial infections (37% to 15%, P<0.00001) MRSA (61% to 13%, P<0.001) and ceftriaxone-resistant Enterobacteriaceae (37% to 13%, P<0.0001) No impact on ceftazidime-resistant P. aeruginosa or ESBL-producing Enterobacteriaceae. Intensive Care Med 2003; 29: 49 54
Outcome of Antibiotic Stewardship in ICUs Rates of antibiotic resistance Unanticipated beneficial effects included an observed reduction in: MRSA with ciprofloxacin restriction J Hosp Infect 2005; 59: 83 9 piperacillin/tazobactam- and imipenem-resistant P. aeruginosa with ceftazidime restriction J Infect Chemother 2006; 12: 190 4 Unanticipated negative effects included an increase in: penicillinase-producing K. pneumoniae with ceftazidime restriction, favouring the use of piperacillin/tazobactam J Infect Chemother 2006; 12: 190 4
Outcome of Antibiotic Stewardship in ICUs Other clinical outcomes Nosocomial infection rates Length of stay Mortality Braz J Infect Dis 2003; 7: 290 6 Crit Care Med 2003; 31: 1088 93 N Engl J Med 1998; 338: 232 8 Intensive Care Med 2003; 29: 49 54 Am J Infect Control 2009; 37: 204 9 Chest 2004; 125: 1791 9 Med Mal Infect 2006; 36: 460 5
Our Model
Antibiotic Stewardship Practice in ICU
Tips Know the local data Define a target (s) Pick a strategy (-ies) Chose the team Audit outcomes Redesign
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