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 Antimicrobial Stewardship Program (ASP) Speaker: Dr. Abdullah Almohaizeie
Objectives Discuss the essential elements of an antimicrobial stewardship program (ASP) business plan. Briefly discuss recent international and local ASP programs Outline current successful ASP activities at King Faisal Specialist Hospital and Research Center (KFSH&RC)
Antimicrobial Stewardship The rapid rise in antimicrobial resistance (AMR) has increased global momentum to establish antimicrobial stewardship programs in health facilities, clinics, and hospitals. The overuse or misuse of antimicrobial medicines is a key driver of AMR and a growing global health problem Antimicrobial stewardship programs can address inappropriate use of antimicrobials and help slow the spread of AMR through systems-level approaches supported by policies, structures, and interventions Holloway K, van dijk L. The World Medicines Situation 2011: Rational Use of Medicines, WHo, 2011 Guidelines for Antimicrobial Stewardship in Hospitals in Ireland. published on behalf of sari by HsE Health protection surveillance Centre, dublin, 2009
Antimicrobial Stewardship Comprehensive antimicrobial stewardship programs have demonstrated success in reducing inappropriate antimicrobial use by as much as 36% in hospitals in the United States. Although many countries have begun to adopt and promote antimicrobial stewardship policies and practices, these programs are largely absent from health facilities in the GCC countries Dellit et al. CID 2007
Antimicrobial Stewardship Programs Antimicrobial Management Programs (AMP) A marriage of infection control and antimicrobial management An activity that promotes: The appropriate selection of antimicrobials The appropriate dosing of antimicrobials The appropriate route and duration of antimicrobial therapy
Goals of Stewardship Programs The combination of effective antimicrobial stewardship with a comprehensive infection control program has been shown to limit the emergence of transmission of antimicrobial resistant bacteria A secondary goal of antimicrobial stewardship is to reduce healthcare costs without adversely impacting quality of care
Potential Active Core Strategies Prospective audit with intervention and feedback that can result in reduced inappropriate use (A-I) Formulary restriction and pre-authorization-can lead to significant and immediate reductions in antimicrobial use and cost (A-II)
Evidence-based Interventions Guidelines and clinical pathways (A-I) Dose optimization (A-II) IV to PO switch (A-I) De-escalation therapy (A-II) Education (A-III, B-II) Antimicrobial order forms (B-II) Antimicrobial cycling (no ranking) Delit et al. CID 2007; 44: 159-177
Feedback Audit ID Clinical pharmacist with ID consultant Targeted units and targeted drugs Review cases within 48-72 hours of starting antimicrobial agents De-escalation Dose optimization IV to PO switch Bug-Drug mismatches
Antimicrobial Stewardship Guidelines Core Strategies Prospective audit with intervention and feedback Formulary restriction with preauthorization Supplemental Strategies Education Guidelines and clinical pathways Antimicrobial cycling Antimicrobial order forms Combination therapy Streamlining or de-escalation of therapy Dose optimization Parenteral to oral conversion Dellit et al. CID 2007.
Antimicrobial Stewardship Guidelines ID Clinical Pharmacist s Perspective: Allows needed FOCUS on a drug class Need to assure appropriate antimicrobial management and safety Assist with educational efforts Assist with formulary standardization Control costs
Identifying Best Practices Across Three Countries: Hospital Antimicrobial Stewardship in the United Kingdom, France, and the United States United Kingdom France United States Number of hospitals 2412 Approximately 2500 Approximately 5723 Antimicrobial stewardship characteristic Legislation Health and Social Care Act of 2008 mandates hospitals implement antimicrobial stewardship practices French Ministry of Health has required hospital antimicrobial stewardship programs since 2002 and annual public reporting of the hospital's compliance with specific antimicrobial stewardship performance indicators since 2007 Trivedi KK, Dumartin C, Gilchrist M, Wade P, Howard P. Clin Infect Dis October 15, Limited to California where the judicious use of antibiotics is required in general acute care hospitals since 2008 and also in Department of Veterans Affairs (VA) medical facilities where antimicrobial stewardship programs are required since in 2014
Identifying Best Practices Across Three Countries: Hospital Antimicrobial Stewardship in the United Kingdom, France, and the United States United Kingdom France United States Number of hospitals 2412 Approximately 2500 Approximately 5723 Antimicrobial stewardship characteristic Infrastructure Infection specialists manage and guide antimicrobial stewardship committees; on occasion, clinical pharmacists without ID training are involved with implementation Antibiotic advisor (physician, pharmacist, microbiologist, or infection preventionist with or without ID training) is responsible for implementation, in close collaboration with hospital pharmacists, microbiologists, and the antimicrobial stewardship committee Trivedi KK, Dumartin C, Gilchrist M, Wade P, Howard P. Clin Infect Dis October 15, Supported by ID physicians and ID pharmacists, but increasing number of non-id physicians and clinical pharmacists are leading programs when ID expertise may not be available
Identifying Best Practices Across Three Countries: Hospital Antimicrobial Stewardship in the United Kingdom, France, and the United States United Kingdom France United States Number of hospitals 2412 Approximately 2500 Approximately 5723 Antimicrobial stewardship characteristic Local strategies Local implementation of antimicrobial stewardship guidance provided in the Start Smart Then Focus program Local implementation of national guidance includes utilization of information technology resources, restricted antibiotic dispensation, practice audits, and education and feedback to prescribers Varies depending on personnel and administrative support; strategies range from post-prescription review and feedback performed by team to low-hanging fruit such as parenteral-to-oral conversion protocols implemented by clinical pharmacists Trivedi KK, Dumartin C, Gilchrist M, Wade P, Howard P. Clin Infect Dis October 15,
Identifying Best Practices Across Three Countries: Hospital Antimicrobial Stewardship in the United Kingdom, France, and the United States United Kingdom France United States Number of hospitals 2412 Approximately 2500 Approximately 5723 Antimicrobial stewardship characteristic Outcomes Recommended that hospitals monitor outcomes as outlined in the Start Smart Then Focus program, including annual monitoring and reporting of antimicrobial consumption trends Structure and process measures are included in composite indicator that is publicly reported annually; monitoring of antimicrobial utilization is required but not publicly reported; rates of specific resistant organisms are monitored as will Most hospitals monitor antimicrobial expenditures; other outcomes vary depending on available electronic systems; many hospitals follow process measures, some follow antimicrobial susceptibility patterns, and antimicrobial utilization if data accessible
The prevalence of antimicrobial resistance in clinical isolates from Gulf Corporation Council Countries Table 1 The data of selected clinical isolates reported by GCC countries Country Population Population % Reports (n) Reports% Isolates (n) Isolates% References Bahrain 1,106,509 2.9% 3 9.1% 2841 7.6% [4-6] Kuwait 2,583,020 6.7% 9 27.3% 20339 54.5% [7-15] Oman 3,173,917 8.2% 3 9.1% 882 2.4% [8,16,17] Qatar 1,608,903 4.2% 2 6.1% 570 1.5% [7,18] Saudi Arabia 25,373,512 65.7% 14 42.4% 12174 32.6% [19-32] UAE 4,765,000 12.3% 2 6.1% 491 1.3% [33,34] GCC total 38,610,861 100.0% 33 100.0% 37295 100.0% n = 33 articles Aly M, Balkhy HH. Antimicrob Resist Infect Control. 2012; 1: 26
The prevalence of antimicrobial resistance in clinical isolates from Gulf Corporation Council Countries Table 2 The prevalence of resistant pathogens in clinical isolates from GCC countries Gram Negative Gram Positive Country Acinetobacter Escherichiaco Klebsiella li pneumoniae Pseudomonas Clostridium aeruginosa difficile Enterococcus MRSA Streptococcu s pneumoniae Bahrain N.R 14.0% 13.9% N.R N.R 76.5% 8.5% N.R Kuwait 16.7% 77.0% 36.2% 2.6% 70.0% N.R 3.3% 66.3% Oman N.R N.R 0.1% 0.3% 0.0% N.R 58.3% N.R Qatar N.R 1.1% 0.8% 0.6% N.R N.R N.R N.R Saudi Arabia 83.3% 7.6% 48.3% 92.3% 30.0% 23.5% 29.9% 30.7% UAE N.R 0.3% 0.7% 4.2% N.R N.R N.R 3.0% Aly M, Balkhy HH. Antimicrob Resist Infect Control. 2012; 1: 26
The prevalence of antimicrobial resistance in clinical isolates from Gulf Corporation Council Countries Geographical distributions of resistant isolates among GCC countries 1990 2011 Aly M, Balkhy HH. Antimicrob Resist Infect Control. 2012; 1: 26
Location Riyadh, Saudi Arabia Abu Dhabi, United Arab Emirates Molecular Characterization of Carbapenemase-Producing Escherichia coli and Klebsiella pneumoniae in the Countries of the Gulf Cooperation Council: Dominance of OXA-48 and NDM Producers Summary of CRE clinical isolates in the GCC states: Kuwait, Kuwait Muscat, Oman Hospital name King Abdulaziz Medical City Sheikh Zayed Military Hospital Al-Ameri Hospital The Royal Hospital Hospital type Tertiary and academic Hospital capacity (no. of beds) Semiautom ated system used for species identification Study and isolates antibiotic received sensitivity (no.) 1,000 Vitek II, biomérieux Tertiary 365 Vitek II, biomérieux Tertiary 398 Vitek II, biomérieux Teaching tertiary 750 Phoenix, Becton, Dickinson No. (%) of isolates with reduced susceptibilit y to ertapenem No. (%) of carbapenemase and CTX-M-15-type genes No. (%) of plasmid replicon typing a NDM type OXA-48 type KPC type IMP type VIM type CTX-M-15 type IncL/M IncA/C E. coli (151) 2 (1.3) 1 (50) 0 0 0 0 2 (100) NT b NT K. pneumoniae (77) 40 (52) 10 (25) 31 (77.5) c 0 0 0 28 (70) 23 (74) 1 (3) E. coli (29) 1 (3) 0 0 0 0 0 1 (100) NT NT K. 4 (25) 3 (75) 0 0 0 0 4 (100) NT NT pneumoniae (16) E. coli (18) 0 NA d NA NA NA NA NA NT NT K. 0 NA NA NA NA NA NA NT NT pneumoniae (13) E. coli (23) 2 (9) 0 0 0 0 0 1 (50) NT NT K. pneumoniae (14) 3 (21) 1 (33) 1 (33) 0 0 0 3 (100) 0 0 Hosam M. Zowawi et al. Antimicrob. Agents Chemother. 2014;58:3085-3090
Molecular Characterization of Carbapenemase-Producing Escherichia coli and Klebsiella pneumoniae in the Countries of the Gulf Cooperation Council: Dominance of OXA-48 and NDM Producers Summary of CRE clinical isolates in the GCC states: Doha, Qatar Manama, Bahrain Total E. coli K. pneumo niae Hamad Medical Coopera tion Samlani ya Medical Comple x Tertiary >1,300 Phoenix, Becton, Dickinso n Tertiary and teaching 1,000 Phoenix, Becton, Dickinso n E. coli (23) K. pneumo niae (16) E. coli (22) K. pneumo niae (11) 4 (17) 0 1 (25) 0 0 0 3 (75) 0 0 5 (31) 1 (20) 2 (40) 0 0 0 5 (100) 0 1 (8) 0 NA NA NA NA NA NA NT NT 1 (0.9) 0 0 0 0 0 1 (100) NT NT 266 (64) 9 (3.4) 1 (6) 1 (6.4) 0 0 0 7 (78) 0 0 147 (36) 53 (36) 15 (28) 34 (63) c 0 0 0 41 (77) 23 (68) 2 (5.9) 413 62 (15) 16 35 (49) 0 0 0 48 (77) 23 (66) 2 (5.7) Hosam (22.5) M. Zowawi et al. Antimicrob. Agents Chemother. 2014;58:3085-3090
Evidence-Based Antimicrobial Stewardship Initiatives in Jordan Improve Antibiotic Prophylaxis for Cesarean Section A recent study conducted by the Jordan Food and Drug Administration (JFDA) found antimicrobials used for prophylaxis during common surgical procedures, like cesarean section, were frequently administered inconsistently or inappropriately Systems for Improved Access to pharmaceuticals and services (SIAPS) provided technical assistance to three hospitals in Jordan to strengthen antibiotic prophylaxis practices for cesarean section. Jordan Food and drug Administration. Rational antibiotic use in Jordan: auditing antibiotic use targeting surgical prophylaxis at Jordanian hospitals. JFDA, Rational Drug use department, may 2009 Gammouh s. and Joshi m. 2013. Improving Antibiotic Prophylaxis in Cesarean Section in Jordanian Hospitals: SIAPS Technical Report. Arlington, VA: management sciences
Evidence-Based Antimicrobial Stewardship Initiatives in Jordan Improve Antibiotic Prophylaxis for Cesarean Section Results from all three hospitals indicate good compliance to the protocols and procedures as measured by the use of the preferred prophylactic antibiotic (cefazolin), the timing of administration, and the number of doses administered. Average surgical site infection rate of 1.59% (within international rates) Average cost for antibiotic prophylaxis per case decreased by 79% The hospitals experienced cost savings of approximately 10,905 Jordanian dinars, or 15,397 USD, in 2012. Based on the experience from the three hospitals Gammouh s. and Joshi m. 2013. Improving Antibiotic Prophylaxis in Cesarean Section in Jordanian Hospitals: SIAPS Technical Report. Arlington, VA: management sciences
Evidence-Based Antimicrobial Stewardship Initiatives in Jordan Improve Antibiotic Prophylaxis for Cesarean Section Indicator 2010 2012 Correct antibiotic use 0% 86% Correct timing of first dose (less than one hour before skin incision) Correct number of doses (single dose except for pre-identified exceptions) 0% 92% 0% 88% Gammouh s. and Joshi m. 2013. Improving Antibiotic Prophylaxis in Cesarean Section in Jordanian Hospitals: SIAPS Technical Report. Arlington, VA: management sciences
Evidence-Based Antimicrobial Stewardship Initiatives in Jordan Improve Antibiotic Prophylaxis for Cesarean Section Based on the result of this study: Antibiotic prophylaxis protocol for cesarean section developed and mandated for all MOH hospitals providing ob/gyn services. Initiation of similar programs by other hospitals not included in the initial pilot Expansion to other surgical procedures (hernia). Contributed to Health Care Accreditation Agency s national quality and safety goals, one of which is appropriate use of prophylactic antibiotics during surgeries. Gammouh s. and Joshi m. 2013. Improving Antibiotic Prophylaxis in Cesarean Section in Jordanian Hospitals: SIAPS Technical Report. Arlington, VA: management sciences
KFSHRC Experience
Antimicrobial Utilization & Evaluation (AUE) Subcommittee Established at KFSH&RC in 1994 Promote optimal antimicrobial therapy Prevent antimicrobial-related complications Evaluate the effectiveness of antimicrobial therapy Improve patient care & establish interdisciplinary consensus on antimicrobial use process. ASP is the systematic, coordinated implementation of the policies of AUE.
Effectiveness? MICU. July 2009-December 2009. 90 patients 52% of initial therapy was not appropriate (47/90) No empirical therapy was initiated (19) Bug is resistant to the drug chosen (17) Failure to de-escalate ( 6) Wrong dose (3) Treatment of colonization (2)
90% of use was 5 drugs Drug Total cost of empiric tx Total cost of de-escalation tx Total Meropenem 34,484 38,718 73,202 Imipenem 13,025 17,013 30,038 Tigecycline 42,375 32,250 74,625 Piperacillin /tazobactam 48,679 45,682 94,361 Vancomycin 27,448 9,418 36,866 Cost of these 5 agents 166,011 142,081 308,092 Total cost of All studied drugs 175,426 168,410 343,836
So we are doing good things, but need to do better Activity Current Status at KFSH&RC Proposal Prospective Audit with Intervention Under Consideration & Feedback The Next Big Step! Formulary Restriction & Active Assess compliance Preauthorization Education Some Enhance Guidelines / Clinical Pathways Antimicrobial order form (CPOE) Combination Therapy Some (Vancomycin, Febrile Neutropenia, Clostridium Difficile) Case by Case Basis Update existing Strategically implement new Develop care sets Streamline or De-Escalation Case by Case Basis 2 nd stage pilot Dosing optimization (including IV to PO conversion) Some Enhance with general and specific projects & program
Prospective Audit with Intervention & Feedback Systematic identification of patients at risk for inappropriate antimicrobial use Targeted antimicrobials, positive cultures etc. Assessment of appropriateness using criteria Gathering patient s data (diagnosis etc.) Develop & implement intervention (active) Contacting prescriber to recommend a change Measure outcome
Antimicrobial stewardship program implementation in a medical intensive care unit at a tertiary care hospital in Saudi Arabia Appropriateness Definition Use optimum antibiotic regimen with regards to dose, frequency, route, and selecting the right antimicrobial agent for disease state and organism according to - Internal criteria (formulary restrictions) - Credible international guidelines Annals of Saudi Medicine. 03/2012; 33(6):547-54
Study Objectives Primary Objective Compare the appropriateness rate of empirical antibiotics therapy before and after implementation of proactive antimicrobial stewardship program Secondary Objectives The rate of clostridium difficile-associated diarrhea (CDAD) Frequency of MDR including methicillin-resistant staphylococcus aureus (MRSA), extended spectrum betalactamases producing strains (ESBL) Primary team acceptance rate for the ASP
Statistical Analysis Study Hypothesis: The appropriateness rate of empirical antibiotics therapy will be higher post ASP implementation Sample Size Calculation: N= 73 participants (49 in historical control arm and 24 in active ASP arm) based on alpha of 0.05 would yield 90 % power to detect a difference of 20 % between groups for the primary outcome Descriptive data were analyzed by using chi-square test for categorical data and student t-test for continuous data. The commercial software SPSS system (version 19) was used for statistical analysis.
Study Result Baseline Characteristics & Demographics Arm Control N= 49 Active ASP N=24 P value Gender Male, no. ( %) Female, no. ( %) 31 (63 %) 18 (37 %) 15 (63%) 9 (38%) 0.949 Age (mean years) (interquartile range) 52.37 30 59.75 24 0.087 APACHE II score* (mean) 10.51 19.38 <0.0001 *APACHE II score was calculated within 24 hours of ICU admission
Study Result Baseline Characteristics & Co-morbidities 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Hospitali zation > 5 days * * * 85.7 85.7 83.6 62.5 25 37.5 Broad steroid spectrum use > 2 AB > 7- wk 14 days 77.5 49 45.8 70 MV Hospitali zation within 90 days of disease onset 53 37.5 34.6 54.2 37.5 30.6 36.7 34.7 33.3 29 25 21 16.3 6.1 18.4 Historical control Active ASP 17 4 8.3 20.4 0 4.2 0 2 0 2% No significant differences between historical control and active ASP arm except for the factors presented with red asterisks (P < 0.05) vasopressor / ESRD DM Dialysis use Immun ologic deficit COPD: chronic obstructive pulmonary disease, DM: diabetes mellitus, ESRD: end stage renal disease, MV: mechanical ventilation, SOT: solid organ transplant >10 mg Predn isone * Severe Structur SOT MRSA COPD al Lung coloniz Disease ation * long Home term infusion care facility Reside nce Prior influe nza 4 Head ANC < Trauma 1,500 4% 0
Study Results Primary Outcomes (Empirical Antibiotics Therapy Appropriateness) Arm Control N= 49 Active ASP N=24 P value Initial appropriateness * Appropriate, no. ( %) Inappropriate, no. ( %) Final appropriateness * Appropriate, no. ( %) Inappropriate, no. ( %) 15 (30.6%) 5 (20.8%) 0.379 34 (69.38%) 1 9 (79.1%) 15 (30.6%) 24 (100%) 0.0001 34 (69.38%) 0 (0 %) * Initial antibiotics appropriateness was defined as the first intervention initiated by physicians * Final antibiotics appropriateness was assessed following ASP team interventions
Study Results Reasons of initial antibiotics inappropriateness, no. Arm Control * N= 49 Active ASP ** N=24 P value No current treatment for positive culture 9 0 0.02 No indication (e.g. colonization) for current treatment 5 0 0.15 Inadequate empiric coverage for indication 14 10 0.37 Excessive empiric coverage for indication 2 2 0.6 Resistant to current antibiotic 12 1.02 Regimen excessive (failure to de-escalate) 8 0.04 Regimen inadequate (wrong dose or frequency) 6 10.006 Total 56 23 * In the historical control arm: each patients with initial inappropriate AB(34 pts) had 1 reason for inappropriateness ** In the active ASP arm: each patients with initial inappropriate AB (19 pts) had 1 reason for inappropriateness
Study Results Interventions made in the active ASP arm to overcome inappropriateness *, No. (%) Discontinue unnecessary antimicrobial therapy 2 (10.50%) 4 (21.10%) 17 (89.50%) 4 (21.10%) Change to drug of choice (more effective, narrower spectrum, more efficient.) Change to broader spectrum antimicrobial Regimen optimization Note: A total of 27 interventions were made, with an acceptance rate of 26 (96.3 %) and 1 (3.7 % ) accepted with minor modifications * In the active ASP arm: each patient with inappropriate AB (19 pts) had 1 interventions
Secondary Outcomes Arm Control N= Active ASP P value 49 N=24 Clostridium difficile-associated diarrhea (CDAD) 1 (2 %) 0 (0 %) 1 Microbiological outcome* MDR, no. ( %) MRSA, no. ( %) ESBL, no. ( %) MRSA/MDR, no. ( %) Patients ICU course Deceased, no. ( %) Transferred to floor, no. ( %) Transfer to another hospital, no. ( %) Still active at the MICU, no. ( %) Study Results 15 (30.6%) 2 (8.3%) 0.034 2 (4.1 %) 0 (0 %) 1 11 (22.4%) 3 (12.5%) 0.36 1 (2%) 0 (0 %) 1 16 ( 32.65%) 4 (16.7%) 0.150 29 (59.2%) 20 (83.3%) 0.091 1 (2%) 0 (0 %) 1 3 (6.1 %) 0 (0 %) 0.55 *Microbiological outcome is defined according to susceptibility reporting test from KFSHRC microbiology lab
Average Cost (SR) Study Results Direct Cost of Antibiotics Utilization Per Patient in Both Groups 1000 800 Average cost of Historical control arm 990 864.8 600 518.3 400 316.7 321.4 293.8 200 0 0 206.6 110.7 2.4 34.6 50.3 Post hoc analysis showed ASP implementation resulted in average cost deduction by 125 SR as compared to historical control arm
How to Implement Active Intervention Component? You need a plan! Tailored to your institution Relates to existing committees, practitioners Respects available resources (especially people) Focuses in an area & with a design to show benefit Builds the case for getting more resources & expanding to other patient care areas Is efficient and evidenced based
Barriers to Establishing ASPs Lack of funding Shortage of adequately trained ID physicians and ID pharmacists Lack of pharmacy leadership supporting / managing ASP Lack of infectious diseases support Competition for funding with other hospital programs Communications with antagonizing colleagues Owens RC, Shorr AF, Deschambeault AL. Antimicrobial stewardship: shepherding precious resources. Am J Health-Syst Pharm. 2009; 66(Suppl 4):S15-22