Antimicrobial Stewardship: Strategies for Appropriate Antimicrobial Use Thomas M. File, Jr, MD, MSc, MACP Chair, Infectious Disease Division Summa Health System; Professor of Internal Medicine, Master Teacher, Chair ID Section NEOMED
IDSA Call-to-Action: Bad Bugs, No Drugs As resistance increases . . . number of new antimicrobials diminishes No. of new antimicrobials IDSA. Infectious Diseases Soc. Of Am. Bad Bugs, No Drugs. Available at: www.idsociety.org/badbugsnodrugs.html.
“Antimicrobial resistance is a major public health crisis.” Clin Infect Dis 2011 Clin Infect Dis. 2011 ‘ Drug resistance follows the drug like a faithful shadow’. Paul Erhlich 1854 -1915 “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them…. there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.” Alexander Fleming Nobel Prize lecture Dec 11, 1945 Antibiotics Should Be Assigned to a Special Drug Class to Preserve Their Power, Says Alliance for the Prudent Use of Antibiotics S. Levy 2010
The Impact of Antimicrobial Resistance Affects clinical outcomes Associated with higher mortality Results in higher healthcare costs Leads to prolonged hospitalization Increase challenge for appropriate management Empiric therapy Directed therapy File TM, Jr. Chest. 1999;115(suppl):3S-8S.
Clinical Practice Guidelines "Clinical practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances" (Institute of Medicine, 1990). Bringing scientific evidence into daily clinical routines “Evidence - based” IDSA > 50 guidelines (www.idsociety.org) “…guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment…” (IDSA guidelines)
From Pirates of the Caribbean Curse of the Black Pearl 2003 Jack Sparrow: I thought you were supposed to keep to the code (referring to the pirates code that “Any man that falls behind stays behind” … when the Black Pearl waits for him to escape) Mr. Gibb: We figured they were more like guidelines rather than actual rules
CMS Measures and Stewardship Core Measures--Effort to improve care of patients 1 Based on Process of care recommendations (within control of HCP) or outcomes Should be complementary to Stewardship • Unintended consequences Effects reimbursement Stewardship Strategies Avoid Antimicrobials if not warranted Stop in not warranted Appropriate agent (based on susceptibility) Stop MRSA therapy if no MRSA Avoid discordant therapy Reduce Duration De-escalation Dose Optimization Switch to oral ID consult 1. File TM Jr. et al. Clin Infect Dis. 2011; 53: S15-S22 2. File TM Jr, Gross PA. Clin Infect Dis. 2007;44:942-944;
Link Between Evidence-based Guidelines, Core Measures, & Outcomes CORE MEASURES & GUIDELINES Reduce variance Improve care GAP Actual Ideal Individual factors justify Practice Practice variance of care
Reasons to Target Antimicrobials Increased rates of bacterial resistance result in part from antimicrobial drug use 50% antimicrobial use is inappropriate Improvements in antimicrobial use have been shown to improve patient outcomes and reduce rates of resistance Pt with resistant infection is 15% more likely to die Stimulus for Antimicrobial Stewardship “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…..Effective antimicrobial stewardship programs can be financially self-supporting and improve patient care. ….” Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship: Dellit T et al. Clin Infect Dis. 2007;44:159-77
Appropriate antimicrobial usage: For optimal outcomes and reduce resistance ‘Antimicrobial Avoidance’ when not indicated 3 ‘Ds’ Right DRUG • Guidelines • Local resistance patterns • Patient risk stratification Right DOSE • Pharmacokinetics/Pharmacodynamics (PK/PD) Right DURATION • Compliance
Who of the following patients are likely to warrant antibacterial therapy? 1. 35 year old afebrile, non-smoking male with mild nasal congestion and non-productive cough for three days 2. 20 year old afebrile college student with non- exudative acute sore throat 3. 35 year old afebrile female with signs of acute sinusitis of three days duration 4. 55 year old smoking male with diabetes and acute fever cough and localised rhonchi 5. All of the above
Antibiotics and Acute Bronchitis 9 studies reviewed (placebo versus ATMB) 1 – Antibiotics had no benefit – Albuterol better than antibiotics (2 studies) – “Treating a condition that is largely viral in origin with antibiotics” promotes resistance Meta-analysis, 8 studies 2 – “Small” benefit (? clinically significant) – “As the benefit must be weighed against the risk of side effects and the societal cost of increasing antibiotic resistance, we believe that the use of antibiotics is not justified in these patients” – Cochrane systematic review (2012) 3 – “the current update provides clearer evidence on the lack of effectiveness of antibiotics for acute bronchitis.” 1 MacKay DN. J Gen Inter Med . 1996;11:557-562. 2 Bent S, et al. Am J Med . 1999;107:62-67. 3. Smith et al. Cochrane Systematic Review 2012
Acute Bronchitis Clinical Cough (50% scant sputum; often green or yellow); occasional wheezing, chest wall discomfort; assoc with common cold Procalcitonin-low if viral Etiology 90% viral; 10%-Mycoplasma, Chlamydophila; B. pertussis CXR-negative Therapy No antimicrobials for viral Antimicrobial only if bacterial (Pertussis > 3 wks cough; treatment to reduce transmission, not for acute resolution) Symptomatic NSAIDS, Aspirin, Ipratroprium (Atrovent ) Delayed prescription File TM Jr. Up-To-Date 2012
Procalcitonin for Antimicrobial Stewardship for RTIs PCT < 0.1 Bacterial NO Consider repeat 6-24hrs ug/ml Infection ANTIMICROBIALS based on clinical status VERY UNLIKELY PCT 0.1- Bacterial NO Use of ABX based on clinical status (‘unstable’) & 0.25 ug/ml infection ANTIMICROBIALS UNLIKELY judgment PCT > 0.25- Bacterial YES Repeat PCT day 3, 5, 7 (for 0.5 ug/ml infection ANTIMICROBIALS Duration) LIKELY PCT > 0.5 Bacterial YES CONSIDER STOP ABX ug/ml infection ANTIMICROBIALS when 80=90% decrease; if VERY LIKELY PCT remains high consdier treatment failure File TM Jr. Clin Cherst Med. 2011; modified from Schuetz P. et al. Eur Respir J 2011;37(2): 384 – 92.
NQF PERFORMANCE MEASURE: ACUTE BRONCHITIS NQF=National Quality Forum www.qualtiyforum.org/Measures_List.aspx
Acute respiratory infection Case: 40-year-old male with non-productive cough x 4 days; non-smoker; no comorbidity Exam: Afebrile; P-72; R-20; lungs – no localized findings Survey of PCPs: No Yes Should antibiotics be used? 90% 10% Would antibiotics be used? 12% 88%
Antimicrobials for Colds — Why? “Patient pressures” Patient satisfaction correlates with quality of patient-doctor intervention, not prescription 1 “Prevent bacterial superinfection” Several controlled studies showed no benefit for URI/colds 2 1 Hamm RM, et al. J Fam Pract . 1996;43:56-62. 2 Rosenstein N, et al. Pediatrics. 1998;101:181-184.
Overuse of antibiotics Receiving an antibiotic reinforces the patients’ belief that antibiotics are warranted when a similar situation arises Patients may continue to consult for acute RTIs and expect antibiotics to be prescribed Doctors may also prescribe antibiotics rather than educate patients Most patients and many doctors view ‘unnecessary’ antibiotic prescribing as a neutral intervention that is, one that cannot harm but may help File T. Curr Opin Infect Dis . 2002;15:149 – 50
Reduce use by reducing demand Primary care: acute bronchitis (> 200 patients) Antibiotics used by: Prescription alone (no leaflet) 62% ( P = 0.04) Prescription plus explanatory leaflet 47% Macfarlane et al. BMJ 2002; 324:1 – 6 Primary care: acute bronchitis (> 2,000 patients) Decline in antibiotic use associated with education of patient and prescriber (74% to 48%, P = 0.003) Gonzales et al. JAMA 1999; 281:1512 – 1519
Restricting antibiotics reduces resistance Finland – reduced erythromycin use led to reduced Streptococcus pyogenes resistance 1 Iceland – reduced antibiotic use led to reduced penicillin-nonsusceptible S. pneumoniae 2 Alaska – reduced antibiotic use led to reduced penicillin-resistant S. pneumoniae 3 1 Seppala et al. N Engl J Med. 1997; 337 :441 – 446 2 Arason et al. BMJ 1996; 313 :387 – 391 3 Petersen et al. 37th IDSA Meeting 1999 [Abstract 62]
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