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Antimicrobial Stewardship Overview: An Urgent Patient Safety Imperative . Ed Septimus , MD, FACP, FIDSA, FSHEA Medical Director Infection Prevention and Epidemiology Professor Internal Medicine Texas A&M Professor, Distinguished Senior Fellow, School of Public Health, George Mason University
Antimicrobial Stewardship Overview: An Urgent Patient Safety Imperative Ed Septimus, MD, FACP, FIDSA, FSHEA Medical Director Infection Prevention and Epidemiology Professor Internal Medicine Texas A&M Professor, Distinguished Senior Fellow, School of Public Health, George Mason University firstname.lastname@example.org
“Microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out…In such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted.” When and Who Said this?
Drug Resistant S. aureusin the Community • Recently, the resistance pattern, formerly seen only in the hospital, is also being replicated in the community. This increase seems to parallel the intensive and often indiscriminant use of antibiotics outside the hospital ambience. Also, it can be conjectured the hospital has served as a locus for the “lateral” dissemination of resistant strains into the community. Ross, et al, JAMA, 1974
Stop the killing of beneficial bacteriaConcerns about antibiotics focus on bacterial resistance — but permanent changes to our protective flora could have more serious consequences, says Martin Blaser.Nature 2011;476:393 Collateral Damage Average child receives 10-20 courses of antibiotics before age 18 Antibiotics affect our resident microbiota and may not fully recover after a course of antibiotics Overuse of antibiotics may be contributing to obesity, DM, IBD, allergies, and asthma
When mediating over a disease, I never think of finding a remedy for it, but instead a means of preventing it Louis Pasteur
Case #1 32 year male presents to the ER with a 4-5 day of sore throat, low grade fever, and myalgias followed by a 1 day history of increasing shortness of breath and cough. Patient has no underlying diseases. In the ER, patient was in respiratory distress, hypoxic, and febrile. CXR extensive left-sided consolidation. The patient required intubation and was admitted to the ICU with the diagnosis of CAP. The patient was started on a macrolide and a third-generation cephalosporin. Does This Meet Core Measures?
CASE 2 This is a 46 year old female admitted with hypotension, fever, and flank pain. She had no underlying medical or urologic problems. Her urine showed pyuria and bacteriuria, the peripheral WBC was 16,000. She was admitted to the ICU and empirically started on _______. What would you start?
Bad Bugs, No Drugs1 • Declining research investments in antimicrobial development2,3 • The Antimicrobial Availability TaskForce of the IDSA identified problematic pathogens including gram-negative bacteria2 • Problematic pathogens can “escape”the activity of antibacterial drugs3 • “ESKAPE”(ESCAPE) pathogens include • Escherichia coli • Staphylococcus aureus • Klebsiellapneumoniae(C.difficle) • Acinetobacterbaumannii • Pseudomonas aeruginosa • Enterobacterspp 1. Infectious Diseases Society of America. Bad Bugs, No Drugs: As Antibiotic Discovery Stagnates, A Public Health Crisis Brews.July, 2004. http://www.idsociety.org/WorkArea/showcontent.aspx?id=5554. Accessed January 15, 2009. 2. Talbot GH, et al.Clin Infect Dis. 2006;42:657-68. 3. Boucher HW, et al. Clin Infect Dis. 2009;48:1-12.
Geographical Distribution of KPC(CRE)-Producers Widespread Sporadic isolate(s) November 2006 Centers for Disease Control and Prevention.
Geographical distribution of extreme-drug resistant Klebsiella bacteria KPCs received August 2010
New Delhi Metallo-β-lactamase (NDM) Lancet Infect Dis 2010
Why We Need to Improve Antibiotic Use • Antibiotics are misused across the continuum of care • Use of antibiotics in animals • Antibiotic misuse adversely impacts patients and society • Antibiotics are the only drug where use in one patient can impact the effectiveness in another. • Improving antibiotic use improves patient outcomes and saves money • Improving antibiotic use is a public health imperative-WHO considers AR an emerging threat to global stability
Magnitude of Antimicrobial Use • Antibiotics are the second most commonly used class of drugs in the United States • More than 8.5 billion dollars are spent on anti -infectives annually • 200-300 million antimicrobials prescribed annually • 53% for outpatient use • 30-50% of all hospitalized patients receive antibiotics • Studies estimate up to 50% of antibiotic use is either unnecessary or inappropriate across all type of health care settings Clin Infect Dis 2007; 44:159-177
Unnecessary Use of Antimicrobials in Hospitalized Patients Prospective observational study in ICU 576 (30%) of 1941 antimicrobial days of therapy deemed unnecessary Most Common Reasons for Unnecessary Days of Therapy Hecker MT et al. Arch Intern Med. 2003;163:972-978.
International Study of the Prevalence and Outcomes of Infection in ICUs • 1-day, prospective, point prevalence study • 14,414 patients in 1265 ICUs from 75 countries • 51% were considered infected • 71% were receiving antibiotics • 62% of infections were due to gram-negative organisms (compared to 39% of infections in 1995) • 47% of infections were due to gram-positive organisms and 19% were fungi • ICU mortality of infected patients was more than twice that of noninfected patients P<.001 JAMA 2009; 302:2323
Antibiotic are misused in a variety of ways • Given when they are not needed • Continued when they are no longer necessary-duration • Given at the wrong dose-renal and weight-based dosing • Broad spectrum agents are used to treat very susceptible bacteria • The wrong antibiotic is given to treat an infection
Antimicrobial StewardshipGoals • Improve patient outcomes • Optimize selection, dose and duration of Rx • Reduce adverse drug events including secondary infection (e.g. C. difficileinfection) • Reduce morbidity and mortality • Limit emergence of antimicrobial resistance • Reduce length of stay • Reduce health care expenditures MacDougall CM and Polk RE. Clin Micro Rev 2005;18(4):638-56. Ohl CA. J. Hosp Med. In press. Dellit TH, et. al. Clin Infect Dis. 2007;44:159-177
Costs of Antimicrobials • Allergy • Resistance • Adverse events Clinical cure vsTherapeutic failure Impact on hospital/outpatient/society
Antimicrobial Resistance • Increases mortality and morbidity • Antimicrobial resistance is accelerated by excessive use of antibiotics • Appropriate use of antibiotics reduces antimicrobial resistance • Inadequate infection control propagates transmission of MDR strains • Antibiotic-resistant infections have been estimated to cost the US healthcare system over $20 billion annually Emerg Infect Dis 2001; 7:286 Arch Intern Med 2003; 163:972 Infect Control HospEpidemiol 2003; 24:642 Nat Rev Microb 2004; 2:251 Clin Infect Dis 2009; 49:1175-84
CLIN INFECT DIS 49(8):1175-1184. Figure 1. Predicted mortality for patients with and without antimicrobial‐resistant infection (ARI). APACHE, Acute Physiology and Chronic Health Evaluation.
Hospital and Societal Costs of Antimicrobial-ResistantInfections in a Chicago Teaching Hospital:Implications for Antibiotic StewardshipCLIN INFECT DIS 49(8):1175-1184. . Projected cost savings if antimicrobial‐resistant infection (ARI) rates were reduced from 13.5% to 10%.
Can Antimicrobial Stewardship Limit the Emergence of Resistance? • Best evidence for: • Decreased resistant Gram-negative bacilli1,5 • Decreased CDI1-4 • Decreased VRE1 1. Carling P, et al. Infect Control HospEpidemiol. 2003;24(9):699-706. 2. Climo MW, et al. Ann Intern Med. 1998;128(12, pt 1):989-995. 3. Pear SM, et al. Ann Intern Med. 1994;120(4):272-277. 4. McNulty C, et al. J AntimicrobChemother. 1997;40(5):707-711. 5. de Man P, et al. Lancet. 2000;355(9208):973-978
Antibiotic misuse adversely impacts patients- C. difficile • Antibiotic exposure is the single most important risk factor for the development of Clostridium difficileinfection (CDI). • Up to 85% of patients with CDI have antibiotic exposure in the 28 days before infection1 • 20% of patients admitted to the ICU with CDI were receiving antibiotics without evidence of infection with an accompanying 28% in-hospital mortality2 1 Infect Control HospEpidemiol 2007; 28:926–931. 2 BMC Infect Dis 2007; 7:42
CDI: Incidence and Mortality are Increasing in US 1. Elixhauser A, et al. Healthcare Cost and Utilization Project: Statistical Brief #50. April 2008. Available at: http://www.hcup-us.ahrq.gov/reports/statbriefs/sb50.pdf. Accessed March 10, 2010. 2. Redelings MD, et al. Emerg Infect Dis. 2007;13:1417-1419. Annual Mortality Rate per Million Population # of CDI Cases per 100,000 Discharges
C. DifficilePCR Ribotype 027: assessing the risks of further worldwide spreadLancet Infect Dis 2010; 10:395
Challenges • Literature often not clear in Infectious Diseases • Everyone thinks they know how to use antibiotics • Providers perceive autonomy is lost • Medico legal implications of responsibility for patients • Difficulty proving impact of program(Ønational measures) • Financial pressures dictating decisions • Pharmaceutical manufacturers • Hospitals • Insurance companies • Patients
Develop New Drugs and Vaccines Improved Diagnostics Reduce Resistance Reservoirs Antimicrobial Stewardship Infection Prevention Research & Public Policy Education Efforts to Control Resistance
Front-end Approach Physician writes order for “restricted drug” Order arrives in pharmacy; pharmacist informs physician that drug is “restricted”/“not part of the pathway”/“nonformulary” Prescribing physician and the “GATE KEEPER” converse Approval or alternative antibiotic selected
Formulary Restriction/PreauthorizationFront-end Approach Advantages Direct control over antimicrobial use Effective control of antimicrobial use during outbreaks Decreased inappropriate use of antimicrobials (and thus costs) Disadvantages Personnel needs Antagonistic relationship (loss of autonomy) Therapy may be delayed De-escalation not addressed ID physicians often exempt Effectiveness in decreasing resistance is less clear
Prospective Audit and FeedbackBack-end Approach Physician writes order 1.) Antibiotic Change/Continued based on Practice Guidelines 2.) Prescribing physician contacted and recommendation made Antibiotic is Dispensed At a later date, antibiotics are reviewed (Targeted list of antibiotics, C/S mismatches, ICU patients, duration)
Prospective Audit and Feedback Advantages Prescriber autonomy maintained Educational opportunity provided Patient information can be reviewed before interaction Inappropriate antimicrobial use decreased De-escalation Disadvantages Compliance voluntary Identification of patients may require computer support Prescribers may be reluctant to change therapy if the patient is doing well Some inappropriate antimicrobial use permitted (with retrospective audit)
Choice of Empiric Agent MAXIMIZE COVERAGE against most likely pathogens MINIMIZESELECTION for resistance
Mortality associated with initial inappropriate therapy in patients with serious infections Initial appropriate therapy Rello et al Infection-related mortality Initial inappropriate therapy Kollef et al Crude mortality Ibrahim et alInfection-related mortality Luna et alCrude mortality 0 20 40 60 80 100 Mortality (%) Rello et al. Am J Respir Crit Care Med 1997;156:196–200; Kollef et al. Chest 1998;113:412–420 Ibrahim et al. Chest 2000;118:146–155; Luna et al. Chest 1997;111:676–685
Impact of Previous Therapy on Outcome of Gram-Negative Severe SepsisCrit Care Med 2011; 39:1859
Considerations in Empiric Choice Host Type of infection Community-Acquired vs LTCvs Nosocomial Underlying comorbidities Microbe Local antibiogram ICU vs Non-ICU Drug Prior antibiotic therapy Selection based on potential for resistance Need for multiple agents
Infected Patient Site (s) of Infection Community vs. Hospital Laboratory tests Collection of infected materials Gram Stain Culture Results Identification of organism Sensitivity Abx Range of Pathogens Baseline Broad- Spectrum Empirical therapy 1 hours 24-48 hours Discontinue Agents 48-72 hours Streamline Therapy 72-96 hours Precision and time Antimicrobial Spectrum of Activity
Design of a `day 3 bundle` to improve the reassessment of inpatient empirical prescriptionsJ Antimicrob Chemotherapy 2008; 61:1384 Process Measures • Review diagnosis • Antibiotic plan • Adaptation to microbiology • IV to PO switch