Presentation on theme: "Antibiotic Stewardship Curriculum Developed by: Vera P. Luther, M.D."— Presentation transcript:
1 “Get Smart About Antibiotics” An Introduction to Prudent Antibiotic Use Antibiotic Stewardship CurriculumDeveloped by:Vera P. Luther, M.D.Christopher A. Ohl, M.D.Wake Forest School of MedicineWith Support from the Centers for Disease Control and PreventionTargeted for 1st year medical students for use during their microbiology or fundamental infectious diseases or pharmacology (antibiotic) blocks.
2 Objectives Discuss untoward effects of antibiotic use Define antibiotic stewardshipDescribe 6 goals of antibiotic stewardship programsDescribe a rationale for antibiotic selectionDescribe directed and empiric antibiotic therapyDescribe and give examples of 4 tenets of appropriate antibiotic use
3 Outline Introduction Untoward Effects of Antibiotics Antibiotic StewardshipPrinciples of Antibiotic SelectionTenets of Appropriate Antibiotic UseConclusion
4 IntroductionThe modern age of antibiotic therapeutics was launched in the 1930s with sulfonamides and the 1940s with penicillinSince then, many antibiotic drugs have been developed, most aimed at the treatment of bacterial infectionsThese drugs have played an important role in the dramatic decrease in morbidity and mortality due to infectious diseasesWhile the absolute number of antibiotic drugs is large, there are few unique antibiotic targetsWhile antibiotics have played a role in decreasing infectious disease related deaths, improved sanitation and vaccine development are extremely important advances as well.
5 Outline Introduction Untoward Effects of Antibiotics Antibiotic StewardshipPrinciples of Antibiotic SelectionTenets of Appropriate Antibiotic UseConclusion
6 Untoward Effects of Antibiotics Antibiotic resistanceAdverse drug events (ADEs)Hypersensitivity/allergyDrug side effectsClostridium difficile infectionAntibiotic associated diarrhea/colitisIncreased health-care costsOhl CA, Luther VP. J. Hosp. Med. 2011;6:S4
7 Clostridium difficile Infection (CDI) A potentially deadly colitis Antibiotics are the single most important risk factor for CDIIncidence and mortality increasingA more virulent NAP1/BI strain also seen with increasing frequency# of CDI Cases per 100,000 DischargesAnnual Mortality Rate per Million PopulationRedelings, et al. EID, 2007;13:1417CDC. Get Smart for health care. Access at
8 % S. pneumoniae who had recent antibiotic use Association Between Antibiotic Use and Nonsusceptible Pneumococcal Infection% S. pneumoniae who had recent antibiotic useStudyInfectionNonsusceptibleSusceptibleOdds Ratiop-valueJacksonInvasive56%14%9.30.009Pallares65%17%<0.001Tan70%39%3.70.02Nava30%11%3.5MorenoBacteremia57%4%3.6BlockOtitis media69%25%6.7Dowell & Schwartz, Am Fam Physician (5):1647
9 Fluoroquinolone Use and Resistance among Gram-Negative Isolates, National ICU Surveillance Study35,790 GN aerobic isolates from ICU pts from 43 US states plus D.C.Overall susceptibility to cipro decreased from 86% in 1994 to 76% in 2000 and was significantly associated with increased national use of fluoroquinolones.Neuhauser, et al. JAMA 2003; 289:885
10 Limited Number of New Antibiotics to Combat Antibiotic Resistance New Systemic Antibiotics Approved by the FDAThe problem of resistance is compounded by the small number of novel antibiotics in development. This slide shows the Number of New Molecular Entity (NME) Systemic Antibiotics Approved by the US FDA Per Five-year Period, Through 3/11. The number is at an extreme low and not expected to increase soon. There are no new novel gram negative agents that are expected in the next few years. The reasons for this are complex and there is no clear response planned by government or the pharmaceutical industry at this time. Legislation has been written and supported by medical professional groups but has not yet moved forward.Despite increasing antimicrobial resistance in the outpatient and inpatient arenas, there has been a decreasing number of novel antimicrobial agents developed in the last 2 decades. This has been labelled as a public health crisis by the Infectious Diseases Society of America, the Centers for Disease Control and Prevention and other governmental agencies.Clin Infect Dis. 2011;52:S397-S428
11 Frequency of ADEs due to Antibiotics in Outpatient Setting 142,505 estimated emergency department visits/year due to untoward effects of antibioticsAntibiotics account for 19.3% of drug related adverse events78.7% for allergic events19.2% for adverse events (e.g. diarrhea, vomiting)Approximately 50% due to penicillin & cephalosporin classes6.1% required hospital admissionNEISS-CADES projectShehab N et al. Clin Infect Dis. 2008;47:735
12 Consequences of Hospital Antibiotic Use At one tertiary care center 70% of Medicare patients received an antibiotic in 2010Approximately 50% of this use was unnecessary or inappropriateUntoward consequences of antibiotic therapy identified in this and other studies:Inadequate treatment of infectionIncreased hospital readmissionsADEsPolk et al. In: PPID, 7th ed. 2010Luther, Ohl. IDSA Abstract 2011
13 Outline Introduction Untoward Effects of Antibiotics Antibiotic StewardshipPrinciples of Antibiotic SelectionTenets of Appropriate Antibiotic UseConclusion
14 Antibiotic Stewardship Definition: A system of informatics, data collection, personnel, and policy/procedures which promotes the optimal selection, dosing, and duration of therapy for antimicrobial agents throughout the course of their usePurpose:Limit inappropriate and excessive antibiotic useImprove and optimize therapy and clinical outcomes for the individual infected patientI will likely substitute the very recent definition on the draft IDSA/SHEA position paper now circulating.Ohl CA. Seminar Infect Control 2001;1:Ohl CA, Luther VP. J. Hosp. Med. 2011;6:S4Dellit TH, et. al. Clin Infect Dis. 2007;44:
15 Antibiotic Stewardship Is pertinent to inpatient, outpatient, and long-term care settingsIs practiced at theLevel of the patientLevel of a health-care facility or system, or networkShould be a core function of the medical staff(i.e. doctors and other healthcare providers)Utilizes the expertise and experience of clinical pharmacists, microbiologists, infection control practitioners and information technologistsI will add later a set of notes here to help guide the lecturer. Also, my presentation audio files for this slide will be very helpful
16 Six Goals of Antibiotic Stewardship Programs Reduce antibiotic consumption and inappropriate useReduce Clostridium difficile infectionsImprove patient outcomesIncrease adherence/utilization of treatment guidelinesReduce adverse drug eventsDecrease or limit antibiotic resistanceHardest to showBest data for health-care associated gram negative organismsTamma PD, Cosgrove SE. Infect Dis Clin North Am :245Ohl CA, Luther VP. J. Hosp. Med. 2011;6:S4
17 Antibiotic Stewardship Improves Clinical Outcomes PercentRR 2.8 ( )RR 1.7 ( )RR 0.2 ( )AMP = Antibiotic Management ProgramUP = Usual PracticeFishman N. Am J Med 2006;119:S53.
18 Antibiotic Stewardship Reduces C. difficile Infection and Gram Negative ResistanceRates of C. difficile AADRates of Resistant EnterobacteriaceaeAntimicrobial Stewardship Reduces Incidence of Clostridium difficile Infection as well as rates of resistant Enterobacteriaceae.Addt’l resource on decreased CDI with antimicrobial stewardship (tertiary care hospital, Quebec) Valiquette, et al. Clin Infect Dis 2007:45 S112Carling P et al. Infect Control Hosp Epidemiol. 2003;24(9):
19 Outline Introduction Untoward Effects of Antibiotics Antibiotic StewardshipPrinciples of Antibiotic SelectionTenets of Appropriate Antibiotic UseConclusion
20 Nine Factors to Consider When Selecting an Antibiotic Spectrum of coveragePatterns of resistanceEvidence or track record for the specified infectionAchievable serum, tissue, or body fluid concentration (e.g. cerebrospinal fluid, urine)AllergyToxicityFormulation (IV vs. PO); if PO assess bioavailabilityAdherence/convenience (e.g. 2x/day vs. 6x/day)Cost
21 Principles of Antibiotic Therapy Empiric Therapy (85%)Infection not well defined (“best guess”)Broad spectrumMultiple drugsEvidence usually only 2 randomized controlled trialsMore adverse reactionsMore expensiveDirected Therapy (15%)Infection well definedNarrow spectrumOne, seldom two drugsEvidence usually strongerLess adverse reactionsLess expensiveCompare and contrast directed and empiric therapy. Which therapy would you rather have if you were the patient? In most medical centers only 15-20% of therapy is directed leaving 85-80% as empiric. Why is this?
22 Why So Much Empiric Therapy? Need for prompt therapy with certain infectionsLife or limb threatening infectionMortality increases with delay in these casesCultures difficult to do to provide microbiologic definition (i.e. pneumonia, sinusitis, cellulitis)Negative culturesProvider BeliefsFear of error or missing somethingNot believing culture data available“Patient is really sick, they should have ‘more’ antibiotics”Myth of “double coverage” for gram-negatives e.g. pseudomonas“They got better on drug X, Y, and Z so I will just continue those”Compare and contrast directed and empiric therapy. Which therapy would you rather have if you were the patient? In most medical centers only 15-20% of therapy is directed leaving 85-80% as empiric. Why is this?
23 To Increase Directed Therapy for Inpatients: Define the infection 3 waysAnatomically, microbiologically, pathophysiologicallyObtain cultures before starting antibioticsUse imaging, rapid diagnostics and special procedures early in the course of infectionHave the courage to make a diagnosisDo not rely solely on “response to therapy” to guide therapeutic decisions; follow recommended guidelinesIf empiric therapy is started, reassess at hoursMove to directed therapy (de-escalation or streamlining)Do not use “response to therapy” to guide therapy as the patient’s “response” is often not directly attributable to your antibiotic prescription.
24 To Increase use of Directed Therapy for Outpatients: Define the infection 3 waysAnatomically, microbiologically, pathophysiologicallyObtain cultures before starting antibioticsOften difficult in outpatients (acute otitis media, sinusitis, community-acquired pneumonia)Narrow therapy often with good supporting evidenceAmoxicillin or amoxicillin/clavulinate for AOM, sinusitis and CAPPenicillin for Group A Streptococcal pharyngitis1st generation cephalosporin or clindamycin for simple cellulitisTrimethoprim/sulfamethoxazole or cipro/levofloxacin for cystitis
25 Outline Introduction Untoward Effects of Antibiotics Antibiotic StewardshipPrinciples of Antibiotic SelectionTenets of Appropriate Antibiotic UseConclusion
26 Tenet 1: Treat Bacterial Infection, not Colonization Many patients become colonized with potentially pathogenic bacteria but are not infectedAsymptomatic bacteriuria or foley catheter colonizationTracheostomy colonization in chronic respiratory failureChronic wounds and decubitiLower extremity stasis ulcersChronic bronchitisCan be difficult to differentiatePresence of WBCs not always indicative of infectionFever may be due to another reason, not the positive culture
27 Tenet 1: Treat Bacterial Infection, not Colonization Example: Asymptomatic bacteriuria ≥105 colony forming units is often used as a diagnostic criteria for a positive urine cultureIt does NOT prove infection; it is just a number to state that the culture is unlikely due to contaminationPyuria also is not predictive on its ownIt is the presence of symptoms AND pyuria AND bacteruria that denotes infection
28 Prevalence of Asymptomatic Bacteriuria Age (years) Women Men% 1%% 15%>70 + long-term care 50% 40%Spinal cord injury 50% 50%(with intermittent catheterization)Chronic urinary catheter % %Ileal loop conduit 100% %Nicolle LE. Int J Antimicrob Agents Aug;28 Suppl 1:S42-8.
29 Treatment of Asymptomatic Bacteriuria in the Elderly Multiple prospective randomized clinical trials have shown no benefitNo improvement in “mental status”No difference in the number of symptomatic UTIsNo improvement in chronic urinary incontinenceNo improvement in survival
30 Summary of Asymptomatic Bacteriuria Treatment Treat symptomatic patients with pyuria and bacteriuriaDon’t treat asymptomatic patients with pyuria and/or bacteriuriaDefine the symptomatic infection anatomicallyDysuria and frequency without fever equals cystitisDysuria and frequency with fever, flank pain, and/or nausea and vomiting equals pyelonephritisRemember prostatitis in the male with cystitis symptomsNote: The two scenarios in which the treatment of asymptomatic bacteriuria is appropriate are: pregnancy and patients undergoing a urologic procedure for which bleeding is anticipated.
31 Tenet 2: Do not Treat Sterile Inflammation or Abnormal Imaging Without Infection Example: community-acquired pneumonia (CAP)CAP: often a difficult diagnosisX-rays can be difficult to interpret. Infiltrates may be due to non-infectious causes.Examples:AtelectasisMalignancyHemorrhagePulmonary edemaAdditional examples of non-infectious causes of pulmonary infiltrates: Heart failure, pulmonary embolism, pulmonary effusions, chronic fibrosis
32 Community-Acquired Pneumonia (CAP) Pneumonia is not present in up to 30% of patients treatedDo not treat abnormal x-rays with antibiotics if the patient does not have systemic evidence of inflammation (fever, wbc, sputum production, etc)Discontinue antibiotics initially started for pneumonia if alternative diagnosis revealed
33 Tenet 3: Do not Treat Viral Infections with Antibiotics Acute bronchitisCommon coldsSinusitis with symptoms less than 7 daysSinusitis not localized to the maxillary sinusesPharyngitis not due to Group A Streptococcus spp.Role of bacteria in acute bronchitis is minimal. Mostly due to viral infections of the upper airways including: influenza A and B, parainfluenza, coronavirus, rhinovirus, respiratory syncytial virus, and human metapneumovirus.Note: May want to make a point that acute bronchitis is different from acute exacerbations of chronic bronchitis which in some situations have better outcomes on antibiotics.Gonzales R, et al. Annals of Intern Med 2001;134:479Gonzales R, et al. Annals of Intern Med 2001;134:400Gonzales R, et al. Annals of Intern Med 2001;134:521
34 Tenet 4: Limit Duration of Antibiotic Therapy to the Appropriate Length Ventilator-associated pneumonia: 8 daysMost community-acquired pneumonia: 5 daysCystitis: 3 daysPyelonephritis: 7 days if fluoroquinolone usedIntra-abdominal with source control: 4-7 daysCellulitis: 5-7 daysHayashi Y, Paterson DL. Clin Infect Dis 2011; 52:1232
35 Other Tenets of Antibiotic Stewardship Re-evaluate, de-escalate or stop therapy at hours based on diagnosis and microbiologic resultsRe-evaluate, de-escalate or stop therapy with transitions of care (e.g. ICU to step-down or ward)Do not give antibiotic with overlapping activityDo not “double-cover” gram-negative rods (i.e. Pseudomonas sp.) with 2 drugs with overlapping activity
36 Other Tenets of Antibiotic Stewardship Limit duration of surgical prophylaxis to <24 hours perioperativelyUse rapid diagnostics if available(e.g. respiratory viral PCR)Solicit expert opinion if neededPrevent infectionUse good hand hygiene and infection control practicesRemove cathetersUse of biomarkers of inflammation (e.g. procalcitonin) is an emerging area in antibiotic stewardship
37 Outline Introduction Untoward Effects of Antibiotics Antibiotic StewardshipPrinciples of Antibiotic SelectionTenets of Appropriate Antibiotic UseConclusion
38 ConclusionThe therapeutic benefit of antibiotics should be balanced with their unintended adverse consequencesInappropriate antibiotic use is associated with increased antibiotic resistance, adverse drug effects and Clostridium difficile infectionAntibiotic stewardship is important for preserving existing antibiotics and improving patient outcomesAntibiotic prescribing should be prudent, thoughtful and rational