抗生素ppt课件（英文精品）antibiotics the root cause for

Antibiotics = the root cause for resistance Darwinism Alexander Flemming Louis Weinstein Native American wisdom Goal of Antibiotic Stewardship Attack the root cause by fine tuning antibiotic use Condense clinical infectious disease, ad absurdum Create mini-ID specialists, by recipe Practicality? Agenda Basics (theory) Specifics (practice) Physician/administration approval Physician response Measurement/reporting Cost implications BREAK Clinical vignettes Summary/Implementation Questions/Discussion What is Antibiotic Stewardship? A program that encourages judicious (vs injudicious) use of antibiotics. Antibiotics are relatively so effective, non-toxic and inexpensiveso easy to usethat they are prone to misuse When the diagnosis is uncertain, antibiotics are often prescribed, viewed as a medical necessity (drugs of fear); but theyre not benign We need a paradigm shift Man has an inborn craving for medicinethe desire to take medicine is one feature which distinguishes man, the animal, from his fellow creatures. Sir William Osler: Teaching and Thinking, in Aequanimitas Risk Perception and Inappropriate Antimicrobial Use: Yes, It can Hurt Powers. Clin Infect Dis 2009;48:1350-3 Sheab et al. Clin Infect Dis 2008; 47:73543 Emergency Department Visits for Adverse Drug Reactions Stewardship strives to fine tune antibiotic Rx in regards to Efficacy/Toxicity Resistance-induction/C. difficile Cost Appropriate discontinuation What are its Limitations? Its difficult dangerous outrageous to practice clinical infectious diseases with limited information Select cases very carefully Primum non nocere Practicality? Does it work? Outcomes of the University of Pennsylvania Hospitals Antibiotic Stewardship Program Gross. et al. Clin Infect Dis. 2001; 289-295. MRSA and C. difficille Rates After Implementation of an Antibiotic Stewardship Program Fowler et al. JAC 2007 59, 990995 Effect of an Antibiotic Stewardship Program on the Rate of Resistant Enterobacter Infections Carling et al. Infect Control Hosp Epidemiol 2003;24:699-706). Recommended by Collaborative Drs. Perl, Bratzler, CW IDSA Dellit et al. Clin Infect Dis 2007; 44: 159-77 CDC Tattevin et al. Emerg Infect Dis 2009; 15: 953-5 Practiced regularly How does it work? A pharmacist, par excellence, or someone else reviews patients on antibiotics and makes recommendations, prn; overseen by a PHYSICIAN CHAMPION, an ID-trained physician, when available Training Contact the prescribing physician Telephone call Announce; non-threatening; dont interrupt (leave message) Chart notation Rx change implemented Physician Pharmacist, verbal order Common Interventions Allergies, interactions Dosing IV-to-po switch Redundancy Cost Empiric Rx, then Streamlining, (de-escalation) When not to use antibiotics in the first place Discontinuation Common Interventions Some are so evident that they should be/are automatic Allergy, e.g. PCN; PCN-cephalosporin cross-reactivity Drug-drug interactions, e.g. Vanco-gentamicin synergistic toxicity Rifampins effect on hepatic drug metabolism Coumadin Address toxicities, e.g. Renal Aminoglycosides Hepatic Dosing Cefazolin: q8h Ceftriaxone: q24h Aminoglycosides: q24h Levels Aminoglycosides Vancomycin Vancomycin Dosing MRSA epidemic MIC creep Dosing reviewed Traditional: 1gm q12 h New recommendation: 15mg/kg q12 h (ATS/IDSA. Am J Respir Crit Care Med 2005;171:388-416) Nomogram for renal impairment Therapeutic and toxic levels uncertain (CID 94) Resistance has led to aiming for trough of 15- 20 (ATS/IDSA) And this has led to nephrotoxicity Measuring levels often leads to under-dosing Management options: Dont do levels Exceptions: 1. Patients receiving vanco/aminoglycoside combination 2. Anephric patients undergoing dialysis 3. Patients with rapidly changing renal function 4. Patients receiving higher-than-usual doses Use a different antibiotic Vancomycin Levels IV-to-po Switch Criteria Afebrile, WBC normalized Maybe the patient doesnt need any further antibiotics in the first place Intact GI tract, i.e. no N/V/D Oral bioavailability, e.g. quinolones Patient can often go home, on po AB, without further in-hospital observation* *Ramirez et al. Arch Intern Med 2001; 161:84850 IV removal = #1 defense vs BSI Requirement for hospitalization “intensity of care” criterion Leave in place “just in case” “what if?” Antibiotic Redundancy vs Anaerobes: PCN/pcn-ase inhibitor (e.g. Zosyn, Unasyn) or carbapenem (e.g. Primaxin) +Flagyl vs C. diff: po Flagyl + po vanco Etc. Promoting use of less costly alternatives: Cascade reporting Cost Issues: Therapeutic Substitutions When the efficacy and safety profiles are almost identical, use the less expensive alternative Quinolones Cephalosporins Cabapenems Echinocandins Empiric broad-spectrum antibiotic Rx, then streamline Empiric, i.e before the diagnosis is determined Must acknowledge the MDRO epidemic vs gpc, gnr, anaerobes, fungi Then, streamline (a.k.a. de-escalate) based on C40:643-54 Definition: pyuria/bacteriuria, without Sx, with normal temperature and WBC Common Asymptomatic UTI Nicolle et al. Clin Infect Dis 2005;40:643-54 Asymptomatic UTI Boscia et al. JAMA 1987; 257:1067-71 Nordenstam et al. NEJM 1986; 314:1152-6 Nicolle et al. NEJM 1983; 369: 1420-5 Ouslander et al. Ann Intern Med 1995;122: 749-54 Abrutyn, E. et. al. Ann Intern Med 1994;120:827-833 Mortality in patients with asymptomatic UTIs treated with antimicrobial agents or placebo Practitioners do not feel comfortable ignoring bacteriuria once they are aware of its presence. Encourage physicians not to screen for asymptomatic bacteriuria U.S. Preventive Services Task Force. Screening for asymptomatic bacteriuria in adults: U.S. Preventive Services reaffirmation recommendation statement. Ann Intern Med 2008;149:43-7 Increase adherence to non-treatment guidelines Gross, Patel. Reducing antibiotic overuse: a call for a national performance measure for not treating asymptomatic bacteriuria. Clin Infect Dis 2007;45:1335-7 Asymtomatic UTI: Is it applicable to catheter- associated bacteriuria? Yes Cope et al. Inappropriate Treatment of Catheter- Associated Asymtomatic Bacteriuria in a Tertiary Care Hospital. Clin Infect Dis. 2009;48:1182-88 Kunin. Editorial Commentary: Catheter-Associated UTIs: A Syllogism Compounded by a Questionable Dichotomy. Ibid: 1189-90 Viral URI Review of Acute Rhinosinusitis. JAMA. 2009;301(17):1798-1807 How do you know its viral and not bacterial? Physical exam: non-specific Temperature WBC Prevailing attitude of physicians and patients: Take an antibiotic, just in case what if Changing paradigm, because of MDROs Side effects C. diff Other Recommendation: Withhold AB for the first 10 days Antibiotics for Treatment of Acute Maxillary Sinusitis JAMA 2008;298:2487-96 Cdc rx Cdc return to school letter Materials order form /ncidod/dbmd/antibiotic resistance/educatio.htm Exacerbation of COPD? Van Der Valk et al. Clin Inf Dis 2004;39: 980-6 How do you know if its bacterial? Tough question, not adequately answered in the literature Antibiotics not unreasonable. 5 days should suffice CHF, misdiagnosed as pneumonia How do you distinguish one from the other? H 44: S27-72. CMS Specifications Manual For National Inpatient Quality Measures Timing of antibiotics for CAP: Controversy Earlier better than later Intuitive Data Embraced by CMS IDSA/ATS response Rebuts the data Points out the negative consequences of injudicious antibiotics Present state of affairs: IDSA/ATS Guidelines A problem of internal consistency is also present, because, in both studies 109, 264, patients who received antibiotics in the first 2 h after presentation actually did worse than those who received antibiotics 24 h after presentation For these and other reasons, the committee did not feel that a specific time window for delivery of the first antibiotic dose should be recommended. However, the committee does feel that therapy should be administered as soon as possible after the diagnosis is considered likely. Conversely, a delay in antibiotic therapy has adverse consequences in many infections. For critically ill, hemodynamically unstable patients, early antibiotic therapy should be encouraged, although no prospective data support this recommendation. Delay in beginning antibiotic treatment during the transition from the ED is not uncommon. Especially with the frequent use of once-daily antibiotics for CAP, timing and communication issues may result in patients not receiving antibiotics for 18 h after hospital admission. The committee felt that the best and most practical resolution to this issue was that the initial dose be given in the ED. If antibiotics started, and patient doesnt have pneumonia discontinue them At once; If continued, 5 days should suffice Dunbar et al. High-dose, short-course levofloxacin for community- acquired pneumonia: a new treatment paradigm. Clin Infect Dis 2003; 37:75260. Etc. VAP: Duration of Rx Shorter than longer Chastre et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003; 290:258898. CoNS bacteremia How do you know if its real or contamination? Real Hospitalized, IV (phlebitis), fever, leukocytosis, multiple positive cultures Contamination Present on admission/no IV, no fever, no leukocytosis, few positive cultures/denominator Additional recommendations SCIP C.difficile Pneumonia CAP HAP Surgical Care Improvement Project (SCIP) Antibiotics for surgical prophylaxis (Bratzler et al. Clin Infect Dis. 2004 Jun 15;38(12):1706-15) Which agent? Function of most common pathogen(s) Staph. aureus First generation cephalosporin If PCN-allergic If high prevalence of MRSA Anaerobes Cefoxitin When to start? 1 hour pre-op When to stop? 1 dose only Within 24 hours HAP Duration: Criteria to d/c antibiotics By the numbers, e.g. 5, 7, 10, 14 days no! Empiric discontinuation, once temperature and WBC have normalized Notable exceptions Endocarditis Osteomyelitis Community-acquired pneumonia: 5 days Healthcare-acquired pneumonia: abbreviate Uncomplicated UTI: 3 days Clin Infect Dis 1999;29:74558 Physician/administration approval and notification Medical Executive Committee Physician champion Physicians Sample letter to physicians Dear Colleague, In an attempt to confront the MDRO (multi-drug resistant organism, e.g. MRSA) and C. difficile epidemics, our Hospital is initiating an Antibiotic Stewardship Program. Our goal is to promote judicious antibiotic use. Implementation will be through review of patients on antibiotics, then physician notification to consider Rx modifications. This has been approved by the Medical Executive Committee. Physician Response Bell-shaped curve Dr. D Dr. S Dr. C Dr. O Antibiotics viewed as “drugs of fear” Fear of omission Law suits Fear of commission Law suits Outcomes: Measure Interventions # patients reviewed # interventions recommended Divided by # patients of reviewed = % # interventions accomplished Divided by # recommended = % Change to avoid allergic reaction: % Drug-drug interactions addressed: % Change to different antibiotic based on C 38:348-56. Results of an Antibiotic Intervention Program in a University-Affiliated Teaching Hospital 2008 Antibiotic Cost Per Month Midwest Regional Medical Center BREAK Vignettes Asymptomatic UTI Viral URI Exacerbation of COPD Pneumonia vs CHF Immunocompromised host with fever Antibiotic duration C. difficile SCIP Asymtomatic UTI An 83 yo woman suffers from dementia and resides in a nursing home. The NH staff is concerned about her increased confusion and decides to send her to the local ER. VS: BP 140/90, P 90, RR 16, T 98.6. PE WNL except for mild confusion. No Foley. WBC 10.1. U/A 5-10 WBC/hpf. Dx: “UTI.” Rx Avelox. The following day her urine culture returns with E.coli, 100K. Avelox is continued x 1 wk. She becomes more confused. And she develops C.diff antibiotic- associated colitis Comments: On occasion, “sepsis” can present with normal or low temperature and WBC, and with confusion However, she wasnt septic based on the normal BP and P An asymptomatic UTI does not need Rx. Avelox is not indicated for UTI. Quinolones can cause CNS problems All antibiotics can cause C.diff AAC. The elderly and NH residents are predisposed Antibiotic Stewardship: Asymptomatic bacteriuria This patient appears to have asymptomatic bacteriuria which does not merit antibiotic Rx. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults Clin Infect Dis 2005; 40: 64354 Viral URI A 72 yo diabetic man developed nasal congestion and cough productive of purulent sputum. He went to his local ER where the evaluation was noteworthy for a temperature of 99.6, normal respirations, mild tenderness to palpation and percussion over his sinuses, clear lungs, a WBC of 7.8 with 6% eosinophils and CXR showing “chronic scarring.” His blood sugar was 311. He was admitted. After a sputum was obtained for C301(17)1798-1807 Exacerbation of COPD Its February, and a 60 yo smoker with COPD developed worsening of his chronic cough and SOB. His sputum has become more copious, thicker, discolored and foul-smelling, and he has noted a fleck of blood. He has not had any chills or fever. On physical exam, he is receiving O2 through nasal prongs. His respiratory rate is 24/min and slightly labored. His temperature is 99.1, BP 95/70, pulse 120. His breath sounds are distant and there are scattered ronchi and wheezes. The WBC is 11.1. A CXR shows emphysema and a faint haze at the bases interpreted as “cannot rule out pneumonia.” Although influenza and RSV has been reported in the community, rapid tests for influenza A&B and RSV are negative.There are many PMNs and mixed flora on the sputum gram stain. It ultimately grows H. influenza and the pneumococcus (PCN MIC 1.0). He is admitted to hospital and is treated with Cipro. Comments: Since its respiratory virus season, this is a good bet. Rapid tests have variable sensitivity. Go with the epidemiology Give an anti-influenza agent, ASAP While the H.flu and pneumococcus could represent otherwise benign colonization, either could be playing a pathogenic role. And colonization is the first step to infection, so why wait? Hes too fragile to risk withholding antibiotics. Use a respiratory quinolone, i.e. not cipro-, but rather levo- or moxi- Make sure he has received influenza and pneumococcal vaccines Antibiotic Stewardship: COPD exacerbation Recommendations: Tamiflu Change from Cipro to Levaquin Pneumonia vs CHF A 90 yo with a h/o CHF has become more short of breath over the past few days. There have been no fevers or chills. On physical exam the temperature is 97, RR 24, BP 160/100 and pulse 80. Bibasilar rales are noted on auscultation. Theres a cardiac gallop. The CXR shows cardiomegaly and pulmonary congestion consistent with CHF, “cannot rule out early pneumonia.” The BNP is 1567. BioZ says CHF. He receives Lasix and improves. Rocephin and Zithromax were also started in the ER, for possible pneumonia. Comments: CHF seems readily apparent. While pneumonia isnt entirely impossibleand he could have boththe potential side-effect of antibiotics dont seem worth the risk in this case. Blame the ER for having started them ER: Hospitals front door, EMTALA Dx often uncertain ABs used liberally ABs can/should be d/cd promptly, once ID unlikely Antibiotic Stewardship: Pneumonia vs CHF Recommendation: CHF is apparent, and pneumonia seems unlikely, so consider d/c antibiotics. Immunocompromised Patient with Fever A 45 yo woman has fever complicating her metastatic breast cancer and its chemotherapy. She presents with chills and shortness of breath. Her temperature is 105, RR 32, BP 90/70, pulse 130. Her lungs are clear. The WBC is 0.3. There are bilateral infiltrates on the CXR. She is started on Fortaz, Vancomycin, Zithromax, Diflucan and Zovirax. Comments: Too complex to intervene. Antibiotic Duration? A 92 yo nursing home resident (where C. diff has been epidemic) is transferred to the hospital for decreased mentation and poor intake. Her BMs are normal. On admission her temperature is 101 and the physical exam non-diagnostic. She has a 16K WBC and her creatinine is 3.1. There are 5-10 WBC in the U/A and the CXR reads “cannot R/O pneumonia.” She is treated empirically with Rocephin, Levaquin and v