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ANTIBIOTICS SMART USE (ASU) การใช้ยาต้านจุลชีพอย่างชาญฉลาด

ANTIBIOTICS SMART USE (ASU) การใช้ยาต้านจุลชีพอย่างชาญฉลาด. Pornpan Koomanachai Division of Infectious diseases and Tropical Medicine Department of Medicine, Faculty of Medicine Siriraj Hospital. ASU. A major threat to public health ปัญหาหลักทางสาธารณสุข. ASU.

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ANTIBIOTICS SMART USE (ASU) การใช้ยาต้านจุลชีพอย่างชาญฉลาด

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  1. ANTIBIOTICS SMART USE (ASU) การใช้ยาต้านจุลชีพอย่างชาญฉลาด PornpanKoomanachai Division of Infectious diseases and Tropical Medicine Department of Medicine, Faculty of Medicine Siriraj Hospital .

  2. ASU A major threat to public health ปัญหาหลักทางสาธารณสุข

  3. ASU Costelloe C et al.BMJ 2010;340:c2096 • Antibiotics • Commonly used in ambulatory care facility (ใช้บ่อย) • Antibiotics can be purchased without prescriptions (ซื้อเองได้) • A systematic review and meta-analysis • Antibiotic prescribing in primary care • Prescribing an antibiotic in primary care for a respiratory or urinary infection develop bacterial resistance to that antibiotic

  4. ASU Asawapokee N et al. J Infect Dis Antimicrob Agents 1984; 3: 141-5 Treebupachatsakul P et al. J Med Assoc Thai 2006;89(8):1178-86 • URI and acute diarrhea: common self-limiting (การติดเชื้อทางเดินหายใจส่วนต้นและท้องร่วง เฉียบพลัน) • The prevalence of group A streptococci (GAS) in adults with sore throat attending Siriraj Hospital • 7.9% to 11.4% • No compelling data on antibiotic treatment of patients with URI other than GAS are beneficial

  5. ASU • In healthy individuals with acute diarrhea • almost always self-limited; หายได้เอง!!!! • Standard guidelines การใช้ยาต้านจุลชีพต้องมีข้อบ่งชี้สำคัญ คือ • empiric antibiotic therapy is recommended only for invasive or inflammatory diarrhea • especially in special hosts with immunocompromised conditions • non-inflammatory diarrhea with moderate or severe dehydration such as cholera

  6. ASU สำนักงานคณะกรรมการอาหารและยา สถาบันวิจัยระบบสาธารณสุข องค์การอนามัยโลก

  7. ASU 1. เป้าหมาย คือ ลดการใช้ยาปฏิชีวนะอย่างพร่ำเพรื่อใน 3 โรคที่พบบ่อย - โรคติดเชื้อทางเดินหายใจส่วนบน - โรคท้องร่วงเฉียบพลัน - แผลเลือดออก 2. ASU เป็นโครงการที่หวังผลให้เกิดการเปลี่ยนแปลงทางพฤติกรรม 3. ASU เหมาะกับสถานพยาบาลที่การสั่งใช้ยาปฏิชีวนะมากเกินจำเป็นมีสาเหตุมาจาก - ความรู้หรือความเชื่อที่คาดเคลื่อนของบุคลากรทาง การแพทย์ - แรงกดดันหรือความคาดหวังของผู้ป่วย 4. ASU ตั้งอยู่บนแนวคิดที่ว่าการเปลี่ยนพฤติกรรมเริ่มจากความรู้ แต่ความรู้อย่างเดียวไม่เพียงพอในการเปลี่ยนพฤติกรรม

  8. PRINCIPLE OF ANTIBIOTIC USED Common Inappropriate Use of Antibiotics • CHOOSING ANTIBIOTIC THERAPY BASED SOLELY ON SPECTRUM เลือกใช้ยาโดยดูแต่ความสามารถในการครอบคลุมเชื้อ • PROLONGED USE OF IV ANTIBIOTICS ใช้ยาฉีดเป็นเวลานาน • USE OF COMBINATION THERAPY TO PREVENT ATB RESISTANCE ใช้ยามากกว่า 1 ขนานเพราะเชื่อว่าจะป้องกันการดื้อยา • OVERRELIANCE ON MICROBIOLOGY RESULTS เลือกใช้ยาตามผลเพาะเชื้อเพียงอย่างเดียว • USE OF ATB FOR PERSISTENT FEVERS ใช้ยาต้านจุลชีพเพราะไข้ไม่ลดลง • INADEQUATE SURGICAL THERAPY AND LACK OF NON-ATB THERAPY OF INFECTION ขาดการรักษาร่วมอื่นๆที่สำคัญ • PROLONGED ATB THERAPY OR PROPHYLAXIS ใช้ยานานเกินความจำเป็น

  9. CHOOSING ATB BASED SOLELY ON SPECTRUM Antibiotic tissue penetration ระดับยาในตำแหน่งที่มีการติดเชื้อ ATB effective in-vitro, unable to reach the site of infection • Urinary tract infections; same pathogens but! • drugs for catheter-associated bacteriuria and cystitis differ from those used for pyelonephritis, prostatitis, or epididymitis • Fluoroqyuinolones: high concentration in the prostate **moxifloxacin; not achieve significant urinary concentration

  10. CHOOSING ATB BASED SOLELY ON SPECTRUM Antibiotic tissue penetration ระดับยาในตำแหน่งที่มีการติดเชื้อ ATB effective;in-vitro, unable to reach the site of infection • Chronic infections - decrease vascular permeability • chronic pyelonephritis, chronic prostatitis, chronic osteomyelitis • Implanted foreign materials • biofilm- slime/glycocalyx on plastic/metal surfaces

  11. CHOOSING ATB BASED SOLELY ON SPECTRUM Antibiotic tissue penetration ระดับยาในตำแหน่งที่มีการติดเชื้อ ATB effective;in-vitro, unable to reach the site of infection • Special barrier or abscesses • ocular, fluid, CSF, abscess cavity, prostate, bone • aminoglycosides; less active in the low-oxygen, low- pH, and high-protein environment of abscesses ** drainage of abscesses to enhance antimicrobial efficacy

  12. CHOOSING ATB BASED SOLELY ON SPECTRUM Antibiotic tissue penetration ระดับยาในตำแหน่งที่มีการติดเชื้อ ATB effective;in-vitro, unable to reach the site of infection • Poor Tissue Concentration of ATB • Tigecycline Urinary tract (Lung, Blood) • Daptomycin Lung • 1st- and 2nd-gen ceph. blood-brain barrier • Macrolides blood-brain barrier

  13. CHOOSING ATB BASED SOLELY ON SPECTRUM Bectericidal vs Bacteriostatic therapy การออกฤทธิ์ของยาในการยับยั้งการติดเชื้อ • Bactericidal agents cause death and disruption of the bacteria • Disruption of cell wall • ß-lactams • cell membrane • daptomycin • Bacterial DNA • fluoroquinolones • Bacteriostatic agents inhibit bacterial replication without killing the organis • inhibiting protein synthesis • sulfonamides • tetracyclines • macrolides *Bactericidal agents are in the serious infections to achieve rapid cure such as endocarditis and meningitis

  14. PROLONGED USE OF IV ANTIBIOTICS IV-to-PO switch therapy เปลี่ยนยาฉีดเป็นยารับประทาน • Barrier for intravenous-to-oral (IV-to-PO) นิสัยไม่ดีเก่าๆแก้ยาก!!!! “ Physicians are creatures of habit, and old habits die hard”…Burke A. Cunha, MD (Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501, USA) • IV therapy: first used for serious systemic infections • Many infections susceptible to IV ATB • IV therapy: the preferred mode of ATB administration

  15. Why! Oral antibiotic therapy Advantages (ข้อดี) Disadvantages (ข้อด้อย) Should not be used in those with impaired gastrointestinal absorption Patient in shock, begin therapy intravenously Increased ecological hazard (oral agent with poor bioavailability potentiate colonization) • Lower ATB acquisition cost • No IV ATB administration costs • Rapid gastrointestinal absorption (<1 h) even in critically ill patients • Eliminates IV-line infections • Decreased length of hospital stay • Earlier discharge Cunha BA. Antibiotic essentials. 5th edition. 2006 Cunha BA. Drugs Today 2001;37:311–9 Quintiliani R, Nightingale CH. Infect DisClin Practice 1994;3(Suppl):161–7

  16. Cost-effectiveness! IV-to-Oral Switch therapy

  17. When! Oral antibiotic therapy • Oral absorption in the critically ill - Oral ATBwith good/excellent bioavailability rapidly/well absorbed achieve blood/target tissue levels **except septic shock - Per oral  per nasogastric tube or per percutaneous enteroscopic gastroscopy tube

  18. Requirements of an oral ATB Antibiotic Factors ปัจจัยด้านยาต้านจุลชีพ Host Factors ปัจจัยด้านผู้ป่วย patient able to sufficiently absorb an oral antibiotic avoid in patients with impaired gastrointestinal absorption • high degree of activity against presumed/known pathogens • high bioavailability • low resistance potential • well tolerated with a good safety profile

  19. Duke University Medical Centre Criteria ตัวอย่าง • Absent of infectious indications requiring parenteral ATB • febrile neutropenia • significantly immunocompromised • meningitis • osteomyelitis • endocarditis • septic shock • disseminated viral infections such as HSV * Modified from Lelekis and Gould. J Hosp Infect 2001; 48: 249 J Infect 1998; 37(suppl 1):3-9

  20. Duke University Medical Centre Criteria • Absent of infectious indications requiring parenteral ATB • Infection is not presently serious or life-threatening • Improved of signs or symptoms of infection • Afebrile or has consistent improvement in fever > 24 hrs • WBC count is normalizing • Normal gastrointestinal absorption of drugs and the patient is able to receive enteral therapy * Modified from Lelekis and Gould. J Hosp Infect 2001; 48: 249 J Infect 1998; 37(suppl 1):3-9

  21. What are types of IV-to-oral switch? • Stream-lining: converting from broad-spectrum ATB to single agent with narrow spectrum • Sequential: converting IV to oral agents with same chemical • Switch: converting IV to oral agents with identical potency • Step-down: converting IV to oral agents with reduced potency ศาสตราจารย์แพทย์หญิงนลินี อัศวโภคี

  22. Bioavailability of oral antibiotics Keflex Meiact Cefspan Cedax Zinacef Vantin

  23. USE OF COMBINATION THERAPY? • Monotherapy; preferred over combination therapy -> reduces the risk of; • drug interactions • medication errors • missed doses and side effects • usually less expensive than combination therapy • Combination Therapy • drug synergy • extended spectrum

  24. Combination Therapy: Synergy • β-lactams and aminoglycosides exhibits synergism for treatment of endocarditis caused by; • Enterococcus spp. • A viridans group streptococci • Staphylococcus aureus • Penicllin and clindamycin: clinical synergism for treatment of S. pyogenes infection

  25. Combination vs monotherapy PRO ข้อมูลสนับสนุน CON ข้อมูลคัดค้าน Higher rates of resistance isolates Higher rates of side effects Lack of the power to showed the consistent of good outcome No top level of grading evidence • Synergistic effect – in vitro • Good outcome in severely ill (Septic shock, neutropenia) • Higher rate of microbiological cure CID 2011;53 (Suppl 2):S33 ICAAC 2011, Chicago & IDSA 2011 Sa n Francisco, USA

  26. COMBINATION THERAPY TO PREVENT ATB RESISTANCE Antibiotic combinations that prevent resistance • Anti-pseudomonal penicillin + aminoglycoside • Rifampin + other TB drugs (INH, ethambutol, pyrazinamide) (3) 5-flucytosine + amphotericin B (4) Anti-retroviral drugs in HIV/AIDS therapy

  27. COMBINATION THERAPY TO PREVENT ATB RESISTANCE Commonly used antibiotic combinations that do not prevent resistance ยาที่นิยมใช้ให้หลายขนาน แต่ในความเป็นจริงไม่ได้ป้องกันเชื้อดื้อยา • TMP-SMX • Ceftazidime in combination with any other ATB • Ciprofloxacin in combination with any other ATB (4) Imipenem in combination with any other ATB (5) Most other ATB combinations

  28. OVERRELIANCE ON MICROBIOLOGY RESULTS • In vitro data do not differentiate between colonizers and pathogens • determine whether the organism is a pathogen or a colonizer • colonization should not be treated • In vitro data do not necessarily translate into in vivo efficacy • "sensitive" or "resistant" to a given antibiotic in-vitro do not necessarily reflect in-vivo activity

  29. OVERRELIANCE ON MICROBIOLOGY RESULTS • In vitro susceptibility testing is dependent on the microbe, methodology, and ATB concentration; assumes the isolate was recovered from blood, and is being exposed to serum concentrations • Usually higher ATB concentrations than in serum: bladder, urine • Lower ATB concentrations than in serum: CSF, ocular • In vitro data may be misleading for non-bloodstream infections

  30. USE OF ANTIBIOTICS FOR PERSISTENT FEVER The most common error in the management of persistent fevers • Changing/adding additional antibiotics instead of determining the cause ปรับยาไม่มีการวินิจฉัย • More important to reassess the patient • Causes of prolonged fevers include • Non-infectious medical disorders (e.g., SLE) • Drug fever • In-vitro susceptibility but inactive in-vivo

  31. USE OF ANTIBIOTICS FOR PERSISTENT FEVER • Inadequate spectrum • Inadequate ATB blood and tissue levels • Undrained abscess, • Foreign body-related infection • Special barrier CSF • Organ hypoperfusion diminished blood supply - chronic osteomyelitis in diabetics) • ATB inactivation, ATB antagonism) • Fungal superinfection • Treating colonization • ATB-unresponsive infectious diseases; viral infections • Undiagnosed causes of leukocytosis • Low-grade fevers should not be treated with prolonged courses of ATB

  32. NON-ATB THERAPY OF INFECTION • Operative drainage or débridement • Get rid of the high organism burden (abscesses) • Corticosteroid: conjunction with ATB therapy • Bacterial meningitis • Tuberculous meningitis • Pneumocystis pneumonia in AIDS • Temporary discontinuation or dose reduction of immunosuppressive agents • CMV disease in organ transplant recipients or patients with rheumatologic disorders • Probiotics Lancet Infect Dis 2004;4(3):139-143 N Engl J Med 2004;351(17):1741-1751 N Engl J Med 1990;323(21):1444-1450 Anaerobe 2009;15(6):274-280

  33. PROLONGED ATB THERAPY OR PROPHYLAXIS Duration of ATB therapy • Prolonged courses of ATB therapy • Potential for adverse reactions • Problems with adherence • Selection of ATB-resistant organisms • High cost

  34. PROLONGED ATB THERAPY OR PROPHYLAXIS Potential for adverse reactions • Direct • Allergy • Toxicity • Drug-drug interaction • Therapeutic failure • Indirect • Effects on commensal flora • Human Clostridium difficile infection • Animal Increased chance of infection with drug-resistant pathogens • Effects on environmental flora

  35. PROLONGED ATB THERAPY OR PROPHYLAXIS Duration of ATB therapy • Examples of optimal duration, shorter but effective course • Uncomplicated UTI in women 3 days • Community-acquired pneumonia 5 days • Ventilator-associated pneumonia 8 days ** not sufficient for the treatment of infections due to P. aeruginosa or in immunocompromised patients • Endocarditis, osteomyelitis, 4-6 weeks and intra-abdominal abscesses Cochrane Database Syst Rev 2005;(2):CD004682 Clin Infect Dis. 2003;37(6):752-760 JAMA. 2003;290(19):2588-2598

  36. PROLONGED ATB THERAPY OR PROPHYLAXIS Duration of ATB prophylaxis • Presurgical ATB prophylaxis • To reduce the incidence of postoperative surgical site infections • The ATB should cover the most likely organisms and be present in the tissues • At the initial incision Clin Infect Dis. 2004;38(12):1706-1715

  37. PROLONGED ATB THERAPY OR PROPHYLAXIS Duration of ATB prophylaxis • Presurgical ATB prophylaxis • Adequate serum concentrations during the procedure • A single dose of a cephalosporin (such as cefazolin) within 1 hour before the initial incision • Avoiding unnecessary broad-spectrum ATB • Duration; should not exceed 24 hours Clin Infect Dis. 2004;38(12):1706-1715

  38. Case Study 48-year-old man • Fever 8 wks • Left cervical lymphadenopathy 8 wks • Nausea, vomiting, and hiccup 8 wks • Weight loss 5kg/6wks • Chronic hepatitis C infection 3 yrs • Hepatomegaly with jaundice • Anemia

  39. Differential diagnosis • Lymphoma • TB/Nontuberculous mycobacterium (NTM) • Infectious mononucleosis (EBV) • Solid tumor: CA nasopharynx, CAesophagus, Hepatoma • *HIV (Opportunistic infection or lymphoma) • Histoplasmosis • CMV • Cat scratch disease • Hepatitis C

  40. Case Study 58-year-old man • Necessary Investigations were performed • Blood smear • H/C for bacteria, mycobacteria, fungus • LN biopsy • BM aspiration and biopsy • CT; Nasopharyx, thorax, abdomen • He was treated with ceftriaxone 2g iv, OD for 3 days. • Fever was still high and LFT (hepatocellula rinjury) was worsening with anemia, thrombocytopenia, leucopenia. • The ATB was changed to meropenem at day-3 of ceftriaxone. • No appropriate provisional diagnosis • Use ATB to treat prolonged fever • Changed ATB without reassessment the patient

  41. Case Study • Bone marrow and LN: Lymphoma with hemophagocytis • Treatment - IVIg, Dexamethasone IV -> clinical improved • Chemotherapy • The patient developed febrile neutropenia. • Septic work up was performed and meropenem was prescribed for 5 days and the fever was decreasing while neutrophil was increasing from 150 to 820. • Sputum culture grew A. baumannii on day-5 of meropenem then colistin was prescribed, continued meropenem. • Use ATB based on culture result to treat colonization • Changed ATB without reassessment the patient • ATB as a risk of adverse effect; renal toxicity without • any benefit • ATB cost, IV administration cost but no “cost • effectiveness

  42. Case Study • The patient still has low grade fever after 7 days of colistin, neutrophil was increasing from 150 to 1,020. Cr rising from 1.2 -> 3.2, sputum C/S grew A. baumannii but resist to colistin. Clinical is similar to previously but this time, no ATB was prescribed. • Increasing adverse effect; renal toxicity without • any benefit

  43. Messages • What is the damage of inappropriate ATB? • Morbidity & mortality • Adverse effects • High cost-ineffectivesness • Emergence of resistant • How to get appropriate ATB? • An accurate diagnosis • The need for ATB, which ATB and timing of ATB Rx • Using the narrowest spectrum and shortest duration of Rx • Switching to oral agents ASAP • Dosing regimens of different agents • Host characteristics • Non-ATB interventions

  44. Thank you Pornpan Koomanachai, MD

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