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Pre-ICU training (Antibiotics)

Pre-ICU training (Antibiotics)

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Pre-ICU training (Antibiotics)

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  1. Pre-ICU training (Antibiotics) 馬偕紀念醫院 感染科 郭建峯醫師

  2. 台北院區院內感染常見10種致病菌歷年變化

  3. 台北院區院內感染各部位感染發生密度(2007年)台北院區院內感染各部位感染發生密度(2007年) Incidence Rate (‰) Incidence rate is the number of isolates reported per 1000 patietn days

  4. 台北院區院內感染各部位分佈圖(2007年) 10.5 All infections = 1,593

  5. 台北院區院內感染常見的15種致病菌(2007年) Total 1,717 %

  6. 台北院區院內感染常見的15種致病菌各部位之感染率(2007年)台北院區院內感染常見的15種致病菌各部位之感染率(2007年)

  7. 台北院區院內感染UTI常見的致病菌(2007年) Total 784

  8. 台北院區院內感染LRTI常見的致病菌(2007年) Total 90

  9. 台北院區院內感染SSI常見的致病菌(2007年) Total 182

  10. 台北院區院內感染BSI常見的致病菌(2007年) Total 583

  11. 台北院區院內感染SSTI常見的15種致病菌(2007年)台北院區院內感染SSTI常見的15種致病菌(2007年) Total 26

  12. What organisms are most likely?何種致病菌是最可能造成此次感染的致病菌? • 適當的經驗療法 • 臨床症候群(Clinical syndrome) • 宿主因素(Host factor) • 流行病學資料(Epidemiological data)

  13. If several antibiotics are available, which is best? (This question involves such factors as drugs of choice, pharmacokinetics, toxicology, cost, narrowness of spectrum, and bactericidal compared with bacteriostatic agents.) 對於一個最可能的致病菌,或是已確定的致病菌,可能有多種藥物可用來治療,何者才是最佳的選擇藥物?

  14. Staphylococcus aureus: Antibiotics Methocillin-sensitive S. aureus (MSSA): • 首選藥物: oxacillin • 替代藥物:第一代頭孢菌素 • 假如 penicillin allergic - Erythromycin, Clindamycin, Glycopeptide (Vancomycin, Teicoplanin) Methocillin-resistant S. aureus (MRSA) : • 首選藥物:Glycopeptide (Vancomycin, Teicoplanin) • 替代藥物: Linezolid • Fusidic acid • Rifampicin

  15. Degree of resistance Minimal inhibitory concentration (MIC) <0.06 ug/mL Susceptible 0.12 to 1 ug/mL Intermediate > 2 ug/mL Resistant Streptococcus pneumoniae • Penicillin-sensitive菌株首選藥物(first choice): Penicillin G Categories of Susceptibility of S. pneumoniae to Penicillin NCCLS 2001

  16. Treatment of S. pneumoniae Pneumonia Penicillin MIC (g/ml) primary alternative 1 penicillin 1st cephalosporins (S) ampicillin or amoxicillin 2 penicillin (high dose) 3rd or 4th cephalosporins (I) ampicillin or amoxicillin 4 3rd or 4th cephalosporins vancomycin or teicoplanin (R) vancomycin or teicoplanin + rifampin or newer fluoroquinolones The infectious diseases society R.O.C. 2000

  17. Treatment of Pneumococcal Meningitis MIC (g/ml) dosage PCN CTX therapy adults children (/kg) <0.12 0.5 penicillin 300,000 u/kg/d 3-400,000 u q4-6h 0.12 0.5 Cefotaxime or 2 g q6h 200-225 mg q6-8h Ceftriaxone 2 g q12h 100 mg q12-24h 1.0 Cefotaxime or 300 mg/kg/d (m.24g) 300 mg q6-8h Ceftriaxone 2 g q12h 100 mg q12-24h +Vancomycin 60 mg/kg/d (M.2g) 60 mg q6h 2.0 Same as 1.0 + Rifampin 300 mg q12h 20 mg q12h Kaplan SL and mason EO jr. Clin microbiol rev 1998

  18. Streptococcus pneumoniae • 依CNS Infection和Non- CNS Infection (Pneumonia, bacteremia) 不同部位感染,按照MIC值選擇藥物治療。 • Invasive Pneumococcal disease經驗治療 • Non- CNS Infection (Pneumonia, bacteremia): high dose penicillin G, or other cephalosporins (ceftriaxone;cefotaxime),or newer fluoroquinolones. Not vancomycin。 • CNS Infection (Meningitis):Not Penicillin, vancomycin + ceftriaxone (cefotaxime, Cefepime, Cefpirome, Meropenem)

  19. Enterococci sp. • E. faecalis, E. faecium • Habitat: commensal of human and animal gut • Lancefield group D, bile resistant • Infections - Urinary tract infection - Intra-abdominal sepsis - Biliary tract infection - Endocarditis

  20. Enterococci sp. • 首選藥物: Ampicillin • 心內膜炎加上gentamicin有加成作用(synergistic effect) • Never use cephalosporins or aminoglycosides alone or Clindamycin, TMP/SMX for Enterococci • 對ampicillin抗藥性: Glycopeptide • Vancomycin-resistant Enterococci(VRE) - • Quinupristin/dalfopristin • Linezoid • Chloramphenicol

  21. 健保規範(Linezolid) • 1.證實為MRSA(methicillin-resistant staphylococcus aureus)感染,且證明為vancomycin抗藥菌株或使用vancomycin、teicoplanin治療失敗者或對vancomycin、teicoplanin治療無法耐受者。 • 2.證實為VER(vancomycin-resistant enterococci)感染,且無其他藥物可供選擇者。 • 3 骨髓炎(osteomyelitis)及心內膜炎(endocarditis)病患不建議使用。 • 4 其他抗藥性革蘭氏陽性菌感染,因病情需要,經感染症專科醫師會診確認需要使用者(申報費用時需檢附會診紀錄及相關之病歷資料)。

  22. Klebsiella pneumoniae • 首選藥物(first choice): cephalosporins • 無併發症感染: cefazolin + aminoglycosides • 嚴重感染合併眼內炎、腦膜炎: third generation cephalosporins為首選藥物 • 不建議使用penicillins類藥物 (Unasyn, augmentin, Timentin, tazocin均不建議使用)

  23. Escherichia coli • Most common possible etiologies: • Cystitis & pyelonephritis • Emphysematous pyelonephritis.(DM) • Acute bacterial prostatitis • 首選藥物(first choice): -lactam antibiotics + aminoglycosides。 • 台灣地區第一線可用cefazolin, 80% 對ampicillin 抗藥性。

  24. Klebsiella sp. & Escherichia coli • In vitro resistant to any of the third generation cephalosporins • Strain produced an extended-spectrum -lactamases (ESBL) • Resistance to all penicillins, cephalosporins & aztreonam 首選藥物(first choice): • Carbapenem • Cephamycins (AmpC -lactamases) • Piperacillin-tazobactam(Tazocin) ( AmpC -lactamases) • Ciprofloxacin • Aminoglycosides

  25. Citrobacter, Enterobacter, Acinetobacter, Serratia, Providencia Species • Hospital acquired pathogens: UTI, ventilator associated pneumonia, septicaemia • Antibiotic susceptibility unpredictable since often multiply antibiotic resistant; need susceptibility test guidance of treatment • Inducible ß- lactamase(Amp C) • 4th cephalosporin(Maxipime, Cefrom), Imipenem-cilastatin, Meropenem

  26. Pseudomonas aeruginosa • Habitat: • GIT of humans & animals, environment • Water; survives in hospitals (In antiseptics) • Obligate aerobe, gram-negative rods, polar flagella, oxidase positive (in contrast to Enterobacteriaceae) • Infections: • Hospital acquired infections: UTI with urinary catheter, pneumonia (cystic fibrosis, ventilator associated), burns infection, septicaemia in immunocompromised (transplantation, oncology, ICU) • Chronic otitis media & externa • Eye infection secondary to trauma

  27. Antipseudomonal Antibiotics: Ceftazidime(Fortum) Cefepime(Maxipime), Cefpirome(Cefrom) Aztreonam Imipenem-cilastatin / Meropenem Piperacillin, Piperacillin-tazobactam(Tazocin) Ticarcillin, Ticarcillin-clavulanate(Timentin) Ciprofloxacin, Levofloxacin Aminoglycosides Pseudomonas aeruginosa

  28. Acinetobacter baumannii • 造成嚴重院內感染之革蘭氏染色陰性菌之一 • 首選藥物(first choice): Imipenem/Cilastatin (Tienam®) / Meropenem • 替代藥物: Ampicillin/sulbactam (Unasyn® ) or sulbactam, Colistin, Tigecycline (Tygacil® )

  29. 健保規範(Tigecycline) • 經細菌培養證實有意義之致病菌且對其他抗微生物製劑均具抗藥性或對其他具有感受性抗微生物製劑過敏,而對tigecycline具有感受性(sensitivity)之複雜性皮膚及皮膚結構感染或複雜性腹腔內感染症使用。 • 複雜性皮膚及皮膚結構感染或複雜性腹腔內感染症,經感染症專科醫師會診,認定需使用者。 • 申報費用時需檢附會診紀錄及相關之病歷資料。

  30. Stenotrophomonas maltophilia • 造成嚴重院內感染之革蘭氏染色陰性菌之一 • 首選藥物(first choice): TMP/SMX ; Co-trimoxazole • 替代藥物 • Moxalactam • Timentin (Ticarcillin-clavulanate) • Ciprofloxacin, Levofloxacin

  31. Is an antibiotic combination appropriate?是否需要合併使用兩種或以上的抗生素? • Febrile leukopenic patient • In infections in which multiple organisms are likely or proved • Synergism • Serial inhibition of microbial growth • One antibiotic enhances the penetration of another • Limiting or preventing the emergence of resistance

  32. Combination Therapy • Tuberculosis • Disseminated Mycobacterium avium complex • Helicobacter pylori • Endocarditis(alpha haemolytic streptococcus, enterococcal ) • Vancomycin-resistant enterococcal disease • Life-threatening infection caused by P. aeruginosa • Empiric treatment ( pneumococcal meningitis; febrile, severely neutropenic host; polymicrobic infection; life-threatening infection with inapparent source)

  33. Gentamicin 加上Gentamicin有加成作用(Synergistic effect) • Enterococci endocarditis(心內膜炎) or bacteremia Gentamicin + Ampicillin or penicillin G • Viridans streptococci endocarditis: Gentamicin + penicillin G • MRSA or S. epidermidis : prosthetic valve endocarditis Vancomycin+Gentamicin • Listeria mononcytogenes: Ampicillin +Gentamicin • Serious Pseudomonas aeruginosa infection Aminoglycosides + Anti-Pseudomonal agents

  34. Pseudomonas aeruginosa • The use of monotherapy with antipseudomonal penicillins or cephalopsorins for patient with severe P. aeruginosa infections can lead to the emergency of antimicrobial-resistant strain. • Combination of 2 antipseudomonalß - lactam antibiotics lacks synergy in animal models & in human • Combination of an aminoglycosides &antipseudomonalß - lactam antibiotics works synergistically against P. aeruginosa & improved clinical outcome. Todd FH et al CID 2000; 31:1349-56

  35. Antifungal agents • Fluconazole (Diflucan) • Itraconazole (Sporanox) • Caspofungin (Cancidas) • Micafungin • Voriconazole (Vfend) • Amphotericin-B

  36. 健保規範(itraconazole) • 1.限用於第一線治療藥物amphotericin-B治療無效或有嚴重副作用之侵入性麴菌症、侵入性念珠菌感染症、組織漿病菌之第二線用藥使用,以14日為限。 • 2.限用於第一線治療藥物無法使用或無效的免疫功能不全及中樞神經系統罹患隱球菌病(包括隱球菌腦膜炎)的病人,並以14日為限。 • 3.符合行政院衛生署核准之適應症,因病情需要,經感染症專科醫師會診確認需要使用者(申報費用時需檢附會診紀錄及相關之病歷資料)。

  37. 健保規範(caspofungin) • 1.限用於其他黴菌藥物治療無效或有嚴重副作用之侵入性麴菌症、侵入性念珠菌感染症之第二線用藥。 • 2.符合衛生署之適應症範圍且經感染症專科醫師認定需使用者,惟治療食道念珠菌感染限用於fluconazole無效或有嚴重副作用者。

  38. 健保規範(micafungin) • 治療16歲以上成人的食道念珠菌感染。 • 預防接受造血幹細胞移植病患的念珠菌感染。

  39. 健保規範(voriconazole) • 無

  40. AMERICAN THORACIC SOCIETY DOCUMENTS:Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare-associated PneumoniaAm. J. Respir. Crit. Care Med. 2005; 171: 388-416

  41. Contents • Executive Summary • Introduction • Methodology Used to Prepare the Guideline • Epidemiology Incidence Etiology Major Epidemiologic Points • Pathogenesis Major Points for Pathogenesis • Modifiable Risk Factors Intubation and Mechanical Ventilation Aspiration, Body Position, and Enteral Feeding Modulation of Colonization: Oral Antiseptics and Antibiotics Stress Bleeding Prophylaxis, Transfusion, and Glucose Control Major Points and Recommendations for Modifiable Risk Factors • Diagnostic Testing Major Points and Recommendations for Diagnosis • Diagnostic Strategies and Approaches Clinical Strategy Bacteriologic Strategy Recommended Diagnostic Strategy Major Points and Recommendations for Comparing Diagnostic Strategies • Antibiotic Treatment of Hospital-acquired Pneumonia General Approach Initial Empiric Antibiotic Therapy Appropriate Antibiotic Selection and Adequate Dosing Local Instillation and Aerosolized Antibiotics Combination versus Monotherapy Duration of Therapy Major Points and Recommendations for Optimal Antibiotic Therapy Specific Antibiotic Regimens Antibiotic Heterogeneity and Antibiotic Cycling • Response to Therapy Modification of Empiric Antibiotic Regimens Defining the Normal Pattern of Resolution Reasons for Deterioration or Nonresolution Evaluation of the Nonresponding Patient Major Points and Recommendations for Assessing Response to Therapy • Suggested Performance Indicators

  42. Executive Summary(1) • Official statement of ATS/IDSA, evidence-based • HCAP: included in the spectrum of HAP/VAP, need therapy of MDR pathogen • Lower resp. tract cultures (LRTCs): quantitative(specificity of diagnosis) or semi-quantitative; non- or bronchoscopical collection for all cases • Negative LRTCs: may stop ABx without ABx changes in the past 72 hrs

  43. Executive Summary(2) • Early, appropriate, broad-spectrum, antibiotic therapy with adequate doses to optimize antimicrobial efficacy • Empiric regimen should include with a different antibiotic class agents than those recently received • Combination therapy for a specific pathogen • Consideration of short-duration (5 days)aminoglycoside, when used in combination with a β-lactam to treat P. aeruginosa pneumonia

  44. Executive Summary(3) • Linezolid: an alternative to vancomycin; may have an advantage for proven VAP due to MRSA (unconfirmed, preliminary data) • Colistin: considered in VAP due to a carbapenem-resistant Acinetobacter species • Aerosolized antibiotics: may have value as adjunctive therapy in VAP due to some MDR pathogens • De-escalation of ABx: should be considered once; according to the results of LRTCs and the patient’s clinical response