1、Pre-ICU training (Antibiotics),馬偕紀念醫院 感染科 郭建峯醫師,台北院區院內感染常見10種致病菌歷年變化,Incidence Rate (),Incidence rate is the number of isolates reported per 1000 patietn days,台北院區院內感染各部位感染發生密度（2007年）,All infections = 1,593,台北院區院內感染各部位分佈圖（2007年）,10.5,%,台北院區院內感染常見的15種致病菌（2007年）,Total 1,717,台北院區院內感染常見的15種致病菌各部位之感染率（20
2、07年）,台北院區院內感染UTI常見的致病菌（2007年）,Total 784,台北院區院內感染LRTI常見的致病菌（2007年）,Total 90,台北院區院內感染SSI常見的致病菌（2007年）,Total 182,台北院區院內感染BSI常見的致病菌（2007年）,Total 583,台北院區院內感染SSTI常見的15種致病菌（2007年）,Total 26,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(Epidem
3、iological data),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?,Staphylococ
4、cus 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 Ri
5、fampicin,Categories of Susceptibility of S. pneumoniae to Penicillin,NCCLS 2001,Streptococcus pneumoniae,Penicillin-sensitive菌株首選藥物(first choice): Penicillin G,Treatment of S. pneumoniae Pneumonia,Penicillin MIC (g/ml) primary alternative1 penicillin 1st cephalosporins (S) ampicillin or amoxicillin2
6、 penicillin (high dose) 3rd or 4th cephalosporins (I) ampicillin or amoxicillin4 3rd or 4th cephalosporins vancomycin or teicoplanin (R) vancomycin or teicoplanin + rifampin or newer fluoroquinolonesThe infectious diseases society R.O.C. 2000,Treatment of Pneumococcal Meningitis,MIC (g/ml) dosagePCN
7、 CTX therapy adults children (/kg)0.12 0.5 penicillin 300,000 u/kg/d 3-400,000 u q4-6h0.12 0.5 Cefotaxime or 2 g q6h 200-225 mg q6-8hCeftriaxone 2 g q12h 100 mg q12-24h1.0 Cefotaxime or 300 mg/kg/d (m.24g) 300 mg q6-8hCeftriaxone 2 g q12h 100 mg q12-24h+Vancomycin 60 mg/kg/d (M.2g) 60 mg q6h2.0 Same
8、 as 1.0 + Rifampin 300 mg q12h 20 mg q12hKaplan SL and mason EO jr. Clin microbiol rev 1998,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, o
9、r other cephalosporins (ceftriaxone;cefotaxime),or newer fluoroquinolones. Not vancomycin。 CNS Infection (Meningitis): Not Penicillin, vancomycin + ceftriaxone (cefotaxime, Cefepime, Cefpirome, Meropenem),Enterococci sp.,E. faecalis, E. faecium Habitat: commensal of human and animal gut Lancefield g
10、roup D, bile resistant Infections - Urinary tract infection- Intra-abdominal sepsis - Biliary tract infection - Endocarditis,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ampicilli
11、n抗藥性: Glycopeptide Vancomycin-resistant Enterococci(VRE) - Quinupristin/dalfopristin Linezoid Chloramphenicol,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 entero
12、cocci)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)。,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(Un
13、asyn, augmentin,Timentin, tazocin均不建議使用),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。,Klebsiella sp. & Esche
14、richia 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 -lactam
15、ases) Ciprofloxacin Aminoglycosides,Hospital acquired pathogens: UTI, ventilator associated pneumonia, septicaemia Antibiotic susceptibility unpredictable since often multiply antibiotic resistant; need susceptibility test guidance of treatment Inducible - lactamase(Amp C) 4th cephalosporin(Maxipime
16、, Cefrom), Imipenem-cilastatin, Meropenem,Pseudomonas aeruginosa,Habitat: GIT of humans 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
17、, pneumonia (cystic fibrosis, ventilator associated), burns infection, septicaemia in immunocompromised (transplantation, oncology, ICU) Chronic otitis media & externa Eye infection secondary to trauma,Pseudomonas aeruginosa,Antipseudomonal Antibiotics: Ceftazidime(Fortum) Cefepime(Maxipime), Cefpir
18、ome(Cefrom) Aztreonam Imipenem-cilastatin / Meropenem Piperacillin, Piperacillin-tazobactam(Tazocin) Ticarcillin, Ticarcillin-clavulanate(Timentin) Ciprofloxacin, Levofloxacin Aminoglycosides,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
19、物: Ampicillin/sulbactam (Unasyn ) or sulbactam, Colistin, Tigecycline (Tygacil ),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。,Stenotrophomonas maltophilia,造成嚴
20、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,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 Synergis
21、m Serial inhibition of microbial growth One antibiotic enhances the penetration of another Limiting or preventing the emergence of resistance,Combination Therapy,Tuberculosis Disseminated Mycobacterium avium complex Helicobacter pylori Endocarditis(alpha haemolytic streptococcus, enterococcal ) Vanc
22、omycin-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),Gentamicin,加上Gentamicin有加成作用 (Synergistic effect) Enter
23、ococci 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
24、infection Aminoglycosides + Anti-Pseudomonal agents,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 antipseudomonal - lactam antibiotics lacks syne
25、rgy in animal models & in human Combination of an aminoglycosides & antipseudomonal - lactam antibiotics works synergistically against P. aeruginosa & improved clinical outcome.,Pseudomonas aeruginosa,Todd FH et al CID 2000; 31:1349-56,Antifungal agents,Fluconazole (Diflucan) Itraconazole (Sporanox)
26、 Caspofungin (Cancidas) Micafungin Voriconazole (Vfend) Amphotericin-B,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)。,健保規範(ca
27、spofungin),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。,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。,健保規範(voriconazole),無,AMERICAN THORACIC SOCIETY DOCUMENTS: Guidelines for the Management of Adults with Hospital-acquired
28、, Ventilator-associated, and Healthcare-associated Pneumonia Am. J. Respir. Crit. Care Med. 2005; 171: 388-416,Executive Summary Introduction Methodology Used to Prepare the Guideline EpidemiologyIncidenceEtiologyMajor Epidemiologic Points PathogenesisMajor Points for Pathogenesis Modifiable Risk Fa
29、ctorsIntubation and Mechanical VentilationAspiration, Body Position, and Enteral FeedingModulation of Colonization: Oral Antiseptics and AntibioticsStress Bleeding Prophylaxis, Transfusion, and Glucose ControlMajor Points and Recommendations for Modifiable Risk Factors Diagnostic TestingMajor Points
30、 and Recommendations for Diagnosis Diagnostic Strategies and ApproachesClinical StrategyBacteriologic Strategy,Recommended Diagnostic StrategyMajor Points and Recommendations for Comparing Diagnostic Strategies Antibiotic Treatment of Hospital-acquired PneumoniaGeneral ApproachInitial Empiric Antibi
31、otic TherapyAppropriate Antibiotic Selection and Adequate DosingLocal Instillation and Aerosolized AntibioticsCombination versus MonotherapyDuration of TherapyMajor Points and Recommendations for OptimalAntibiotic TherapySpecific Antibiotic RegimensAntibiotic Heterogeneity and Antibiotic Cycling Res
32、ponse to TherapyModification of Empiric Antibiotic RegimensDefining the Normal Pattern of ResolutionReasons for Deterioration or NonresolutionEvaluation of the Nonresponding PatientMajor Points and Recommendations for Assessing Response to Therapy Suggested Performance Indicators,Contents,Executive
33、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 sto
34、p ABx without ABx changes in the past 72 hrs,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
35、 a specific pathogen Consideration of short-duration (5 days) aminoglycoside, when used in combination with a -lactam to treat P. aeruginosa pneumonia,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 patients clinical response,
