台湾大学附属医院抗生素使用培训精选文档.ppt

全民健康保險醫院醫療費用審查注意事項,對於以痰之培養結果做為使用高價抗生素者,應注意是否適當,嚴加審查應優先使用第一線抗生素使用抗生素,原則上以同時不超過兩種為限,否則需附相關之微生物學培養結果,抗生素誤用的不良後果,非醫學使用，或醫療時過度使用:-破壞微生物生態平衡，促成抗藥性細菌散佈，後患無窮。抗生素引起之不良反應。不必要之藥費支出，消耗醫療資源。應使用而未使用，或延誤使用:-耽誤病情造成不必要之併發症甚至死亡，有醫療糾紛之危險。為治療併發症需額外之加護病房照護或外科手術，消耗醫療資源。診療方向不正確:,合理的使用抗生素,-是否有足夠的證據使用抗生素-使用抗生素之前是否有做好病原體檢查-那些微生物為可能之致病原-對於已知致病菌，是否仍需使用後線抗生素-需要合併使用抗生素治療嗎-宿主因素，抗生素穿透力-給藥方式(注射或口服)，抗生素劑量，毒性，抗生素使用時間-前次使用抗生素之種類，是否為抗藥性病原,#1.是否有足夠的證據使用抗生素?,全民健康保險藥品給付規定摘錄(2004.7.12),10.抗微生物劑 10.1.抗微生物劑用藥給付規定通則 3.上呼吸道感染病患如屬一般感冒（common cold）或病毒性感染者，不應使用抗生素。如需使用，應有細菌性感染之臨床佐證，例如診斷為細菌性中耳炎、細菌性鼻竇炎、細菌性咽喉炎，始得使用抗生素治療（90/2/1增訂）。,急性上呼吸道感染抗微生物製劑建議治療準則 中華民國感染症醫學會（2002.3.2）,Common cold with mucopurulent nasal discharge does NOT mean bacterial infectionAcute pharyngotonsillitis:(a)Symptoms highly suggestive of streptococcal pharyngitis are:severe sore throat,exudative pharyngitis,and cervical lymphadenopathy(b)Symptoms not suggestive include cough,rhinorrhea,pharyngeal ulcer,diarrhea,and conjunctivitis,Note:,J Microbiol Immunol Infect 2002;35:272,急性上呼吸道感染抗微生物製劑建議治療準則 中華民國感染症醫學會（2002.3.2）,Diagnosis Drug of choice AlternativeCommon cold Acute pharyngotonsillitis:streptococcal penicillin V macrolides,1o cephem,clindamycinAcute sinusitis amoxicillin augmentin,2o oral cephem Acute otitis media amoxicillin augmentin,2o or 3o oral cephemAcute bronchitis Influenza*amantadine(A only)oseltamivir,J Microbiol Immunol Infect 2002;35:272,#2.在使用抗生素之前是否已取得臨床檢體做好病原體培養：革蘭式染色及各種培養?,Advantages and disadvantages of gram smear in Pneumonia,AdvantagesQuick and inexpensiveQuality of sputumAid interpretation of cultures resultsEarly indication of possible etiology,DisadvantagesCriteria for interpretationExperience of lab operatorCorrelates poor with culture results,及早使用抗生素敗血症或敗血性休克的病人。疑似細菌性腦膜炎、急性心內膜炎的病人。白血球缺乏而有發燒的病人。有明顯部位感染情形。病人為老年人、幼童或有免疫機能缺損者院內感染。,經驗性療法(Empirical therapy),可能是嚴重感染症的前驅症兆,Persisted hyperpyrexia 39oCShaking chillsAppearance of skin lesionsChange of mental statusDIC with thrombocytopeniaHemolysisTachypnea,hyperventilation or respiratory alkalosisHypotension,shock,Increased fluid volume requirementSevere localized painMetabolic acidosisOliguria,Modified from Young LS.Fever and septicemia.In:Rubin RH,Young LS.Clinical approach to Infections in compromised host.2nd ed.1994,Thrombosis,DIC,Livedo reticularis,Vascular phenomenon of sepsis,#3.那些微生物為可能之致病原?,951127,951128,Staphylococcus aureusStreptococcus pneumoniaeKlebsiella pneumoniaeLegionella pneumophilia,69 y/o male,smoking for 40 years.,AM:Ampicillin RAMC:Amoxi./Clavu R CZ:Cefazolin RCMZ:Cefmetazole RCTX:Cefotaxime RGM:Gentamicin 10g RAN:Amikacin SIPM:Imipenem SCIP:Ciprofloxacin RFEP:Cefepime RAZM:Aztreonam R,True Pathogen?Colonization?,1.,這是真的嗎?,先確定病原是否有意義,血液或無菌體液培養(腦脊髓液，肋膜積水.).痰液培養：聽診有囉音或敲診有濁音新發生的膿痰或是痰液的顏色改變。血液培養陽性或由bronchial washing或biopsy培養出菌。肺部X光有新增或惡化的浸潤，開洞或肋膜積水。泌尿道培養：泌尿道症狀及尿液培養有大於105菌落/ml。培養出的微生物需小於三種。泌尿道症狀加上WBC esterase或nitrate陽性，或膿尿(10 WBC/HPF)或重複培養出同一之細菌102菌落/ml。傷口培養：必須要有膿液或紅腫熱痛存在，不可只是單純的根據傷口培養結果用藥。,Am J Infect Control 1988;16:128-40.,移生(Colonization),Positive sputum,urine,bile,stool,skin swab culture but without symptoms原則上不建議使用抗生素例外:asymptomatic bacteriuria before urological work up and in pregnancy should be treated,常見的移生污染菌,Coagulase-negative staphylocciStaphylococcus epidermidisViridans streptococciMicrococciBacillus speciesCorynebacterium species Neisseria speciesNonfermentative gram-negative bacilli Acaligenes,Flavobacterium,Sphingomonas.,#4.對於可能致病的微生物，若已知有多種抗生素有效，該選擇何種抗生素?,參考drug of choice Guidelines Costs,肺炎抗微生物製劑建議治療準則 中華民國感染症醫學會（1999.3.7）,Drug of choice AlternativeCommunity-acquired pneumonia Adults(60 y)mild-moderate PCN or 2o cephem Unasyn/Aug/FQ macrolides/tetracyclines severe 3o cephem AG Timentin/Tazocin/4ocephem macrolides/FQ AG macrolides Aspiration pneumonia PCN or clindamycin Unasyn/Aug/cefoxitin/cef-metazole/PCN+AnergynHospital-acquired pneumonia mild-moderate 2o or 3o cephem or Timentin/Tazocin/Azactam/Unasyn/Aug AG FQ AG,J Microbiol Immunol Infect 1999;32:292-294.,#5.需要合併使用抗生素治療嗎?,Antibiotics Combination-Synergistic effects,Kuo LC,et al.Clin Microbiol Infect 2007;13:196-8.,MDR-Acinetobacter baumannii bacteremia,加成作用(synergism)多重細菌感染(如腹腔內、骨盆腔感染)避免多重抗藥性菌株出現,合併抗生素使用之優點,合併抗生素使用之缺點,藥物毒性機會增加高抗藥性菌株移生而造成另一波感染拮抗作用花費較高,Enterococci or pneumococciPenicillin+GMVancomycin+(?GM)or rifampinPCN+FQMRSAVancomycin(or teicoplanain)+GM or RIFLinezolid+GM or RIF,For Drug-resistant GPC,for Pseudomonas,drug-resistant E.coli,KP,ProteusPrevent emergence of resistant mutantAnti-pseudomonal b-lactams+GM/AMKFQs+b-lactams or FQs+carbapenemsFQs+aminoglycosides-still controversial!,For Drug-resistant GNB,#6.宿主因素,Who are you dealing with?,Old vs.youngCommunity vs.HospitalizedSubstance abuse,prosthesis in placeBarrier disruption and anatomic abnormalyPre-existent medical or surgical illnessImmune-competent vs.-compromizedtypes of immune suppression(steroid)or therapies administeredSeverity of the diseases.,泌尿道感染抗微生物製劑建議治療準則 中華民國感染症醫學會（2000.3.11）,Drug of choice AlternativeAsymptomatic bacteriuria non-pregnant*pregnant 1o or 2o cephem amoxicillin(for enterococci)Acute bacterial cystitis non-pregnant TMP/SMZ,Dolcol FQ,amoxicillin pregnant 1o or 2o cephem amoxicillin Acute uncomplicated pyelonephritis(APN)1o or 2o cephem ampicillin,AG Acute prostatitis 3ocephem or FQ TMP/SMZ,J Microbiol Immunol Infect 2000;33:271-272.,#7.藥物動力學哪種給藥方式(靜脈注射或口服)較為合適,Time-Dependent Antibiotics,AUC/MIC 125,40 50%,Concentration-Dependent Antibiotics,Cmax/MIC 8-12 X,Once-daily Dose of Aminoglycosides,Characteristics in pharmacology:Concentration-dependent bacterial killingPost-antibiotic effect(PAE):neutrophil dependentAdaptive resistance of bacteria during prolong exposureToxicity more related to long exposure time and less related to transient high serum levelDosage:(IBW)Gentamicin,Tobramycin,Netilmicin:3-5 mg/kg/day Amikacin,Streptomycin:12-15 mg/kg/daySerum level monitor 72 hrs after use:check Trough level only!adjust dosing interval!No loading dose,Not to use once daily dose,CcR20%TBSA)Pregnancy*,children*Neutropenic feverEndocarditis;enterococciLiver cirrhosis with decompensation*Avoid aminoglycosides,#8.抗生素合適的劑量,Loading Dose of Vancomycin,Suboptimal conc.of Vancomycin with 7.5 mg/Kg Q6h during first 48 hoursLoading dose with Vancomycin 25 mg/Kg(約 1-1.5 g)increase drug concentration during 24 48 hrsFor difficult MRSA infections Trough of Vancomycin 15 ug/mL,Wang JT,et al.J Antimicrob Chemother 2001,Teicoplanin 成年人臨床使用劑量,針對敗血性關節炎、重度燒燙傷或心內膜炎者起始劑量：12 mg/Kg(約800毫克)維持劑量：靜脈注射12 mg/Kg，給藥間隔視腎功能而定,38,With/Without Loading Dose,JAC 2003;51:9715.,Empiric Antibiotic for Nosocomial Pneumonia with Multidrug Resistant Bacteria,Anti-pseudomonal b-lactamsCefepime 1-2g q8-12h Cefpirome 1-2g q8-12hCeftazidime 2g q8h Imipenem 500mg q6h-1g q8hMeropenem 1g q8h q6hPiperacillin-tazobactam 4.5g q6h Aztreonam 2 g q6-8h,*Doses are based on normal renal and hepatic function of adult(US-HAP Guidelines 2005),AminoglycosidesGentamicin5-7mg/kg/day*Tobramycin5-7mg/kg/day*Amikacin20mg/kg/day*QuinolonesLevofloxacin750mg qdCiprofloxacin400mg q8h,Indication of maximal dose,Better tissue penetrationMeningitis and CNS infection EndocarditisSeptic arthritis and osteomyelitisEmpyemaSeptic shock or other life-threatening infectionsBorderline susceptible pathogens,依腎功能調整抗生素劑量,Tetracyclines,gentamicin,sulfonamides,polymyxins,vancomycin,penicillins(oxacillin除外),cephalosporins,acyclovir.加重因子:脫水,年紀大,同時合併腎毒性藥物,本身腎功能不好,低體重.可給予充足水份減少腎毒性腎毒性:creatinine上升0.5mg/dl.不一定會水腫或乏尿.,Ideal Body Weight vs.Real Body Weight IBW=(BH-80)x 0.7 in male patients IBW=(BH-70)x 0.6 in female patients*Estimated Ccr=,(140-Age)x BW 72 x Cre,Calculating the dosage using IBW and estimated Ccr,*0.85 in female patients Use IBW in obese patients,#9.抗生素在培養結果出來後是否需要改藥或進一步調查?,De-Escalation Therapy(降階治療),減少不必要的抗生素以避免抗藥性發生,Initial adequate broad-spectrum therapy follow by antibiotic de-escalation,給予足夠的抗生素以改善患者預後,2,一旦培養出較不抗藥之致病菌則應考慮降階治療,抗生素為何無效,Delay in initiation of appropriate therapyWrong diagnosis:non-infectious inflammatory process,non-bacterial infectionMisinterpretation or errors derived from susceptibility results:in vitro discrepancy;inappropriate interpretationInadequate concentration drugs at site of infection:inadequate dose,drug interaction,poor delivery(vascular diseases,obstruction,permeability barrier),抗生素為何無效,Decreased activity at site of infection:pH(aminoglycoside)Biofilm formation,decreased metabolic activity of microorganism(vegetation,foreign body)Accumulation of pus,presence of dead bone or necrotic tissueHost factors:immunodeficiencyDevelopment of drug resistanceSuperinfection or multiple infections,#10.抗生素使用的時間,抗生素治療期間,一般感染症(肺炎、腦炎、腹膜炎、膽管炎、骨盆腔炎、手術傷口血流,呼吸道,上泌尿道,腸胃道感染)10-14天下泌尿生殖道感染或輕微皮膚組織感染 3-7天骨骼,心臟血管,內臟膿瘍(如肝膿瘍等)4-6 週特殊細菌,如結核菌治療 6-12 月宿主免疫功能,抗生素障礙及是否有異物植入,須依個別臨床狀況而定,額外的問題:錢,抗生素費用被刪除的問題,健保審查藥物費用剔退約佔三分之一以上。其中絕大部分是抗生素！抗生素費用被刪除的最重要原因是病歷書寫不夠清楚，看不出為什麼用藥、用此藥？為什麼改藥？而不是因為一開始就用後線抗生素。第一線抗生素被刪除的費用並不少於後線抗生素。,內科之健保核刪金額項目,藥費為最大項目(一般:42.2%;高額:62.4%);而抗生素核刪金額又為佔藥費核刪金額之最大項目(60-90%)其中大多數為”高價抗生素或兩週以上的抗生素使用”常見核減理由:“適應症/種類/用量(天數)不符合該品項藥品給付”或“依據病歷記載及病況不足以支持實施本項治療”在使用高價抗生素的病例中,超過九成未能在開立該抗生素的24小時內於病歷中適當詳實的記載(1)臨床評估結果;(2)為何要用抗生素;(3)為何要使用此抗生素,避免抗生素被核刪的病歷書寫,為什麼需要住院、為什麼需要使用抗生素本次住院相關的可能診斷及潛在疾病住院時的情況、與診斷相關之異常理學檢查發現及生化實驗結果,必要時以繪圖表示為什麼用此抗生素、為什麼改藥藥物名稱,劑量,頻率,輸注途徑,過敏及副作用診斷及治療計劃適當的時機是否有照會感染科醫師對藥物治療的臨床反應及併發症,如何避免抗生素費用被健保剔退？,呈現感染確實存在，必須經驗性使用抗菌藥物。WBC異常增加(減少)、分類異常、CRP增加。有發燒。（有感染也不一定會發燒）有其他症狀：例如咳嗽、濃痰、呼吸急促等理學檢查有徵候：rales、紅、腫、熱、痛其他：CXR、U/A、CSF、aspirates、pus培養結果照相、繪畫！每一、兩天詳細描寫徵候、症狀、數值的升降，改善惡化。用抗生素者，至少每五到七天記載需要繼續用藥的理由。換用抗生素者，一定要寫換藥的理由。,Daily Cost of Antibiotics,Tigecycline約3510元Imipenem ertapenem約4170元 約1600元 Imipenem+high dose sulbactam約6002元Vancomycin+imipenem約5386元,