《抗生素简介》PPT课件.ppt

抗 生 素 簡 介,“The future is not what it used to be”-Yogi Berra,細菌抗藥性產生,有效治療病人,抗生素,抗生素Antibiotics ： 是指一些由黴菌所產生的物質，能抑制細菌的生長。人類利用這種物質稍加改變，而用來對抗細菌對人類的侵襲。 Antimicrobial agents: 能抑制生長或殺死對人類能造成疾病的微生物（寄生蟲、黴菌、細菌、立克次體、病毒）的製劑（天然或合成）,Chinese Emperor Shen Nung (神農氏) wrote a treatise on the use of chang shan(常山） in fever.,2735 BC,History of infectious diseases,抗生素的歷史,約2500年前中國用黃豆發霉發酵後製成膏藥用於治療疔瘡等感染 Early 1900s: arsenic and bismuth for syphilis 1929 Fleming(佛來明)：實驗室受黴菌(Penicillium)污染而發現。 1940年代：純化後製成第一種用於人類之抗生素-青黴素(Penicillin),細菌的分類,革蘭性陽性菌 葡萄球菌 Staphylococcus： MSSA, MRSA (methacillin resistant S. aureus) 鏈球菌 Sreptococcus Group A, B, C, G. 腸球菌 Enterococcus 革蘭性陰性菌 腸菌屬：E. coli, Klebsiella pneumoniae 綠膿桿菌 Pseudomonas aeruginosa; Acinetobacter 厭氧菌 Bacteroides fragilis,如何選擇抗生素,病人 年齡、原本疾病。 疾病：感染部位 細菌 抗生素 效果 副作用 價格,發燒、休克 意識不清,感染？,不需使用抗生素,細菌、病毒 黴菌或其他,感染部位？ 泌尿道、呼吸道,取得適當檢體做培養 Urine, Blood, Sputum.,有抗微生物藥劑 可有效治療？,選擇適當 抗微生物藥劑,否,是,是,否,臨床上抗生素用在下列三方面,1. Empirical Therapy(經驗式療法)：治療由經驗推想的病原菌造成的感染。 2. Well-known infection：治療已知致病病源體的感染症。 3. Prophylaxis：預防可能發生的感染症。,抗生素使用原則,1. 由各項臨床資料來判斷病人是否需要使用抗生素。 2. 若決定使用抗生素，是否已採取適當的、足夠的檢體送檢。 3. 此次感染最有可能的致病菌是什麼？ 4. 對可能或已確定的病菌，最佳的藥物是什麼？ 5. 是否需要合併使用兩種以上的抗生素？ 6. 病人本身有無須特別考量的問題？ 7. 經由何種途徑給藥是最佳的給藥方式？ 8. 應該給予多少劑量？ 9. 細菌培養得到結果後，初始之抗生素是否要做調整？ 10. 應該要給予多久？,1. 由各項臨床資料來判斷病人是否需要使用抗生素。,有明顯的細菌感染症狀 蜂窩組織炎、傷口感染 肺炎：膿痰、高燒、X光片 泌尿道感染：頻尿、腰酸、高燒、濁尿 由臨床資料判斷可能有細菌感染 明顯的畏寒、發燒、白血球增多 病情危急時 疑似有敗血症 白血球缺乏而有發燒時 疑有腦膜炎或急性心內膜炎,2. 若決定使用抗生素，是否已採取適當的、足夠的檢體送檢。,細菌培養 血液、痰液、尿液 嗜氧、厭養菌 結核菌、黴菌 抹片染色 Gram stain Acid Fast stain Indian ink stain,3. 此次感染最有可能的致病菌是什麼？,感染部位 UTI: E. coli Pneumonia: Streptpcoccus pneumoniae Cellulitis: S. aureus, Group A sreptococcus 格蘭氏染色 (Gram +/-) 病人之年齡、原本疾病 流行病學資料,4. 對可能或已確定的病菌，最佳的藥物是什麼？,該致病菌的首選藥物 S. aureus: oxacillin, cephalosporin MRSA: Vancomycin, Teicoplanin S. pyogenes, S. pneumoniae: penicillin G K. pneumoniae, E. coli: Cephalosporin Pseudomonas aeruginosa: anti-pseudomonas penicillin or cephalosporin Legionella pneumophila: erythromycin Mycoplasma penuomia: eythromycin,4. 對可能或已確定的病菌，最佳的藥物是什麼-2？,是否有對抗生素過敏的病史 抗生素對組織的穿透性 CSF: BBB的穿透性 膽道感染：肝臟排泄 泌尿道感染：腎臟排泄 藥物可能的副作用 孕婦、兒童 殺菌性(bactericidal)或抑菌性藥物(Bacteriostatic) 廣效性(broad-spectrum)或窄效性藥物(narrow-spectrum) 藥物的費用,5. 是否需要合併使用兩種以上的抗生素？,需合併兩種以上抗生素的情況有 敗血症或白血球過低的病人 多種細菌感染 需對致病菌有更強的殺菌力時 為了避免抗藥細菌產生 常用之合併用法 Penicillin + gentamicin: streptococci, enterococci Pipril or Fortum+ aminoglycoside: Pseudomonas aeruginosa -lactamase inhibior+-lactam: drug resistant bacteria,6. 病人本身有無須特別考量的問題？,腎功能情形 肝功能情形 病人的年齡 老年人、嬰幼兒 藥物過敏史 先天遺傳上的問題 G-6-P-D,7. 經由何種途徑給藥是最佳的給藥方式？,靜脈注射 肌肉注射 有出血傾向或休克狀態（因肌肉循環不佳、藥物吸收不良）避免使用 口服投予,8. 應該給予多少劑量？,病人年齡 老年人、嬰幼兒 體重 腎功能 肝功能 PK/PD,9. 細菌培養得到結果後，初始之抗生素是否要做調整？,根據培養盡可能改用較窄效、傳統、無副作用、價錢便宜的藥物。 病人在療程中的變化： 是否退燒 病情時否已獲得改善 是否需要考慮其他致病菌 膿瘍是否已經引流,如何評估抗生素的使用效果,臨床： 發燒減退 生理狀況改善： - 血壓穩定、呼吸速率改善、意識狀況進步、痰量減少。 全身狀況改善： - 胃口進步、疼痛減少、活動力增加。 實驗室診斷： WBC count (血液、CSF、Ascites、Pleural effusion etc.) 放射線等檢查 (CxR, CT, MRI, abdominal echo, Bone scan gallium scan etc.) CRP, ESR,抗生素治療未達預期效果原因,1. 診斷錯誤 2. 抗生素的劑量或給藥間隔有誤 3. 藥物吸收不足或代謝增加 4. 膿瘍未引流或異物未移除 5. 感染部位的抗生素濃度不夠 6. 併用抗生素有拮抗作用 7. 出現具抗藥性或耐受性的菌株 8. 另有不同的細菌造成繼發性感染,10. 應該要給予多久？,Meningitis:7-14days Pneumonia:10-14days Lung/liver abscess:4-6weeks Empyema:4-6weeks Infective endocarditsi:4-6weeks Pyelonephritis: 14-21dys Cystitis:3-7days,抗生素分類,Beta-Lactam Penicillins Cephalosporins and Cephamycins Carbapenem Beta-lactamase inhibitors Aminoglycosides gentamicin, netilmicin, tobramycin, amikacin Quinolone,Others Tetracycline Glycopeptide Macrolide, Clindamycin Sulfonamide and Trimethoprim Metronidazole Rifampicin Anti-TB, fungal, virus agent,-lactam antibiotics,Penicillins, Cephalosporins, Monobactams, Carpapenems,Classification of Penicillins,Natural penicillins Penicillin G, Penicillin G benzathine, penicillin V Aminopenicillins Ampicillin, Amoxicillin Penicillinase-resistant penicillins Methicillin, Oxacillin, cloxacillin, dicloxacillin Carboxypenicillins Piperacillin Penicillins Combined with Beta-lactamase inhibitor Augmentin, Unasyn, Timentin, Tazocin,Natural penicillin,有效範圍 對革蘭氏陽性菌中的 Streptococcus及 Enterococcus有效；但台灣地區的Streptococcus pneumoniae 50-70%具抗藥性。 Treponema pallidum（梅毒）有效。 對厭氧菌中的革蘭氏陽性菌如Peptococcus, Peptpstreptococcus, Clostridium tetani（破傷風）, C. perfringens等有效。 MSSA, MRSA均無效。 Penicillin(3MU/vial), Benzathine Penicillin (Retarpen 2.4MU),Aminopenicillins,有效範圍： 對革蘭氏陽性菌中的 Streptococcus及 Enterococcus有效；但對MRSA, MSSA無效。 對簡單的革蘭氏陰性菌如E. coli, Proteus有效，但台灣地區的抗藥性超過50%。 對其他革蘭氏陰性菌及厭氧菌無效。 Amoxicillin (Hiconcil 250,500mg, 25mg/ml); Ampicillin (Servicillin, Pentrexyl),Extended-spectrum penicillins,有效範圍： 此類藥物對更多的革蘭氏陰性細菌有效，包括簡單的E. coli, Klebsiella, Proteus，以及部分較困難的陰性腸內菌，對Pseudomonas aeruginosa亦有效。 對Streptococcus及Enterococcus亦可有效。 但對MRSA及MSSA則仍無效。 Sulbenicillin (Lilacillin), Piperacillin (Pipril),Penicillinase-Resistant Penicillin,有效範圍： 對MSSA最為有效，對Streptococcus也有效，但較Natural Penicillin差。 對MRSA, Enterococcus, 即Gram negative 無效。 Dicloxacillin (Diclocin), Oxacillin (Prostaphlin): 500mg/vial, 1-2g q4-6h,Beta-lactamase inhibitor,-lactamase inhibitor:clavulanic acid, sulbactam ,tazobactam. 上市之商品有： Unasyn:Ampicillin+Sulbactam Augmentin:Amoxicillin+Clavulanic acid Timentin: Ticarcillin+Clavulanic acid Tazocin: Piperacillin+Tazobactam 細菌因製造-lactamase而具抗藥性時，可藉此恢復抗菌力 對厭氧菌效果更加強。,Chemical structures of ampicillin, sulbactam and sultamicillin1,2,S,N,O,O,O,O,CH2,O,C,CH3,S,O,N,CONH,H,NH2,C,O,Sultamicillin,N,S,NH2,CHCONH,H,CH3,CH3,COOH,O,Ampicillin,N,S,O,O,CH3,CH3,COOH,O,Sulbactam,Esterase,1. Campoli-Richards DM, Brogden RN. Drugs 1987;33:577609. 2. Friedel HA et al. Drugs 1989;37:491522.,CH3,C,O,CH3,CH3,H,Mechanism of action of -lactamase inhibitors,Williams JD. Int J Antimicrob Agents 1999;12(Suppl 1):S3S7.,Inhibitor inactivates -lactamase,-Lactam can reach penicillin-binding protein (PBP),-Lactam alone may be degraded by -lactamase,PBP,PBP,PBP,With inhibitor,Without inhibitor,-Lactam,-Lactamase inhibitor,-Lactamase,In vitro activity versus key Gram-positive organisms,Susceptibility (% isolates)a Ampicillin A/S Staphylococcus aureus, OR (n=110)1 NR 58.2 Staphylococcus epidermidis, OR (n=80)1 NR 98.8 Streptococcus pneumoniae, Pen-S (n=53)2 0.03b 0.03b Streptococcus pyogenes (n=294)3 0.25b 0.25b A/S, ampicillin/sulbactam; OR, oxacillin-resistant isolates; NR, not reported; Pen-S, penicillin-susceptible isolates. aUsing NCCLS breakpoints. bNo NCCLS breakpoints available; data presented as MIC90 (g/ml).,1. Marshall SA et al. Diagn Microbiol Infect Dis 1995;21:15368. 2. Johnson DM et al. Diagn Microbiol Infect Dis 1996;25:13741. 3. Cullman W. J Chemother 1995;7:215.,In vitro activity versus key Gram-negative organisms,Susceptibility (% isolates)a Ampicillin A/S Haemophilus influenzae, -lac+ (n=35)1 0.0 84.0 Moraxella catarrhalis (n=111)1 16b 0.25b Klebsiella pneumoniae (n=319)2 7.2 89.3 Klebsiella oxytoca (n=75)2 0.0 88.0 Proteus mirabilis (n=196)2 93.4 99.5 Escherichia coli (n=1354)2 62.3 79.0 Acinetobacter spp. (n=70)2 17.1 95.7 Pseudomonas aeruginosa (n=569)2 1.8 5.3 A/S, ampicillin/sulbactam; -lac+, -lactamase-producing isolates. aUsing NCCLS breakpoints. bNo NCCLS breakpoints available; data presented as MIC90 (g/ml).,1. Smayevsky J et al. Diagn Microbiol Infect Dis 2000;37:2614. 2. Marshall SA et al. Diagn Microbiol Infect Dis 1995;21:15368.,In vitro activity versus key anaerobic organisms,MIC90 (g/ml) Species Ampicillin A/Sa Bacteroides fragilis 100256 48 Other Bacteroides fragilis group species 256 16 Bacteriodes thetaiotamicron 25 3.1 Bacteroides vulgatus 25 6.3 Clostridium difficile 4 4 Fusobacterium spp. 32 2 Peptostreptococcus spp. 8 1 A/S, ampicillin/sulbactam aMIC90 based on ampicillin concentration,Ednie LM et al. Antimicrob Agents Chemother 1998;42:5962.,Summary,Broad-spectrum antimicrobial activity Gram-positive aerobes Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes Gram-negative aerobes Haemophilus influenzae, Moraxella catarrhalis, Enterobacteriaceae (Klebsiella pneumoniae, Enterobacter spp., Proteus spp., Escherichia coli) Anaerobes Bacteroides fragilis, Bacteroides spp., Clostridium, Fusobacterium and Peptostreptococcus spp.,Piperacillin-tazobactam(Tazocin) 抗菌範圍,Gram (+): 大部分有效但下列無效 MRSA, MRSE Penicillin resistant streptococcus Ampicillin resistant enterococcus Gram (-): Enerobacteriae: E. coli, P. mirabilis, K. pneumoniae H. influenzae, B. catarrhalis Pseudomonae aeruginosa 多重抗藥性G(-) bacilli Anaerobes,Dosage,Amoxicillin-Clavulanic aicd:Augmentin 600mg/vial, 1(875/125)g/tab, 457(400/57)mg/5ml IV: 1.2g q6hrs, PO: 1# q12hrs, 40-45mg/kg/day Ampicillin-Sulbactam:Unasyn 1.5gm/vial 1.5-3gm q6hrs Piperacillin-Tazobactam: Tazocin 2.25gm/vial 2.25-4.5 q4-6hrs,Allergic reactions to Penicillins,Immediate reaction(2-30min) Erythema or pruritus Urticaria Angioenema Wheezing, rhinitis Hypotension or shock Accelerated ractions(1-72hr) Eyhthema or pruritus Urticaria Angioedema Laryngela endema Wheezing, rhinitis,Late reaction(72hrs) Morbilliform eruptions Uritcaria-agioedema Urticaria-arthralgia Serum sickness Less common reaction Immune hemolytic anemia Pulmonary infiltration with eosinophilia Interstitial nephritis Granulocytopenia Thrombocytopenia Drug fever Hypersensitivity vasculitis Erythema multiform Drug-induced systemic lupus erythematosus,Cephalosporin (Cephem) 頭芽孢菌素,此類藥物的正確名稱為cephem類 依結構再分為 cephalosporin(對厭氧菌無效) cephamycin(對厭氧菌有效) 依抗菌範圍分為第一、二、三及第四代,第一代Cephalosporins,有效範圍： 以革蘭氏陽性細菌為主：MSSA、Streptococcus 部分簡單的革蘭氏陰性桿菌：E. coli, Klebsiella, Proteus等。 所有的cephalosporin對腸球菌(Enterococcus)均無效。 Cephalothin、 Cephalexin (Keflex)、 Cefadroxil (Duracef)、 Cephaloridin、Cephradin (Lofadine, Recef-A, U-save, Lacef )、Cefazolin (Cefamezin, Winzolin)等。,第一代Cephalosporins,Routine surgical prophylaxis Methicillin-susceptible S. aureus infection An alternative agents for penicillin-susceptible S. pneumoniae, S. pyogenes, Viridans streptococci. Community-acquired gram-negatives pathogen such as E. coli, K. pneumoniae. Cellulitis, community acquired pneumonia UTI, mild acute cholecystitis.,第二代Cephalosporins True cephalosporin,有效範圍： 對革蘭氏陰性細菌的活性增加如E. coli, Klebsiella, Proteus，對H. influenzae也有效。 對革蘭氏陽性細菌中的MSSA較第一代差，對Streptococcus大致有效。 對MRSA及Enterococcus無效。 Cefaclor (Keflor)、Cefotiam (Pansporin)、Cefuroxime (Zinacef, Zinnant): 0.75-1.5gm q6-8hrs,第二代Cephalosporins True cephalosporin,UTI:尤其是可能或已知對第一代具抗藥性 Community pneumonia COPD with 2nd infection. Cefuroxime不建議用來治療腦膜炎,第二代Cephalosporins cephamycin,有效範圍： 對革蘭氏陰性細菌的活性增加如E. coli, Klebsiella, Proteus，對H. influenzae也有效。 對革蘭氏陽性細菌中的MSSA較第一代差，對Streptococcus大致有效。 大部分的厭氧菌有效 對MRSA及Enterococcus無效。 Cefoxitin (Mefoxin, Lofatin)、Cefmetazole (Metacin): 1g q6-8hrs,第二代Cephalosporins cephamycin,Intraabdominal infections Peritonitis(原發性或次發性如盲腸炎破裂） Intraabdominal abscess Pelvic inflammatory disease, tuboovarian abscess Soft tissue infections Pressure sores Diabetic foot infections Aspiration pneumonia,Unasyn和2oCephalosporin的比較,第三代Cephalosporins non-anti-Pseudomonas agent,有效範圍 具更強的對革蘭性陰性細菌的活性，對簡單的及較困難的陰性菌均有效。 對MSSA無效，但Streptococcus則仍具效力。 對MRSA及Enterococcus仍無效。 對Pseudomonas無效 Cefixime (Cefspan)、Cefpodoxime (Banan)、Cefotaxime (Claforan)、Ceftriaxone (Rocephin)、Ceftizoxime (Epocelin)、*Flomoxef (Flumarin),第三代Cephalosporins non-anti-Pseudomonas agent,Meningitis Salmonella infection Gram negative Sepsis Gonorrhea Severe intraabdominal infection: Flomoxef Drug resistant Gram negative bacilli,第三代Cephalosporins Anti-Pseudomonas agent,有效範圍 具更強的對革蘭性陰性細菌的活性，對簡單的及較困難的陰性菌均有效。 對MSSA無效，對Streptococcus效果差。 對MRSA及Enterococcus仍無效。 對Pseudomonas有效。 Cefoperazone (Cefobid)、Ceftazidime (Fortum),第四代Cephalosporins,有效範圍： 具更強的對革蘭性陰性細菌的活性，對簡單的及較困難的陰性菌均有效。 對MSSA，Streptococcus均有效。 對MRSA及Enterococcus仍無效。 對Pseudomonas有效。 Cefepime (Maxipime), Cefpirome,Monobactam,Aztreonam (Azactam) 效力類同於：Anti-pseudomonas第三代cephalosporin 但對所有格蘭氏陽性菌無效。 對Penicillin or Cephalosporin無交叉過敏性。 Azactam 1-2 gm q8hrs.,Carbapenem,Imipenem (Tienam), Meropenem (Mepem) 對各種格蘭氏陽性陰性菌及厭養菌均有效。 但MRSA, 腸球菌, Stenotrophomonas maltophilia, Burkholderia cepacia具抗藥性。,Tienam,Imipenem-cilastatin(250/250, 500/500mg) Cilastatin: 避免imipenem被腎臟代謝 維持imipenem的濃度 減少imipenem的腎毒性 Dosage 500mg q6-8hr Side effect: Seizure 1% Renal insufficiency Head injury, meningitis, seizure history patients.,Meropenem,Activity & Clinical use similar to Tienam 無腎毒性不需combine with “cilastatin” 500mg-1g q6-8hrs 較不易發生seizure,Aminoglycoside,抗菌範圍,Gram(-) Enterobacteriaceae:E. coli,P. mirabilis, K. pneumoniae P. aeruginosa Other Gram(-) bacilli Gram(+):輔助治療(+-lactam or quinolone) S. aureua Enterococci Viridans streptococi,Aminoglycoside,臨床上主要是針對革蘭氏陰性菌，包括腸內菌及P. aeruginosa等之較具抗藥性的細菌。 對陽性菌，通常合併其他抗革蘭氏陽性菌之抗生素使用，可加強殺菌力。如MSSA,viridans Streptococcus, Enterococcus的感染。 對H. influenzae及厭氧菌是無效的。,製劑,Gentamicin (GM): Better for Serratia spp. Netilmicin (Netromycin) Tobramycin(Tobra): for P. aeruginosa Amikacin (Amikin): for drug resistant Streptomycin: for TB Isepamicin: Exacin 200mg/vial,Toxicity,Renal toxicity Proximal tubule 5-10% Concomitant drug use: vancomycin, amphotericn B hypotension Ototoxicity Auditory toxicity:2-14% hearing loss Vestibular:1-3%, dizziness, vertigo Neuromuscular weakness Myasthenia gravis,Dosage,Gentamicin, Tobramycin, Netilmicin Loading dose:2mg/kg Maintenance dose: 1.5-1.7mg/kg q8h Amikacin Loading dose: 7.5mg/kg Maintenance dose 15mg/kg/day Exacin 400mg QD-q12hrs,Single (Once)-daily dose,Concentration-dependent killing of bacteria Post-antibiotics effect (PAE) Nephrotoxicity: less toxic Gentamicin, Tobramycin, Netilmicin:5-7mg/kg/day Amikacin: 15mg/kg/day,Not advised for SDD,Renal insufficiency: Ccr 20% body surface area) Ascites Severe sepsis symptom Cystic fibrosis,Neonates/children Pregnant Endocarditis Hepatic diseases,Fluoroquinolone,特點,3rd and 4th generation enhanced gram-positive and anaerobic activity Fluoroquinolones的優點 broad spectrum of antimicrobial activity excellent bioavailability good tissue penetration long serum half-life few side effect use these agents prudently and minimize the development of resistance,Structure,In vitro activity: Critical structure: Carboxy group at position C-3 and Keto group at C-4 All new agents contain a fluorine at C-6 C-7 and C-8 substitutions significantly change the antimicrobial activity, and pharmacokinetics and metabolism of there compounds.,Mechanism of Action,Interfere with DNA synthesis by inhibiting DNA gyrase, inhibiting DNA supercoiling. They inhibit the activity of DNA gyrase, a bacterial enzyme essential for DNA replication. And they promote gyrase-mediated double-stranded DNA breakage at specific sites.,1st generation,Nalidixic acid, Cinoxacin Enterobacteriaceae: E. coli, K. pneumonia. P. mirabilis 易產生抗藥性 用於單純下泌尿道感染 Negacid(500mg) 1-2#bid-qid,2nd generation,Norfloxacin, ciprofloxacin, ofloxacin 抗菌範圍 G(-) bacilli, 包括P. aeruginosa Some G(+): S. aureus Mycoplasma, Rickettesia, Mycobacterium, Legionella,Norfloxacin,UTI, acute prostatitis, travel diarrhea Less anti-pseudomonas effect Baccidial(100mg) 2# bid,Ciprofloxacin,對P. aeruginosa效力最強的Quinolone For osteomyelitis, UTI, Pneumonia 200-400mg q12hrs 2#-3# bid po (1#=250mg) 空腹服用,3rd generation,Levofloxacin, sparfloxacin, gatifloxacin 加強對Gram(+)的作用，尤其是S. pneumoniae Levofloxacin Oflxacin的新一代產品 Cravit(100mg):5#QD,4th generation,Moxifloxacin, Trovafloxacin,Moxifloxcin,Moxifloxcin,Moxifloxcin,健保規定 1. 現用於成人(十八歲以上)之慢性支氣管炎的急性惡化或社區性肺炎。 2. 每日限使用一粒(400mg)，使用期間以不超過十天為原則。,Side effects,Gastrointestinal symptoms: 5% such as nausea and vomiting Allergic reactions: rash, urticaria, and phototoxicity: 1-2% Lomefloxacin and sparfloxacin had higher rate of phototoxicity. CNS symptoms: can occur in 1-4% patients headache, slight dizziness, mild sleep disturbance, alteration of mood with agitation, anxiety, or depression. Seizures had been reported The use NSAID and enoxacin had increase CNS side effect In Psychotic pt and convulsion should be avoided QT prolongation wih orsades de pointes: sparfloxacin, grepafloxacin and moxifloxacin. Tendon rupture: achilles tendon most common followed by hand and shoulder. more common in 50y/o age with steroides usages. at the first sign of tendon pain or inflammation, quit quinolone.,Precaution in use,Do not use in patients with history allergic to quinolones Avoid use in children (18y/o), except - cystic fibrosis - n special circumstances Avoid in pregnancy and nursing mothers Drug interaction: - do not take with antacids, multivalent metal cations - Monitor theophylline levels Caffeine Warfarin Cyclosporine,Glycopeptides,Vancomycin Teicoplanin,抗菌範圍,只對Gram(+)有效 Staphylococci species Streptococci species Streptococcus pneumoniae Enterococci species Corynebacterium diphetheriae Clostridium difficile,臨床使用,具抗藥性的Gram(+)感染 MRSA Coagulase negative Staphylococci Ampicillin-Resistant Enterococci Penicillin-Resistant S. pneumoniae 對-lactam過敏的Gram(+)感染 如Infective endocarditis, meningitsi, bacterema, UTI. Pseudomembranous colitis 口服，第二線用藥。,Toxicity of Vancomycin,Ototoxicity Nephrotoxicity 不常發生 併用Aminoglycosides或腎功能異常患者需小心追蹤 Peak 20-40ug/ml, Trough 5-10ug/ml Red man syndrome Infused too rapidly Flushing of the face, neck, pruritus or hypertension. Rashes, Phlebitis, Fever, Neutropenia,Toxicity of Teicoplanin,Allergic reactions in 2.6% (rashes are said to be more common with higher doses) the “red man syndrome“ are rarely. Local intolerance in 1.7% Fever in 0.8% Ototoxicity in 0.3% Alterations in liver and renal function are uncommon Thrombocytopaenia,Dosage of Vancomycin,Teicoplanin, Vancomycin比較,Teicoplanin is less toxic than vancomycin Administration is more convenient Overall costs are similar,Glycopeptide,主要是針對革蘭氏陽性菌有效，建議保留用於具抗藥性的細菌如MR