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抗生素正確使用原則

抗生素正確使用原則. 張恩本醫師 為恭醫院感染科 2010.03.26. 今日討論的主題. 抗生素一般使用原則 抗生素 相關 過敏反 應 常見的感染症致病菌 抗生素的分類 抗生素使用常見錯誤 抗素使用的適應症 常見感染症的抗生素療程. 抗生素一般使用原則. Narrow spectrum 一種細菌用一種藥物治療 足量藥物治療 完整療程. 使用抗生素之前應. 用手取得檢體染色、培養 用眼觀察染色特徵 用腦社區型感染或院內感染 ? 想想看最可能的致病菌是什麼 ? 藥物敏感性如何 ?.

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抗生素正確使用原則

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  1. 抗生素正確使用原則 張恩本醫師 為恭醫院感染科 2010.03.26

  2. 今日討論的主題 • 抗生素一般使用原則 • 抗生素相關過敏反 應 • 常見的感染症致病菌 • 抗生素的分類 • 抗生素使用常見錯誤 • 抗素使用的適應症 • 常見感染症的抗生素療程

  3. 抗生素一般使用原則 Narrow spectrum 一種細菌用一種藥物治療 足量藥物治療 完整療程

  4. 使用抗生素之前應.... • 用手取得檢體染色、培養 • 用眼觀察染色特徵 • 用腦社區型感染或院內感染? • 想想看最可能的致病菌是什麼? • 藥物敏感性如何?

  5. 理想的抗生素 • Maximal damage to the bacteria, minimal damage to the host –selective toxicity • Single use • High effectiveness • Low cost • No side-effect

  6. Principles of antibiotic therapy • Host factors • Allergy history • Age, Body weight, Renal/liver function • Immune status • Site of infection: pathogen, route of antibiotics • Disease severity • Pregnancy

  7. Empirical therapy must be adjusted after culture become available • Definite antimicrobial therapy –change broad- spectrum coverage to specific pathogen • De-escalating therapy

  8. Pathogens of community-acquired infection • Pulmonary: S. pneumoniae, H. influenzae, M. catarrhalis • Skin & soft tissue: Streptococci, Staphylococci, Enterobacterioceae • Intraabdomen: Enterobacterioceae, Anaerobes, Enterococci • CNS: S. pneumoniae, H. influenzae, N. meningitidis

  9. Pathogens of community-acquired infection • Pulmonary: S. pneumoniae, H. influenzae, M. catarrhalis • Skin & soft tissue: Streptococci, Staphylococci, Enterobacterioceae • Intraabdomen: Enterobacterioceae, Anaerobes, Enterococci • CNS: S. pneumoniae, H. influenzae, N. meningitidis

  10. Pathogens of nosocmial infection • Pulmonary: Enterobacterioceae, Pseudomonas, Acinetobacter,MRSA • Intraabdomen: Enterobacterioceae, Pseudomonas, Anaerobes, Enterococci,Candida • CNS: MRSA, Pseudomonas

  11. Allergic reactions to antibiotics • Fixed drug eruption • Skin rash (maculopapular) • Exfoliativedermatitis • Stevens-Johnson Syndrome (Toxic epidermal necrolysis) • Anaphylactic shock

  12. Fixed rug eruption

  13. Skin rash (maculopapular)

  14. Stevens-Johnson Syndrome (Toxic epidermal necrolysis)

  15. Penicillins Beta-lactmase inhibitors Cephalosporins Carbapenems Monobactams Sulfonamides & trimethoprim Aminoglycosides Quinolones Tetracycline Metronidazole Macrolides Tigecycline Glycopeptide Colistimethate sodium Antibiotics

  16. Penicillins • Natural PCNs Penicillin G, Penicillin V, benzathine PCN • Penicillinase-resistant PCNs Oxacillin, Prostaphylin • Amionopenicillins Amoxicillin, Ampicillin • Anti-pseudomonal PCNs Ticarcillin, Piperacillin

  17. Antimicrobial spectrum of Penicillin-G • Streptococcus spp. • Anaerobes • Neisseria spp. (Meningococcus, Gonococcus) • Actinomycosis • Animal bite (Pasteurella multocida) • 螺旋體: Syphilis, Leptospirosis

  18. Penicillinase-resistant Penicillinsoxacillin • Penicillinase (β-lactamase) inhibitor • Anti-staphylococcal penicillins • Less active than penicillin-G against all other penicillin-susceptible microorganisms C.Y.T.

  19. Adverse effects-PCNs • Anaphylaxis, anemia, leukopenia • Oxacillin: hepatitis • Ticarcillin: coagulation abnormality bleeding

  20. Beta-lactam/beta-lactamatase inhibitor

  21. Antipseudomonal Penicillins • Pip./tazo, Ticarcillin + Clavulanate • Pseudomonas species • Many strains of Enterobacter • Anaerobics except β-lactamase producing Bacteroides species • Less active against gram positive isolates

  22. Adverse effects of penicillin • Anaphylaxis, anemia, leukopenia • Oxacillin: hepatitis • Ticarcillin: coagulation abnormality bleeding

  23. Sulbactam (Maxtam) • Sulbactam is an irreversible inhibitor of beta-lactamase • Combinations of sulbactam with beta-lactam antibiotics • Dose: 0.5 ~ 1.0 gm 6 ~ 8 with other antibiotics not > 4.0 gm/day • Cefoperazone/sulbactam • Ampicillin/sulbactam

  24. Cephalosporins • First generation • Second generation • Third generation • Fourth generation

  25. Cephalosporins • Against GPC 1st > 2nd > cephamycins > 3rd • Against GNB 1st < 2nd < cephamycins < 3rd

  26. Cefazolin Cefadroxil Ceflexin Cephradine First Generation Streptococcus Staphylococcus (methicillin-susceptible) E. coli P. mirabilis K. pneumoniae

  27. Cefmetazole Cefuroxime Cefalor Cefuroxime Second Generation above the diaphragm: cefuroxime. below the diaphragm: cefmetazole (cephamycins, B. fragilis) Cefmatazole : ESBL-producing Enterobacteriaceae

  28. Cefoperazone Cefotaxime Ceftazidime Ceftriaxone Flumarin Cefixime Cefpodoxime ceftibuten Third generation Resistant Gram-negative microorganisms（Nosocomial infections） : Serratia, Citrobacter, Enterobacter, Pseudomonas, β-lactamase producing H. influenzae. Better BBB penetration among cephalosporins (except cefoperazone) Indication: nosocomial infections (mainly GNB), GNB meningitis

  29. Fourth Generation • Cefepime • Cefpirome Good anti-pseudomonal effect Good CNS penetration Preserve antimicrobial effect to G(+) bacteria

  30. Adverse effects of cephalosporins • Cefamandole, cefmetazole, cefoperazone, cefotetan vitamin K-dependent clotting factor metabolism

  31. Monobactam (Aztreonam) • Only gram-negative aerobes • Alternative in penicillin- and cephalosporin- allergic patients

  32. Sulfonamides and trimethoprim • Inhibit folic acid metabolism • Treatment of PCP, Nocardia, Toxaplasma, Sternotrophomonus • Aderverse effect: cholestatic jaudice, bone marrow suppression, severe hypersensitivity (Stevens-Johnson syndrome)

  33. Carbapenem J Antimicrob Chemotherapy

  34. Side effect of Carbapenems • Anaphylaxis • Interstitial nephritis • Anemia • Leukopenia • Precipitate seizure activity, especially old patients, CRI, preexisting seizure disorder or CNS pathology

  35. Aminoglycosides • Antimicrobial Spectrum: - All Gram negative bacilli - Staphylococcus aureus • Dosage: - • Gentamicin: loading ~ 2 mg/kg maintenance ~ 3-5 mg/kg/day • Amikacin: loading ~ 7.5 mg/kg maintenance ~ 5 mg/kg Q8H or 7.5 mg/kg q12H • Exacin : 8mgs/kg/day • Single daily (once-daily) dosing (SDD) • Short course (3-5 days)

  36. Adverse effects of aminoglycosides • Nephrotoxicity • Ototoxicity • Neuromuscular paralysis ~ High dose/infrequent administration DECREASES the rate of tissue uptake — DELAY the onset of toxicity, doesn’t prevent it from happening ~ All patients, if treated for a long enough time, will eventually develop toxicity

  37. Fluoroquinolones • Group I: - Nalidixic acid - Enteric or urinary tract infections • Group II: - Ciprofloxacin, Ofloxacin, Levofloxacin - GNR (P. aeruginosa), S. pneumoniae, atypicals • Group III: - Moxifloxacin, Gemifloxacin - GPB ( S. pneumoniae↑), atypicals, anaerobes, GNR (P. aeruginosa↓) - Respiratory tract infections

  38. Glycopeptides • Vancomycin & Teicoplanin • Non-β-lactam cell wall synthesis inhibitor • Spectrum: GPC & GPB • Avoid oral use, except AAC (antibiotic-associated colitis)

  39. STD - Chlamydial diseases - Gonorrhea (doxycycline + ceftriaxone) - Syphilis Rickettsial diseases Brucellosis Tularemia Relapsing fever Tetracyclines

  40. Tigecycline (a new class Glycylcyclines) Gram-positive Bacteria 。Staphylococcus: MRSA, MRSE 。VRE: E. faecium, E. faecalis 。Streptococcus agalactiae 。Streptococcus anginosus group 。Streptococcus pyogenes Anaerobes 。B. fragilis group 。Prevotella spp. 。Peptostreptococcus spp. 。C. perfringens Atypical 。Chlamydia pneumoniae 。Mycoplasma pneumoniae 。Legionella Gram-negative Bacteria 。E. coli (including ESBLs) 。Klebsiellapneumoniae (including ESBLs) 。K. oxytoca 。Acinetobacter baumannii (Resistant strains) 。Citrobacter freundii 。Enterobactercloacae 。Enterobacter aerogenes 。Stenotrophomonas maltophilia Does not have good activity against P. aeruginosa Proteus. Providencia

  41. Colistimethate sodium • Colistimethate sodium Pseudomonas aeruginosa infections in cystic fibrosis , multidrug-resistant Acinetobacter infection • E-coli , Klebsiella sp ( ESBL) ,Enterobacter • Colomycin 1,000,000 units = 80 mg colistimethate • 6 to 12 mg/kg colistimethate sodium per day • 60 kg man, recommended dose for Colomycin is 240 to 480 mg of colistimethate sodium • Nephrotoxicity (damage to the kidneys) and neurotoxicity

  42. 抗生素使用常見的五大錯誤 Antibiotic = scanol (antipyretic) S vs R (susceptible vs resistant) 4 > 3 >2 > 1 Treat colonization Vancomycin+ imipenem(atomic bomb)

  43. Colonization Positive culture for sputum, urine, bile, stool and skin swab without symptoms or signs of infection, Not recommend for using antibiotics Except: asymptomatic bacteriuria before urological work up and in pregnancy should be treated

  44. 抗生素使用的適應症 • 明顯的細菌感染 • 極可能的細菌感染 • 敗血症 • 白血球過低合併發燒 • 懷疑急性心內膜炎 • 細菌性腦膜炎 • 壞死性筋膜炎

  45. 常見感染症之抗生素療程(一)

  46. 常見感染症之抗生素療程(二)

  47. 抗生素治療失敗之原因 • 選用藥物不恰當 • 藥物交互作用, 降低療效 • 異異物阻塞或膿瘍未引流 • 病人免疫力太差 • 分離菌之判讀錯誤 • 新的院內感染

  48. THANKS FOR ATTENTION

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