1. 抗生素正確使用原則
張恩本醫師 為恭醫院感染科

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

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 Penicillins oxacillin
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
Sulbactam
Ampicillin + Sulbactam
Clavulanic acid
Amoxycillin + Clavulanate
Ticarcillin + Clavulanate
Tazobactam
Piperacillin + Tazobactam

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

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

28. Third generation Cefoperazone Cefotaxime Ceftazidime Ceftriaxone
Flumarin
Cefixime
Cefpodoxime
ceftibuten
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. J Antimicrob Chemotherapy
Carbapenem
Group
Classification
Group 1
Broad-spectrum carbapenems, with limited activity against non-fermentative Gram-negative bacilli (NFGNB, e.g. Pseudomonas, Acinetobacter) , that are particularly suitable for community-acquired infections (e.g. ertapenem)
Group 2
Broad-spectrum carbapenems, with activity against non-
fermentative Gram-negative bacilli (e.g. Pseudomonas,
Acinetobacter), that are particularly suitable for nosocomial infections (e.g. imipenem and meropenem)
Group3
Carbapenems with clinical activity against Methicillin-
Resistant Staphylococcus (e.g. In development)
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. Tetracyclines STD - Chlamydial diseases - Gonorrhea
(doxycycline + ceftriaxone)
- Syphilis
Rickettsial diseases
Brucellosis
Tularemia
Relapsing fever

40. Tigecycline (a new class Glycylcyclines)
Gram-positive Bacteria
。Staphylococcus: MRSA, MRSE
。VRE: E. faecium, E. faecalis
。Streptococcus agalactiae
。S treptococcus 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)
。Kl ebsiella pneumoniae
(including ESBLs)
。K. oxytoca
。Acinetobacter baumannii
(Resistant strains)
。Citrobacter freundii
。Enterobacter cloacae
。Enterobacter aerogenes
。Stenotrophomonas maltophilia
Does not have good activity
against
P. aeruginosa
Proteus.
Providencia
TYGACIL 2004,
p5, B-D
TYGACIL 2004,
p6, E-G
TYGACIL 2004,
p7, H
Disease State Overview: Tigecycline In Vitro Activity
The OL reviews the in vitro activity of tigecycline against common pathogens and then transitions presentation over to Wyeth Medical.
Tigecycline has been shown to be active against a wide variety of pathogens.1 Specifically, tigecycline has broad-spectrum in vitro activity against the following organisms (note that some of the organisms listed below have not been included on the slide):
Gram-positive Bacteria: S. aureus, S. epidermidis, E. faecalis, E. faecium, E. avium, E. casseliflavus, E. gallinarum, S. agalactiae, S. anginosus group, and S. pyogenes
Gram-negative Bacteria: C. freundii, E. cloacae, E. aerogenes, E. coli, K. oxytoca, K. pneumoniae and Stenotrophomonas maltophilia
Anaerobes: B. fragilis, B. thetaiotaomicron, B. uniformis, B. vulgatus, B. distasonis, B. ovatus, C. perfringens, P. micros, Prevotella spp.
Although this list is not all inclusive, it shows the broad spectrum of activity against pathogens that is displayed by tigecycline.
Reference
Tygacil* [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals; 2004.
*trademark
TYGACIL 2004,
p5, B-D
TYGACIL 2004,
p6, E-G
TYGACIL 2004,
p7, H
TYGACIL 2004
p9, Y
2017/4/21 40

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)
感染症療程
(天)
菌血症/敗血症 14
肝膿瘍 21
軟組織感染
7-10
急性腎炎
細菌性腦膜炎 10

46. 常見感染症之抗生素療程(二) 感染症療程 (天) 􀂙 肺炎雙球菌肺炎 14 (??) 革蘭氏陰性桿菌肺炎 21 (??) 退伍軍人協會症
奴卡氏菌肺炎
感染性心內膜炎
28-42

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