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
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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?
理想的抗生素
 Maximal damage to the bacteria, minimal
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damage to the host –selective toxicity
Single use
High effectiveness
Low cost
No side-effect
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
Empirical therapy must be adjusted after culture
become available
 Definite antimicrobial therapy –change broadspectrum coverage to specific pathogen
 De-escalating therapy
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
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
Pathogens of nosocmial infection
 Pulmonary:
Enterobacterioceae, Pseudomonas,
Acinetobacter, MRSA
 Intraabdomen:
Enterobacterioceae, Pseudomonas,
Anaerobes, Enterococci, Candida
 CNS:
MRSA, Pseudomonas
Allergic reactions to antibiotics
 Fixed drug eruption
 Skin rash (maculopapular)
 Exfoliativedermatitis
 Stevens-Johnson Syndrome (Toxic
epidermal necrolysis)
 Anaphylactic shock
Fixed rug eruption
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Skin rash (maculopapular)
Stevens-Johnson Syndrome
(Toxic epidermal necrolysis)
Antibiotics
 Penicillins
 Aminoglycosides
 Beta-lactmase inhibitors
 Quinolones
 Cephalosporins
 Tetracycline
 Carbapenems
 Metronidazole
 Monobactams
 Macrolides
 Sulfonamides &
trimethoprim
 Tigecycline
 Glycopeptide
 Colistimethate sodium
Penicillins
 Natural PCNs
Penicillin G, Penicillin V, benzathine PCN
 Penicillinase-resistant PCNs
Oxacillin, Prostaphylin
 Amionopenicillins
Amoxicillin, Ampicillin
 Anti-pseudomonal PCNs
Ticarcillin, Piperacillin
Antimicrobial spectrum of
Penicillin-G
 Streptococcus spp.
 Anaerobes
 Neisseria spp. (Meningococcus, Gonococcus)
 Actinomycosis
 Animal bite (Pasteurella multocida)
 螺旋體: Syphilis, Leptospirosis
Penicillinase-resistant Penicillins
oxacillin
 Penicillinase (β-lactamase) inhibitor
 Anti-staphylococcal penicillins
 Less active than penicillin-G against all other
penicillin-susceptible microorganisms
Adverse effects-PCNs
 Anaphylaxis, anemia, leukopenia
 Oxacillin: hepatitis
 Ticarcillin: coagulation abnormality bleeding
Beta-lactam/beta-lactamatase inhibitor
Sulbactam
Ampicillin + Sulbactam
Clavulanic acid
Amoxycillin + Clavulanate
Ticarcillin + Clavulanate
Tazobactam
Piperacillin + Tazobactam
Antipseudomonal Penicillins
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Pip./tazo, Ticarcillin + Clavulanate
Pseudomonas species
Many strains of Enterobacter
Anaerobics except β-lactamase producing
Bacteroides species
 Less active against gram positive isolates
Adverse effects of penicillin
 Anaphylaxis, anemia, leukopenia
 Oxacillin: hepatitis
 Ticarcillin: coagulation abnormality bleeding
Sulbactam (Maxtam)
 Sulbactam is an irreversible inhibitor of betalactamase
 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
Cephalosporins
 First generation
 Second generation
 Third generation
 Fourth generation
Cephalosporins
 Against GPC
1st > 2nd > cephamycins > 3rd
 Against GNB
1st < 2nd < cephamycins < 3rd
First Generation
 Cefazolin
 Cefadroxil
 Ceflexin
 Cephradine
Streptococcus
Staphylococcus (methicillin-susceptible)
E. coli
P. mirabilis
K. pneumoniae
Second Generation
 Cefmetazole
 Cefalor
 Cefuroxime
 Cefuroxime
above the diaphragm: cefuroxime.
below the diaphragm: cefmetazole (cephamycins, B. fragilis)
Cefmatazole : ESBL-producing Enterobacteriaceae
Third generation
 Cefoperazone
 Cefixime
 Cefotaxime
 Cefpodoxime
 Ceftazidime
 ceftibuten
 Ceftriaxone
 Flumarin
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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
Fourth Generation
 Cefepime
 Cefpirome
Good anti-pseudomonal effect
Good CNS penetration
Preserve antimicrobial effect to G(+) bacteria
Adverse effects of cephalosporins
 Cefamandole, cefmetazole, cefoperazone,
cefotetan vitamin K-dependent clotting factor
metabolism
Monobactam (Aztreonam)
 Only gram-negative aerobes
 Alternative in penicillin- and cephalosporin-
allergic patients
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)
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 nonfermentative 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 MethicillinResistant Staphylococcus (e.g. In development)
J Antimicrob Chemotherapy
Side effect of Carbapenems
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Anaphylaxis
Interstitial nephritis
Anemia
Leukopenia
Precipitate seizure activity, especially old
patients, CRI, preexisting seizure disorder or
CNS pathology
Aminoglycosides
 Antimicrobial Spectrum: - All Gram negative bacilli
- Staphylococcus aureus
 Dosage: -
 Gentamicin: loading ~ 2 mg/kg
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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)
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
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
Glycopeptides
 Vancomycin & Teicoplanin
 Non-β-lactam cell wall synthesis inhibitor
 Spectrum: GPC & GPB
 Avoid oral use, except AAC (antibiotic-
associated colitis)
Tetracyclines
 STD
 Rickettsial diseases
- Chlamydial diseases
 Brucellosis
- Gonorrhea
 Tularemia
(doxycycline +
ceftriaxone)
- Syphilis
 Relapsing fever
Tigecycline (a new class Glycylcyclines)
Gram-positive Bacteria
Gram-negative Bacteria
。Staphylococcus: MRSA, MRSE
。E. coli (including ESBLs)
。VRE: E. faecium, E. faecalis
。Kl ebsiella pneumoniae
。Streptococcus agalactiae
(including ESBLs)
。S treptococcus anginosus group
。K. oxytoca
。Streptococcus pyogenes
。Acinetobacter baumannii
(Resistant strains)
Anaerobes
。Citrobacter freundii
。B. fragilis group
。Enterobacter cloacae
。Prevotella spp.
。Enterobacter aerogenes
。Peptostreptococcus spp.
。Stenotrophomonas maltophilia
。C. perfringens
Atypical
。Chlamydia pneumoniae
Does not have good activity
。Mycoplasma pneumoniae
against
。Legionella
P. aeruginosa
Proteus.
Providencia
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
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)
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
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
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
14
細菌性腦膜炎
10
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
21
奴卡氏菌肺炎
180-360
感染性心內膜炎
28-42
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