抗生素正確使用原則0326
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Transcript 抗生素正確使用原則0326
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?
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
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
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
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
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
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
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