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

抗生素正確使用原則

張恩本醫師 為恭醫院感染科

20100326

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 ndashselective toxicity Single use High effectiveness Low cost No side-effect

Principles of antibiotic therapy Host factors Allergy history Age Body weight Renalliver 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 ndashchange broad- spectrum coverage to specific pathogen

De-escalating therapy

Pathogens of community-acquired infection Pulmonary

S pneumoniae H influenzae M catarrhalis Skin amp 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 amp 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 Beta-lactmase

inhibitors Cephalosporins Carbapenems Monobactams Sulfonamides amp

trimethoprim

Aminoglycosides Quinolones Tetracycline Metronidazole Macrolides Tigecycline Glycopeptide Colistimethate

sodium

Penicillins

Natural PCNsPenicillin 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-lactambeta-lactamatase inhibitor

Sulbactam Ampicillin + Sulbactam

Clavulanic acid Amoxycillin + ClavulanateTicarcillin + Clavulanate

Tazobactam Piperacillin + Tazobactam

Antipseudomonal Penicillins Piptazo 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 beta-lactamase

Combinations of sulbactam with beta-lactam antibiotics

Dose 05 ~ 10 gm 6 ~ 8 with other antibiotics not

gt 40 gmday Cefoperazonesulbactam Ampicillinsulbactam

Cephalosporins

First generation Second generation Third generation Fourth generation

Cephalosporins

Against GPC 1st gt 2nd gt cephamycins gt 3rd Against GNB 1st lt 2nd lt cephamycins lt 3rd

First Generation

Cefazolin Cefadroxil Ceflexin Cephradine

StreptococcusStaphylococcus (methicillin-susceptible)E coliP mirabilisK pneumoniae

Second Generation

Cefmetazole Cefuroxime

Cefalor Cefuroxime

above the diaphragm cefuroximebelow the diaphragm cefmetazole (cephamycins B fragilis) Cefmatazole ESBL-producing Enterobacteriaceae

Third generation

Cefoperazone Cefotaxime Ceftazidime Ceftriaxone Flumarin

Cefixime Cefpodoxime ceftibuten

Resistant Gram-negative microorganisms （ Nosocomial infections ） Serratia Citrobacter Enterobacter Pseudomonas β-lactamase producing H influenzaeBetter BBB penetration among cephalosporins (except cefoperazone)Indication nosocomial infections (mainly GNB) GNB meningitis

Fourth Generation

Cefepime Cefpirome

Good anti-pseudomonal effectGood CNS penetrationPreserve antimicrobial effect to G(+) bacteria

Adverse effects of cephalosporins

Cefamandole cefmetazole cefoperazone cefotetan vitamin K-dependent clotting factor metabolism

Monobactam Monobactam (Aztreonam(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)

CarbapenemGroup Classification

Group 1 Broad-spectrum carbapenems with limited activity against non-fermentative Gram-negative bacilli (NFGNB eg Pseudomonas Acinetobacter) that are particularly suitable for community-acquired infections (eg ertapenem)

Group 2 Broad-spectrum carbapenems with activity against non-

fermentative Gram-negative bacilli (eg Pseudomonas

Acinetobacter) that are particularly suitable for nosocomial infections (eg imipenem and meropenem)

Group3 Carbapenems with clinical activity against Methicillin-

Resistant Staphylococcus (eg 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

AminoglycosidesAminoglycosides

Antimicrobial Spectrum Antimicrobial Spectrum - All Gram negative bacilli

- Staphylococcus aureus Dosage Dosage - Gentamicin loading ~ 2 mgkg maintenance ~ 3-5 mgkgday Amikacin loading ~ 75 mgkg maintenance ~ 5 mgkg Q8H or 75

mgkg q12H Exacin 8mgskgday Single daily (once-daily) dosing (SDD) Short course (3-5 days)

Adverse effects of Adverse effects of aminoglycosidesaminoglycosides Nephrotoxicity Ototoxicity Neuromuscular paralysis ~ High doseinfrequent administration

DECREASES the rate of tissue uptake mdash DELAY the onset

of toxicity doesnrsquot 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 pneumoniaeuarr) atypicals anaerobes GNR

(P aeruginosadarr)

- Respiratory tract infections

GlycopeptidesGlycopeptides

Vancomycin amp Teicoplanin

Non-β-lactam cell wall synthesis inhibitor

Spectrum GPC amp GPB

Avoid oral use except AAC (antibiotic-associated colitis)

Tetracyclines

STD

- Chlamydial

diseases

- Gonorrhea

(doxycycline +

ceftriaxone)

- Syphilis

Rickettsial diseases

Brucellosis

Tularemia

Relapsing fever

Tigecycline (a new class Glycylcyclines)Gram-positive BacteriaGram-positive Bacteria Staphylococcus MRSA

MRSE VRE E faecium E faecalis Streptococcus agalactiae S treptococcus anginosus

group Streptococcus pyogenes

AnaerobesAnaerobes B fragilis group Prevotella spp Peptostreptococcus spp C perfringensAtypicalAtypical Chlamydia pneumoniae Mycoplasma pneumoniae Legionella

Gram-negative BacteriaGram-negative Bacteria E coli (including ESBLs) Kl ebsiella pneumoniae (including ESBLs) K oxytoca Acinetobacter baumannii (Resistant strains)Resistant strains) Citrobacter freundii Enterobacter cloacae Enterobacter aerogenes Stenotrophomonas

maltophilia

Does not have good activity Does not have good activity againstagainst 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 1000000 units = 80 mg

colistimethate 6 to 12 mgkg 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 gt 3 gt2 gt 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 )

1048729

肺炎雙球菌肺炎 14 ()

革蘭氏陰性桿菌肺炎1048729

21 ()

退伍軍人協會症1048729

21

奴卡氏菌肺炎1048729

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

• Slide 15
• Slide 26
• Slide 27
• Slide 28