Pre-ICU training (Antibiotics)

馬偕紀念醫院感染科

郭建峯醫師

0

2

4

6

8

10

12

14

16

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

YEAR

(%)

E. coli

P. aeruginosa

*C. albicans

Yeast form fungi

K. pneumoniae

S. aureus

Enterococcus

*A. baumannii

Coag. (-) staph.

E.cloacae

*2000年開始鑑定

台北院區院內感染常見 10種致病菌歷年變化

1 . 7 1

0 . 4 50 . 5 3

0 . 1 2 0 . 1 3 0 . 0 9 0 . 0 6

0

0 .5

1

1 .5

2 U T I

B S I

S S I

L R I

E E N T I

G I S I

S S T I

O t h e r S i t e

Incidence Rate (‰)

Incidence rate is the number of isolates reported per 1000 patietn days

台北院區院內感染各部位感染發生密度（ 2007年）

2 8 . 9

1 . 9

1 . 8

1 2 . 6

1 0 . 5

1 . 0 1 . 5

4 1 . 6

U T I

B S I

E E N T I

G IS I

S S I

L R I

O t h e r S it e

S S T I

All infections = 1,593

台北院區院內感染各部位分佈圖（ 2007年）

10.5

1 0 .1

9 .9

9 .5

9 .3

8 .6

7 .7

4 .3

1 .5

1 0 .3

8 .9

2 .7

1 .7

1 .7

1 .4

1 .2

0 .0 2 .0 4 .0 6 .0 8 .0 10 .0 12 .0

B . f r a gilis

R ot a v ir us

O t h e r S t r e pt oc oc c us

O t h e r G N F b a c t e r ia

S . ma r c e s c e ns

E . c loa c a e

C oa gula s e (- ) S t a ph y loc oc c us

E nt e r oc oc us

K. pne umonia e

P. a e r uginos a

C . a lb ic a ns

S . a ur e us

A . b a uma nnii

Y e a s t f or m f ungi

E . c oli

%

台北院區院內感染常見的 15種致病菌（ 2007年）

Total 1,717

PATHOGEN LRI SSI GISIEENT

IBSI UTI SSTI

Others

TOTAL ISOLAT

E%

E. coli 0.0 3.3 0.0 0.0 10.8 13.5 7.0 0.0 177 10.3

Yeast form fungi 0.0 2.2 0.0 0.0 6.7 16.6 0.0 0.0 173 10.1

A. baumannii 55.6 2.2 0.0 0.0 8.1 8.5 3.8 7.7 170 9.9

S. aureus 11.1 18.7 0.0 30.0 14.6 2.3 30.8 38.5 163 9.5

C. albicans 0.0 3.8 3.0 0.0 3.9 16.3 0.0 0.0 159 9.3

P. aeruginosa 8.9 12.1 7.0 20.0 3.9 11.7 11.5 7.7 153 8.9

K. pneumoniae 1.1 3.3 0.0 10.0 10.1 9.9 7.7 7.7 148 8.6

Enterococcus 1.1 9.9 0.0 0.0 7.0 8.9 7.7 0.0 132 7.7

Coagulase(-) Staphylococcus

0.0 5.5 0.0 0.0 9.1 1.1 3.8 7.7 74 4.3

E. cloacae 1.1 1.6 0.0 0.0 3.6 2.6 3.8 0.0 46 2.7

S. marscens 0.0 0.5 0.0 0.0 3.3 1.0 3.8 7.7 30 1.7

Other GNF bacteria 1.1 1.6 0.0 0.0 3.8 0.4 0.0 7.7 30 1.7

Other Streptococcus 0.0 6.6 0.0 0.0 1.2 0.9 0.0 0.0 26 1.5

Rotavirus 0.0 0.0 83.0 0.0 0.0 0.0 0.0 0.0 24 1.4

B. fragilis 0.0 6.6 0.0 0.0 1.4 0.0 0.0 7.7 21 1.2

All others 20.0 22.0 7.0 40.0 12.5 6.1 19.2 7.7 191 11.1

NUMBER OF ISOLATES

90 182 29 10 583 784 26 13 1,717 100.00

台北院區院內感染常見的 15種致病菌各部位之感染率（ 2007年）

1 7 .9

1 6 .3

1 3 .5

1 1 .7

9 .9

8 .9

8 .5

2 .6

2 .3

1 .4

1 .1

1

0 .9

0 .8

0 .8

0 .9

0 5 1 0 1 5 2 0

%

C it ro b a c te r sp p .

M . m o rg a n ii

C o ry n e b a c te r sp p .

O th e r st re p to c o c c u s

S . m a rc e sc e n s

C o a g u la se ( - ) sta p h y lo c o c c u s

P . m ira b ilis

S . a u re u s

E . c lo a c a e

A . b a u m a n n ii

E n te ro c o c c u s

K . p n e u m o n ia e

P . a e ru g in o sa

E . c o li

C . a lb ic a n s

Y e a st f o rm f u n g i

台北院區院內感染 UTI常見的致病菌（ 2007年）

Total 784

5 5 .6

1 5 .6

1 1 .1

8 .9

3 .3

1 .1

1 .1

1 .1

1 .1

1 .1

0 1 0 2 0 3 0 4 0 5 0 6 0

%

E n t e r o c o c c u s

K . p n e u m o n ia e

E . c lo a c a e

H . in fl u e n z a e

O t h e r G N F b a c t e r ia

S . m a lt o p h ilia

P . a e r u g in o sa

S . a u r e u s

R S V

A . b a u m a n n ii

台北院區院內感染 LRTI常見的致病菌（ 2007年）

Total 90

1 8 .7

1 2 .1

9.9

7 .1

6 .6

6.6

5 .5

3 .8

3 .3

3 .3

2 .7

2 .2

2.2

2.2

1 .6

1 2 .1

0 5 10 15 2 0

%

A ll o th e rs

C o ry n e b a c te r sp p .

A . b a u m a n n ii

M . m o rg a n ii

Y e a st f o rm f u n g i

A n a e ro b ic G( +) c o c c i

K . p n e u m o n ia e

E . c o li

C . a lb ic a n s

C o a g u la se ( - ) sta p h y lo c o c c u s

B . f ra g ilis

O th e r st re p to c o c c u s

F u so b a c te r iu m sp p .

E n te ro c o c c u s

P . a e ru g in o sa

S . a u re u s

台北院區院內感染 SSI常見的致病菌（ 2007年）

Total 182

1 4 .6

10 .8

1 0 .1

9 .1

8 .1

7

6 .7

3 .9

3 . 9

3 .8

3 .6

3 .3

1 .4

1 .4

1

1 1 .3

0 5 10 15

%

A ll ot her s

Klebs iella s pp.

S . malt iohilia

B . c epac ia

S . mar c es c ens

E . c loac ae

O t her G N F bac t er ia

C. albic ans

P. aer uginos a

Y eas t f or m f ungi

E nt er oc oc c us

A . baumannii

Coagulas e(- ) s t aphyloc oc c us

K. pneumoniae

E . c oli

S . aur eus

台北院區院內感染 BSI常見的致病菌（ 2007 年）

Total 583

3 0 .8

1 1 .5

7 .7

7 .7

7 .7

7 .7

3 .8

3 .8

3 .8

3 .8

0 10 2 0 3 0 4 0

%

H . in fl u e n z a e

S . m a rc e sc e n s

E . c lo a c a e

Gro u p B st re p to c o c c u s

K . p n e u m o n ia e

E . c o li

C o ry n e b a c te r sp p .

E n te ro c o c c u s

P . a e ru g in o sa

S . a u re u s

台北院區院內感染 SSTI常見的 15種致病菌（ 2007年）

Total 26

What organisms are most likely?

何種致病菌是最可能造成此次感染的致病菌 ?

• 適當的經驗療法• 臨床症候群 (Clinical syndrome)

• 宿主因素 (Host factor)

• 流行病學資料 (Epidemiological data)

If several antibiotics are available, which is best?

(This question involves such factors as drugs of choice, pharmacokinetics, toxicology, cost, narrowness of spectrum, and bactericidal compared with bacteriostatic agents.)

對於一個最可能的致病菌，或是已確定的致病菌，可能有多種藥物可用來治療，何者才是最佳的選擇藥物 ?

Staphylococcus aureus: Antibiotics Methocillin-sensitive S. aureus (MSSA): 首選藥物 : oxacillin 替代藥物 : 第一代頭孢菌素 假如 penicillin allergic - Erythromycin, Clinda

mycin, Glycopeptide (Vancomycin, Teicoplanin)

Methocillin-resistant S. aureus (MRSA) : 首選藥物 :Glycopeptide (Vancomycin, Teicopl

anin) 替代藥物 : Linezolid Fusidic acid Rifampicin

Categories of Susceptibility of S. pneumoniae to Penicillin

NCCLS 2001

Minimal inhibitory concentration (MIC)

Degree of resistance

<0.06 ug/mL Susceptible

0.12 to 1 ug/mL Intermediate

> 2 ug/mL Resistant

Streptococcus pneumoniae Penicillin-sensitive 菌株首選藥物 (first choice):

Penicillin G

Treatment of S. pneumoniae Pneumonia

Penicillin MIC (g/ml) primary alternative

1 penicillin 1st cephalosporins(S) ampicillin or amoxicillin 2 penicillin (high dose) 3rd or 4th cephalosporins(I) ampicillin or amoxicillin

4 3rd or 4th cephalosporins vancomycin or teicoplanin(R) vancomycin or teicoplanin + rifampin or newer

fluoroquinolones

The infectious diseases society R.O.C. 2000

Treatment of Pneumococcal Meningitis

MIC (g/ml) dosage

PCN CTX therapy adults children (/kg)

<0.12 0.5 penicillin 300,000 u/kg/d 3-400,000 u q4-6h

0.12 0.5 Cefotaxime or 2 g q6h 200-225 mg q6-8h

Ceftriaxone 2 g q12h 100 mg q12-24h

1.0 Cefotaxime or 300 mg/kg/d (m.24g) 300 mg q6-8h

Ceftriaxone 2 g q12h 100 mg q12-24h

+Vancomycin 60 mg/kg/d (M.2g) 60 mg q6h

2.0 Same as 1.0

+ Rifampin 300 mg q12h 20 mg q12h

Kaplan SL and mason EO jr. Clin microbiol rev 1998

Streptococcus pneumoniae 依 CNS Infection 和 Non- CNS Infection (P

neumonia, bacteremia) 不同部位感染，按照 MIC 值選擇藥物治療。

Invasive Pneumococcal disease 經驗治療 Non- CNS Infection (Pneumonia, bacteremia): hig

h dose penicillin G, or other cephalosporins (ceftriaxone;cefotaxime),or newer fluoroquinolones. Not vancomycin 。

CNS Infection (Meningitis): Not Penicillin, vancomycin + ceftriaxone (cefotaxime, Cefepime, Cefpirome, Meropenem)

Enterococci sp.

• E. faecalis, E. faecium• Habitat: commensal of human and animal gut • Lancefield group D, bile resistant • Infections

- Urinary tract infection

- Intra-abdominal sepsis

- Biliary tract infection

- Endocarditis

Enterococci sp. 首選藥物 : Ampicillin

心內膜炎加上 gentamicin 有加成作用 (synergistic effect)

Never use cephalosporins or aminoglycosides alone or Clindamycin, TMP/SMX for Enterococci

對 ampicillin 抗藥性 : Glycopeptide

Vancomycin-resistant Enterococci(VRE) -

Quinupristin/dalfopristin

Linezoid

Chloramphenicol

健保規範 (Linezolid)

• 1.證實為 MRSA(methicillin-resistant staphylococcus aureus) 感染，且證明為 vancomycin 抗藥菌株或使用 vancomycin 、 teicoplanin 治療失敗者或對 vancomycin 、 teicoplanin 治療無法耐受者。

• 2.證實為 VER(vancomycin-resistant enterococci) 感染，且無其他藥物可供選擇者。

• 3 骨髓炎 (osteomyelitis) 及心內膜炎 (endocarditis) 病患不建議使用。

• 4 其他抗藥性革蘭氏陽性菌感染，因病情需要，經感染症專科醫師會診確認需要使用者(申報費用時需檢附會診紀錄及相關之病歷資料)。

Klebsiella pneumoniae 首選藥物 (first choice): cephalosporins

無併發症感染 : cefazolin + aminoglycosides

嚴重感染合併眼內炎、腦膜炎 : third generation ce

phalosporins 為首選藥物 不建議使用 penicillins 類藥物 (Unasyn, augmentin,

Timentin, tazocin 均不建議使用 )

Escherichia coli

• Most common possible etiologies:

1. Cystitis & pyelonephritis

2. Emphysematous pyelonephritis.(DM)

3. Acute bacterial prostatitis• 首選藥物 (first choice):

-lactam antibiotics + aminoglycosides 。 • 台灣地區第一線可用 cefazolin ， 80% 對 am

picillin 抗藥性。

Klebsiella sp. & Escherichia coli In vitro resistant to any of the third generation cep

halosporins Strain produced an extended-spectrum -lactama

ses (ESBL) Resistance to all penicillins, cephalosporins & aztr

eonam首選藥物 (first choice): Carbapenem Cephamycins (AmpC -lactamases) Piperacillin-tazobactam(Tazocin) ( AmpC -lactamases) Ciprofloxacin Aminoglycosides

Citrobacter, Enterobacter, Acinetobacter, Serratia, Providencia Species

• Hospital acquired pathogens: UTI, ventilator associated pneumonia, septicaemia

• Antibiotic susceptibility unpredictable since often multiply antibiotic resistant; need susceptibility test guidance of treatment

• Inducible ß- lactamase(Amp C)• 4th cephalosporin(Maxipime, Cefrom), Imipene

m-cilastatin, Meropenem

Pseudomonas aeruginosa• Habitat: • GIT of humans & animals, environment• Water; survives in hospitals (In antiseptics)• Obligate aerobe, gram-negative rods, polar flagella, o

xidase positive (in contrast to Enterobacteriaceae)• Infections:• Hospital acquired infections: UTI with urinary catheter,

pneumonia (cystic fibrosis, ventilator associated), burns infection, septicaemia in immunocompromised (transplantation, oncology, ICU)

• Chronic otitis media & externa• Eye infection secondary to trauma

Pseudomonas aeruginosaAntipseudomonal Antibiotics: Ceftazidime(Fortum) Cefepime(Maxipime), Cefpirome(Cefrom) Aztreonam Imipenem-cilastatin / Meropenem Piperacillin, Piperacillin-tazobactam(Tazocin) Ticarcillin, Ticarcillin-clavulanate(Timentin) Ciprofloxacin, Levofloxacin Aminoglycosides

Acinetobacter baumannii

造成嚴重院內感染之革蘭氏染色陰性菌之一 首選藥物 (first choice): Imipenem/Cilastatin (Ti

enam®) / Meropenem

替代藥物 : Ampicillin/sulbactam (Unasyn® ) o

r sulbactam, Colistin, Tigecycline (Tygacil® )

健保規範 (Tigecycline)• 經細菌培養證實有意義之致病菌且對其他抗微

生物製劑均具抗藥性或對其他具有感受性抗微生物製劑過敏，而對 tigecycline 具有感受性 (sensitivity) 之複雜性皮膚及皮膚結構感染或複雜性腹腔內感染症使用。

• 複雜性皮膚及皮膚結構感染或複雜性腹腔內感染症，經感染症專科醫師會診，認定需使用者。

• 申報費用時需檢附會診紀錄及相關之病歷資料。

Stenotrophomonas maltophilia

造成嚴重院內感染之革蘭氏染色陰性菌之一 首選藥物 (first choice): TMP/SMX ; Co-trimoxazole

替代藥物

1. Moxalactam

2. Timentin (Ticarcillin-clavulanate)

3. Ciprofloxacin, Levofloxacin

Is an antibiotic combination appropriate?

是否需要合併使用兩種或以上的抗生素 ?

• Febrile leukopenic patient• In infections in which multiple organisms are likely or p

roved• Synergism Serial inhibition of microbial growth One antibiotic enhances the penetration of another• Limiting or preventing the emergence of resistance

Combination Therapy• Tuberculosis• Disseminated Mycobacterium avium complex• Helicobacter pylori• Endocarditis(alpha haemolytic streptococcus, ente

rococcal )

• Vancomycin-resistant enterococcal disease

• Life-threatening infection caused by P. aeruginosa

• Empiric treatment ( pneumococcal meningitis; febrile, severely neutropenic host; polymicrobic infection; life-threatening infection with inapparent source)

Gentamicin加上 Gentamicin 有加成作用 (Synergistic effect) Enterococci endocarditis( 心內膜炎 ) or bacterem

ia Gentamicin + Ampicillin or penicillin G Viridans streptococci endocarditis: Gentamicin + penicillin G MRSA or S. epidermidis : prosthetic valve endoc

arditis Vancomycin+ Gentamicin Listeria mononcytogenes: Ampicillin + Gentamici

n Serious Pseudomonas aeruginosa infection Ami

noglycosides + Anti-Pseudomonal agents

The use of monotherapy with antipseudomonal penicillins or cephalopsorins for patient with severe P. aeruginosa infections can lead to the emergency of antimicrobial-resistant strain.

Combination of 2 antipseudomonal ß - lactam antibiotics lacks synergy in animal models & in human

Combination of an aminoglycosides & antipseudomonal ß - lactam antibiotics works synergistically against P. aeruginosa & improved clinical outcome.

Pseudomonas aeruginosa

Todd FH et al CID 2000; 31:1349-56

Antifungal agents

• Fluconazole (Diflucan)• Itraconazole (Sporanox)• Caspofungin (Cancidas)• Micafungin• Voriconazole (Vfend)• Amphotericin-B

健保規範 (itraconazole)• 1. 限用於第一線治療藥物 amphotericin-B 治療無效或有嚴重副作用之侵入性麴菌症、侵入性念珠菌感染症、組織漿病菌之第二線用藥使用，以14 日為限。

• 2. 限用於第一線治療藥物無法使用或無效的免疫功能不全及中樞神經系統罹患隱球菌病 (包括隱球菌腦膜炎 )的病人，並以 14 日為限。

• 3. 符合行政院衛生署核准之適應症，因病情需要，經感染症專科醫師會診確認需要使用者 (申報費用時需檢附會診紀錄及相關之病歷資料 )。

健保規範 (caspofungin)• 1. 限用於其他黴菌藥物治療無效或有嚴重副作用之侵入性麴菌症、侵入性念珠菌感染症之第二線用藥。

• 2. 符合衛生署之適應症範圍且經感染症專科醫師認定需使用者，惟治療食道念珠菌感染限用於 fluconazole 無效或有嚴重副作用者。

健保規範 (micafungin)• 治療 16 歲以上成人的食道念珠菌感染。• 預防接受造血幹細胞移植病患的念珠菌感

染。

健保規範 (voriconazole)•無

AMERICAN THORACIC SOCIETY DOCUMENTS:

Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated,

and Healthcare-associated Pneumonia

Am. J. Respir. Crit. Care Med. 2005; 171: 388-416

• Executive Summary• Introduction• Methodology Used to Prepare the Guideline• Epidemiology

Incidence

Etiology

Major Epidemiologic Points• Pathogenesis

Major Points for Pathogenesis• Modifiable Risk Factors

Intubation and Mechanical Ventilation

Aspiration, Body Position, and Enteral Feeding

Modulation of Colonization: Oral Antiseptics and Antibiotics

Stress Bleeding Prophylaxis, Transfusion, and Glucose Control

Major Points and Recommendations for Modifiable Risk Factors

• Diagnostic Testing

Major Points and Recommendations for Diagnosis• Diagnostic Strategies and Approaches

Clinical Strategy

Bacteriologic Strategy

Recommended Diagnostic Strategy

Major Points and Recommendations for Comparing Diagnostic Strategies

• Antibiotic Treatment of Hospital-acquired Pneumonia

General Approach

Initial Empiric Antibiotic Therapy

Appropriate Antibiotic Selection and Adequate Dosing

Local Instillation and Aerosolized Antibiotics

Combination versus Monotherapy

Duration of Therapy

Major Points and Recommendations for Optimal

Antibiotic Therapy

Specific Antibiotic Regimens

Antibiotic Heterogeneity and Antibiotic Cycling• Response to Therapy

Modification of Empiric Antibiotic Regimens

Defining the Normal Pattern of Resolution

Reasons for Deterioration or Nonresolution

Evaluation of the Nonresponding Patient

Major Points and Recommendations for Assessing Response to Therapy

• Suggested Performance Indicators

Contents

Executive Summary(1)

• Official statement of ATS/IDSA, evidence-based• HCAP: included in the spectrum of HAP/VAP, ne

ed therapy of MDR pathogen• Lower resp. tract cultures (LRTCs): quantitative

(specificity of diagnosis) or semi-quantitative; non- or bronchoscopical collection for all cases

• Negative LRTCs: may stop ABx without ABx changes in the past 72 hrs

Executive Summary(2)

• Early, appropriate, broad-spectrum, antibiotic therapy with adequate doses to optimize antimicrobial efficacy

• Empiric regimen should include with a different antibiotic class agents than those recently received

• Combination therapy for a specific pathogen • Consideration of short-duration (5 days) amin

oglycoside, when used in combination with a β-lactam to treat P. aeruginosa pneumonia

Executive Summary(3)

• Linezolid: an alternative to vancomycin; may have an advantage for proven VAP due to MRSA (unconfirmed, preliminary data)

• Colistin: considered in VAP due to a carbapenem-resistant Acinetobacter species

• Aerosolized antibiotics: may have value as adjunctive therapy in VAP due to some MDR pathogens

• De-escalation of ABx: should be considered once; according to the results of LRTCs and the patient’s clinical response