Transcript Pre-ICU training (Antibiotics) 馬偕紀念醫院 感染科 郭建峯醫師

Pre-ICU training (Antibiotics)
馬偕紀念醫院
感染科
郭建峯醫師
(%) 16
台北院區院內感染常見10種致病菌歷年變化
14
E. coli
12
P. aeruginosa
*C. albicans
10
Yeast form fungi
K. pneumoniae
8
S. aureus
Enterococcus
6
*A. baumannii
Coag. (-) staph.
4
E.cloacae
2
*2000年開始鑑定
0
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
YEAR
台北院區院內感染各部位感染發生密度（2007年）
Incidence Rate (‰)
1. 95
2
1.71
UTI
BSI
1.5
SSI
LRI
1
0.45
0.5
EENTI
0.53
0.120.13 0.09 0.06
GISI
SSTI
0
Other Site
Incidence rate is the number of isolates reported per 1000 patietn days
台北院區院內感染各部位分佈圖（2007年）
12.6
10.5
10.5
1.01.5
UTI
BSI
1.8
EENTI
1.9
GISI
SSI
LRI
28.9
41.6
Other Site
SSTI
All infections = 1,593
台北院區院內感染常見的15種致病菌（2007年）
B. fragilis
1.2
Rotavirus
Total 1,717
Other Streptococcus
1.4
1.5
Other GNF bacteria
1.7
S. marcescens
1.7
E. cloacae
2.7
Coagulase(-) Staphylococcus
4.3
Enterococus
7.7
K. pneumoniae
8.6
P. aeruginosa
8.9
C. albicans
9.3
S. aureus
9.5
A. baumannii
9.9
10.1
10.3
0.0
2.0
4.0
6.0
8.0
10.0
Yeast form fungi
E. coli
12.0
%
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）
PATHOGEN
LRI
SSI
GISI
EENT
I
BSI
UTI
SSTI
Other
s
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
90
182
29
10
583
784
26
13
1,717
100.00
NUMBER OF
ISOLATES
台北院區院內感染UTI常見的致病菌（2007年）
Citrobacter spp.
0.9
M. morganii
Total 784
0.8
Corynebacter spp.
0.8
0.9
Other streptococcus
1
S. marcescens
1.1
Coagulase(-) staphylococcus
1.4
P. mirabilis
2.3
%
S. aureus
2.6
E. cloacae
8.5
8.9
A. baumannii
9.9
Enterococcus
11.7
K. pneumoniae
13.5
P. aeruginosa
16.3
E. coli
17.9
C. albicans
0
5
10
15
20
Yeast form fungi
台北院區院內感染LRTI常見的致病菌（2007年）
Enterococcus
K. pneumoniae
1.1
Total 90
1.1
E. cloacae
1.1
H. influenzae
1.1
1.1
%
Other GNF bacteria
3.3
S. maltophilia
8.9
11.1
P. aeruginosa
15.6
55.6
S. aureus
RSV
0
10
20
30
40
50
60
A. baumannii
台北院區院內感染SSI常見的致病菌（2007年）
All others
12.1
Corynebacter spp.
1.6
A. baumannii
2.2
Total 182
M. morganii
2.2
Yeast form fungi
2.2
Anaerobic G(+) cocci
2.7
3.3
%
K. pneumoniae
3.3
E. coli
3.8
C. albicans
5.5
Coagulase(-) staphylococcus
6.6
B. fragilis
6.6
7.1
Other streptococcus
9.9
Fusobacterium spp.
12.1
18.7
Enterococcus
P. aeruginosa
0
5
10
15
20
S. aureus
台北院區院內感染BSI常見的致病菌（2007年）
All others
11.3
Klebsiella spp.
1
1.4
S. maltiohilia
1.4
Total 583
B . cepacia
3.3
S. marcescens
3.6
%
3.8
E . cloacae
3.9
Other GNF bacteria
3.9
C. albicans
6.7
P. aeruginosa
7
Y east form fungi
8.1
E nterococcus
9.1
10.1
A. baumannii
10.8
Coagulase(-) staphylococcus
14.6
K. pneumoniae
E . coli
0
5
10
15
S. aureus
台北院區院內感染SSTI常見的15種致病菌（2007年）
3.8
H. influenzae
3.8
Total 26
S. marcescens
3.8
E. cloacae
3.8
Group B streptococcus
7.7
%
K. pneumoniae
7.7
E. coli
7.7
7.7
Corynebacter spp.
11.5
Enterococcus
30.8
P. aeruginosa
S. aureus
0
10
20
30
40
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,
Clindamycin, Glycopeptide (Vancomycin,
Teicoplanin)
Methocillin-resistant S. aureus (MRSA) :
 首選藥物:Glycopeptide (Vancomycin,
Teicoplanin)
 替代藥物: Linezolid
 Fusidic acid
 Rifampicin
Streptococcus pneumoniae
 Penicillin-sensitive菌株首選藥物(first choice):
Penicillin G
Categories of Susceptibility of S. pneumoniae to
Penicillin
Minimal inhibitory
concentration (MIC)
Degree of resistance
<0.06 ug/mL
Susceptible
0.12 to 1 ug/mL
Intermediate
> 2 ug/mL
Resistant
NCCLS 2001
Treatment of S. pneumoniae Pneumonia
Penicillin
MIC (g/ml)
primary
alternative
1
(S)
penicillin
ampicillin or amoxicillin
2
(I)
penicillin (high dose)
ampicillin or amoxicillin
4
(R)
3rd or 4th cephalosporins vancomycin or teicoplanin
vancomycin or teicoplanin + rifampin or newer
fluoroquinolones
1st cephalosporins
3rd or 4th cephalosporins
The infectious diseases society R.O.C. 2000
Treatment of Pneumococcal Meningitis
MIC (g/ml)
PCN
CTX
<0.12
0.5
0.12
dosage
therapy
adults
children (/kg)
penicillin
300,000 u/kg/d
3-400,000 u q4-6h
0.5
Cefotaxime or
Ceftriaxone
2 g q6h
2 g q12h
200-225 mg q6-8h
100 mg q12-24h
1.0
Cefotaxime or
Ceftriaxone
+Vancomycin
300 mg/kg/d (m.24g)
2 g q12h
60 mg/kg/d (M.2g)
300 mg q6-8h
100 mg q12-24h
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
(Pneumonia, 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):
high 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
cephalosporins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
•
1.
2.
3.
•
•
Most common possible etiologies:
Cystitis & pyelonephritis
Emphysematous pyelonephritis.(DM)
Acute bacterial prostatitis
首選藥物(first choice):
-lactam antibiotics + aminoglycosides。
台灣地區第一線可用cefazolin， 80% 對
ampicillin 抗藥性。
Klebsiella sp. & Escherichia coli
 In vitro resistant to any of the third generation
cephalosporins
 Strain produced an extended-spectrum lactamases (ESBL)
 Resistance to all penicillins, cephalosporins &
aztreonam
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),
Imipenem-cilastatin, Meropenem
Pseudomonas aeruginosa
•
•
•
•
•
•
•
•
Habitat:
GIT of humans & animals, environment
Water; survives in hospitals (In antiseptics)
Obligate aerobe, gram-negative rods, polar flagella,
oxidase 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 aeruginosa
Antipseudomonal 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
(Tienam®) / Meropenem
 替代藥物: Ampicillin/sulbactam (Unasyn® ) or
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
proved
• 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,
enterococcal )
• 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
bacteremia Gentamicin + Ampicillin or penicillin
G
 Viridans streptococci endocarditis:
Gentamicin + penicillin G
 MRSA or S. epidermidis : prosthetic valve
endocarditis Vancomycin+ Gentamicin
 Listeria mononcytogenes: Ampicillin +
Gentamicin
 Serious Pseudomonas aeruginosa infection
Aminoglycosides + Anti-Pseudomonal agents
Pseudomonas aeruginosa
 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.
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, Ventilatorassociated, and Healthcare-associated
Pneumonia
Am. J. Respir. Crit. Care Med. 2005; 171: 388-416
Contents
•
•
•
•
•
•
•
•
Executive Summary
Recommended Diagnostic Strategy
Introduction
Major Points and Recommendations for
Comparing Diagnostic Strategies
Methodology Used to Prepare the
Guideline
•
Antibiotic Treatment of Hospitalacquired Pneumonia
Epidemiology
General Approach
Incidence
Initial Empiric Antibiotic Therapy
Etiology
Appropriate Antibiotic Selection and
Major Epidemiologic Points
Adequate Dosing
Pathogenesis
Local Instillation and Aerosolized Antibiotics
Major Points for Pathogenesis
Combination versus Monotherapy
Modifiable Risk Factors
Duration of Therapy
Intubation and Mechanical Ventilation
Major Points and Recommendations for
Aspiration, Body Position, and Enteral
Optimal
Feeding
Antibiotic Therapy
Modulation of Colonization: Oral Antiseptics
Specific Antibiotic Regimens
and Antibiotics
Antibiotic Heterogeneity and Antibiotic
Stress Bleeding Prophylaxis, Transfusion,
Cycling
and Glucose Control
•
Response to Therapy
Major Points and Recommendations for
Modifiable Risk Factors
Modification of Empiric Antibiotic Regimens
Diagnostic Testing
Defining the Normal Pattern of Resolution
Major Points and Recommendations for
Reasons for Deterioration or Nonresolution
Diagnosis
Evaluation of the Nonresponding Patient
Diagnostic Strategies and Approaches Major Points and Recommendations for
Clinical Strategy
Assessing Response to Therapy
Bacteriologic Strategy
•
Suggested Performance Indicators
Executive Summary(1)
• Official statement of ATS/IDSA, evidencebased
• HCAP: included in the spectrum of HAP/VAP,
need 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)
aminoglycoside, 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