重症病患之抗生素使用原則重症病患之抗生素使用原則

財團法人為恭紀念醫院財團法人為恭紀念醫院感染科 曾政尹 醫師感染科 曾政尹 醫師

抗生素使用抗生素使用一般原則重症病患使用原則 ( 降階治療 )重症感染抗藥性問題結語

抗生素一般使用原則抗生素一般使用原則Narrow spectrumNarrow spectrum一種細菌用一種藥物治療一種細菌用一種藥物治療足量藥物治療足量藥物治療完整療程完整療程

- Balance between- Balance between Efficacy Efficacy and and Collateral Collateral

damage !damage !

Choice of proper antimicrobial agentChoice of proper antimicrobial agent

Identity of the infecting Identity of the infecting ORGANISMORGANISM

Information about the Information about the ANTIMICROBIALANTIMICROBIAL

SUSCEPTIBILITYSUSCEPTIBILITY

HOSTHOST FACTORSFACTORS

Golden TriangleGolden Triangle

Antimicrobial agent

Microorganism Host

Immune system

Microbiological

profilePharmacokinetics

Host factorsHost factors

HISTORYHISTORY of previousof previous ADVERSEADVERSE reactions toreactions to

antibiotics.antibiotics. AGEAGE GENETIC or METABOLIC ABNORMALITIESGENETIC or METABOLIC ABNORMALITIES PREGNANCYPREGNANCY RENALRENAL andand HEPATICHEPATIC functionfunction SITESITE of infectionof infection

Initial Selection of Antibiotics

SUSPECTED DIAGNOSIS

CLINICAL EVALUATION (site of infection, host, lab. data)

Initial Selection of Penicillin-G

1.1. PENUMOCOCCAL INFECTIONPENUMOCOCCAL INFECTION

2.2. STREPTOCOCCAL INFECTIONSTREPTOCOCCAL INFECTION

3.3. MENINGOCOCCAL INFECTIONMENINGOCOCCAL INFECTION

4.4. GONOCOCCAL INFECTIONGONOCOCCAL INFECTION

5.5. ANAEROBIC GRAM + & GRAM - BACTERIAL INFECTIONANAEROBIC GRAM + & GRAM - BACTERIAL INFECTION††

6.6. ACTINOMYCOSISACTINOMYCOSIS

7.7. ANIMAL BITE (ANIMAL BITE (Pasteurella multocidaPasteurella multocida))

8.8. DIPHTHERIADIPHTHERIA

9.9. SYPHILISSYPHILIS

10.10. LEPTOSPIROSISLEPTOSPIROSIS

†† Except Except B. tragilisB. tragilis

Third Generation Cephalosporins

Resistant Gram-negative microorganismsResistant Gram-negative microorganisms

（（ Nosocomial infectionsNosocomial infections ））––

Serratia, Citrobacter, Enterobacter, Serratia, Citrobacter, Enterobacter,

Pseudomonas, Pseudomonas, ββ-lactamase producing-lactamase producing

H. influenzaeH. influenzae.. Better BBB penetrationBetter BBB penetration among cephalosporins among cephalosporins

(except cefoperazone)(except cefoperazone)

Indications of Third-generaIndications of Third-generation Cephalosporinstion Cephalosporins

Absolute indicationAbsolute indication

~ GNB ~ GNB meningitismeningitis Relative indicationRelative indication

~ ~ nosocomial infectionsnosocomial infections (mainly (mainly GNBGNB))

Extended-spectrum -lactamase (ESBL)

1963~ 1963~ E.coliE.coli ：： TEM-1,4,6,12,19TEM-1,4,6,12,19 、、 SHV-1SHV-1….…. 1984~ 1984~ K. pneumoniaeK. pneumoniae ：： TEM-3, 5, 8, 9, 10, TEM-3, 5, 8, 9, 10,

11…11… 、、 SHV-3, 4, 5SHV-3, 4, 5 1969~ 1969~ P. aeruginosaP. aeruginosa ：： TEM-2TEM-2 1990~ 1990~ M. morganiiM. morganii ：： TEM-13TEM-13 Proteus mirabilisProteus mirabilis

Antimicrobial Agents And Chemotherapy 1131-1136, 1989

抗生素使用抗生素使用一般原則重症病患使用原則 ( 降階治療 )重症感染抗藥性問題結語

The Role of The Role of De-escalation TherapyDe-escalation Therapy

Getting It Right From Start To FinishGetting It Right From Start To Finish

De-escalation De-escalation ttherapyherapy ( ( 降階治降階治療療 ))

Stage 1Stage 1 - - improve outcomesimprove outcomes ↳↳ decrease mortality decrease mortality prevent organ dysfunctionprevent organ dysfunction decrease length of stay decrease length of stay

Stage 2Stage 2 - - minimize resistanceminimize resistance - - improve cost-effectivenessimprove cost-effectiveness

De-escalation therapy (De-escalation therapy ( 降階治療降階治療 ))

適當的起始治療適當的起始治療是決定重症病患治療結果的一項是決定重症病患治療結果的一項 重要因子。重要因子。 以以「「適當適當」」 (appropriate)(appropriate) 治療涵蓋治療涵蓋「「足夠足夠」」 (adequate)(adequate) 治療的概念。治療的概念。 目標：目標：「「在在提供給高危險群病患足夠的起始抗生提供給高危險群病患足夠的起始抗生 素治療，和避免會造成抗藥性的不必要抗生素素治療，和避免會造成抗藥性的不必要抗生素使使

用，兩者之間取得平衡用，兩者之間取得平衡。。」」

Initial Appropriate TherapyInitial Appropriate Therapy

Serious infectionSerious infection: empiric broad-spectrum : empiric broad-spectrum

therapytherapy Antibiotic: Antibiotic: coverage of all likely pathogenscoverage of all likely pathogens.. Hitting hard: Hitting hard:

- local microbiological data - local microbiological data

- correct pathogens will be covered- correct pathogens will be covered

(( 每一個醫療機構都要根據當地最新的微生物數據每一個醫療機構都要根據當地最新的微生物數據 ，，以評估可能的感染性病原菌和敏感性型態。以評估可能的感染性病原菌和敏感性型態。 ))

Local microbiological dataLocal microbiological data

De-escalateDe-escalate

CCulture resultsulture results

CClinical responselinical response

Choose broad-spectrum, empiric treatment regimen Choose broad-spectrum, empiric treatment regimen based onbased on clinical symptomsclinical symptoms andand unit-specificunit-specific

antibiogram dataantibiogram data andand guidelinesguidelines. Obtain culture prior . Obtain culture prior to antibiotic administration.to antibiotic administration.

Obtain and analyze microbiological dataObtain and analyze microbiological data

Modify regimen accordinglyModify regimen accordingly

Reassess patientReassess patient

Process for Initial Appropriate TherapyProcess for Initial Appropriate Therapy

Factors in Selecting Initial Factors in Selecting Initial Appropriate TherapyAppropriate Therapy

Patient featuresPatient features

~ based on site and severity of infection ~ based on site and severity of infection

~ assessment of deterioration and mortality~ assessment of deterioration and mortality Local susceptibility and epidemiologyLocal susceptibility and epidemiology Initial antibiotic therapy dosing and durationInitial antibiotic therapy dosing and duration Combination vs. monotherapyCombination vs. monotherapy

~ broad enough coverage~ broad enough coverage

~ avoid emergence of resistance~ avoid emergence of resistance

~ have the potential for synergy~ have the potential for synergy

Indications for CombinationIndications for Combination

SYNERGISMSYNERGISM PseudomonasPseudomonas group group

infectionsinfections Severe sepsisSevere sepsis Initial therapy/Unknown Initial therapy/Unknown

etiologyetiology Mixed infection Mixed infection

(Polymicrobial infection(Polymicrobial infections)s)

Anti-TB treatmentAnti-TB treatment Immunocompromised Immunocompromised

hosthost Decreased toxicityDecreased toxicity Prevention of emergence Prevention of emergence

of resistant organismof resistant organism

Initial Empiric Antibiotic TherapyInitial Empiric Antibiotic Therapy

Early onset or late onsetEarly onset or late onset Different antibiotic class: if recent Different antibiotic class: if recent

exposure to a class of antibioticsexposure to a class of antibiotics Appropriate & adequate antibiotic dosageAppropriate & adequate antibiotic dosage Local antibiotics susceptibility patterns Local antibiotics susceptibility patterns

((regular updateregular update)) De-escalation therapy De-escalation therapy

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

Initial Inadequate TherapyInitial Inadequate Therapy

The antibiotic did not cover the infecting

pathogen(s).1,2

The pathogen was not susceptible to the

antibiotic due to resistance.1,2

Dosing was not adequate. Further consideration: combination therapy was

not used, if indicated.

→→ increase mortalityincrease mortality

1Kollef MH et al. Chest 1999;115:462-474.2Ibrahim EH et al. Chest 2000;118:146-155.

Appropriate Therapy Leads to Lower Appropriate Therapy Leads to Lower Mortality in Gram-Negative SepsisMortality in Gram-Negative Sepsis

<0.001<0.00149%49%

(47-51%)(47-51%)

28%28%

(22-32%)(22-32%)

TotalTotal

<0.001<0.00129%29%

(23-31%)(23-31%)

10%10%

(0-13%)(0-13%)

Non-fatalNon-fatal

<0.001<0.00167%67%

(63-72%)(63-72%)

42%42%

(39-45%)(39-45%)

Ultimately Ultimately fatalfatal

NSNS85%85%

(71-100%)(71-100%)

84%84%

(80-86%)(80-86%)

Rapidly fatalRapidly fatal

P-valueP-valueMortality without appropriate Mortality without appropriate therapy Combined data therapy Combined data

(range)(range)

Mortality with appropriate Mortality with appropriate therapy Combined data therapy Combined data

(range) (range)

Underlying Underlying DiseaseDisease

Bochud P-Y et al. Intensive Care Med 2001;27:S33-S48.

Mortality Associated With Initial Inadequate Mortality Associated With Initial Inadequate Therapy In Critically Ill Patients With Serious Therapy In Critically Ill Patients With Serious

Infections in the ICUInfections in the ICU

0% 20% 40% 60% 80% 100%

Luna, 1997

Ibrahim, 2000

Kollef, 1998

Kollef, 1999

Rello, 1997

Alvarez-Lerma,1996 Initial appropriatetherapy

Initial inadequatetherapy

*Mortality refers to crude or infection-related mortalityAlvarez-Lerma F et al. Intensive Care Med 1996;22:387-394.Ibrahim EH et al. Chest 2000;118L146-155.Kollef MH et al. Chest 1999; 115:462-474Kollef MH et al. Chest 1998;113:412-420.Luna CM et al. Chest 1997;111:676-685.Rello J et al. Am J Resp Crit Care Med 1997;156:196-200.

Mortality*

Reassess therapy whenReassess therapy when

Etiologic agent identifiedEtiologic agent identified

Antibiotic sensitivities establishedAntibiotic sensitivities established

抗生素使用抗生素使用一般原則重症病患使用原則 ( 降階治療 )重症感染抗藥性問題結語

Empirical Broad-Spectrum Empirical Broad-Spectrum Antimicrobial TherapyAntimicrobial Therapy

~ ~ Critically ill patients with serious infectionsCritically ill patients with serious infections Ventilator-associated Ventilator-associated pneumoniapneumonia (VAP) (VAP) Nosocomial Nosocomial pneumoniapneumonia Severe community-acquired Severe community-acquired pneumoniapneumonia Bloodstream infection (Bloodstream infection (BSIBSI)) MeningitisMeningitis

Hospital acquired infection Hospital acquired infection -- 定義定義An infection found to be An infection found to be activeactive, or , or under under

active treatmentactive treatment at the time of the survey, at the time of the survey, which as which as not present on admissionnot present on admission..

In general: after In general: after 48 hours48 hours of admission. of admission.Established infection which has Established infection which has resulted resulted

from an earlier admissionfrom an earlier admission (incubated on (incubated on admission) admission)

Patients With VAP Suffer ExcessPatients With VAP Suffer Excess Morbidity and MortalityMorbidity and Mortality

32.3% relative risk increase in 32.3% relative risk increase in mortalitymortality Significantly Significantly longer durationlonger duration of hospital of hospital

stay (19 vstay (19 v..s. 14 days, p<0.001)s. 14 days, p<0.001) Trend towards longer attributable Trend towards longer attributable length length

of stay in the ICUof stay in the ICU with infection caused by with infection caused by

high risk organismshigh risk organisms (9.1 vs. 2.9 days) (9.1 vs. 2.9 days)

Heyland DK. Am J Respir Crit Care Med 1999;159:1249-1256.

Spectrum of Potential Pathogens in Hospital-Acquired Pneumonia*Based on Severity of Illness

Campbell GD et al. Am J Respir Crit Care Med 1996;153:1711-1725

* Excludes patients with immunosuppression.** Includes severe HAP without risk factors (early onset)

*** Severe HAP with risk factors (onset any time) or severe HAP without unusual risk factors (late onset)

Mild-to-Moderate(With risk factors) Severe***

Core OrganismsEnteric GNB

Core Organisms, PlusAnaerobes

Core Organisms, PlusP. aeruginosa

(Non-pseudomonal) (recent abdominal • Enterobacter surgery; witnessed Acinetobacter

• E. coli aspiration) species

• Klebsiella • Proteus Consider MRSA • Serratia marcescens

Haemophilus influenzae

S. aureus(including MRSAif coma, head trauma,DM, renal failure)

Methicillin-sensitive Legionella Staphylococcus aureus (high-dose steroids)

Streptococcus pneumoniae P. aeruginosa(prolonged ICU,

steroids, antibiotics)structural lung disease,

Mild-to-Moderate(No unusual risks)**

HAP: risk factors for HAP: risk factors for resistant pathogensresistant pathogens

Late onset (Late onset (≥≥5 days)5 days) Prior antibiotic usePrior antibiotic use Comorbid illnessComorbid illness Intensive care unit (ICU)Intensive care unit (ICU)

Risk Factors for Resistance in VAPRisk Factors for Resistance in VAP

Use of antibiotics within 15 daysUse of antibiotics within 15 days11

Duration of hospitalizationDuration of hospitalization22

Duration of mechanical ventilation Duration of mechanical ventilation ≥≥ 7 7

daysdays11

1Trouillet J-L et al. Am J Respir Crit Care Med 1998;157:531-539.

2Lautenbach E et al. Clin Infect Dis 2001;32:1162-1171.

Risk Factors for Resistance in VAPRisk Factors for Resistance in VAP

Adapted from Trouillet J-L et al. Am J Respir Crit Care Med 1998;157:531-539.

MRSA, MRSA, P. aeruginosaP. aeruginosa, , A. baumanniiA. baumannii, ,

S. maltophiliaS. maltophilia

More More sensitive sensitive bacteria thanbacteria thanin Group 2in Group 2

More More resistant resistant bacteria than bacteria than in Group 3in Group 3

Antibiotic-sensitiAntibiotic-sensitive organisms (e.ve organisms (e.g., pneumococci, g., pneumococci,

H. influenzaeH. influenzae))

MV MV ≥7 days; ≥7 days; prior use of prior use of antibioticsantibiotics

MV MV ≥7 days; ≥7 days; no prior no prior antibioticsantibiotics

MV <7 days; MV <7 days; prior use ofprior use of antibioticsantibiotics

MV <7 days; MV <7 days; no prior no prior antibioticsantibiotics

Group 4Group 4Group 3Group 3Group 2Group 2Group 1Group 1

ATS recommendations: IATS recommendations: I

Early onset VAP & no risk factorsEarly onset VAP & no risk factors Pathoge Pathogens: ns: S. pneumoniaeS. pneumoniae, , H. influenzaeH. influenzae, , S. aureusS. aureus, non-resistant GNB Regimen: c, non-resistant GNB Regimen: cephalosporin II or IIIephalosporin II or III quin quinolone III or IVolone III or IV -lac-lactam/ tam/ -lactamase inhibitor -lactamase inhibitor Monotherapy is Monotherapy is adequateadequate

ATS recommendations: IIATS recommendations: II

Late onset VAP, early onset VAP with risk factorsLate onset VAP, early onset VAP with risk factors

Pathogens: resistant GNB, Pathogens: resistant GNB, P. aeruginosaP. aeruginosa,, MRSAMRSA

Regimen: Carbapenem, Tazocin, Ceftazidime,Regimen: Carbapenem, Tazocin, Ceftazidime,

+ quinolone or aminoglycoside + quinolone or aminoglycoside

+/- vancomycin +/- vancomycin

Combination therapy is betterCombination therapy is better

血流感染血流感染 ((Bloodstream Infection)Bloodstream Infection)

病人病人住院以後住院以後 , , 血流遭受微生物侵入所引血流遭受微生物侵入所引起起

之感染。之感染。 Mortality rateMortality rate: 15% : 15%

- In critically ill patient: 12 ~ 25% - In critically ill patient: 12 ~ 25% Vascular cathetersVascular catheters: : 87%87% in critically-ill in critically-ill

patientspatients

Prevention and Control of Nosocomial Infections, 4th ed. P.281-2

Resistant Pathogens Account for High Number Resistant Pathogens Account for High Number of Bloodstream and Nosocomial Infectionsof Bloodstream and Nosocomial Infections

Kollef MH et al. Clin Inf Dis 2000;31(Suppl. 4):S131-S138.

Coagulase-negativeStaphylococci

P= .001

0

10

20

30

40

50

Bloodstream infection

Nosocomial pneumonia Urinary tract infection

Invasive device present

Per

cen

tag

e o

ccur

renc

e

P. aeruginosaP= .002

A. baumanniiP= .006 E. coli

P= .023

C. albicansP= .009

Invasive device absent

CVC-Associated Bloodstream InfectionCVC-Associated Bloodstream Infection

Skin commensals: Skin commensals: ≥≥2 blood cultures2 blood culturesDiphtheroids Diphtheroids

BacillusBacillus spp. spp.

Propionibacterium Propionibacterium spp.spp.

Coagulase-negative staphylococciCoagulase-negative staphylococci

MicrococciMicrococci

抗生素使用抗生素使用一般原則重症病患使用原則 ( 降階治療 )重症感染抗藥性問題結語

抗藥性細菌增加的原因抗藥性細菌增加的原因抗藥性細菌抗藥性細菌產生增加產生增加 (( 抗生素選擇性壓力抗生素選擇性壓力 , ,

selection pressureselection pressure):): 由於醫師過多的使用抗由於醫師過多的使用抗 生素生素 , , 造成對造成對基因突變基因突變及及抗藥基因轉移抗藥基因轉移的抗藥的抗藥 性細菌進行了篩選。性細菌進行了篩選。抗藥性細菌抗藥性細菌傳播增加傳播增加 :: 透過透過醫護人員醫護人員 (( 尤其尤其手手 ))

的接觸的接觸 , , 細菌在病患間交叉寄生細菌在病患間交叉寄生 , , 造成在造成在醫院醫院 內內傳播傳播 ; ; 之後並經由宿主病人的轉移之後並經由宿主病人的轉移 , , 在在醫院醫院 間間甚至甚至社區社區進行傳播。進行傳播。

抗生素的抗藥性抗生素的抗藥性 (ICU, 2004 NNIS Repor(ICU, 2004 NNIS Report)t)

抗生素的抗藥性抗生素的抗藥性 (2004 NNIS Repor(2004 NNIS Report)t)

哪些抗生素的附加損害哪些抗生素的附加損害(collateral damage)(collateral damage) 最大最大 ??

CephalosporinCephalosporinFluoroquinoloneFluoroquinoloneCarbapenemCarbapenemββ-lactam/-lactam/ββ-lactamase inhibitor-lactamase inhibitorAminoglycosideAminoglycosideMacrolideMacrolide

Collateral damageCollateral damage

~ ~ High riskHigh risk 22ndnd/3/3rdrd Gen. cephems: Gen. cephems:

ESBLsESBLs Fluoroquinolones:Fluoroquinolones:

MRSA, ESBLs, MRSA, ESBLs,

MDR MDR P. aeruginosaP. aeruginosa Carbapenems (imipeneCarbapenems (imipene

m, meropenem): m, meropenem):

MDRAB, MDRPAMDRAB, MDRPA

~ ~ Low riskLow risk ββ-lactam/-lactam/ββ-lactamase -lactamase

inhibitorinhibitor 44thth Gen. cephems Gen. cephems

Multidrug-Resistant Organisms (MDROs)Multidrug-Resistant Organisms (MDROs)

- - Gram-positiveGram-positive::

S. aureusS. aureus

Coagulase-negative staphylococcusCoagulase-negative staphylococcus

Streptococcus pneumoniaeStreptococcus pneumoniae

--

Enterococcus spp.Enterococcus spp.

- VRE - VRE

- - Gram-negativeGram-negative: : MDR-GNBMDR-GNB P. aeruginosaP. aeruginosa

E. coliE. coli

K. PneumoniaeK. Pneumoniae

Enterobacter spp.Enterobacter spp.

- - 33rdrd cephem cephem

- - QuinoloneQuinolone

- - CarbapenemCarbapenem

- MRSA, VISA, VRSA

- MRCNS

MDRSP

Most Frequently Reported Pathogens from Most Frequently Reported Pathogens from ICU Patients with Nosocomial PneumoniaICU Patients with Nosocomial Pneumonia

1. Pseudomonas aeruginosa

2. Staphylococcus aureus

3. Enterobacter spp.

4. Klebsiella pneumoniae

5. Acinetobacter spp.

Richards MJ et al. Crit Care Med 1999; 887-892.

9595 年年 TNISTNIS 加護病房院內感染最常見菌株前三加護病房院內感染最常見菌株前三名名

醫學中心醫學中心：： Pseudomonas aeruginosaPseudomonas aeruginosa

Escherichia coliEscherichia coli

Acinetobacter baumanniiAcinetobacter baumannii

區域醫院區域醫院：： Pseudomonas aeruginosaPseudomonas aeruginosa

Klebsiella pneumoniaeKlebsiella pneumoniae

Acinetobacter baumanniiAcinetobacter baumannii

Preventing the emergence and transPreventing the emergence and transmission of MDROsmission of MDROs

AdministrativeAdministrative involvement and measures involvement and measures Education and training of personnelEducation and training of personnel Judicious antibiotic useJudicious antibiotic use Comprehensive Comprehensive surveillancesurveillance for targeted MDROs for targeted MDROs Application of Application of infection controlinfection control precautions precautions EnvironmentalEnvironmental measures measures Decolonization therapy when appropriateDecolonization therapy when appropriate

–The prevention and control of MDROs is a national priority.

Control of antibiotic resistance will mandate Control of antibiotic resistance will mandate

more effective more effective nosocomial infection controlnosocomial infection control

and and

more more restrictive use of anti-infectivesrestrictive use of anti-infectives..

- Ann Intern Med- Ann Intern Med. 2002;136:834-44. . 2002;136:834-44.

- Ann Intern Med. - Ann Intern Med. 2006;145:582-591.2006;145:582-591.

抗生素使用抗生素使用一般原則重症病患使用原則 ( 降階治療 )重症感染抗藥性問題結語

SummarySummary

Initial inadequate therapyInitial inadequate therapy:: Inadequate initial empiric therapy leads to increased Inadequate initial empiric therapy leads to increased

mortalitymortality in patients with serious infection. in patients with serious infection.

Initial appropriate therapyInitial appropriate therapy:: Means starting with a broad-spectrum antibiotic and then Means starting with a broad-spectrum antibiotic and then

focusing based on focusing based on clinicalclinical and and microbiological microbiological data.data. Should be based on Should be based on patient stratificationpatient stratification, and , and local local

epidemiology and susceptibility patternsepidemiology and susceptibility patterns.. Includes use of appropriate Includes use of appropriate drugdrug, , dosedose, and , and durationduration..

De-escalation TherapyDe-escalation Therapy

Get It Right The First TimeGet It Right The First Time

Prevent rapid declinePrevent rapid decline Avoid resistanceAvoid resistance Save livesSave lives

Antibiotic TherapyAntibiotic Therapy

Know your bugsKnow your bugs Adhere to antibiotic guidelinesAdhere to antibiotic guidelinesGive appropriate dosageGive appropriate dosageNarrow spectrum once culture and Narrow spectrum once culture and

susceptibility is availablesusceptibility is availableTreat for shorter periodsTreat for shorter periods

Antibiotic TherapyAntibiotic Therapy

In the current era of resistance, drugs can In the current era of resistance, drugs can

no longer be held “In Reserve”no longer be held “In Reserve”

Don’t use those antibiotics implicated in Don’t use those antibiotics implicated in

collateral damagecollateral damage

Therapy and Infection ControlTherapy and Infection Control

Isolation of patient and contact precaution Isolation of patient and contact precaution

or cohort careor cohort careTreat infection, Treat infection, not colonizationnot colonizationAseptic technique and hand washingAseptic technique and hand washing

MDRABMDRAB: carbapenem + sulbactam, : carbapenem + sulbactam,

tigecycline, colistin.tigecycline, colistin.

結語結語照顧重症病患的工作人員必須要有高度的照顧重症病患的工作人員必須要有高度的 警覺心，以能及時思考感染的診斷正不正警覺心，以能及時思考感染的診斷正不正 確。確。Use Use culture dataculture data and and clinical responseclinical response to to

focus therapy and shorten the duration of focus therapy and shorten the duration of

therapy, or stop therapy.therapy, or stop therapy.

Thank you for your attention !