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THE DIAGNOSTIC AND THERAPEUTIC DEVELOPMENT OF HOSPİTAL

ACQUIRED PNEUMONIA

Turhan Ece, MDProfessor of Pulmonary Medicine

İstanbul University, İstanbul Medical School,Department of Pulmonary Medicine

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HEALTCARE ASSOCIATED PNEUMONIA

• Hospital Acquired Pneumonia

(HAP)

• Ventilator Associated Pneumonia

(VAP)

• HealtCare Associated Pneumonia (HCAP)

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HEALTCARE ASSOCIATED PNEUMONIA

• HAP; occurs ≥ 48 hours after admission

• VAP; occurs ≥ 48 hours after intubation

• HCAP; occurs ≥ 48 hours hospitalized within 90 days, resided in a nursing home, received recent IV antibiotic, chemotherapy, or wound care within the past 30 days, attended a hemodialysis clinic

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HEALTCARE ASSOCIATED PNEUMONIA

• HAP, VAP, HCAP• Multidsiplinary• Epidemiology and Pathogenesis• Modifiable risk factors• The variability of bacteriology• Early onset pneumonia without MDR*

pathogen riskLate onset pneumonia with MDR* pathogen risk

*P.aeruginosa, Acinetobacter spp, MRSA

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HAP- Epidemiology

• The socond most common nosocomial infection

• HAP increases hospital stay 7-9 days and cost 40.000 USD

• HAP occurs 5-10 cases per 1000 hospital admission ( 6-20 fold in MV patients)

• HAP accounts 25 % of all ICU infections

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

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The Epidemiology of HCAP• An increase in mortolity for HAP and VAP is

associated with MDR pathogens• Bacteria cause most cases of HAP and VAP is

polymicrobial espacially high in patients with ARDS• HAP, VAP, and HCAP are commonly caused

by AGNB ( P.aeruginosa,K.pneumoniae,

Acinetobacter sp. Enterobacter sp.) 55- 85%

by GPC ( S.aureus, MRSA) 20- 30%• Rates of L.pneumophila is high when water supply

colonisation and ongoing construction• Nosocomial virus and fungal infections are

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

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VAP- Epidemiology

• VAP occurs in 9-27 % of all ıntubated patients• During the first 5 days 3%

During 5 to 10 days 2%

After 10 days 1%• Half of VAP occur within 4 days of MV

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The Pathogenesis of HAP

• Sources of pathogenesis for HAP include healthcare devices, the environment and the transfer of microorganism

• Host and treatment related colonization factors; severity of underlying disease, prior surgery, exposure to antibiotics and invasive respiratory devices

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The Pathogenesis of HAP

• Aspiration of oropharyngeal pathogens, or leakage of secretions

• Inhalation or direct inoculation of pathogens, hematogenous spread from infected IV catheters

bacterial translocation from GI tract

• Infected biofilm in the tracheal tube

• The stomach and sinuses may be potential reservoirs

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Clasification of HAP and VAP

• Early- onset HAP and VAP

Occurring within the first 4 days

Caused by antibiotic sensitive bacteria

Prior antibiotics or hospitalization within 90 days are at greater risk for MDR

• Late- onset HAP and VAP

Occurring after 4 days

Caused by MDR pathogens

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HCAP- Risk factors for MDR pathogens

• Antimicrobial therapy in preceiding 90 d• Current hospitalization of 5 d or more• High frequency of antibiotic resistance in the

community or hospital unit• Presence of risk factors for HCAP:

Hospitalization for ≥ 2 d within 90 dResidence nursing home or extended care facilityHome infusion therapy, wound careChronic dialysis within 30 dFamily member with MDR pathogen

• Immunosupressive disease and/ or therapyAJRCCM 2005; 171: 388- 416

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The Pathogen of HAP and VAP in Turkey (%)

P. aeruginosa

Acinetobacter sp.

Klebsiella spp.

S.aureus

HAP

23-24

23-36

15-17

14-17

ICU

35-36

13-31

17-18

27-28

VIP

4-26

20-66

7-21

12-54

Toraks Dergisi 2002;3 Ek 4: 1-13

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Mojor Points and Recommendations for Diagnosis

• Medical history and physical examination• CXR ( multilobar? Effusion? Cavitation?)• Purulent tracheobronchitis vs tracheal colonization• Arterial blood gas, CBC and biochemistry• All patients with suspected VAP should have blood

cultures collected.• Diagnostic thorocentesis• Samples of LRT secretions should be obtained• A sterile culture of LRT secretions rules out bacterial

pneumonia• For patients with ARDS should be done more

diagnostic testing

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The Diagnosis of VAP

PITA* PSB,BAL,PTC**

• Sensitivity (%) 77 75• Specificity (%) 84 88• PPV 4.80 6.25• NPV 0.27 0.28

Conclusion: PITA may be a reliable alternative to PSB,BAL,PTC

* Postintubation tracheal aspiration (PITA)** Plugged telescoping catheter (PTC)

Chest 2006;130: 956- 961

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Clinical strategy

• New or progressive radiologic infiltrate + fever > 38 C, leukocytosis or leukopenia and prulent secretions

• The results of emiquantitative LRTS cultures and serial clinical evaluations, by Day 3

• High probability of pneumonia or sepsis , prompt therapy is required

• Delays in the initiation of appropriate antibiotic therapy can increase the mortality of VAP

• The clinical pulmonary infection score (CPIS)< 6 : low risk for early discontinuation of empiric treatment

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Empiric Antibiotic Therapy for HAP

HAP, VAP or HCAP Suspected

Late Onset (≥ 5 days) or Risk Factors for MDR Pathogens

Limited Spectrum Antibiotic Therapy

Broad Spectrum Antibiotic Therapy

For MDR Pathogens

No Yes

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HKP- Hasta grupları ve etkenler

Grup 1

Erken başlangıçlı HKP

( 4. gün)

Grup 2

Geç başlangıçlı HKP

( 5. gün)

Grup 3

Yüksek çoğul dirençli bakteri infeksiyonu ve mortalite riskli HKP

Temel Etkenler:

S. Pneumoniae

H. influenzae

M.catarrhalis

S. Aureus (MSSA)

Enterobacter spp.

K. pneumoniae

S. marcescens

E. coli

Diğer Gram negatif çomaklar

S. aureus

Temel etkenler

P.aeruginosa

Acinetobacter spp.

S.aureus (MRSA**)

K.pneumoniae

S. maltophilia

Grup 2 etkenleri

Toraks Dergisi 2002;3 Ek 4: 1-13

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Empiric Antibiotic Therapy for Early Onset HAP

Potential Pathogen Recommended Antibiotic• S. Pneumoniae Ceftriaxone• H. Influenzae or• S. aureus ( MSSA) R. Fleuroquinolons• Antibiotic sensitive EGNB or

E.coli Ampicillin/ sulbactam

K. Pneumoniae orEnterobacter spp. ErtapenemProteus spp.S. marcescens

Toraks Dergisi 2002;3 Ek 4: 1-13

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Empiric Antibiotic Therapy for HAP

Erken 4. gün Temel etkenler• S. pneumoniae• H. influenzae• M.catarrhalis

• S. aureus ( MSSA)

Monoterapi• Betalaktam+betalakmaz

inhibitörü *

veya• 2.-3. kuşak

nonpseudomonal sefalosporin

veya• Yeni kinolon**

Toraks Dergisi 2002;3 Ek 4: 1-13

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Empiric Antib iotic Therapy for Late Onset HAP

Potential Pathogen Recommended Antibiotic• Pathogens of Antipseudomonal SS

Early Onset HAP (Cefepime, Ceftazidime)

• MDR pathogens; orP.aeruginosa Antipseudomonal carbapenK.pneumoniae (ESBL) (imipenem or meropenem)

Acinetobacter spp. orβ- lactam/ β- lactamase

inhibitor (piperacillin- tazobactam)

plus Antipseudomonal FQ or AG

plus• MRSA Vancomycin or Linezolid• Legionella pneumophila

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HKP- Grup 2

Geç 5 gün• Enterobacter spp.• K. pneumoniae• S. marcescens• E. coli• Diğer Gram negatif

çomaklar• S. aureus• Temel etkenler

Monoterapi** • Betalaktam+betalakmaz

inhibitörü*veya

• 3.kuşak nonpsödomonal sefalosporin

veya• Kinolon (Ofloksasin /Siprofloks)

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HKP- Grup 3

Yüksek riskli, çokludirençli bakteri inf.• Son 15 günde AB kullanımı• MV> 6 gün • YBÜ> 48 saat • Acil entübasyon

Mortalite artıran faktör• Bilateral, multilober, kaviter

tutulum, apse, ampiyem, hızlı radyolojik progresyon,

• PaO2/FiO2< 250

• Ağır sepsis/ septik şok

Kombine tedavi • Antipseud. Penisilin

veya

Antipseud. sefalosporin

veya

Karbapenem

+

Aminoglikozid veya Kinolon (Ofloks/Siprofl)

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The prognosis of HCAP

• The crude mortality rate for HAP 30- 70 %• The mortality related to the HAP 33- 50 %• Increased mortality rates;

bacteremia ( P.aeruginosa, Acinetobacter spp)

medical illness

ineffective antibitic therapy

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Mojor Points and Recommendations for Initial Antibiotic Therapy

• Select an empiric therapy based on risk factors and local mycrobiliogic data

• Initial antibiotic therapy should be given promptly

• Inapropriate therapy is a major risk factor for excess mortality

• Select a different antibiotic class for patients who have recently received an antibiotic

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Mojor Points and Recommendations for Optimal Antibiotic Therapy

• Initial therapy should be administered to all patient intravenously

• Aerosolized antibiotics may be considered as adjunctive therapy

• Combination therapy should be used• The aminoglycoside can be stopped after 5-7 days• Monotherapy can be used after the results of LRTS

culture • If patients receive an appropriate therapy, efforts

should be made to shorten ( 7-8 days)

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VIP’ li erişkinlerde 8- 15 günlük antibiyotik tedavisinin karşılaştırılması

• Amaç- VİP’li hastalarda 8 günlük tedavinin 15 günlük tedavi kadar etkili olabileceğini belirlemek

• Kurgu- Prospektif, randomize, çift kör, 401 VİP’li hasta

• Bulgular- Tedavi: 15 gün- 8 gün

mortolite artışı yok: %18.8- %17.7rekürren infeksiyon:%28.9- %26.0Antibiyotiksiz gün: 13.1- 8.7 p< 0.01

• Sonuç- 8 günlük tedavi 15 günlük tedavi ile karşılaştırılabilir etkinliktedir. Kısa süreli tedavi antimicrobial direnç oluşumunu azaltabilir. JAMA 2003;290:2588-2598

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Mojor Points and Recommendations for selected MDR pathogens

• If P.aeruginosa pneumonia is documented, combination therapy is recommended

• If Acinetobacter speices are documented, the most active agents are the carbapenems, sulbactam, colistin and polymyxin

• If ESBL Enterobacteriaceae are isolated, then monotherapy should be avoided ( 3.JSS)

• Adjunctive therapy with an inhaled AG or polymyxin for MDR GN pneumonia should be considered

• Linezolid is an alternative to vancomycin for the treatment of MRSA VAP

• Antibiotic restriction and cycling may reduce the frequancy of antibitic resistance

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VİP- Levofloxacin vs Imipenem/cilistatin

Levo + Imip+ pKlinik başarı(%) 58.6 63.1 NSMortalite (%) 11 13.1 NS

VİP empirik tedavisinde; Levofloxacin,Imipenem/cilistatin kadar etkili

Levo.( 750 mg/ gün) + Vancomycin APABImip.(3-4 x 500-1000mg/ gün) + Vancomycin APAB

Chest 2003; 124(4): 79s- 80s

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MRSA-HKP: Linezolid vs Vancomycin

• Gram pozitif : 1019

S. Aureus: 339

MRSA : 160

• Linezolid 600 mg 2x1 ve Aztreonam 1-2 gr 3x1

vs• Vancomycin 1 gr 2x1 ve

Aztreonam 1-2 gr 3x1

Lin. Van.

Sağ kalım %: 80 63.5

p= 0.03

Klinik kür %: 59 35.5

p< 0.01

Chest 2003; 124: 1789- 1797

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VİP- P. aeruginosa/Piperacilin

• Dirençli suşlar: % 25

• Betalactam/AG/ Ciprofloxacin direncide

• Önceden FQ kullanımı direnç olasılığını

• Dirençli suşlarda mortalite: % 59 Clin Infect Dis 2002; 34: 1047

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VİP- Lokal AB• Travmalı hastalarda: Enterik Gram neg.

bak.VİP’de TOBi yararlıYBÜ(gün) MV(gün) Sürvi(%)

İki IV AB 16 15.4 80IV AB+ TOBI 11 9.9 91• Yüksek dirençli Gram netatif bak. VİP’ de

Colistin yararlı Colistin 50 mg + SF 50 ml trakeal tüp yoluyla 8/ 11 olgu iyileşmiş Chest 2003; 124(4): 79s- 80s

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VİP- AB değişikliğiGrup 0 1 2 3Olgu (n=56) 19 8 19 10Yetersiz AB (%) 12.7 8.1 6.9 5.9Kültür- değ. (%) 37.5 15.8 14Kanıtsız- değ. (%) 1.25 23.7 37.2Mortalite (%) 21.1 25 57.9 80YBÜ ve MV süresi uzaması ile değişiklik Kanıtsız AB değişimi mortalite artışı ile koreleYetersiz AB bir kez değiş. mortalite artmıyor

Chest 2003; 124(4): 79s

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Assessment of Nonresponders

Wrong OrganismDrug resistance Pathogen:

(bacteria,mycobacteria,virus,fungus)

Inadequate AB Therapy

Wrong DiagnosisAtelectasis,PE, ARDSPulmoner hemorrhage

Underlying diseaseNeoplasm

ComplicationEmpyema or Lung abscess

C.difficile ColitisOccult Infection

Drug fever

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HAP, VAP or HCAP Suspected

Obtain LRTS for Microscopy & Culture

Days 2 & 3: Check Cultures & Assess Clinical ResponseClinical Improvement

No Yes

Begin Empiric Antimicrobial Therapy Based on Algorithms and Local Microbiologic Data

Cultures +Adjust Antibiotic

Therapy

Cultures –Search for

other pathogens, Complications

Cultures +De-escelate Antibiotics

Cultures –Consider Stopping Antibiotics

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HAP- Take Home Messages

• Avoid untreated or inadequate treated HCAP

• Recognize the variability of bacteriology from one hospital to another

• Avoid the overuse of antibiotics by focusing on accurate diagnosis

• Apply prevention strategies aimed at modifiable risk factors

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Trakeal aspirasyon kateterleri

• Açık tek kullanımlık

• Kapalı çok kullanımlık*

daha ekonomik

çapraz kontaminasyon için daha güvenli

• Biofilm koruma teknolojisi***CDC. Infect Control Hosp Epidemiol 1998;19: 304

** Jansen B. Journal of Industrial Microbiology 1995;15: 391- 6

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NP korunma önlemleri

I- Genel: surveyans, eğitim, el yıkama-bariyer, dezenf- steril,izolas,AB kontrolü, aşılamaII-Hastalara yönelik: kısa yatış,oral hijyen, AB profl- tedavi, ortak araçkullanmama, hasta eğitimi,post op analjezi, gereksizs.ülser profilaks. kaçınma

III-YB hastalarına yönelik: NPPV önceliği, beslenmedesteği, enteral beslenme,aspir.önlenme, oral entüb,kuf basıncı, erken ekstüb,subglottik asp, kapalı asp.kateteri, ventilator devreleribakımıIV- Özel: SGID, Ig, IFG

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Subglottik aspirasyon- Tüp Kafı

• Tüp kafı üstünde kolonize sekresyon;

kaf basıncı azalması

tüp değiştirme- çıkarma• Tüp kafı basıncı yeterli olmalı• Tüp kafı üst kısmının drenajı

VİP insidensi azalmaktaValles J. Ann Intern Med 1995; 122: 179- 86

Rello J. Am J Respir Crit Care Med 1996; 154: 111- 5

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Ventilatör devrelerinin değişimi-VAP

Değişim 2 gün 7 gün p

VAP n= 38 8

VAP /gün 16.7/ 1000 8.2/ 1000 < 0.001

7 günde değişim daha güvenliHan JN. Respir Care 2001; 46(9): 891- 6

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Surveyans

• En yüksek infeksiyon oranı ve

antibiyotik direnci olan bölümler

• İnfeksiyon endemi oranını belirlemek

• Sonuçlar ilgili bölümlere ulaştırılmalı

Hastane inf. %32 azalmaktaHaley RW.Am J Epidemiol 1985;121: 183-205

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Trakeal aspirasyon kateterleri

• Açık tek kullanımlık

• Kapalı çok kullanımlık*

daha ekonomik

çapraz kontaminasyon için daha güvenli

• Biofilm koruma teknolojisi***CDC. Infect Control Hosp Epidemiol 1998;19: 304

** Jansen B. Journal of Industrial Microbiology 1995;15: 391- 6

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Personel kaynaklı risk azaltma

• Inluenza virus aşısı• MRSA taşıyıcılığı

Mupirocin nazal krem 2x1 1 haftaClindamycine 150 mg/gün 1 ayRifampicin 600 mg/gün + TMP-SMX fort tb/ gün 10 gün Vitamin C

JID 1997; 173: 1502

JAC 1987; 19: 1

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El yıkama

• Çalışanların uyumu < %50*• NP % 25- 50 azalma saptanmış**• Chlorhexidine > isopropyl alcohol

AB dirençli inf. üstün**• Alkol bazlı ajanlar yeterli el dezenfek. sağlar• Görülebilir kirlenme varsa mutlaka yıkanmalı

* Graham M. Am J Infect Control 1990; 18: 77

**Doebbeling BN. N Engl J Med 1992; 327: 88- 93

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El yıkama- dezenfektan

• El yıkama, kurulama 60 sn• Alkollü el dezenfektanı 15 sn

(MRSA kolonizasyon ve inf. azalıyor)

Görülebilir kirlilik ve/veya organik materyal yıkanmalı

Voss A. Infect Control Hosp Epidemiol 1997; 18: 205

Pittet D. Ann Intern Med 1999; 130: 126

APIC. Am J Infect Control 1995; 23: 251

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HAP- Key points• Use evidence based guidelines

• Early, appropriate antibiotics in adequate doses

• De-escalation of initial antibiotic therapy

• The variability of bacteriology

• Early onset pneumonia without MDR pathogen riskLate onset pneumonia with MDR pathogen risk

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

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HEALTCARE ASSOCIATED PNEUMONIA • Use evidence based guidelines• Collection of culture before antibiotic therapy• Quantitative culture according to the basis of local

expertise• Early, appropriate antibiotics in adequate doses• Empiric therapy should include different class

antibiotics and/ or combination therapy• To stop antibitic therapy according to negative LRT

cultures• Additional diagnostic and therapeutic evaluations

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HEALTCARE ASSOCIATED PNEUMONIA

• Linezolid is an alternative to vancomycin for MRSA

• Colistin should be considered for carbapenem resistance Acinetobacter spp.

• Aerosolized antibiotics may have value as adjunctive therapy

• De-escalation of antibiotics based on clinical and mycrobiological response

• A shorter duration of therapy (7-8 days)

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The principles of the management of HCAP

• Avoid untreated or inadequate treated HCAP

• Recognize the variability of bacteriology from one hospital to another

• Avoid the overuse of antibiotics by focusing on accurate diagnosis

• Apply prevention strategies aimed at modifiable risk factors

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Modifiable risk factors

• General prophylaxis– Effective infection control measures– Surveillance of ICU infections

• Aspiration, body position, and enteral feeding– Patients should be kept in the semirecumbent

position– Enteral nutrition is preferred

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Modifiable risk factors

• Intubation and mechanical ventilation– Intubation and reintubation should be avoided– NIMV should be used– Orotracheal intubation and orogastric tubes– Continuous aspiration of subglottic secretions– The endotracheal tube cuff pressure ≥20 cm H2O– Contaminated condensate should be emtied– Passive humidifiers or heat moisture exchangers– Reduced duration of intubation and MV– Maintaining adequate staffing levels in the ICU

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Modifiable risk factors

• Modulation of colnization– Selective decontamination of digestive tract

( Not for routine use)– Prior or prophylactic administration of systemic antibiotics– Modulation of oropharyngeal colonization (clorhexidine)– Use daily interruption or lightening of sedation

• Stress bleeding prophylaxis– H2 antagonists or sucralfate is acceptable

• Leucocyte depleted red blood cell transfusions• Intensive insulin therapy is recommended

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HCAP guidelines

• ATS 1996, 2005

• CTS

• Thorax

• STS

• TTS 2002, 2007?

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Hastane Kökenli Pnömoni

• Her HKP(VIP) atağı 40.000 USD

• SDD koruyucu, ancak seçici davranılmalı

• Erken ekstübasyon

• NIMV

• HKP tedavi rehberleri koruyucu önlemlerden daha fazla dikkate alınmakta

• Etkili empirik tedavi başlanması çok önemli

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