Antibiotic Strategy in Severe

CAP and Nosokomial

Pneumonia

Yohanes WH George
 Why Guidelines?
1. Evidence based practice
1.Best outcome for patients
2.Best use of resource
3.Constrain idiosyncratic behaviours
2. Legal protection
3. Identify research needs
4. A tool for education
5. Gain public confidence
 HAP/VAP Guidelines
Name Year Method Scope Country Treatment Prevention Diagnosis
BSAC 2006 SR HAP UK
ATS 2005 SR HAP USA

GALANN 2005 EO HAP Lat/Am

CCCS 2004 SR VAP Canada

HICPAC 2004 SR HAP USA

GEIH etc. 2004 EO VAP Spain (severe)

Corona 2004 EO VAP Italy

Collard 2003 SR VAP USA

ICCC 2002 EO VAP Global
Rello 2001 EO VAP Spain
ERS 2001 EO VAP Europe

SR = Systematic Review EO = Expert Opinion

 A First consensus report
by the Asian HAP Working Group
(Expert Opinion)

1. Epidemiology, etiology, and diagnosis of hospital-acquired

pneumonia and ventilator-associated pneumonia in Asian
countries (Rajesh Chawla, MD. Delhi, India) Antimicrobial resistance
in major pathogens of hospital-acquired pneumonia in Asian
countries. (Evelina N. Lagamayo, MD Manila and Quezon City, Philippines)
Treatment recommendations of hospital-acquired pneumonia
in Asian countries. (Jae-Hoon Song, MD, PhD, and the Asian HAP
Working Group .Seoul, Korea)
 PNEUMONI
A

CAP = HAP = VAP = HCAP =

Communit Hospital Ventilator Health Care
y Community
Aquired Aquired Associated Associated
pneumonia
Pneumonia Pneumonia
pneumonia yang timbul Pneumonia Pneumonia
dalam waktu 48 jam
setelah rawat inap, dan pneumonia yang timbul 1.pasien yang dirawat
tidak dalam masa dalam waktu 48-72 jam dalam perawatan
inkubasi saat pasien setelah intubasi akut, selama dua hari
masuk rumah sakit. endotrakeal atau lebih karena
infeksi dalam waktu
90 hari terakhir;
2.tinggal di panti
wreda atau fasilitas
perawatan jangka
panjang lainnya;
3.menerima terapi
antibiotika intravena,
kemoterapi, atau
4.perawatan luka
dalam waktu 30 hari
INCIDENCE OF NOSOCOMIAL INFECTIONS IN
COMBINED MEDICAL-SURGICAL ICUs

Medical Patients Surgical Patients

Pneumonia 30% Pneumonia 33%

UTI 30% UTI 18%
Bloodstream SSTI 14%
infection 16% Bloodstream
Lower resp. infection 13%
tract 6% Lower resp.
(not pneumonia) tract 6%
(not pneumonia)

(Richards et al. Infect Control Hosp Epidemiol 2000;21:510-515)

Asian working group 2008
 High Mortality with HAP and

Severe Sepsis
Included among the most frequent serious infections in
the ICU are:
Hospital-acquired pneumonia (HAP)
Severe sepsis.

HAP and severe sepsis are

associated with high mortality rates.
Inadequate therapy for HAP and severe sepsis increases
mortality.

Kollef MH. Clin Infect Dis Dis 2000;31(Suppl Bernard GR et al. N

2000;31(Suppl 4):S131-S138.
4):S131-S138. N Engl
Engl JJ Med
Med 2001;344:699-709.
2001;344:699-709.
Richards MJ et al. Crit
Crit Care
Care Med
Med 1999;27:887-892. Alvarez-Lerma F et al. Intensive CareCare Med 1996;22:387-394.
Ibrahim
Ibrahim EH
EH et al. Chest
et al. Chest 2000;118:146-155.
2000;118:146-155. et al. Antimicrob
Pfaller MA et Antimicrob Agents
Agents Chemother
Chemother 2000;44:747-751.
2000;44:747-751.
Van der Poll T. Lancet
Van der Poll T. Lancet Infect Dis 2001;1:165-174.
2001;1:165-174. Garnacho-Montero J et al. Crit Care Med 2003;31:2742-2751.
2003;31:2742-2751.
Risk Factors for HAP
& VAP
 Risk Factors for HAP/VAP
Co-morbid
ICU Therapies Injuries Ventilation
Illnesses
Cancer CPR Burns Duration of
Chronic Corticosteroid use Coma mechanical
obstructive General surgery Head injury ventilation
pulmonary Neurosurgery Multiple organ Intracuff pressure
disease (COPD) Antacids system failure <20 cm H20
Chronic cardiac Paralytic agents (MOSF) Reintubation
disease Prior antibiotic Acute respiratory
Kidney failure therapy distress
Tracheostomy syndrome
Use of a nasogastric (ARDS)
tube
Large-volume
gastric aspiration

(Mehta RM. J Intensive Care Med 2003;18:175-88)

(Patel PJ, et al. Seminar Respir Crit Care Med 2002;23:415-25)
(American Thoracic Society. Am J Respir Crit Care Med 2005;171:388-416)
 Pathogenesis of
HAP/VAP and
Causative Pathogens
- Komensal
- Saphrophyt
Pathogenesis of HAP/VAP
Retrograde infection:
Enterobacteriaceae.
refluks from duodenum to stomach --> to nasopharynx

19
Frequency of bacterial pathogens in HAP in
North America: 2,712 strains (SENTRY,
Antimicrobial Surveillance Program, Jan.-June
2000)

Rank Organism No. of isolates (%)

1 S. aureus 760 (28.0) (43.7% MRSA)
2 P. aeruginosa 543 (20.0)
3 S. pneumoniae 246 (9.1)
4 Klebsiella spp. 203 (7.5)
5 H. influenzae 199 (7.3)
6 Enterobacter spp. 156 (5.8)
7 E. coli 105 (3.9)
8 Serratia spp. 96 (3.5)
9 S. maltophilia 94 (3.5)

(Hoban DJ et al. Diag Microbiol Infect Dis 2003;45:279-285)

Etiologi HAP (termasuk VAP): frekuensi
rerata dari patogen etiologik*
 Etiologi VAP in ICU RSCM

Dari studi yang dilakukan pada 35 pasien ICU

RSCM dengan VAP, hasil spesimen protected
specimen brush menunjukkan patogen tersering
adalah
Acinetobacter anitratus 91% (n=32/35),

Pseudomonas aeruginosa 63% (n=22/35),

dan Klebsiella pneumonia 31% (n=11/35).
Etiologi VAP in ICU RS. Persahabatan

Data ICU RS Persahabatan menunjukkan etiologi

patogen yang paling sering didapatkan dari kultur
sputum adalah
Pseudomonas aeruginosa (23%), Acinetobacter

baumanii (13%), Enterobacter cloacae (13%),

dan Klebsiella pneumonia (10%).
Acute Lung Oedema ec. heart failure with
HAP
Post ops Laparatomi with VAP
DSS dengan VAP
Post Craniotomy dengan VAP
 Classification of HAP & VAP:
Risk Stratification
Time from Hospitalization (days)

0 1 2 3 4 5 6 7

Early-onset HAP Late-onset HAP

Time from Intubation (days)

0 1 2 3 4 5 6 7

Early-onset VAP Late-onset VAP

(American Thoracic Society. Am J Respir Crit Care Med 2005;171:388-416)

 Pathogens to Consider When
Treating HAP/VAP

Early HAP/VAP Late HAP/VAP

Timing Within five days of admission Five days or more after admission or
or mechanical ventilation mechanical ventilation

Bacteriology S. pneumoniae P. aeruginosa

H. influenzae Acinetobacter
Methicillin-sensitive Methicillin-resistant S.
S. aureus aureus
Susceptible gram-negative Other multi-resistant organisms
bacteria

Prognosis Less severe, little impact on Higher attributable mortality and

outcome morbidity
Mortality minimal
Diagnosis of HAP
Diagnosis of HAP/VAP

Clinical approach

Vs.

Invasive approach
 Non-invasive Strategy for
Diagnosing HAP/VAP

Clinical approach:
New lung infiltrate
new onset fever, leukocytosis or purulent sputum
non-quantitative bacterial analysis of endotracheal
aspirate
 Non-invasive Strategy for
Diagnosing HAP/VAP

Clinical approach:

CPIS clinical pulmonary infection score

Quantitative prediction model using clinical criteria
May improve clinical diagnosis of HAP
72%-85% sensitive, 85%-91% specific
Only validated in several small studies

(Pugin J, Auckenthaler R, Mili N, et al. Am Rev Respir Dis 1991;143:1121-1129)

(Hubmayr RD et al ATS Consensus Statement Intensive Care Med 2002;28:1521-1536)
Initial Therapy of
HAP/VAP
 Strategi dan pendekatan diagnostik
Dugaan HAP, VAP atau HCAP

Ambil kultur dan pemeriksaan mikroskopik sekret saluran napas bawah

Bila secara klinis curiga pneumonia dan hasil mikroskopi sekret saluran napas bawah positif, terapi
antimikrobial empirik dimulai dengan menggunakan algoritme Gb.2 dan data mikrobiologi lokal
Tabel 3. Terapi antibiotika empirik awal untuk
pasien dengan onset awal (early onset)

Patogen potensial Antibiotika yang direkomendasi

Streptococcus pneumoniae Ceftriaxone
atau
Haemophilus influenzae
Levofloxacin, moxifloxacin, atau
Methicillin sensitive Staphylococcus ciprofloxacin
aureus atau
Basil gram negatif enterik sensitif ampicillin / sulbactam
terhadap antibiotika atau
Escherichia coli ertapenem
Klebsiella pneumoniae
Enterobacter spp
Proteus spp
Serratia marcesens
Faktor risiko untuk kejadian HAP, HCAP dan VAP
yang disebabkan oleh patogen-patogen MDR
bacteria.
Tabel 4. Terapi antibiotika empirik awal untuk HAP,
HCAP atau VAP pada pasien dengan penyakit onset
lanjut (Late onset)

Patogen potensial Antibiotika yang direkomendasikan

Patogen-patogen dari tabel 3 dan patogen- Cephalosporin antipseudomonas
patogen MDR BACTERIA (cefepim, ceftazidime)
Pseudomonas aeruginosa atau
Klebsiella pneumoniae (ESBL) Carbapenem antipseudomonas
Acinetobacter spp (imipenem atau meropenem)
Methicillin resistant Staphylococcus aureus atau
(MRSA) Beta laktam / beta laktamase inhibitor
(piperacilin tazobactam)
PLUS
Legionella pneumophilla Fluoroquinolon antipseudomonas (ciprofloxacin,
levofloxacin)
atau
Aminoglikosida
(amikacin, gentamicin, atau tobramicin)
PLUS
Linezolid atau vancomycin
 Strategi dan pendekatan diagnostik

Dugaan HAP, VAP atau HCAP

Ambil kultur dan pemeriksaan mikroskopik sekret saluran napas bawah

Bila secara klinis tidak curiga pneumonia dan hasil mikroskopi sekret saluran napas bawah negatif,
terapi antimikrobial empirik dimulai dengan menggunakan algoritme Gb.2 dan data mikrobiologi lokal

Hari ke 2 dan 3 : cek hasil kultur dan keadaan klinis (temperatur, leukosit, foto rontgen dada, oksigenasi,
sputum, perubahan hemodinamik dan fungsi organ)

Perbaikan klinis dalam 48 sampai 72 jam

Tidak Ya
Kultur Kultur + Kultur Kultur +

Sesuaikan jenis antibiotika, Pertimbangkan De-eskalasi antibiotika,

Cari infeksi dan penyulitnya obati pasien selama 7-8
dan cari kuman lain dan penghentian
di tempat lain. komplikasinya hari dan evaluasi
antibiotika
Table 7. Recommended empirical antibiotics
for community acquired pneumonia.
Outpatient treatment
1. Previously healthy and no use of antimicrobials within the previous 3 months
- A macrolide (strong recommendation; level I evidence)
- Doxycyline (weak recommendation; level III evidence)
2. Presence of comorbidities such as chronic heart, lung, liver or renal disease;
diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing
conditions or use of immunosuppressing drugs; or use of antimicrobials within the
previous 3 months (in which case an alternative from a different class should be
selected)
- A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or
levofloxacin [750 mg]) (strong recommendation; level I evidence)
- A -lactam plus a macrolide (strong recommendation; level I evidence)
3. In regions with a high rate (>25%) of infection with high-level (MIC 16 mg/mL)
macrolide-resistant Streptococcus pneumoniae, consider use of alternative
agents listed above in (2) for patients without comorbidities (moderate
recommendation; level III evidence)
Table 7. Recommended empirical antibiotics
for community acquired pneumonia.

Inpatients, non-ICU treatment

A respiratory fluoroquinolone (strong recommendation; level I
evidence)
A -lactam plus a macrolide (strong recommendation; level I evidence)
Inpatients, ICU treatment
A -lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus
either azithromycin (level II evidence) or a respiratory
fluoroquinolone (level I evidence) (strong recommendation) (for
penicillin-allergic patients, a respiratory fluoroquinolone and
aztreonam are recommended)
Table 7. Recommended empirical antibiotics
for community acquired pneumonia.
Special concerns
- If Pseudomonas is a consideration
An antipneumococcal, antipseudomonal -lactam
(piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus
either ciprofloxacin or levofloxacin (750mg)
or
The above -lactam plus an aminoglycoside and azithromycin
or
The above -lactam plus an aminoglycoside and an
antipneumococcal fluoroquinolone (for penicillin-allergic patients,
substitute aztreonam for above -lactam) (moderate
recommendation; level III evidence)
- If CA-MRSA is a consideration, add vancomycin or linezolid
(moderate recommendation; level III evidence)
 SUMMARY
Negative lower respiratory tract cultures can be used to stop
antibiotic therapy if obtained in the absence of an antibiotic change
in past 72 hours
Early, appropriate, broad spectrum therapy, antibiotic therapy
should be prescribed with adequate doses to optimize antimicrobial
efficacy
An empiric therapy regimen should include agents that are from a
different antibiotic class than the patient is currently receiving
De-escalation of antibiotic should be considered once data are
available on the results of the patients cultures and clinical
response
A shorter duration of therapy (7-8 days) is recommended for
patients with uncomplicated HAP, VAP, or HCAP who have had a
good clinical response