Transcript Management of Community Acquired Pneumonia

Dr. Prayudi Santoso, SpPD-KP, M.Kes,FCCP, FINASIM
E-mail: [email protected]
Education :
MD
Internal Med
Pulmonology Consultant
MSc
Medical School, Padjadjaran University, Bandung, Indonesia
Medical School, Padjadjaran University, Bandung, Indonesia
Collegiums of Internal Medicine, Indonesia
Medical School, Padjadjaran University, Bandung Indonesia
Occupation :
Staf of Respirology Division & Critical Care Internal Medicine, Faculty of Medicine Padjadjaran
university/Hasan Sadikin General Hospital, Indonesia
Coordinator of MDR-TB Team Hasan Sadikin General Hospital Bandung, Indonesia
Organization :
Society of Internal Medicine West Java, - Indonesia
Society of Respirologi Indonesia (PERPARI)
Fellow American College of Chest Physcian (ACCP)
Member European Respiratory Society (ERS)
Penggunaan Antibiotik yang Rasional
dalam Penanganan Infeksi CAP dan
AECB
Prayudi Santoso
Departemen Ilmu Penyakit Dalam, Divisi Respirologi
dan Kritis Respirasi,RSHS, FK UNPAD
Bandung, Indonesia 2016
[email protected]
Pneumonia
 Infectious
/inflammatory disorders
of the lung parenchyma
 Pathology : pulmonary
alveoli and or
interstitium are filled
with WBC, RBC and
fibrin
In Indonesia based on Indonesia Health Profiles
on 2009:
• Pneumonia is one of the 10 most common
diseases in hospitals leading to highest
crude fatality rate of 7.6%, while the
respiratory tract infection rate is 0.43%.
3
Treat as
outpatient or inpatient
EXTREMELY IMPORTANT
DECISION
- Nature of investigational tests
- Type & route of drugs selected of treatment
- Cost of care
4
Community-Acquired Pneumonia Guidelines:
Associated Organisms
• Outpatient
–
–
–
–
–
Streptococcus pneumoniae
Mycoplasma pneumoniae
Haemophilus influenzae
Chlamydophila pneumoniae
Respiratory viruses
• Inpatient: non-ICU
–
–
–
–
–
–
–
S pneumoniae
M pneumoniae
C pneumoniae
H influenzae
Legionella spp
Aspiration
Viruses
• Inpatient: ICU
–
–
–
–
–
S pneumoniae
Staphylococcus aureus
Legionella spp
Gram-negative bacteria
H influenzae
Mandell LA, et al. Clin Infect Dis. 2007;44(suppl 2):S27-S72.
5
S. pneumoniae Is the Most Commonly Identified
Organism Overall Causing CAP (8 Asian Countriesa)
Pathogens isolated (N=390)
S. pneumoniae
No. of isolates (%)
114 (29.2)
Klebsiella pneumoniae
60 (15.4)
Hemophilus influenzae
59 (15.1)
Pseudomonas aeruginosa
26 (6.7)
Staphylococcus aureus
19 (4.9)
Mycobacterium tuberculosis
13 (3.3)
Moraxella catarrhalis
12 (3.1)
Other pathogens
77 (19.7)
Mycoplasma pneumoniae
61/556 (11.0)
Chlamydia pneumoniae
55/411 (13.4)
Legionella pneumoniae
7/648 (1.1)
aSouth
Korea, China, Taiwan, Hong Kong, India, Singapore, Vietnam, and the Philippines.
Study by ANSORP (Asian Network for Surveillance of Resistant Pathogens Study Group).
Adapted from Song J-H et al. Int J Antimicrob Agents. 2008;31(2):107-114.
Atypical Pathogens are Commonly Implicated in Hospitalized
Community - Acquired Pneumonia (CAP)
22% of CAP cases are caused by Atypical Pathogens
22%
Streptococcus
pneumoniae
Atypical pathogens:
Legionella spp
Chlamydia spp
Mycoplasma spp
34%
6%
Staphylococcus
aureus
Other
15%
Haemophilus influenzae and
Moraxella catarrhalis
15%
Aerobic gram-negative rods
8%
(Adapted from Eron JJ et al. Hospital Formulary, 1994.)
• Due to the difficulty of culturing atypical bacteria, the prevalence of these organisms in CAP is likely to be underestimated
(File TM et al. Infect Dis Clin North Am, 1998)
Etiology Pneumonia Atypical
Patients (n)
Mp (%)
Cp (%)
Lp (%)
Bohte et al, 1994 (Dutch)
334
6
3
2
Marrie et al, 1996 (Canada)
149
26
14
1
Neill et al, 1996 (New Zealand)
251
16
3
11
Steinhoff et al, 1996 (Germany)
237
9
11
2
Lieberman et al, 1996 (Israel)
346
29
18
16
File et al, 1997 (USA)
456
9
22
2
Sopena et al, 1998 (Spain)
173
3
24
28
Ngeow et al, 2005 (Asia)
1374
12,2
4,7
6,6
Mp= Mycoplasma pneumonia
Cp= Chlamydia pneumonia
LP = Legionella pneumonia
Lieberman D. Clin Chest Med 1999;20:489-97
Marrie TJ, et al. Am J Med 1996;101:508-15
File TM, et al. Antimicrob Agents Chemother 1997;41:1965-72
Sopena N, et al. Chest 1998;113:1195-200
Steinhoff D, et al. Clin Infect Dis 1996;22:958-64
Lieberman D, et al. Eur Respir J 1996;9:2630-4
Neill AM, et al. Thorax 1996;51:1010-6
Bohte R, et al. Thorax 1995;50:543-7
Ngeow YF, et al. Int J Infect Dis 2005 May;9:144-53
Clinical characteristics of the study
population at enrollment (Esposito S et al. CID 2002)
S. pneumoniae
infection (%)
Characteristics
(N=48)
Males
25 (52.1)
Mean age  SD, yrs
3.66  0.899
Onset
Gradual
23 (47.9)
Acute
25 (52.1)
Similar illness within
the family
6 (12.5)
Cough
31 (64.5)
Tachypnea
12 (25.0)
Fever
42 (91.3)
Rales
45 (93.7)
Wheezes
6 (12.5)
Days of hosp.  SD 6.857  3.523
12.325  6.065
Atypical bacteria Mixed S. pneum.infection (%)
atypical bacteria
(N=46)
infection (%) (N=16)
22 (47.8)
8 (50.0)
3.75  1.030
3.76  1.030
26 (56.5)
20 (43.5)
8 (50.0)
8 (50.0)
9 (19.5)
33 (71.7)
11 (23.9)
39 (84.7)
41 (89.1)
7 (15.2)
6.744  2.672
13.3075.089
3 (18.7)
11 (68.7)
4 (25.0)
14 (87.5)
15 (93.7)
2 (12.5)
7.110  2.370
13.7145.517
No significant differences were observed
Laboratory data in the various
aetiological groups (Esposito S et al. CID 2002)
Parameter
WBC (cells/L)
Neutrophils, %
Lymphocytes,%
Monocytes, %
Eosinophils, %
Basophils, %
CRP (g/dL)
ESR (mm/1h)
S. pneumoniae
infection (%)
(N=48)
16,669 
8,831*°
69  17*°
22  15
73
12
0.3  0.6
109  110*°
57  28
Atypical bacteria Mixed S.pneum.infection (%)
atypical bacteria
(N=46)
infect. (%) (N=16)
12,5545,404* 13,141  4,540°
59  18*
28  17
83
11
0.4  0.7
63  16°
25  16
73
12
0.3  0.4
59  88*
47  27
77  79°
52  44
Mean values  SD. *p < 0.05 vs *atypical bacteria infection and °mixed
S. pneumoniae-atypical bacteria infection; no other significant differences were
observed. WBC, white blood cell count; CRP, C-reactive protein, ESR, erythrocyte
sedimentation rate
Management of Pneumonia
 Supportive : oxygen, fluid, nutrition
 Antimicrobial treatment
 Drainage (source infections)
- postural drainage
- Mucolytic
- Bronchodilator
- Anti-inflammation : corticosteroids
- bronchoscopy/bronchial toilet
- Physical therapy
Empiric Therapy in CAP: IDSA/ATS
Healthy
Outpatient
New macrolide
(azithromycin,
clarithromycin
OR
Doxycycline
Outpatient at Risk Inpatient, nonfor DRSP
ICU
Respiratory
fluoroquinolone*
OR
Beta-lactam plus
New macrolide
(azithromycin,
clarithromycin)
Respiratory
fluoroquinolone
OR
Beta-lactam**
plus
macrolide
Inpatient, ICU†
Beta-lactam plus
azithromycin
OR
Beta-lactam plus
fluoroquinolone
(Special concerns:
Pseudomonas
CA-MRSA)
†Treatment
of Pseudomonas or MRSA is the main reason to modify standard therapy for ICU patients.
•gemifloxacin, moxifloxacin 400 mg QD, levofloxacin 750 mg QD
•** ceftriaxone, cefotaxime, ampicillin/sulbactam, ertapenem
IDSA= Infectious Diseases Society of America; ATS=American Thoracic Society; DRSP=Drug resistance; ICU =
intensive care unit
Mandell L, et al. Clin Infect Dis. 2007;44(Suppl 2):S27-S72.
Empiric Therapy in CAP: Australia
Mild (outpatient)
Amoxicillin
(Penicillin allergy:
New macrolide
(azithromycin,
clarithromycin)
Inpatient, non-ICU
Inpatient, ICU
Penicillin (Pen
Penicillin (Pen
allergy: ceftriaxone)
allergy: ceftriaxone)
AND
PLUS
Gentamicin
Doxycyline or New
AND
macrolide
New macrolide
(azithromycin,
(azithromycin,
clarithromycin)
clarithromycin)
www.safetyandquality.gov.au/.../3.3-Adult-Pneumonia-CPG-CAP-HAP
COPD
Airflow limitation;
10-14 million visits/yr in US
Bronchiectasis
Emphysema
Chronic bronchitis
• Chronic productive cough for 3 months
in each of 2 successive years
• 85% of COPD
AECB
• Increased dyspnea
• Increased sputum volume
• Increased sputum purulence
COPD = chronic obstructive pulmonary disease;
AECB = acute exacerbations of chronic bronchitis
McCrory et al. Chest. 2001 Apr;119(4):1190-209
AECB: Etiology Pathogens
Developed with the collaboration of the professional corporations (CMQ, OPQ), the federations (FMOQ,
FMSQ) and Québec associations of pharmacists and physicians
AECB Stratification
Increased dyspnea
Increased Sputum
Sputum purulence
Type I:
all three
symptoms
Treat
Type II: two
symptoms
Probably
Treat if
include
Purulence
Type III: one
symptom
No
treat
Anthonisen NR et al. Ann Intern Med. 1987;106:196.
Guidelines for management of AECB
I, Chronic bronchitis w/o
risk factors (Simple)
II, Chronic bronchitis w
Risk factors (Complicated)
III, Chronic suppurative
bronchitis
< 4 exacerbations/yr
>4 exacerbations/yr
As in group II
No comorbid illness
Cardiac disease
FEV1 usually <35%
FEV1 >50%
FEV1 <50%
Multiple risk factors
Home O2
Chronic oral steroids
Ab use in past 3 mo
H. influenzae
H. Spp
M. catarrhalis
S. pneumoniae
Group I plus
Klebsiella spp +
Other gram-negatives
Increased b-lactam
resistance
Group II plus
P. Aeruginosa &
Multi-resistant
Enterobacteriaceae
Balter MS, et al. Can Respir J. 2003;10(Suppl B):3B-32B.
Guidelines for management of AECB
I, Chronic bronchitis w/o
risk factors (Simple)
II, Chronic bronchitis w
Risk factors (Complicated)
III, Chronic suppurative
bronchitis
< 4 exacerbations/yr
>4 exacerbations/yr
As in group II
No comorbid illness
Cardiac disease
FEV1 usually <35%
FEV1 >50%
FEV1 <50%
Multiple risk factors
Home O2
Chronic oral steroids
Ab use in past 3 mo
2nd generation macrolide
(Azithromycin or
Claritromycin)
2nd/3rd cephalosporin,
Amoxicillin
Doxycycline
Trimeth/sulfameth
Fluoroquinolone
b-lactam/b-lactamase
inhibitor
Tailor to pathogen
Ciprofloxacin
Balter MS, et al. Can Respir J. 2003;10(Suppl B):3B-32B.
Always ask
about
antibiotic
use in
previous 3
months
Risk Stratification and Acute
Exacerbations of COPD
Exacerbations
MILD
Only 1 of the 3 cardinal symptoms:
• Increased dyspnea
• Increased sputum volume
• Increased sputum purulence
MODERATE OR SEVERE
At least 2 of the 3 cardinal symptoms:
• Increased dyspnea
• Increased sputum volume
• Increased sputum purulence
Simple COPD
No antibiotics
• Cephalosporin (cefuroxime,
cefpodoxime, cefdinir),
• Ketolide (telithromycin),
• Advanced macrolide
(azithromycin,
clarithromycin),
• Doxycycline,
•TMP/SMX
Complicated COPD
• Fluoroquinolone
(moxifloxacin, gemifloxacin,
levofloxacin),
• Amoxicillin-clavulanate
• If at risk for Pseudomonas,
consider ciprofloxacin and
obtain sputum culture
Worsening clinical status or inadequate response in 72 hrs
Sethi S, Murphy TF. Infect Dis Clin N Am. 2004;18:861-82.
Reevaluate
Consider sputum culture
Pathogenesis of Exacerbations
Impaired host defenses:
respiratory virus
new strains of bacteria
environmental irritants
Acute
cycle
Antibio
tics
Smoking/Irritants
Chronic bacterial
colonization
Damaged respiratory
epithelium
Acute on chronic
inflammation
(bacterial + host
mediated inflammatory
factors)
Chronic
cycle
Chronic inflammation
Progressive loss of
lung function and
deteriorating quality of
life
(bacterial + host
mediated
inflammatory factors)
Azithromycin (gol azalides)
• Azithromycin inhibits bacterial protein synthesis by binding
to the 50S ribosomal subunit of susceptible bacterial
species1–3
– The ribosome is the site of protein synthesis in bacteria and other cells
– This action interferes with the translocation of the growing peptide chain from
one side of the ribosome to the other
• A key point of differentiation between azithromycin and other
macrolides is that it demonstrates a marked post-antibiotic
effect (PAE)4
– Generally, antibiotics having PAE allows for less frequent dosing than those
with minimal PAE while remaining effective
• Azithromycin is bactericidal: it prevents bacteria from growing
by interfering with their protein synthesis2,4
1. Murray PR. Medical Microbiology; 2. Retsema J, et al. Antimicrob Agents Chemother 1987;31:1939–47; 3. Pfizer Egypt, Product Document,
Zithromax®; 4. Lode H, et al.
J Antimicrob Chemother 1996;37(Suppl. C):1–8
21
Azithromycin
• Azithromycin has a comprehensive spectrum of activity for its
indications in adults and children1–3
• Azithromycin shows significant activity against Gram-positive
and Gram-negative pathogens1 (Typical and Atypical)
• The antibacterial spectrum includes most of the frequent
causes of community-acquired infections, including:1
–
–
–
–
Haemophilus influenzae
Streptococcus pneumoniae
Moraxella catarrhalis
Streptococcus pyogenes
• The distinctive pharmacokinetic profile results in high and
sustained concentration in a wide range of cells and tissues2
1. Murray PR. Medical Microbiology; 2. Retsema J, et al. Antimicrob Agents Chemother 1987;31:1939–47; 3. Pfizer Egypt, Product Document,
Zithromax®; 4. Lode H, et al.
J Antimicrob Chemother 1996;37(Suppl. C):1–8
22
Beneficial Effects of Macrolide Activities as Antibacterial
and Immunomodulatory
Soichiro Kanoh, and Bruce K. Rubin Clin. Microbiol. Rev. 2010;23:590-615
Azithromycin Achieves High and Sustained up to 10-day
Concentration at Macrophages and White Blood Cells
Serum Neutrophil and Lung Concentrations of
Azithromycin vs Time1
Concentrations (mg/L)
10
1000
Azithromycin Concentration (µg/ml)
100
Serum
Neutrophil
sLung
1
S. pneum. 0.25 mg/L
Azithromycin Provides Sustained 10-day
Concentration1,2
Aveolar macrophages*
100
Peripheral blood monocytes*
10
MIC90 2.0 Haemophilis influenzae
1
MIC90 0.25 Chlamydia pneumoniae
MIC90 0.25
Streptococcus
pneumoniae
Moraxella catarrhalis
0.1
0.01
0.1
0.001
MIC90 0.00024 Mycoplasma pneumoniae
0
0.01
0
100
Time (hr)
200
300
Serum neutrophil concentrations vs time when
azithromycin is administered orally 500mg daily for
3 days and lung concentrations vs time after a
single 500mg oral dose.
0 1 2 3 4 5 6 7 8 9 10
Time (Days)
Graph to show the sustained effect of 5 days of azithromycin. 25
healthy volunteers each received 500mg of azithromycin, followed by
250mg once daily for 4 days.
*Drug concentrations are in micrograms per milliliter of
monocyte/macrophage volume
1. Amsden GW et al. Short-Course Antimicrobial Therapy. A Clinical Guide. Reprinted 2003 Elsvier Health
Communications: Page 7-15; 2. Olsen et al. Antimicrob Agents Chemother 1996; 40(11):2584
Pharmacokinetics and Contraindication
Pharmacokinetics
•
•
•
•
Oral bioavailability : 37%
Tmax : 2-3 hrs
Half-life: 68 hours
Oral : Biliary excretion is a
major route of elimination
for unchanged drug
• IV : Renal excretion is a
major route of elimination
for unchanged drug
Contraindications
• Contraindicated in
patients with known
hypersensitivity to
azithromycin,
erythromycin,
or any macrolide
antibiotic
Azithromycin Demonstrates Reliable Efficacy in
LRTIs vs Moxifloxacin
• Proven clinical success in AECB
• Proven bacteriological success in AECB:
– S. pneumoniae: 44.4% moxifloxacin vs
100% azithromycin
– H. influenzae: 75% moxifloxacin vs 94.4%
azithromycin
– Haemophilus parainfluenzae: 76%
moxifloxacin vs 89.5% azithromycin
• Overall bacteriological success* rates†
were significantly higher with
azithromycin than with moxifloxacin
(P = 0.022)
A randomised, investigator-blinded, multicentre trial comparing the efficacy of azithromycin (500 mg once daily for 3 days) with moxifloxacin
(400 mg once daily for 5 days) for the treatment of outpatients with AECB
Adapted from Zervos M, et al. 2007
*Bacteriological success rate for respiratory pathogens in bacteriologically evaluable subjects by treatment group at the end of study visits
†The clinical modified intent-to-treat population received at least one dose of study drug and had a diagnosis of AECB at baseline
#Clinical efficacy in patients, who were culture-positive at baseline for S. pneumoniae, H. influenzae, M. catarrhalis or H. parainfluenzae
AECB, acute exacerbations of chronic bronchitis; LRTI, lower respiratory tract infection
Zervos M, et al. Int J Antimicrob Agents 2007;29:56–61
Azithromycin Shows Proven Efficacy in CAP vs Other
Macrolides
• Proven clinical
efficacy in CAP
A randomised, multicentre study
comparing the efficacy of azithromycin
(500 mg once daily for 3 days) with
clarithromycin (250 mg twice daily for 10
days) in the oral treatment of mild to
moderate CAP in adults
Adapted from O’Doherty B, et al. 1998
*Clinical evaluation occurred at days 19–23 of those patients who had improved by days 12–16; in the azithromycin group
(n=24) and in the clarithromycin group (n=22)
CAP, community-acquired pneumonia
O’Doherty B, Muller O. Eur J Clin Microbiol Infect Dis 1998;17:828–33
Indikasi & Dosis Azithromycin
Indikasi
Dosis
Pasien Upper RTI: Faringitis,
Tonsilitis, Otitis Media Acute dan
Sinusitis
Pasien Lower RTI: CAP and AECB
outpatient outpatient
500 mg oral OD selama 3 hari
(total dosis 1500 mg)
Pasien CAP yang memerlukan terapi
awal IV
500 mg IV ≥ 2 hari OD  lanjut
500 mg oral OD hingga total lama
terapi 7-10 hari
Pasien PID yang memerlukan terapi
awal IV
500 mg IV 1-2 hari OD  lanjut
250 mg oral OD hingga total lama
terapi 7 hari
Konversi IV  oral, berdasar penilaian dokter sesuai dengan respon
klinis
CAP: Community Acquired Pneumonia
AECB: Acute Exacerbation Chronic Bronchitis
PID: Pelvic Inflammatory Diseases
Azithromycin I.V + Oral pada Community-Acquired Pneumonia:
Studi Komparatif
291 Pasien CAP
rawat inap
Azithromycin I.V.
500mg
1x/hari
2 - 5 hari
Oral Azithromycin
500mg
1x/hari
Cefuroxime
750 mg I.V.
3x/hari
2 - 5 hari
Oral Erythromycin
500mg
or 500mg - 1 g I.V.
4x/hari
+/-
Oral Cefuroxime Axetil
500mg
2x/hari
Hingga 21 hari
Untuk melengkapi lama terapi
7 - 10 hari
Source: Date on File. Pfizer Inc. New York, NY
Respon Bakteriologi: Studi Komparatif
% Eradikasi
97%
93%
94%
73%
P=NS
Azithro
(N=31)
Cefuroxime ±
Erythromycin
(N=28)
Streptococcus pneumoniae
Source: Data on File. Pfizer Inc. New York, NY.
P=NS
Azithro I.V.
(N=16)
Cefuroxime ±
Erythromycin
(N=11)
Haemophilus influenzae
Keberhasilan Klinis* 10 - 14 Hari Paska Terapi
(studi hari ke 17 - 24): Studi Komparatif
% Keberhasilan klinis
10 - 14 hari
78%
74%
P=NS
Azithro®
(N=137)
Cefuroxime ±
Erythromycin
(N=131)
Total rata-rata lama Terapi pada Evaluable Patients (I.V. & Oral) - (Hari)
• Azithromycin : 8,6 hari
• Cefuroxime + Erythromycin : 10,3 hari
Cured Plus Improved
Source: Data on File. Pfizer Inc. New York, NY.
Keseluruhan Respon Bakteriologi dengan Azithromycin I.V.
untuk Patogen Tipikal
% Eradikasi
96%
Streptococcus
pneumoniae
(N=67)
95%
Haemophilus
influenzae
(N=43)
Source: Data on File. Pfizer Inc. New York, NY.
90%
90%
Staphylococcus
aureus
(N=10)
Moraxella
catarrhalis
(N=10)
Keseluruhan Respon Klinis dengan Azithromycin I.V. pada
Pasien dengan Patogen Atipikal*
% Sembuh atau membaik
90%
89%
82%
Mycoplasma
pneumoniae
(N=18)
% Sembuh
Chlamydia
pneumoniae
(N=34)
81%
Legionella
pneumophila
(N=16)
10 - 14 hari paska terapi†
* Evidence Based on Serology and/or Culture
† Time Point Described in Package Insert
Source: Data on File. Pfizer Inc. New York, NY.
Mycoplasma
pneumoniae
(N=20)
85%
Chlamydia
pneumoniae
(N=33)
84%
Legionella
pneumophila
(N=19)
4 - 6 minggu paska terapi
Efek Samping Terkait Terapi & Penghentian Terapi: Studi CommunityAcquired Pneumonia Komparatif & Non-Komparatif
Event
Azithro® I.V.
(N=414) n (%)
Gastrointestinal
Diare
18 (4.3)
Mual
16 (3.9)
Nyeri perut
Muntah
Lokasi infus
11 (2.7)
6 (1.4)
Nyeri
Infeksi/radang
27 (6.5)
13 (3.1)
 Only 1.2% Discontinued I.V and Only 2.4% Discontinued I.V./Oral Therapy with Azitro
Because of Clinical or Laboratory Side Effects
Source: Data on File. Pfizer Inc. New York, NY.
Azithromycin+Ceftriaxone vs Levofloxacin
pada CAP Sedang-Berat
Azithro I.V.500mg
1x/hari
Ceftriaxone I.V.1g
1x/hari
2-5 hari
Oral Azithro 500mg
1x/hari
Total terapi 7-10
hari
VS
Levofloxacin I.V.500mg
1x/hari
≥ 2 hari
Oral Levofloxacin 500mg
1x/hari
Total terapi 714 hari
Azithromycin+Ceftriaxone vs Levofloxacin pada
CAP Sedang-Berat
% Sembuh atau membaik
91.5%
Azithromycin +
Ceftriaxone
n=82
89.3%
Levofloxacin
n=75
14 hari paska terapi
% Sembuh
89.2%
Azithromycin +
Ceftriaxone
n=74
85.1%
Levofloxacin
n=74
4-5 minggu paska terapi
Macrolide in CAP
Azithromycin vs Clarithromycin
CAP Patients (PORT score ≥ 71)
Ceftriaxone + Macrolide
Azithromycin
n=383
Clarithromycin
n=220
Azithromycin
Clarithromycin
p
Length of stay
7.4 ± 5 days
9.4 ± 7 days
<0.01
Mortality rate
3.6%
7.2%
<0.05
Sanchez F, et al.CID 2003;36:1239-45
Keuntungan
Penambahan
Makrolid Pada
Terapi CAP:
Angka
Kematian
Paling Rendah
Advantages of Azithromycin for Acute Bacterial
Lower Respiratory Tract Infection Out Patient
Once daily dose
Short duration
therapy (3 or 5
days)
Bactericidal
activity (Typical
and Atypical)
AZITHROMYCIN
High concentrations
lung
MICs Concentration
up to 10 days
Well tolerated
“Yes, Azithromycin Is Recommended in
Guidelines of Respiratory Tract Infections”
• Recommended as a first-line choice by reputable adult and paediatric regional
and international guidelines including:
– IDSA/ATS (Infectious Diseases of America/American Thoracic Society) consensus
guidelines on the management of community-acquired pneumonia in adults
(2007)1
– IDSA the management of community-acquired pneumonia in infants and children
older than 3 months of age: clinical practice guidelines by the Pediatric Infectious
Diseases Society and the Infectious Diseases Society of America (2011)2
– IDSA clinical practice guideline for the diagnosis and management of group A
streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of
America (2012)3
– GCC (Gulf Cooperation Council) practice guidelines for the management of
community-acquired pneumonia (2007)4
– Medical Associates clinical practice guideline for the management of acute ear
infection in children 2 months to 12 years (2012)5
Take Home Messages
• LRTIs are most common infections requiring antibiotic tx in
outpatient or inpatient setting
• Abuse of antibiotics is frequent for these indications
– Strict criteria are required for treatment
• Atypical bacteria have a roles in etiology of LRTI CAP
• Macrolides are effective and safe agents for LRTIs
– Azithromycin with properities is suitable for all these
indications
• Long-high life, high tissue penetration, immunomodulatory
properities, confidence compliance and safety.
Thank You
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