Management of Community Acquired Pneumonia in The Asia Pacific Region

MANAGEMENT OF
COMMUNITY ACQUIRED PNEUMONIA

IN THE ASIA PACIFIC REGION
Chong-Kin LIAM
Department of Medicine
Faculty of Medicine
University of Malaya
Kuala Lumpur
liamck@ummc.edu.my
XA common disorder
XAnnual incidence in USA

- 12 per 1000 adults
- 25-44 per 1000 in those aged >65 years
Marfarlane J. Semin Respir Infect 1994; 9:153-65

In Japan
XAnnual incidence: 15 per 1000 adults and children
XAnnual incidence requiring hospitalisation:
3.4 per 1000 adults and children
6th leading cause of death worldwide
JRS guidelines (2005). Respirology 2006; 11:S79-S133

CAP: Key Bacterial Pathogens
• In most studies,
Streptococcus pneumoniae
is the most commonly identified
S. pneumoniae
pathogen followed by H. influenzae
Haemophilus influenzae
40%
20%
Bartlett JG, et al. Clin Infect Dis. 1998;26:811-838; Marrie TJ. Infect Dis Clin North Am. 1998;12:723-
740; Reimer LG, Carroll KC. Clin Infect Dis.1998;26:742-748.
.. and atypical pathogens:
Mycoplasma pneumoniae
Chlamydophila pneumoniae
and Legionella spp. S. pneumoniae
H. influenzae
6% Legionella spp.
40%
M. pneumoniae
Atypical 10% C. pneumoniae
pathogens:
23%
7%
20%
Other bacteria include
Moraxella catarrhalis, Staphylococcus aureus,
Klebsiella spp., and
other gram-negative bacilli
1% 16% S. pneumoniae
H. influenzae
6% Legionella spp.
40%
M. pneumoniae
Atypical 10% C. pneumoniae
pathogens: M. catarrhalis
23% Others
7%
20%
Clinical Practice Guidelines
Hospitalised patients Severe
Ambulatory patients
(non-ICU) (ICU)
CAP patients are generally categorised into 3 groups

• outpatients
• inpatients
• intensive care patients
IDSA / ATS Consensus Guidelines on the management of CAP in adults. Clin Infect Dis 2007; 44:S27-72
Most common microbial aetiologies of CAP (in the West)

Inpatient Inpatient
Outpatient
(non-ICU) (ICU)
S. pneumoniae S. pneumoniae S. pneumoniae
M. pneumoniae M. pneumoniae Staph. aureus
H. influenzae C. pneumoniae Legionella spp.
C. pneumoniae H. influenzae Enterobacteriaceae spp.
Respiratory viruses* Legionella species Pseudomonas spp.
Influenza A and B, adenovirus, Aspiration H. Influenzae
RSV & parainfluenza
Respiratory viruses*
• Forall 3 categories of patients, the number one
pathogen is pneumococcus
Ref: File TM. Community-acquired pneumonia. Lancet 2003; 362:1991-2001

[Based on collective data from recent studies]
Most common microbial aetiologies of CAP (in the West)

Inpatient Inpatient
Outpatient
(non-ICU) (ICU)
M. pneumoniae M. pneumoniae Staph. aureus
H. influenzae C. pneumoniae Legionella spp.
C. pneumoniae H. influenzae Gram-negative bacilli
Respiratory viruses* Legionella species H. Influenzae
Influenza A and B, adenovirus, Aspiration
RSV & parainfluenza
Respiratory viruses*
• Forall 3 categories of patients, the number one
pathogen is pneumococcus
• Atypical pathogens are also prominently represented
• Legionella - an important pathogen in patients with severe CAP
Aetiologies of CAP Requiring Hospitalization in Asia 1
No. of Rank order / Frequency of microbial cause (%)
Location
patients 1 2 3 4 5 Unknown
Okayama1 S pneumoniae H influenzae M pneumoniae K pneumoniae S milleri

Ishida T, et al. 326
Chest
1998;114:1588-
1998;114:1588-93 23 7 5 4 4 39
Okayama2 S pneumoniae H influenzae M pneumoniae C pneumoniae S aureus
3 hospitals
Miyashita N, et al. 200
Chest
2000;119:1295-
2000;119:1295-6
21 11 10 8 5 42
Korea3 S pneumoniae K pneumoniae Ps aeruginosa S aureus S viridans
Woo JH, et al.
562
Korean J Infect Dis
2001, 33:1-
33:1-7 (588 cases) 22 15 10 10 6 62
Hong Kong4 M tuberculosis S pneumoniae Chlamydia spp Viral H influenzae
CHS Chan, et al.
al. 90
Chest
1992;101:442-
1992;101:442-6 12 12 6 6 4 59
• The aetiology of CAP in Japan is quite similar to that of Western countries

• High incidence of infection by Gram –ve bacilli
• Infection due to M tuberculosis may commonly present as CAP in
countries with a high prevalence of TB
Location
Khon Kaen5
Reechaipichitkul W, S pneumoniae B pseudomallei K pneumoniae M pneumoniae C pneumoniae
et al. Southeast 254
Asian J Trop Med
Public Health 11 11 10 9 4 43
2005; 36:156-
36:156-61 Bangkok5a
1.4% in Bangkok
Bangkok5a S pneumoniae Gram -ve bacilli C. pneumoniae M pneumoniae L pneumophila
3 hospitals
Wattanathum,
Wattanathum, et al.
al. 147 18
Chest
2003;123:1512-
2003;123:1512-9
22 (K. pneum 10) 16 7 5 29
Singapore6 M tuberculosis S pneumoniae Gram -ve H influenzae M pneumoniae
Hui KP, et al.
al. 96 bacilli
Singapore Med J
1992;101:442-
1992;101:442-6 21 12 10 5 5 42
K. Lumpur7 K pneumoniae S pneumoniae H influenzae M pneumoniae Ps aeruginosa
Liam CK, et al. 127
Respirology
2001;6:259-
2001;6:259-64 10 6 6 4 4 58
Penang8 M tuberculosis K pneumoniae Ps aeruginosa S aureus S pneumoniae
Hooi LN, et al. 98
Med J Malaysia
2001;56:275-
2001;56:275-83 15 7 6 5 3 57
• Studies in Singapore and Malaysia (countries with a high prevalence of TB)
also show pulmonary TB commonly presents as CAP
Location
Khon Kaen5
Reechaipichitkul W, S pneumoniae B pseudomallei K pneumoniae M pneumoniae C pneumoniae
et al. Southeast 254
Asian J Trop Med
Public Health 11 11 10 9 4 43
2005; 36:156-
36:156-61 Bangkok5a
1.4% in Bangkok
Bangkok5a S pneumoniae Gram -ve bacilli C. pneumoniae M pneumoniae L pneumophila
3 hospitals
Wattanathum,
Wattanathum, et al.
al. 147 18
Chest
2003;123:1512-
2003;123:1512-9
22 (K. pneum 10) 16 7 5 29
Singapore6 M tuberculosis S pneumoniae Gram -ve H influenzae M pneumoniae
Hui KP, et al.
al. 96 bacilli
Singapore Med J
1992;101:442-
1992;101:442-6 21 12 10 5 5 42
K. Lumpur7 K pneumoniae S pneumoniae H influenzae M pneumoniae Ps aeruginosa
Liam CK, et al. 127
Respirology
2001;6:259-
2001;6:259-64 10 6 6 4 4 58
K. Lumpur9 K pneumoniae M pneumoniae L pneumophila M tuberculosis S pneumoniae
Liam CK, et al. 346
Respirology
2006;11:786-
2006;11:786-92 11 9 6 5 4 53
• Studies in Singapore and Malaysia (countries with a high prevalence of TB)
also show pulmonary TB commonly presents as CAP
Aetiologies of Severe CAP Requiring ICU Admission
Location
United S pneumoniae Legionella spp Viruses S aureus Influenza A
Kingdom 185 &B
(4 studies) 22 18 10 9 5 32
Other parts S pneumoniae Gram –ve S aureus C pneumoniae Legionella spp
of Europe 1148 enteric bacilli
(10 studies) 22 9 7 7 6 43
Singapore K pneumoniae H influenzae S aureus B pseudomallei S pneumoniae
NUH Lee KH, et al.
59
Singapore Med J
1996;37:374-
1996;37:374-77
15 8 7 7 5 32
Singapore B pseudomallei M tuberculosis Klebsiella spp S aureus M pneumoniae
SGH Tan YK, et al. 57
Eur Respir J
1998;12:113-
1998;12:113-15
18 16 9 9 7 28
Khon Kaen B pseudomallei S pneumoniae K pneumoniae H influenzae S aureus
Reechaipichitkul W,
et al.Southeast Asian 105
J Trop Med Public
Health 2004;35:430-
2004;35:430-3
29 21 19 12 6 41
XPatients who met ATS criteria for severe CAP

X91.4% of patients had co-morbidity, most common was diabetes mellitus; Mortality: 21%
Aetiologies of Severe CAP Requiring ICU Admission
Location
United Burkholderia
Kingdom 185
pseudomallei
S pneumoniae Legionella spp
should
Viruses
be considered
S aureus Influenza A
&B
a
(4 studies) causative 22organism 18 in patients
10 with9severe CAP 5 32
Other parts S pneumoniae inGram
Southeast
–ve Asia
S aureus C pneumoniae Legionella spp
of Europe 1148 enteric bacilli
(10 studies) particularly
22 if the patient
9 has
7 diabetes 7 mellitus
6 43
Singapore K pneumoniae H influenzae S aureus B pseudomallei S pneumoniae
NUH Lee KH, et al.
59
Singapore Med J
1996;37:374-
1996;37:374-77
15 8 7 7 5 32
Singapore B pseudomallei M tuberculosis Klebsiella spp S aureus M pneumoniae
SGH Tan YK, et al. 57
Eur Respir J
1998;12:113-
1998;12:113-15
18 16 9 9 7 28
Khon Kaen B pseudomallei S pneumoniae K pneumoniae H influenzae S aureus
Reechaipichitkul W,
et al.Southeast Asian 105
J Trop Med Public
Health 2004;35:430-
2004;35:430-3
29 21 19 12 6 41
Aetiologies of CAP treated on an ambulatory basis
Location
Nova Scotia1 M pneumoniae C pneumoniae M pneumoniae
&
Influenza A C burnetii
Marrie TJ, et al.
Am J Med
149 C pneumoniae
1996;101:508-
1996;101:508-15 23 11 3 3 3 48
Argentina S pneumoniae M pneumoniae C pneumoniae Influenza A Cryptococcus

Erard PH, et al.
al. 54 spp
Am Soc Microbiol
1991;108:56A 13 7 4 4 4 65
Lausanne S pneumoniae M pneumoniae Influenza virus C pneumoniae C burnetii

Bochud PY, et al.
al. 170
Medicine
2001;80:752-
2001;80:752-87 23 14 12 5 2 46
Finland S pneumoniae M pneumoniae Chlamydiae Viruses H influenzae

Jokinen C, et al.
al. 169
Clin Infect Dis
2001;15:1141-
2001;15:1141-54
37 14 9 8 4 45
Aetiologies of CAP treated on an ambulatory basis
Location
Nova Scotia1 M pneumoniae C pneumoniae M pneumoniae
&
Influenza A C burnetii
Marrie TJ, et al.
Am J Med
149 C pneumoniae
1996;101:508-
1996;101:508-15 23 11 3 3 3 48
Argentina S pneumoniae M pneumoniae C pneumoniae Influenza A Cryptococcus

Erard PH, et al.
al. 54 spp
Am Soc Microbiol
1991;108:56A 13 7 4 4 4 65
Lausanne S pneumoniae M pneumoniae Influenza virus C pneumoniae C burnetii

Bochud PY, et al.
al. 170
Medicine
2001;80:752-
2001;80:752-87 23 14 12 5 2 46
Finland S pneumoniae M pneumoniae Chlamydiae Viruses H influenzae

Jokinen C, et al.
al. 169
Clin Infect Dis
2001;15:1141-
2001;15:1141-54
37 14 9 8 4 45
Bangkok C pneumoniae M pneumoniae S pneumoniae L pneumophila Mixed infection

3 hospitals
Wattanathum,
Wattanathum, et al.
al. 98 25
Chest 37 30 13 8 13
2003;123:1512-
2003;123:1512-9
Japan M pneumoniae S pneumoniae C pneumoniae H influenzae

Viruses 2
3 hospitals (Okayama) M
Miyashita N, et al.
al. 106 catarrhalis 47
J Med Microbiol 27 12 11 5 2
2005; 54:395-
54:395-400
AsiA-CAP Study
Ngeow YF, et al. Int J Infect Dis 2005 May;9:144-53
X Results from 1374 patients with paired sera showed

infection rates for
Mycoplasma pneumoniae 12.2%
Chlamydophila pneumoniae 4.7%
Legionella pneumophila 6.6%
Overall infection rate by atypical

respiratory pathogens = 23.5%
Severity Assessment
The key to deciding initial site of care
X Outpatient
X Medical ward
X Critical care ward / ICU
Severity assessment is made on the basis of prognostic criteria:

• patients’ age
• comorbidities
• physical, laboratory and radiographic findings
Severity assessment
& Prognostication
X Severity of illness score (e.g., CURB-65)
X Prognostic models (e.g., PSI)
can be used to identify patients who may be
treated as outpatients (Strong recommendation;
level I evidence)
Severity Assessment
Pneumonia Severity Index (PSI)
Requires computation of a score based on 20 variables
Fine MJ, et al. A prediction rule to identify low-risk patients with CAP. N Engl J Med 1997;336:243-50
Severity Assessment
stratifies patients into 5 mortality risk classes:
Risk Risk class Score 30-day mortality
Low I No predictors 0.1%
Low II < 70 0.6%
Low III 71 – 90 0.9%
Moderate IV 91 – 130 9.3%
High V > 130 27.0%
Severity Assessment
On the basis of associated mortality rates, patients in
Risk class 30-day mortality
I 0.1%
Treat as outpatients
II 0.6%
Treat in an observation unit
III 0.9% or short hospitalisation
IV 9.3%
Treat as inpatients
V 27.0%
Severity Assessment
CURB-65 score (6-point) – adopted by BTS
Score 1 point for each feature present

X Confusion
X Urea > 7 mmol/L
X Respiratory rate > 30/min
X Blood pressure (SBP < 90 mmHg or DBP < 60 mmHg)
X Age > 65 yrs
Lim WS, et al. Thorax 2003;58:377-382

Recommendations
CURB-65 score Risk of mortality
Patients who have a CURB-65
X Score 0 0.7% score of 0 or 1 are at low risk of
death - can be treated as having
X Score 1 3.2% non-severe pneumonia and may
be suitable for home treatment
At increased risk of death - should

be considered for short stay inpatient
X Score 2 13% treatment or hospital supervised
outpatient treatment (use clinical
judgement)
X Score 3 17% Patients who have a CURB-65

score of 3 or more are at high risk
X Score 4 41.5% of death and should be managed
X Score 5 57% as severe pneumonia
Lim WS, et al. Thorax 2003;58:377-382

X There is growing evidence that CURB,
CURB-65 and CRB-65 all allow for similar
predictions of death from CAP as compared
to the PSI
X A prospective observational study of 1016
consecutive inpatients with CAP
X in an Emergency Department
X mean (SD) age: 72 (+ 17) yrs
X The ability of the three rules to predict 30 day
mortality was compared
Yan Man S, et al. Prospective comparison of 3 predictive rules (PSI, CURB-65, CRB-65) for assessing
severity of CAP (and to predict 30-day mortality) in Hong Kong. Thorax 2007; 62: 348-53
PSI class 30-day mortality (%)
I 0
II 0.8
III 5
IV 9.3
V 22.1
CURB-65
0 0.9
All 3 predictive rules showed the
1 3.6 same trend of increasing mortality
2 7.3 with worsening risk groups (p <0.001)
3 16.4
4 26.6
5 37.5
CRB-65
0 2.3
1 5.1
2 11.2
3 23.2
4 40 Yan Man S, et al. Prospective comparison of 3 predictive rules for
assessing severity of CAP in Hong Kong. Thorax 2007; 62: 348-53
Sensitivity, specificity, positive and negative predictive
values of 30 day mortality of the different predictive rules
All 3 clinical decision rules had high negative predictive values but low positive
predictive values at all cut-off points and are therefore more useful in ruling out
serious illness
Yan Man S, et al. Prospective comparison of 3 predictive rules for
Sensitivity, specificity, positive and negative predictive
values of 30 day mortality of the different predictive rules
PSI : complicated computation of a score may not be

practical for routine application in busy hospital emergency
departments or primary care settings
CURB-65 : simpler to apply
CRB-65 : is also easily applicable in primary care settings
All 3 clinical decision rules had high negative predictive values but low positive
predictive values at all cut-off points and are therefore more useful in ruling out
serious illness
ICU admission rates also increased with the risk levels of each rule, but were only
statistically significant in CURB-65 and CRB-65
Sensitivity and specificity for high-risk group of
the 3 predictive rules in identifying ICU admission
Sensitivity (%) Specificity (%)

PSI 29.3 82.7
CURB-65 41.5 75.0
CRB-65 24.4 90.3
Because of their low sensitivities, none of the 3 rules appears to be useful for
identifying patients requiring ICU care
Modified ATS 90.2 59.1

†
rule†
Ewig S, et al. Severe CAP: assessment of severity criteria.
Am J Respir Crit Care Med 1998;158:1102–8.
Sensitivity and specificity for high-risk group of
the 3 predictive rules in identifying ICU admission
Sensitivity (%) Specificity (%)

PSI 29.3 82.7
CURB-65 41.5 75.0
CRB-65
Although far from24.4 90.3
being perfect, the modified American
Thoracic
Because of Society
their lowscore is currently
sensitivities, the
none of the bestappears
3 rules tool intoidentifying
be useful for
patients
identifying patients requiring ICUfor ICU admission
care
Modified ATS 90.2 59.1

†
rule†
Ewig S, et al. Severe CAP: assessment of severity criteria.
Am J Respir Crit Care Med 1998;158:1102–8.
Site-of-care decisions 1
X Prediction rules give an indication of disease severity
X Prediction rules have not been found to be useful in
predicting ICU admission
X Generally, patients of higher risk classes have higher rates
of ICU admission
X Unlike 30 day mortality, the association is not strong enough
to allow for individual predictions and decisions
X Criteria for ICU admission vary from country to country and
from hospital to hospital
X Criteria for ICU admission: disease severity is not the only
factor to consider; other factors to consider: disease
prognosis, pre-morbid status, age of patient, and the
availability of ICU resources
Site-of-care decisions 2
X All predictive rules serve only as a guide to clinical
management
X Severity of illness is not the only factor to be
considered when deciding on admission
X Social and home circumstances must be
considered as well
X Physicians should always exercise clinical
judgment and common sense in making these
decisions
Criteria for severe CAP
2007 IDSA / ATS Consensus Guidelines
Major criteria
X Need for mechanical ventilation
X Septic shock requiring vasopressors
Criteria for severe CAP
Major criteria
X Need for mechanical ventilation
X Septic shock requiring vasopressors
Minor criteria
X Respiratory rate >30 breaths/min
X PaO2/FiO2 ratio <250
X Multilobar infiltrates
X Confusion/disorientation
X Uraemia (BUN level, >20 mg/dL)
X Leukopenia (WBC count, <4 x 109/L)
X Thrombocytopenia (platelet count, <100 x 109/L)
X Hypothermia (core temperature, <36ºC)
X Hypotension requiring aggressive fluid resuscitation
ICU admission decision
Direct admission to an ICU is required for patients with
X septic shock requiring vasopressors or
X with acute respiratory failure requiring intubation and
mechanical ventilation
(Strong recommendation; level II evidence)
Direct admission to an ICU or high-level monitoring unit is

recommended for patients with
X 3 of the minor criteria for severe CAP
(Moderate recommendation; level II evidence)
Mandell LA, et al. IDSA / ATS Consensus Guidelines on the management of CAP in adults.
Clin Infect Dis 2007; 44:S27-72
ICU admission decision
Direct admission to an ICU is required for patients with
X septic shock requiring vasopressors or
X with acute respiratory failure requiring intubation and
mechanical ventilation
(Strong recommendation; level II evidence)
Direct admission to an ICU or high-level monitoring unit is

recommended for patients with
X 3 of the minor criteria for severe CAP
(Moderate recommendation; level II evidence)
This recommendation requires prospective validation
Effects of antibiotic administration within 4 hrs of arrival
at the hospital on in-hospital & 30-day mortality *
OR:0.87
18
16
14
OR:0.86
12
10 < 4h
8 >4h
6 OR:0.62
4
2
0
Hosp Fine II-III Hospital IV-V 30 days Fine II- 30 days Fine
III IV-V
*In Medicare patients older than 65 yrs who had not received
pre-hospital antibiotic therapy (n = 13,771)
Houck PM, et al. A retrospective study on Medicare patients.
Arch Intern Med 2004;164:637–44
Effects of antibiotic administration within 4 hrs of arrival
at the hospital on in-hospital & 30-day mortality *
OR:0.87
15%
18 reduction in both in-hospital and 30-day mortality
16
14
OR:0.86
12
10 < 4h
8 >4h
6 OR:0.62
4
2
0
Hosp Fine II-III Hospital IV-V 30 days Fine II- 30 days Fine
III IV-V
*In Medicare patients older than 65 yrs who had not received
pre-hospital antibiotic therapy (n = 13,771)
Arch Intern Med 2004;164:637–44
X Treat early
Initiation of antimicrobial therapy
X within 4 hrs of arrival at the hospital was associated with a
0.4 day shorter mean LOS
Arch Intern Med 2004; 164:637-44
Guidelines for managing CAP
Principles of empirical therapy
X Treat early
Initiation of antimicrobial therapy
X within 4 hrs of arrival at the hospital was associated with a
0.4 day shorter mean LOS
Arch Intern Med 2004; 164:637-44
In the 2003 IDSA guidelines (also JRS guidelines 2005), initiating antibiotic therapy
within 4 hrs after registration for hospitalised patients was a performance indicator
2007 IDSA / ATS Consensus Guidelines: Rather than designating a

specific window in which to initiate treatment, hospitalized patients with
CAP should receive the first antibiotic dose in the ED
X Treat early
X Cannot reliably differentiate aetiology based on
clinical and radiological findings
X Treat early
X Treat the most likely pathogens
– S. pneumoniae (?DRSP*); H. influenzae
– Atypicals
– Others (co-morbidity and local epidemiology)
X Treat early
X Treat the most likely pathogens
– S. pneumoniae (?DRSP*); H. influenzae
– Atypicals
– Others (co-morbidity and local epidemiology)
X Likely antibiotic sensitivity of presumed pathogens
Antibiotic Resistance Issues
X Resistance to commonly used antibiotics for CAP is major
consideration in choosing empirical therapy
X Resistance patterns vary by geography
X Therefore, antibiotic recommendations must be modified

based on local susceptibility patterns
Mandell
MandellLA, al.IDSA
LA,etetal. IDSA/ /ATS
ATSConsensus
ConsensusGuidelines.
Guidelines.Clin
ClinInfect Dis2007;
InfectDis 2007;44:S27-72
44:S27-72
American
AmericanThoracic
ThoracicSociety
SocietyGuidelines
GuidelinesAm
AmJJRespir
RespirCrit
CritCare Med2001;
CareMed 2001;163:1730-54
163:1730-54
Risk factors for infection with β-lactam-resistant

•Age <2 yrs or >65 yrs
•β-lactam therapy within the previous 3 months
•Alcoholism
•Medical comorbidities
•Immunosuppressive illness or therapy
•Exposure to a child in a day care centre
Probably related to greater exposure to antibiotics among these categories of

individuals and increased selection of antibiotic-resistant strains
Risk factors for infection with β-lactam-resistant
•Age <2 yrs or >65 yrs
•β-lactam therapy within the previous 3 months
•Alcoholism
Recent treatment
•Medical with antimicrobials - the most
comorbidities
significant:
•Immunosuppressive illness or therapy
Recent therapy
•Exposure to aorchild
repeated
in acourses of therapy
day care centrewith
β-lactams, macrolides, or fluoroquinolones are risk
factors for pneumococcal resistance to the same
class of antibiotic
Prevalence of penicillin-resistant S. pneumoniae*
in 12 Asian countries (1996-1997 and 2000-2001)
Asian Network for Surveillance of Resistant Pathogens (ANSORP) * Clinical isolates
China (Beijing, Shanghai) South Korea
9.8% → 19.8% 24.3% → 9.7%
0% → 23.4% 55.4% → 54.8%
Vietnam
28.2% → 20.6% Taiwan
Saudi Arabia 9.3% → 24.6%
32.6% → 71.4%
NA → 20.5% Hong Kong 29.4% → 38.6%
NA → 10.3% India NA → 24.1%
3.8% → 7.8% Philippines
NA → 43.8%
0% → 0% NA → 27.3%
NA → 0%
Thailand
35.7% → 26.9%
Singapore
22.2% → 26.9%
4.9% → 28.6 %
18.2 % → 17.1%
Malaysia
6.0% → 9.1%
3.0% → 29.5%
Penicillin-intermediate (MIC 0.12–1 mg/L)

Penicillin-resistant (MIC ≥2 mg/L)
Song JH, et al. ANSORP. Antimicrob Agents Chemother June 2004; 48:2101-7
Prevalence of penicillin-resistant S. pneumoniae*
in 12 Asian countries (1996-1997 and 2000-2001)
Asian Network for Surveillance of Resistant Pathogens (ANSORP) * Clinical isolates
China (Beijing, Shanghai) South Korea
9.8% → 19.8% 24.3% → 9.7%
0% → 23.4% 55.4% → 54.8%
Vietnam
28.2% → 20.6% Taiwan
Saudi Arabia 9.3% → 24.6%
32.6% → 71.4%
NA → 20.5% Hong Kong 29.4% → 38.6%
NA → 10.3% India NA → 24.1%
Philippines
Overall, 23% of S 3.8%
pneumoniae isolates were
→ 7.8% penicillin-intermediate
NA → 43.8%
NA → 27.3%
0% → 0%
and 29.4% were penicillin-resistant NA → 0%
Thailand
35.7% → 26.9%
Singapore
22.2% → 26.9%
4.9%
IDSA / ATS Consensus Guidelines on the management of CAP in adults. CID → 28.6
2007; %
44:S27-72
18.2 % → 17.1%
The available data suggest that the clinically relevant level of
Malaysia
penicillin resistance
6.0% is a MIC of at least 4 mg/L
→ 9.1%
3.0% → 29.5%
Feikin DR,, et al. Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance, 1995–1997.
Am J Public Health 2000; 90:223–9.
Penicillin-intermediate (MIC 0.12–1 mg/L)
Penicillin-resistant (MIC ≥2 mg/L)
Prevalence of resistance of S. pneumoniae to other
β-lactams and erythromycin in Asia Jan 2000 – Jun 2001 ANSORP
China (Beijing, Shanghai) South Korea Taiwan
Co-amoxiclav 2.7%, 7.3% Co-amoxiclav 6.5%, 9.7% Co-amoxiclav 3.5%, 1.8%
Cefuroxime 4.5%, 19.8% Cefuroxime 3.2%, 61.3% Cefuroxime 8.8%, 40.4%
Ceftriaxone 0.0%, 1.1% Ceftriaxone 3.2%, 3.2% Ceftriaxone 1.8%, 0.0%
Erythromycin 0.9%, 73.9% Erythromycin 0.0%, 80.6% Erythromycin 1.8%, 86.0%
Hong Kong
Co-amoxiclav 0.9%, 3.6%
Cefuroxime 10.0%, 50.0%
Ceftriaxone 3.7%, 0.0%
Erythromycin 0.0%, 76.8%
Vietnam
Co-amoxiclav 14.3%, 22.2%
Cefuroxime 4.8%, 74.2%
Ceftriaxone 9.5%, 3.2%
Erythromycin 1.6%, 92.1%
Intermediate
Resistant
Prevalence of resistance of S. pneumoniae to other
β-lactams and erythromycin in Asia Jan 2000 – Jun 2001 ANSORP
Saudi Arabia India

Co-amoxiclav 0.0%, 0.0% Co-amoxiclav 0.0%, 0.0%
Cefuroxime 2.6%, 12.8% Cefuroxime 0.0%, 1.3%
Ceftriaxone 0.0%, 0.0% Ceftriaxone 0.0%, 0.0%
Erythromycin 0.0%, 10.3% Erythromycin 0.0%, 1.3%
Thailand Philippines
Erythromycin 5.8%, 36.5% Erythromycin 4.5%, 18.2%
Malaysia Singapore
Intermediate Erythromycin 6.8%, 34.1% Erythromycin 2.9%, 40.0%
Resistant
Susceptibilities of S. pneumoniae isolates to
fluoroquinolones in 11 Asian countries Jan 2000 – Jun 2001
China (Beijing, Shanghai) South Korea Taiwan
Levofloxacin 0.0%, 0.0% Levofloxacin 0.0%, 0.0% Levofloxacin 0.0%, 1.8%
Gatifloxacin 0.0%, 0.0% Gatifloxacin 0.0%, 0.0% Gatifloxacin 1.8%, 1.8%
Moxifloxacin 0.0%, 0.0% Moxifloxacin 0.0%, 0.0% Moxifloxacin 1.8%, 0.0%
Ciprofloxacin 3.6% Ciprofloxacin 6.5% Ciprofloxacin 7.0%
Saudi Arabia India Hong Kong
Gatifloxacin 0.0%, 0.0% Gatifloxacin 0.0%, 1.4%
Gatifloxacin 0.9%, 8.3%
Moxifloxacin 0.0%, 0.0% Moxifloxacin 1.3%, 0.0%
Ciprofloxacin 2.6% Ciprofloxacin 4.0% Moxifloxacin 6.3%, 1.8%
Ciprofloxacin 11.8%
Thailand Vietnam Philippines
Gatifloxacin 0.0%, 0.0% Gatifloxacin 0.0%, 0.0% Gatifloxacin 0.0%, 0.0%
Moxifloxacin 0.0%, 0.0% Moxifloxacin 0.0%, 0.0% Moxifloxacin 0.0%, 0.0%
Ciprofloxacin 3.8% Ciprofloxacin 4.8% Ciprofloxacin 9.1%
Malaysia Singapore
Levofloxacin 0.0%, 0.0% Levofloxacin 2.9%, 0.0%
Gatifloxacin 0.0%, 0.0% Gatifloxacin 0.0%, 0.0%
Moxifloxacin 0.0%, 0.0% Moxifloxacin 0.0%, 0.0%
Intermediate Ciprofloxacin 4.6% Ciprofloxacin 5.9%
Resistant
Multi-drug resistant S pneumoniae (i.e., resistance to at least 3
classes of antibiotics) in 12 Asian countries Jan 2000 – Jun 2001
Overall rate of multi-drug resistant S pneumoniae was

26.8%
MDR S pneumoniae :
X 71.4% of isolates from Vietnam
X 44.9% of isolates from Hong Kong
X 42.5% of isolates from Korea
X 30.9% of isolates from Taiwan
Song JH, et al. ANSORP. Antimicrob Agents Chemother 2004; 48:2101-7

e
of Drug-resistant S. pneumoniae (DRSP)

ce to
e X The clinical relevance of DRSP for pneumonia is uncertain

X Current levels of β-lactam resistance do not generally result in
ed CAP treatment failures when appropriate agents (amoxicillin,
ished
ceftriaxone, or cefotaxime) and doses are used (even in
ses bacteremia)
tive
X There are data to suggest that resistance to macrolides and
am older FQs (ciprofloxacin and levofloxacin) results in clinical
.e.,
failure
oses
a
X To date, no failures have been reported for the newer
e fluoroquinolones (moxifloxacin and gemifloxacin)
is a
sted
ccal
vitro,
es
.
ERS, ATS2001, IDSA2003, IDSA/ATS2007
algorithm for CAP
CAP
Outpatient
Outpatient treatment
treatment Inpatient
Inpatient treatment
treatment
No
No History
History of
of Mild
Mild to
to moderate
moderate Severe
Severe CAP
CAP
cardiopulmonary
cardiopulmonary cardiopulmonary
cardiopulmonary illness
illness
disease
disease disease
disease
Risks
Risks
for
for Ps
Ps aeruginosa
aeruginosa
No
No modifiers
modifiers +/-
+/- modifiers
modifiers
No
No C/P
C/P ++ C/P
C/P
disease
disease disease
disease
No
No +/or
+/or Yes
Yes No
No
Modifier
Modifier Modifier
Modifier
CAP: empirical antibiotic therapy
IDSA/ATS2007
Empirical antibiotic recommendations have not changed
significantly from those of previous guidelines
IDSA/ATS Consensus Guidelines on the management of CAP in adults
Recommended empirical antibiotics for CAP
Site of
treatment Outpatient Inpatient, non-ICU ICU
Previously healthy and
no antimicrobial use
IDSA / within previous 3 mths
MacrolideI [strong recommendation, level 1 evidence] or
ATS
DoxycyclineIII [weak recommendation, level 3 evidence]
Guidelines
2007
Mandell LA, et al. Clin Infect Dis 2007; 44:S27-72

Site of
MacrolideI [level 1 evidence] or
ATS
DoxycyclineIII [level 3 evidence]
Guidelines
Presence of
2007 comorbidities or
Comorbidities: chronic heart,
lung, liver or renal disease;
antimicrobial use within
previous 3 mths or other diabetes mellitus; alcoholism; Increase the
risks for DRSP infection malignancies; asplenia; likelihood of
Respiratory FQI or immunosuppressing conditions or infection with
β-lactam + macrolideI use of immunosuppressive drugs DRSP and
enteric gram-
Use of antimicrobials within the
negative
previous 3 months: an alternative
bacteria
from a different class should be
selected

Site of
ATS
Guidelines
Presence of
previous 3 mths or other
risks for DRSP infection
Respiratory FQI or Moxifloxacin, gemifloxacin or levofloxacin [750 mg]
β-lactam + macrolideI High-dose amoxicillin 1 g 3 times daily, or
high-dose amoxicillin-clavulanate 2 g 2 times daily or
cefuroxime 500 mg 2 times daily

Site of
ATS
Guidelines
Presence of
Respiratory FQI or
β-lactam + macrolideI
In regions with high rate
(>25%) of infection with
high-level (MIC >16 µg/mL)
macrolide-resistant S.
pneumoniae
Respiratory FQIII [moderate recommendation, level 3 evidence] or
β-lactam + macrolideIII [moderate recommendation, level 3 evidence]
Site of
Previously healthy and Respiratory FQ aloneI The major discriminating
no antimicrobial use or factor between the 2
IDSA / within previous 3 mths β-lactam + macrolideI regimens is the patient’s
MacrolideI [level 1 evidence] or prior antibiotic exposure
ATS (within the past 3 months).
Guidelines Preferred β-lactams
Presence of
include cefotaxime,
ceftriaxone, and ampicillin;
antimicrobial use within ertapenem for selected
previous 3 mths or other patients
Respiratory FQI or
pneumoniae
Respiratory FQIII or
β-lactam + macrolideIII Mandell LA, et al. Clin Infect Dis 2007; 44:S27-72
Site of
Previously healthy and Respiratory FQ aloneI
no antimicrobial use or
IDSA / within previous 3 mths β-lactam + macrolideI
ATS
Presence of
include cefotaxime,
Respiratory FQI or
pneumoniae
Site of
ATS
Presence of
include cefotaxime,
Respiratory FQI or Doxycycline is an
alternative to the macrolide
β-lactam + macrolideI [level III evidence]
pneumoniae
Site of
ATS For penicillin-allergic
Guidelines patients
Presence of
Respiratory FQI
Respiratory FQI or
pneumoniae
Site of
Previously healthy and Respiratory FQI For all patients admitted to
no antimicrobial use or the ICU, coverage for S.
IDSA / within previous 3 mths β-lactam + macrolideI pneumoniae and Legionella
MacrolideI [level 1 evidence] or species should be ensured
DoxycyclineIII [level 3 evidence] by using a potent
Guidelines patients
Presence of antipneumococcal β-lactam
Respiratory FQI and either a macrolide or a
antimicrobial use within FQ
Respiratory FQI or
pneumoniae
Most common microbial aetiologies of CAP

Inpatient Inpatient
Outpatient
(non-ICU) (ICU)
M. pneumoniae M. pneumoniae Legionella spp.
H. influenzae C. pneumoniae H. Influenzae
C. pneumoniae H. influenzae Enterobacteriaceae spp.
Respiratory viruses Legionella species Staph. aureus
Aspiration Pseudomonas spp.
Respiratory viruses
A review of 9 recent studies (that included 890 patients with CAP admitted to the ICU):
the most common pathogens in the ICU population were (in descending order of frequency)
S. pneumoniae, Legionella species, H. influenzae, Enterobacteriaceae species, S. aureus,
and Pseudomonas species.
The atypical pathogens collectively account for 20% of severe CAP episodes. The dominant
atypical pathogen in severe CAP is Legionella.
File TM. Community-acquired pneumonia. Lancet 2003; 362:1991-2001
Site of
Previously healthy and Respiratory FQI The recommended
no antimicrobial use or standard empirical
IDSA / within previous 3 mths β-lactam + macrolideI regimen should routinely
cover the 3 most common
DoxycyclineIII [level 3 evidence] pathogens that cause
Guidelines patients
Presence of severe CAP, all of the
Respiratory FQI atypical pathogens, and
antimicrobial use within most of the relevant
previous 3 mths or other Enterobacteriaceae
risks for DRSP infection species.
Respiratory FQI or
pneumoniae
Site of
Previously healthy and Respiratory FQI β-lactam* + azithromycinII
no antimicrobial use or or
IDSA / within previous 3 mths β-lactam + macrolideI β-lactam* + respiratory FQI
Guidelines patients
Presence of
Respiratory FQI
previous 3 mths or other *β-lactam
risks for DRSP infection cefotaxime, ceftraxone,
Respiratory FQI or ampicillin/sulbactam,
pneumoniae
Site of
ATS For penicillin-allergic For penicillin-allergic
Guidelines patients patients
Presence of
Respiratory FQI Respiratory FQ + aztreonam
Respiratory FQI or
pneumoniae
Site of
Presence of
antimicrobial use within If Pseudomonas is a
previous 3 mths or other considerationIII
risks for DRSP infection Anti-pneumococcal, anti-
Respiratory FQI or pseudomonal β-lactam
β-lactam + macrolideI (piperacillin-tazobactam, cefepime,
In regions with high rate imipenem, or meropenem) + either
(>25%) of infection with ciprofloxacin or levofloxacin
high-level (MIC >16 µg/mL) (750 mg) or
pneumoniae
Site of
Presence of
β-lactam + macrolideI + aminoglycoside +
In regions with high rate azithromycin or
pneumoniae
Site of
Presence of
β-lactam + macrolideI + aminoglycoside + anti-
In regions with high rate pneumococcal FQ (for
(>25%) of infection with penicillin-allergic patients,
high-level (MIC >16 µg/mL) substitute the β-lactam with
macrolide-resistant S. aztreonam)
pneumoniae
Site of
Presence of
β-lactam + macrolideI + aminoglycoside + anti-
In regions with high rate pneumococcal FQ (for
(>25%) of infection with penicillin-allergic patients,
high-level (MIC >16 µg/mL) substitute the β-lactam with
macrolide-resistant S. aztreonam)
pneumoniae
If CA-MRSA is a
Respiratory FQIII or consideration
β-lactam + macrolideIII Add vancomycin or linezolidIII
Duration of antibiotic therapy

X Patients with CAP should be treated for a minimum of
5 days (level I evidence)
X Before discontinuation of therapy

- should be afebrile for 48–72 h
- should have no more than 1 CAP-associated sign of
clinical instability (level II evidence)
Criteria for clinical stability
Temperature <37.8C
Heart rate < 100 /min
Respiratory rate < 24 /min
Systolic blood pressure >90 mm Hg
Arterial oxygen saturation > 90% or pO2 > 60 mm Hg on room air
Ability to maintain oral intake*
Normal mental status*
Adjusted OR for 30-day all-cause mortality plotted against
compliance with guideline-recommended antibiotics
at Intermountain Healthcare hospitals
Adjusted
OR for
30-day
all-cause
mortality
Circle area reflects the number of admissions per hospital
The odds of mortality are 0.92 (p = 0.007) for

each 10% increase in compliance
Dean, N. C. et al. Chest 2006;130:794-799
Any advantages in following guidelines?
X Reduction in hospital admission rate

X Shortens length of hospital stay (LOS)
X Reduction in in-hospital and 30-day mortality
X ? Help control bacterial resistance in the
community (minimise use of excessive antibiotics and improves
accuracy of therapy) – However, the impact of guidelines on
resistance remains to be shown
THANK YOU
liamck@ummc.edu.my

Management of Community Acquired Pneumonia in The Asia Pacific Region

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Management of Community Acquired Pneumonia in The Asia Pacific Region

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MANAGEMENT OF

COMMUNITY ACQUIRED PNEUMONIA

XAnnual incidence in USA

Marfarlane J. Semin Respir Infect 1994; 9:153-65

6th leading cause of death worldwide

JRS guidelines (2005). Respirology 2006; 11:S79-S133

CAP patients are generally categorised into 3 groups

Most common microbial aetiologies of CAP (in the West)

Ref: File TM. Community-acquired pneumonia. Lancet 2003; 362:1991-2001

Most common microbial aetiologies of CAP (in the West)

Okayama1 S pneumoniae H influenzae M pneumoniae K pneumoniae S milleri

• The aetiology of CAP in Japan is quite similar to that of Western countries

XPatients who met ATS criteria for severe CAP

Argentina S pneumoniae M pneumoniae C pneumoniae Influenza A Cryptococcus

Lausanne S pneumoniae M pneumoniae Influenza virus C pneumoniae C burnetii

Finland S pneumoniae M pneumoniae Chlamydiae Viruses H influenzae

Argentina S pneumoniae M pneumoniae C pneumoniae Influenza A Cryptococcus

Lausanne S pneumoniae M pneumoniae Influenza virus C pneumoniae C burnetii

Finland S pneumoniae M pneumoniae Chlamydiae Viruses H influenzae

Bangkok C pneumoniae M pneumoniae S pneumoniae L pneumophila Mixed infection

Japan M pneumoniae S pneumoniae C pneumoniae H influenzae

X Results from 1374 patients with paired sera showed

Overall infection rate by atypical

Severity assessment is made on the basis of prognostic criteria:

Score 1 point for each feature present

Lim WS, et al. Thorax 2003;58:377-382

At increased risk of death - should

X Score 3 17% Patients who have a CURB-65

Lim WS, et al. Thorax 2003;58:377-382

 PSI : complicated computation of a score may not be

Sensitivity (%) Specificity (%)

Modified ATS 90.2 59.1

Sensitivity (%) Specificity (%)

Modified ATS 90.2 59.1

Direct admission to an ICU or high-level monitoring unit is

Direct admission to an ICU or high-level monitoring unit is

2007 IDSA / ATS Consensus Guidelines: Rather than designating a

X Resistance patterns vary by geography

X Therefore, antibiotic recommendations must be modified

Risk factors for infection with β-lactam-resistant

Probably related to greater exposure to antibiotics among these categories of

Penicillin-intermediate (MIC 0.12–1 mg/L)

Saudi Arabia India

Overall rate of multi-drug resistant S pneumoniae was

Song JH, et al. ANSORP. Antimicrob Agents Chemother 2004; 48:2101-7

of Drug-resistant S. pneumoniae (DRSP)

e X The clinical relevance of DRSP for pneumonia is uncertain

Mandell LA, et al. Clin Infect Dis 2007; 44:S27-72

Mandell LA, et al. Clin Infect Dis 2007; 44:S27-72

Mandell LA, et al. Clin Infect Dis 2007; 44:S27-72

Most common microbial aetiologies of CAP

Duration of antibiotic therapy

X Before discontinuation of therapy

Circle area reflects the number of admissions per hospital

The odds of mortality are 0.92 (p = 0.007) for

X Reduction in hospital admission rate

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PSI : complicated computation of a score may not be