Transcript Mycoplasma pneumoniae

 Hippocrates (c. 460 BC – 370 BC):
 Peripneumonia, and pleuritic affections, are
to be thus observed: If the fever be acute, and
if there be pains on either side, or in both, and
if expiration be if cough be present, and the
sputa expectorated be of a blond or livid color, or likewise thin,
frothy, and florid, or having any other character different from the
common... When pneumonia is at its height, the case is beyond
remedy if he is not purged, and it is bad if he has dyspnoea, and
urine that is thin and acrid, and if sweats come out about
the neck and head, for such sweats are bad, as proceeding from
the suffocation, rales, and the violence of the disease which is
obtaining the upper hand.
 Also reported the results of surgical drainage of empyemas
 Sir William Osler (1849-1919), "the father of modern
medicine," described pneumonia as
the "captain of the men of death"
in 1918. (The phrase was originally
coined by John Bunyan with regard
to consumption, or tuberculosis)
 Died in 1919 due to pneumonia with abscess formation
: aspirated pus contained “Pfeiffer's bacillus”
 Sixth leading cause of death
 Number one cause of death from infectious disease &
childhood mortality
 Annual incidence in community 5–11 / 1000 adult population
 India accounts for the maximum, 43 million new cases / year
 CAP requiring admission to hospital 1.1 - 4 / 1000 population
 Mortality rate in severe CAP in ICU in the UK > 50%
 USA : annual CAP costs $8.4 billion, 52% of the costs being
for the inpatient care of 1.1 million patients
Pneumococcal iron acquisition and uptake
Polysaccharide capsule
.
Hyl=hyluronate lyase. LTA=lipoteichoic acid.
PspC=pneumococcal surface protein C. PspA=pneumococcal
surface protein A. PAF=platelet-activating factor.
PsaA=pneumococcal surface antigen A.
PsrP=pneumococcal serine-rich repeat protein.
NanA=neuraminidase. Eno=enolase. PavA=pneumococcal
adhesion and virulence. LytA=autolysin
van der Poll T et al; Lancet 2009; 374: 1543–56
van der Poll T et al; Lancet 2009; 374: 1543–56
 Two gross patterns of anatomic distribution:
Lobar pneumonia
Bronchopneumonia
4 stages of the inflammatory response
Congestion :
Gross : heavy, boggy, and red.
Microscopic : vascular engorgement, intra-alveolar fluid with few
neutrophils, and often the presence of numerous bacteria.
Red hepatization
Gross : lobe appears distinctly red, firm, and airless, with a liver-like
consistency.
Microscopic : massive confluent exudation with red cells
(congestion), neutrophils, and fibrin filling the alveolar spaces .
Gray hepatization
Gross : appearance of a grayish brown, dry surface.
Microscopic : progressive disintegration of red cells and the
persistence of a fibrinosuppurative exudate ,
Resolution
Consolidated exudate undergoes progressive enzymatic digestion to
produce a granular, semifluid, debris that is resorbed, ingested by
macrophages, coughed up, or organized by fibroblasts growing into it
Most common etiologies of community‐acquired pneumonia.
Patient type
Outpatient
Etiology
Streptococcus pneumoniae
Mycoplasma pneumoniae
Haemophilus influenzae
C. pneumoniae
Respiratory viruses
Inpatient (non‐ICU)
Streptococcus pneumoniae
M. pneumoniae
C. pneumoniae
H. influenzae
Legionella species
Aspiration
Respiratory viruses
Streptococcus pneumoniae
Inpatient (ICU)
Staphylococcus aureus
Legionella species
Gram‐negative bacilli
H. influenzae
File TM. Lancet 2003; 362: 1991–2001
Other causes
 Virus
 Influenza, Adenoviruses, Respiratory syncytial
viruses, Parainfluenza viruses, Coronavirus,
Hantavirus etc.
 Tubercular
 Fungal : Aspergillus, Fusarium etc.
 Parasitic
 Leptospira
Udwadia et al
2003 (n=100)
Bansal et al 2004
(n=70)
Oberoi et al
2006 (n=233)
S. Pneumoniae
22
35.8
32.8
K. pneumoniae
3
22.6
10.2
H. influenzae
9
22.6
S. aureus
1
17
1.4
GNB
9
20
-
L. pneumophila
3
-
-
M. pneumoniae
3
15
16.5
C. pneumoniae
14
-
17.6
Viruses
-
-
-
Organism
 13% patients had a conventional bacterial aetiology
and 15% had serological evidence of recent infection
with L. pneumophila
Chaudhry R et al; Trop Doct; 2000 Oct;30(4):197-200.
 35.5% patients with CAP had Mycoplasma
pneumoniae. 60% patients immunocompromised &
40% immunocompetent.
Dey AB et al; Natl Med J India 2000; Mar-Apr;13(2):66-70.
AIIMS Data (Thesis: ongoing)
 Microbial etiology established so far : 11/36 cases (30.5%)
 No.of cases with polymicrobial etiology : 0
 AFB detected in 4/36 (11.1%)
 Sputum in 2
 Tracheal aspirate in 1
 Pleural fluid in 1
 Pseudomonas aeruginosa(ESBL negative) isolated in 3/36
 Mini BAL & tracheal aspirate in 2
 Sputum in 1
 K.pneumoniae isolated from Blood in 2/36
 Staphylococcus aureus (MRSA) isolated in BAL in 1/36
 E.coli(ESBL positive) isolated in BAL in 1/36
Clinical feature
 Generally begins with a mild upper-airway irritation.
 Shaking chill, fever, malaise, cough, and dyspnoea.
 Purulent sputum, sometimes with brownish or blood-
tinged, chest pain.
 Acute respiratory failure, septic shock, multiorgan
failure, and death
 Can be subtle in its early phases in neonates, elderly
people, severely immunocompromised patients,
Clinical features
 Streptococcus pneumoniae
 Increasing age, comorbidity, acute onset, high fever and
pleuritic chest pain, female sex, excess alcohol, diabetes
mellitus, Non
COPD specific clinical features
 Legionella pneumophila
can suggest etiology but not
 Younger patients, smokers, absence of comorbidity,
helpful multisystem involvement
diarrhoea, neurological symptoms,
 Mycoplasma pneumoniae
 Younger patients, prior antibiotics, less multisystem
involvement
 Chlamydia pneumoniae
 Longer duration of symptoms before hospital admission,
headache
Complications
 Pulmonary
 Parapneumonic effusion
 Empyema
 Lung abscess
 Adult respiratory distress syndrome
(ARDS)
 Pneumatocele/pneumothorax
 Extrapulmonary
 Phlebitis at intravenous cannula site
 Metastatic infection
 Septicaemia
 End organ sequelae of septicaemia (e.g.
renal failure)
Site of care
 Cost of inpatient care for pneumonia is up to 25 times




greater than that of outpatient care
Outpatients are able to resume normal activity sooner
Patient preference
Hospitalisation increases thromboembolic events and
superinfection by more-virulent or resistant hospital
bacteria
Severity score
 PSI
 CURB 65
Patients with communityacquired pneumonia
Demographic factor
Is the patient more than 50
years of age?
History of coexisting
conditions : Neoplastic disease,
CHF, Cerebrovascular disease ,
Renal or, Liver disease
Altered mental status
Pulse≥125/minute, RR≥30/min,
SBP<90,Temp <35°C or ≥40°C
NO
Assign patient to risk class I
Assign
patient
to risk
class
II–V
POINTS
ASSIGNED*
Demographic factorfindings POINTS
Physical-examination
ASSIGNED*
Altered mental status
+20
Age
Respiratory rate ≥30/min
+20
Men
Age in year
SBP <90 mm Hg
+20
Women
Age in year – 10
Temperature <35°C or ≥40°C
+15
Nursing home resident
+10
Pulse >125/min
+10
Coexisting illnesses
Lab and radiographic findings
Neoplastic disease
+30
Arterial pH < 7.35
+30
Liver disease
+20
Blood urea nitrogen ≥ 30
+20
Congestive
heart
+10
mg/dl
failure
Sodium < 130 mmol/liter
+20
Cerebrovascular
+10
Glucose
+10
disease > 250 mg/dl
Hematocrit
< 30%
Renal disease
+10 +10
II : ≤70
III : 71-90
IV : 91-130
V : > 130
PaO2<60 mm Hg
+10
Pleural effusion
+10
Fine MJ et al; N Engl J Med 1997; 336: 243-50
Risk
class
Medisgroups
Derivation Cohort
Medisgroups
Validation Cohort
Pneumoniaport
Validation Cohort
No.
% Died
No.
% Died
No.
% Died
I
1372
0.4
3034
0.1
772
0.1
II
2412
0.7
5778
0.6
477
0.6
III
2632
2.8
6790
2.8
326
0.9
IV
4697
8.5
13104
8.2
486
9.3
V
3086
31.1
9333
29.2
226
27
Total
14199
10.2
38039
10.6
2287
5.2
•PSI I-II : OPD
•PSI III : Observation unit/short hospitalisation
•PSI IV-V : Inpatient
Fine MJ et al; N Engl J Med 1997;336:243-50
Relationship between number of CURB criteria and risk of mortality
Features
No.
present
Derivation cohort (n=718)
Validation cohort (n=214)
Total
Died (%)
Total
Died (%)
CURB
0
217
3 (1.4)
55
0
(Confusion
1
247
14 (5.4)
86
5 (5.8)
BUN>20mg/dl
2
162
23 (14.2)
46
8 (17.4)
RR>30
3
85
28 (32.9)
23
6 (26)
SBP<90, DBP<60)
4
7
1 (14.3)
4
1 (25)
CURB-65
CRB-65
0•CURB
65137score 0-1 : OPD
1 (0.7)
36
score 2 : wards
1•CURB 65187
4 (2.1)
54
score 3-4 :17often
2•CURB 65184
(9.2) require ICU
60
5 (8.3)
3
138
20 (14.5)
42
9 (21.4)
4
65
26 (40)
19
5 (26.3)
5
7
1 (14)
3
1 (33.3)
0
167
2 (1.2)
45
0
1
266
14 (5.3)
78
4 (5.1)
2
189
23 (12.2)
62
7 (11.3)
3
85
28 (32.9)
26
8 (30.8)
4
11
2 (18.2)
3
1 (33.3)
0
0
Lim WS et al; Thorax 2003;58:377–382
 Comparison of 3 scoring systems : PSI, CURB and CURB-65
in predicting 30-day mortality in community-acquired
pneumonia in 3181 patients.
 PSI (risk classes I-III) classified a greater proportion of
Severity score to be calculated for all patients
patients as low risk (68%) than CURB score <1 (51%) or a
CURB score
65 is equivalent
CURB-65
<2 (61%). to PSI & is easy to use
 Low-risk patients identified based on the PSI had a
slightly lower mortality (1.4%) than patients classified
based on the CURB (1.7%) or the CURB-65 (1.7%).
Aujesky D et al; Am J Med. 2005 Apr;118(4):384-92.
Criteria for ICU admission (any major or, 3 minor )
Minor criteria
Respiratory rate ≥30 breaths/min
PaO2/FiO2 ratio ≤250
Multilobar infiltrates
Confusion/disorientation
Uremia (BUN level, ≥20 mg/dL)
Leukopenia (WBC count, <4000 cells/mm3)
Thrombocytopenia (platelet count, <100,000 cells/mm3)
Hypothermia (core temperature, <36°C)
Hypotension requiring aggressive fluid resuscitation
Major criteria
Invasive mechanical ventilation
Septic shock with the need for vasopressors
IDSA/ATS Consensus Guidelines. Clinical Infectious Diseases 2007; 44:S27–72
Investigations
 CBC
 RFT & LFT
 CXR : PA, Lat, Decubitus
 Opacity appears 12 hrs
after symptoms
 Observer variation
 False negatives
 CT
 Pulse Oxymetry
 ABG
 Specific investigations for
 All inpatients
 OPD



The diagnosis is in doubt and
CXR will help in diagnosis
and management. [D]
Progress is not satisfactory
At risk of underlying lung
pathology such as lung
cancer.
etiology
BTS guideline for CAP, Thorax 2009;64:iii1-iii55
CT scan
 CT sp HRCT has higher sensitivity than CXR
 Detects ~15% cases which are missed by CXR
 30% cases diagnosed on CT develop patch on CXR 5 days
later
 Indications
 Clinical pneumonia but normal or non specific CXR
 Suspected complication
 Underlying lung lesion
 Persistent or recurrent opacity
Imaging of pulmonary infections; Nestor L. Muller 7th ed 49-55
CT scan
 Bacterial : Airspace consolidation, segmental
distribution in middle & outer zone of lung
 Atypical : Centrilobular opacities, airspace nodules,
airspace consolidation, ground glass opacity in lobular
distribution
 Extensive ground glass opacity without air space
consolidation : PCP
 Centrilobular nodules & lobular ground glass opacity :
Mycoplasma
 However, considerable overlap & non-specific
Imaging of pulmonary infections; Nestor L. Muller 7th ed 49-55
Specific investigations for etiology
 78/M, R/O Gurgaon
 21/M, R/O UK
 Fever, cough & expectoration
 Fever, cough & expectoration
Cefoperazone-Sulbactum
+ Azithromycin
Cefoperazone-Sulbactum
+ Azithromycin
3 days
Good response
Partial response
5 days
Sputum AFB +ve
Started on ATT
Specific investigations for etiology
 The spectrum of antibiotic therapy can be broadened,
narrowed, or completely altered on the basis of
diagnostic testing.
 Decreased cost, drug adverse effects, and antibiotic
resistance pressure.
 Routine diagnostic tests to identify an etiologic
diagnosis are optional for outpatients with CAP.
(III)
IDSA/ATS Consensus Guidelines. Clinical Infectious Diseases 2007; 44:S27–72
Clinical indications for more extensive diagnostic testing.
Blood
culture
X
Indication
Intensive care unit admission
Failure of outpatient antibiotic therapy
Cavitary infiltrates
Leukopenia
Active alcohol abuse
Chronic severe liver disease
X
X
X
X
Severe obstructive/structural lung disease
Asplenia (anatomic or functional)
Sputum
culture
X
Legionella
UAT
X
Pneumococcal
UAT
X
X
X
X
X
X
X
X
X
X
X
X
X
Recent travel (within past 2 weeks)
X
Positive Legionella UAT result
X
Positive pneumococcal UAT result
X
X
Pleural effusion
X
X
NA
NA
X
X
IDSA/ATS Consensus Guidelines. Clinical Infectious Diseases 2007; 44:S27–72
Blood culture
 Positive in 5%–14% in hospitalized patients with CAP
 Yield for positive blood culture results is halved by
prior antibiotic therapy , should be obtained before
antibiotic
 However, when multiple risk factors for bacteremia are
present, blood culture results after initiation of
antibiotic therapy are still positive in up to 15% of cases
Yield of blood culture according to severity
•Yield of blood culture increases with severity
of disease & with associated co-morbidities
•2 blood culture to be taken prior to
antibiotic
Waterer GW et al, Resp Med (2001) 95, 78–82
Sputum culture
Study & Year
Sensitivity (%)
Specificity (%)
British Thoracic Society, 1987
15
98
Dans et al, 1984
52
88
Kalin et al, 19835
84
85
Boerner and Zwadyk, 1982
94
64
•Yield of
sputum
culture doesn’t100increase with severity
Thorsteinsson
et al,
1975
67
•Yield
increases
with good
Gleckman
et al,
1988
quality
69 samples
83
Rein et al, 1978
60
61
Lentino and Lucks, 1987
55
94
Merrill et al, 1973
96
11
Xiaoping et al, 1 988
88
85
Lim et al, 1989
67
100
Fine et al, 1 991
86
72
Garcıa-VazquezReed
E et WW
al; Arch
et al;
Intern
WestMed.
J Med2004;164:1807-1811
1996; 165:197-204
Streptococcus pneumoniae
Staphylococcus aureus
Haemophilus influenzae
Klebsiella pneumoniae
Bronchoscopy
 Diagnostic
 Non resolving pneumonia
 When in doubt
 Possible malignancy
 Therapeutic
 Foreign body
 Atelectasis
Pneumococcal urinary antigen test
 Immunochromatographic assay (Binax NOW)
 Detects urinary C-polysaccharide antigen, a cell wall antigen
shared by all pneumococcal serotypes, S. oralis and S. mitis
 Rapid test; takes 15 min
 Sensitivity 72.7-89.8 % & specificity 97-98.8 %
 Similar results with HIV infected patients 1
 Can also be done from pleural fluid (sensitivity 70.6% &
specificity 93.3%) 2
1.Boulware DR et al; J Infect. 2007; 55(4): 300–309.
2.Porcel JM et al; Chest 2007;131;1442-1447;
Urinary antigen test mechanism
Pneumococcal antigen from specimen
Other substances
Labelled rabbit antibody
Unlabelled rabbit antibody
Anti rabbit Ig
1. Test Device
2. Citrate / Phosphate buffer with sodium lauryl
sulfate, Tween® 20, and sodium azide
3. Sample Swab
4. Positive control Swab
5. Negative control Swab
Diagnosis of atypical pneumonia : Legionella
 Non-specific lab features
 Hyponatremia
 Early and transient hypophosphatemia
 Early mild/transient elevations of the serum
transaminases
 Unexplained microscopic hematuria
 Elevated CPK
 Highly elevated CRP, that is at least 35
 Elevated procalcitonin level
Cunha BA; Curr Op Pulm Med 2008, 14:183–194
Diagnosis of atypical pneumonia : Legionella
 Culture on buffered-charcoal yeast extract (BCYE) plates is the
gold standard for the laboratory diagnosis
 Serological diagnosis by 4 fold rise in titres : sensitivity of 41 91%
 Urinary antigen testing
 Detects limited serogroups
 Provide results within 30 min and have sensitivities of between
60 and 100% for L. pneumophila serogroup 1
 PCR assays
 Detect all serogrouos
 Specific target regions within the 16S rRNA genes, 23S-5S spacer
region, 5S rRNA gene, or macrophage inhibitor potentiator gene
Electron Microscopic
Gram’s stain
(mip)
 Sensitivity : 86-92%; Specificity : 95-98%
BCYE Culture
Diederen BMW et al; J Clin Microbiol 2008; 46;2: 671–677
Diagnosis of atypical pneumonia : M. pneumoniae
 Culture
 Gold standard
 Slow growth (1-4 weeks)
 Compared to PCR, culture sensitivity is ≈61%
‘Fried Egg’ colony
 Cold agglutinin 1
 Sensitivity 50-60% specificity 50%
 Higher the cold agglutinin titer over 1 : 64, the more likely the cold
agglutinins are due to M. pneumoniae
 Very high cold agglutinin titers (>1 : 1052) are associated with
neurologic involvement
1.Cunha BA; Curr Op Pulm Med 2008, 14:183–194
Vervloet LA et al; Brazilian J Infect Dis 2007;11(5):507-514.
Diagnosis of atypical pneumonia : M. pneumoniae
 Antigen detection
 Nasopharyngeal aspirate or sputum
 Limited sensitivity and specificity
 Antibody Detection
 ELISA, complement fixation assay (CFA), indirect
immunofluorescence assay (IFA), particle agglutination
assay (PA)
 Detects antibody against glycolipids, purified proteins
(including P1 adhesin), synthetic peptides etc.
 Sensitivity 89-100% & specificity 89-98% with ELISA
Vervloet LA et al; Brazilian J Infect Dis 2007;11(5):507-514.
Diagnosis of atypical pneumonia : M. pneumoniae
 Molecular Biology Techniques
 DNA probes
Target 16S rRNA genes.
 Relatively
of six weeks,
high cost,
•Serology
& short
PCR lifespan
have equivalent
efficacy
 sensitivity 89-100 % & specificity 89-98 %

is most
used but PCR is preffered
•Serology
Polymerase
Chaincommonly
Reaction (PCR)




Result within hours
Early diagnosis (does not depend on serological conversion or
agent growth)
Blood and airway secretions
Sensitivity 78-100% & specificity 92-100%
Vervloet LA et al; Brazilian J Infect Dis 2007;11(5):507-514.
Diagnosis of atypical pneumonia : Chlamydia
 Culture
 Yolk sacs of embryonated chicken eggs
 HL and HEp-2 cell lines
 Oropharyngeal swab.
 Satisfactory techniques for isolation from sputum have not
been developed
 Serology
 MIF : C. pneumoniae specific or CF : common chlamydia LPS
 Fourfold titer rise; or high titre (IgM ≥ 16 for MIF & ≥ 64 for CF)
 High titer IgM found in 16.5% of patients with stable chronic
lung diseases and in 8.6% of asymptomatic healthy subjects.#
 Concordance with isolation and/or PCR in 62 to 75%
Chlamydia inclusion body
Kuo CC et al; Clin Microbiol Rev 1995; 8; 4: 451–461
#Miyashita N et al; Int med; July 9; 1127-31
Diagnosis of atypical pneumonia : Chlamydia
 Antigen detection
 Species-specific Mabs useful in detection of the
organism in cell culture
 Insensitive for demonstration of the organism in direct
Serology
is most
commonly used
smears from
clinical
specimens.
PCR is evolving as better alternative
 PCR
 rRNA gene sequences, MOMP gene, 60-kDa cysteinerich outer membrane protein gene
 Pharyngeal swab, nasopharyngeal swab,
bronchoalveolar lavage and sputum
Kuo CC et al; Clin Microbiol Rev 1995; 8; 4: 451–461
Diagnosis : PCP
 95% of cases occur in HIV-infected with CD4+ < 200 cells/µL
 Prolonged prodromal illness ≥ 2 weeks in HIV infected
 Fever in 86%, cough 91%, and dyspnea 95% of patients
Gomori methenamine
Wright–Giemsa
 CXR : bilateral, symmetrical perihilar reticular or granular opacities
 Sputum induction with hypertonic saline : diagnostic yield of 50-90 %
 Initial induced sputum is negative for pneumocystis : bronchoscopy
with BAL
 PCR using the gene for mitochondrial large-subunit rRNA has greater
sensitivity and specificity
Calcofluor white
Immunofluorescence
Thomas CF, Jr. et al; N Engl J Med 2004;350:2487-98
Diagnosis : PCP
 Suspected cases with normal or unchanged radiograph
 Pulmonary function testing


Restrictive ventilatory defect with decreased lung volumes and
increased expiratory airflow
DLCO ≤ 75% of the predicted value, corrected for hemoglobin
has sensitivity of 90% also found a specificity of 53% in
patients normal CXR.
 HRCT.


Patchy areas of ground-glass opacity through which vessels are
seen and a background of interlobular septal thickening
Sensitivity ~100% & specificity ~89%
Thomas CF, Jr. et al; N Engl J Med 2004;350:2487-98
 Fluoroquinolone resistance of S. pneumoniae is rare—
surveillance studies demonstrate resistance rates of 1%
or less.
 Risk factors for infection with MDR pathogen
 Hospitalization for >48 hr in last 30 days
 Broad spectrum antibiotic ≥7 days in last 30 days
 CKD Class V
 Neutropenia
 PEM (BMI <16)
 Severe structural lung disease e.g. bronchiectasis
(FEV1<30%), COPD (FEV1<30%), ILD (FVC<30%),
 Immunosuppressive illness or therapy
 Alcohoholism
PGIMER Practice Guideline for CAP & HAP. Lung India 2006; 23: 115-120
 Study from the CDC found that after hospital day 4, the
risk of death was 7 times greater in patients infected with
high-level PRSP
 However, treatment and severity of disease were not
recorded.
Feikin DR et al; Am J Public Health. 2000;90(2):223-29.
 Follow-up,
study
of patients with
bacteremic
Withcase-control
appropriate
antibiotic
selection
pneumococcal pneumonia, which controlled for risk
factors,
severity, and
treatment.
resistance
doesn’t
increase mortality
 No contribution of antimicrobial resistance to mortality or
requirement for ICU admission
Moroney JF et al; Clin Infect Dis. 2001;33(6):797-805.
 Large observational study suggest that current levels of β-
lactam resistance generally do not cause treatment failures
when appropriate agents (i.e., amoxicillin, ceftriaxone,
cefotaxime) and doses are used.
Yu VL et al; Clin Infect Dis. 2003;37(2):230-37.
OPD Patients
 Six RCTs involving a total of 1857 patients
 Clarithromycin Vs Erythromycin (Anderson 1991; Chien 1993)
 Clarithromycin Vs Telithromycin (Mathers Dunbar 2004)
 Clarithromycin Vs Azithromycin (Drehobl 2005)
 Azithromycin Vs Levofloxacin (D’Ignazio 2005)
 Telithromycin Vs Levofloxacin (Kohno 2003)
 Insufficient to make evidence-based recommendations for
the choice of antibiotic to be used in the treatment of CAP
in ambulatory patients.
 Individual study results do not reveal significant
differences in efficacy between various antibiotics and
antibiotic groups.
Bjerre LM et al; The Cochrane Library 2009, Issue 4
Treatment n/N
control n/N
Weight %
RR (95% CI)
Kinasewitz
MacFarlane
Donowitz
O’Doherty
Salvarezza
Petitpretz
Overall
Macrolide vs. fluoroquinolone
30/32
174/214
122/168
87/114
30/30
39/41
482/599
39/39
191/212
115/162
85/111
29/30
37/40
496/594
18.66
21.13
11.37
10.30
24.02
14.52
100
0.94 (0.86–1.03)
0.90 (0.83–0.98)
1.02 (0.89–1.17)
1.00 (0.86–1.15)
1.03 (0.97–1.11)
1.03 (0.92–1.15)
0.98 (0.93–1.04)
Fogarty
Ramirez
Hoeffken
Gotfried
Sokol
Overall
Cephalosporins vs. β-lactams/βlactamase inhibitors
178/188
145/175
164/174
113/128
74/85
674/750
184/194
133/167
336/357
107/124
63/66
823/908
34.82
8.40
37.80
9.78
9.20
100
1.00 (0.95–1.05)
1.04 (0.94–1.15)
1.00 (0.96–1.05)
1.02 (0.93–1.12)
0.91 (0.83–1.01)
1.00 (0.97–1.03)
Higuera
Fogarty
Overall
55/55
268/301
323/356
49/51
130/144
179/195
50.33
49.67
100
1.04 (0.97–1.11)
0.99 (0.92–1.05)
1.01 (0.95–1.08)
Studies
Atypical vs. no atypical coverage
No differences in mortality were observed between
patients who received atypical coverage
(fluoroquinolones or macrolides) versus other
drugs (p= 0.34).
No differences in mortality were observed between
macrolides and fluoroquinolones (p=0.70).
Maimon N et al; Eur Respir J 2008; 31: 1068–1076
Outpatient treatment (ATS/IDSA Guideline 2007)
1. Previously healthy and no use of antimicrobials within the previous 3 mths
A macrolide (I)
Doxycyline (III)
2. Comorbidities e.g. chronic heart, lung, liver or renal disease; DM;
alcoholism; malignancies; asplenia; immunosuppressing conditions or use of
immunosuppressives;
Respiratory fluoroquinolone (I)
A β‐lactam plus a macrolide (I)
3. High rate (>25%) of macrolide‐resistant Streptococcus pneumoniae, or
antimicrobial use within the previous 3 months (alternative from a different
class should be selected from 2(III)
IDSA/ATS Consensus Guidelines. Clinical Infectious Diseases 2007; 44:S27–72
Indian guideline : PGIMER 2006
 No medical comorbidities
 Oral β lactam
 Macrolide
 Fluoroquinolone
 Limit the use of
Fuoroquinolones
 Can delay diagnosis of
 Medical comorbidities
 Oral β lactam + Macrolide
 Oral β lactam +
Doxycycline
 Oral β lactam +
Fluoroquinolone
tuberculosis
 Acquisition of MDR
strains by efflux pumps
against fluoroquinolones,
β lactams, carbapenems
PGIMER Practice Guideline for CAP & HAP. Lung India 2006; 23: 115-120
 Secondary analysis performed using two comprehensive
international databases:
 University of Louisville infectious diseases atypical pathogens
reference laboratory database (4,337 patients)
 The Community-Acquired Pneumonia Organization (CAPO)
database. (2,208 patients)
 Patients treated with atypical coverage had
 Decreased time to clinical stability (3.7 vs. 3.2 d, p 0.001)
 Decreased length of stay (7.1 vs. 6.1 d, p 0.01),
 Decreased total mortality (11.1 vs. 7%, p 0.01)
 Decreased CAP-related mortality (6.4 vs. 3.8%, p 0.05).
Arnold FW et al; Am J Respir Crit Care Med 2007; 175: 1086–93
Meta-analysis
 24 RCTs comparing atypical antibiotic Vs β lactum
 No difference in mortality (RR, 1.13 [95% CI, 0.82-
1.54]).
 Atypical arm had trend toward clinical success &
bacteriological eradication. Both disappeared when
evaluating methodologically high-quality studies
alone.
 Atypical arm had significant advantage in clinical
success for Legionella
Shefet D et al; Arch Intern Med. 2005;165:1992-2000
Meta-analysis
 18 double blind RCT comparing lactam antibiotics
with antibiotics active against atypical pathogens in
adults with non-severe CAP
 No advantage of atypical coverage over lactam
antibiotics (RR : 0.97).
 Subgroup analysis in those with a specific diagnosis
involving atypical pathogens.
 Significantly lower failure rate in Legionella (RR : 0.40).
 Equivalence Mycoplasma pneumoniae and Chlamydia
Mills GD et al; BMJ, doi:10.1136/bmj.38334.591586.82
 25 RCTs
 All butAntibiotic
two compared
a single
atypical
antibiotic
to a betaagainst
atypical
organism
reduces
lactam, no trials assessing the addition of an atypical
clinical failure in legionella
antibiotic to a beta-lactam
 No difference in mortality
(RR 1.15;
95% CI 0.85 to 1.56).
No mortality
benefit
 Clinical success for the atypical arm was significantly
However
there is no trial of lactam alone Vs
higher for
Legionella.
lactam + atypical
coverage
 Further trials, comparing
BL or cephalosporins
therapy to
BL or cephalosporins combined with a macrolide in this
population, using mortality as its primary outcome, should
be performed.
Robenshtok E et al; The Cochrane Library 2009, Issue 4
Inpatients, non‐ICU treatment
A respiratory fluoroquinolone (I) or,
A β‐lactam + a macrolide (I)
Inpatients, ICU treatment
A β‐lactam + azithromycin
(II) or,guideline : PGIMER 2006
Indian
A β‐lactam + respiratory fluoroquinolone (I)
(for
penicillin‐allergic
patients, aonly
respiratory
fluoroquinolone
and aztreonam
)
Use
fluoroquinolones
if macrolide/
β lactam
can not
Special concernsExclude tuberculosis prior to use of
be used
FQ
If Pseudomonas is a consideration
PGIMER Practice Guideline for CAP & HAP. Lung India 2006; 23: 115-120
An antipneumococcal, antipseudomonal β‐lactam + either ciprofloxacin or levofloxacin
or
The above β‐lactam + an aminoglycoside and azithromycin
or
The above β‐lactam + an aminoglycoside + an antipneumococcal fluoroquinolone
(for penicillin‐allergic patients, substitute aztreonam for above β‐lactam) (III)
If CA‐MRSA is a consideration, add vancomycin or linezolid (III)
IDSA/ATS Consensus Guidelines. Clinical Infectious Diseases 2007; 44:S27–72
AIIMS Data : Thesis (ongoing)
Number of patients
received single antibiotics : 0
60.00%
Percentage(%)
50.00%
Number of patients
received combination of
antibiotics : 36
20
15
15
40.00%
30.00%
9
9
20.00%
10.00%
0.00%
5
2
2
4
Duration of treatment
 Meta-analysis of 7 RCTs in patients not requiring
ICU, comparing short (≤ 7 days) versus long (≥2 days
difference) course .
 No differences regarding
 Clinical success at end-of-therapy
 Clinical success at late follow-up
 Microbiological success
 Relapses
 Mortality
 Adverse events
 Withdrawals as a result of adverse events.
Dimopoulos G et al; Drugs 2008;68(13):1841-54.
Duration of treatment
 Meta-analysis of 15 RCTs comparing short-course (≤7
days ) vs extended-course (>7 days) monotherapy
(same antibiotic or of the same class)
 No difference in
 Risk of clinical failure (RR 0.89).
 Mortality (RR 0.81)
 Bacteriologic eradication (RR 1.11).
 In subgroup analyses, there was a trend toward
favorable clinical efficacy for the short-course
regimens in all antibiotic classes
Li JZ et al; Am J Med 2007 Sep;120(9):783-90
Duration of treatment
 Minimum of 5 days (I), should be afebrile for 48–72 h, and
should have no more than 1 CAP-associated sign of clinical
instability before discontinuation of therapy (II).
 Longer duration of therapy may be needed if
 Initial therapy was not active against the identified pathogen
 Complicated by extrapulmonary infection, such as meningitis
or endocarditis.
 Presence of cavities or other signs of tissue necrosis
 Infected with other, less common pathogens (e.g.,
Burkholderia pseudomallei or endemic fungi)
IDSA/ATS Consensus Guidelines. Clinical Infectious Diseases 2007; 44:S27–72
Discharge
Criteria for clinical stability.
Temperature 37.8°C
Heart rate 100 beats/min
 Switch from intravenous to oral therapy.
Respiratory rate 24 breaths/min
 Hemodynamically stable
Systolic blood pressure 90 mm Hg
 Improving clinically
Arterial oxygen saturation 90% or pO2 60 mm Hg on room air
 Able to ingest medications
Ability
maintain functioning
oral intake gastrointestinal tract. (II)
 Haveto
a normally
Normal mental status
 Patients should be discharged as soon as they are
 Clinically stable
 Have no other active medical problems
 Have a safe environment for continued care.
 Inpatient observation in oral therapy is not necessary. (II)
IDSA/ATS Consensus Guidelines. Clinical Infectious Diseases 2007; 44:S27–72
Corticosteroid
 Salluh JI et al. 2006
 Cortisol level in 40 patients with severe CAP admitted to the ICU
 65% met criteria for adrenal insufficiency (< 20 µg/dl)
 47.5% had cortisol levels <15 µg/dl
 In patients with
septic shock (n=19)patients
63% had adrenal
insufficiency
Hypotensive,
fluid-resuscitated
with severe
CAP
 should
Salluh JI et
2008
beal.screened
for occult adrenal insufficiency. (II)
 72 patients with severe CAP admitted to the ICU
 Cortisol deficiency in 40.8%.
Baseline Cortisol Level : Thresholds To Predict Mortality
BaselineCutoffs
cortisol
levels are better predictors of severity
(μg/dL)
%
Specificity, %
and outcome in severeSensitivity,
CAP than
postcorticotropin
100
41.7
cortisol, 15.6
APACHE II, SOFA,
and CURB-65,
CRP,
76
25.7
leukocyte75 count
34.3
33.3
88.3
Salluh JI et al; Intensive care med 2006 Apr;32(4):595-8
Salluh JI et al;Chest 2008;134;947-954;
Effects of corticosteroids versus placebo on of severe community-acquired pneumonia studies
Short-term mortality in corticosteroid-treated severe community-acquired pneumonia
Clinical course
First author Corticosteroid
Corticosteroid Treatment
Reference
Mortality %
regimen regimen
Wagner et al
1/52
7.1 vs 18.8 (P =
shock
to be
NS)
control
LOS, days
1/61
Weight % RR (95% CI)
MODS
AB duration
2.08
1.17 (0.08–
18.30)
N/A
0.69 (0.47–
1.00)
10
Marik, et al.CAPHC
4.6 vs 4.3
with
septic
treated
with N/A
mg/kg 30 min
(50-mg
Annane et al beforeHC
21/47
35/54
73.51
antibiotics
Hydrocortisone
300
mg/day
iv every 6 hours)
HC
200
Confalonieri, et
0 vs 30 (P =
10 vs 18 (P = 0.3 vs 1.0 (P =
N/A
mg + and FC (50-μg
Severe
CAP
without
shock
:
role
of
steroid
is
not
clear
al.
0.009)
0.01)
0.003)
HC 10tablet OD)
200-mg
Confalonieri et
al HC
0/23
6/23
14.67
0.08 (0.00–
mg/hr
for iv
7 days
bolus f/b 10
1.29)
11.3
vs
15.5
(P
=
8.5
vs
12.3 (P =
mg/hr for
7 days.
Mikami, et al. Prednisolone
6 vs 0 (P = 0.99)
N/A
40 mg
0.182)
0.026)
Nawab et al qd for 3 days
3/18
3/7
9.75
0.39
(0.10–
Total
Garcia-Vidal,
et Methylprednisolone
14.5 mg qd for
al.
11.4 days
14095% 7.1 vs 13.8
145(P =
OR, 0.287;
CI, 0.113 to 0.732
0.005)
100.00
N/A
1.49)
0.58 (0.40–
N/A
0.83)
AnnaneSalluh
D et al;
JI et
Eur
alCritical
Respir J Care
2008;2008,
31: 1150–1152
12:R76
Management of complication :
Para-pneumonic effusion
 As many as 40% of
hospitalized patients with
bacterial pneumonia have
an accompanying pleural
effusion
 Parapneumonic effusion
increases risk of mortality
upto 7 times
Light RW; Proc Am Thorac Soc 2006; 3: 75–80
Risk stratification
Pleural Space Anatomy
A0 minimal, free-flowing
effusion (< 10 mm on
lateral decubitus)
Pleural Fluid
Bacteriology
BX culture and
Gram stain
results
&
unknown
&
A1 small to moderate freeflowing effusion (> 10 mm
and < 1/2 hemithorax)
&
A2 large, free-flowing
effusion (≥ 1/2
hemithorax) loculated
effusion, or effusion with O
thickened parietal pleura R
Pleural
Fluid
Chemistry
Risk of
Poor Drainag
pH in ABG
Category Outcome
e
machine
CX pH
unknown
1
Very low
NO
B0 negative
culture and
Gram stain
& C0 pH ≥ 7.20
2
Low
NO
B1 positive
culture or
Gram stain
OR C1 pH < 7.20
3
Moderate
4
YES
YES
High
B2 pus
ACCP Guideline; Gene L. Colice et al; Chest 2000;118;1158-1171
Treatment options
 Therapeutic Thoracentesis
 Tube Thoracostomy
 Intrapleural Fibrinolytics
 Loculated effusions
 Urokinase is 100,000 IU
 Streptokinase 150,000 IU
 Tissue plasminogen activator (tPA) 10 mg
Light RW; Proc Am Thorac Soc 2006; 3: 75–80
 7 RCTs streptokinase or urokinase via ICD vs control,




or a comparison of the two agents.
Significant benefit in reducing surgical intervention
Treatment benefit in loculated effusions in subgroup
analysis
Data are incomplete and the benefit is not significant
in the subgroup of high quality trials.
Do not significantly increase adverse events, but the
confidence interval is too wide to firmly exclude this
possibility.
Cameron RJ, Davies HRHR; The Cochrane Library 2009, Issue 3
 RCT comparing intrapleural
STK or placebo
 No significant difference
mortality or surgery (RR=1.14;
P=0.43)
 Serious adverse events (chest
pain, fever, or allergy) more
common with streptokinase
(RR=2.49; P=0.08).
Maskell NA et al; N Engl J Med 2005;352:865-74.
PPE
Lateral decubitus CXR/USG/CT
Effusion ≤ ½ hemithorax
No loculation
Diagnostic pleural tap
Cat 1/2
Observation
Cat 3/4
Tube Thoracostomy
Light RW; Proc Am Thorac Soc 2006; 3: 75–80
PPE
Lateral decubitus CXR/USG/CT
Effusion ≥ ½ hemithorax; No loculation
Combined therapeutic & diagnostic tap
Resolution
Recollection; Risk factor +ve
Repeat therapeutic tap
Recollection
Tube Thoracostomy
Light RW; Proc Am Thorac Soc 2006; 3: 75–80
PPE
Lateral decubitus CXR/USG/CT
Loculated effusion; Any size
Tube Thoracostomy & Fibrinolytic
Resolution
No
Repeat Fibrinolytic
Resolution
No
Thoracoscopy
No expansion
Decortication
Light RW; Proc Am Thorac Soc 2006; 3: 75–80
 Metronidazole penetrates pleural cavity most easily, f/b
penicillin, clindamycin, vancomycin, ceftriaxone, and
gentamicin.
 Quinolones and clarithromycin penetrate the infected
pleural space well.
 The duration of treatment has not been assessed in
detailed clinical trials and remains controversial.
 Antibiotics are often continued for several weeks
 Treatment for about 3 weeks is probably appropriate.
 In prolonged treatment antibiotic regimen changed to an
oral after the fever and sepsis syndrome has settled.
BTS guideline, Davies CWH et al,Thorax 2003 58: ii18-ii28
Pleural Diseases, Light RW, 5th edition
Recommendations for vaccine prevention of community‐acquired pneumonia.
Factor
Pneumococcal polysaccharide vaccine
Route of administration
Intramuscular injection
Type of vaccine
polysaccharide capsule
Recommended groups
≥65 years of age
High‐risk persons 2–64 years
Available evidence is insufficient to recommend routine use of PPV in adults.
Current smokers
Although PPV is efficacious in preventing invasive pneumococcal disease
among adults, routine PPV administration to adults is not likely to be costeffective
in India.
Specific
high‐risk
Chronic cardiovascular, pulmonary, renal, or liver disease
indications
Moreover, PPV has no proven effect on all-cause mortality.
Diabetes mellitus
Cerebrospinal
fluid leaks
Pneumococcal vaccination
is recommended
in patients undergoing
Alcoholism
splenectomy (Level IV, Grade
C); and one-time revaccination after 5 years .
Asplenia
No evidence to support the
efficacy of PPV in preventing
IPD in populations
Immunocompromising
conditions/medications
considered at high-risk (Level
Grade A) and Alaska natives
NativeIa;
Americans
Long‐term
care facility
residents
API Guidelines
on Adult
Immunization; JAPI 2009; 57: 345-56
Revaccination schedule
One‐time revaccination after 5 yrs for (1) ≥65 years of age,
if the first dose is received before age 65 years; (2) asplenia;
and (3) immunocompromised persons
Recommendations for vaccine prevention of community‐acquired pneumonia.
Factor
Route of
administration
Type of vaccine
Recommended
groups
Inactivated
influenza vaccine
Intramuscular injection
Live attenuated
influenza vaccine
Intranasal spray
Killed virus
Live virus
All persons ≥50 years
Healthy persons 5–49 years
High‐risk persons 6 mths–49 years
including health care
In the absence
of epidemiological
surveillance
regarding
the
Household
contacts of high‐risk
providers
and household
persons in our country, use of influenza
contactsvaccine
of high‐risks
influenza serotypes
in
Health care
providers
India
is not recommended.
Children 6–23 months of age
Specific high‐risk
Chronic cardiovascular or pulmonary Avoid in high‐risk persons
No
evidence
to recommend the use of influenza vaccine in
indications
disease
adults (<
65 years)
with disease
select chronic health conditions
Chronic
metabolic
Revaccination
API Guidelines on Adult Immunization; JAPI 2009; 57: 345-56
Renal dysfunction
Hemoglobinopathies
Immunocompromised
Compromised respiratory function or
increased aspiration risk
Pregnancy
Residence in a long‐term care facility
Aspirin therapy in persons ≤18 years
Annual
Annual
Case summary
 78/M, Clerk, R/O Gurgaon, NEW/19
 K/C/O HTN & T2 DM for 5 yrs on regular treatment.
 Non smoker, no h/o alcohol intake.
 Fever, cough with mucopurulent expectoration for 5 days &
drowsy for 1 day.
 No h/o chest pain or dyspnoea.
 Intubated in casualty for gasping state (RR 40).
 On examination
 E1M1V T
 P : 128/min, BP : 80 sys, Temp : 100 F, Pallor +
 Crepitations in Rt ISA
 Required inotropic support even after volume correction
Investigations
HB
Hct
TLC
DLC
ESR
Bl. Urea
BUN
Creat.
Sodium
Potassium
Bilirubin
SGOT
SGPT
SAP
Bl.sugar
8.1
19.3
24000
N88L10
56
112
52.3
2.1
148
5.8
1.4
256
123
114
256
ABG
ph
pO2
PCO2
SpO2
HCO3
FiO2
paO2/FiO2
7.01
67
24
90
12.1
0.4
168
Demographic
Criteria for ICU admission
(any majorfactor
or, 3 minor ) POINTS
ASSIGNED*
Minor criteria
Physical-examination findings
Demographic
Altered mental
factor
status
Respiratory rate ≥30 breaths/min
POINTS +20
ASSIGNED*
+20
Respiratory
 CURB
652/FiO2 ratio ≤250

PSI rate ≥30/min
PaO
Age
SBP <90 mm Hg
infiltrates
 C :Multilobar
+ve
 Total score 228
Men
Temperature <35°C or ≥40°C
Confusion/disorientation
 U : +ve
>125/min
Class V
Women
Pulse
Uremia (BUN level, ≥20 mg/dL)
resident
 R : +ve
home
Mortality
31.1%
LabNursing
and radiographic
findings
3)
Leukopenia (WBC count, <4000
cells/mm
Coexisting
illnesses
Arterial
pH
< 7.35
 B :Thrombocytopenia
+ve
(platelet count,Neoplastic
<100,000 disease
cells/mm3)
Blood urea nitrogen ≥ 30
 65 Hypothermia
: +ve
(core temperature, mg/dl
<36°C)
II : ≤70
Liver disease
Hypotension
fluid
resuscitation
<III
130 mmol/liter
 Total
score 5 requiring aggressiveSodium
Congestive
:heart
71-90
failure> 250 mg/dl
Glucose
Major criteria
 Mortality 33.3%
IV : 91-130
Cerebrovascular
Hematocrit < 30%
disease
Invasive mechanical ventilation PaO2<60
mm Hg
Renal disease
Septic shock with the need for vasopressors
Pleural effusion
V : > 130
Inpatient
Needscare,
ICU admission
probably ICU
+20
78
+10
+30
+20
+10
+10
+10
Clinical indications for more extensive diagnostic testing.
Indication
Intensive care unit admission
Sputum
culture
X
X
X
X
X
X
X
X
X
X
X
Failure of outpatient antibiotic therapy
Cavitary infiltrates
Leukopenia
Active alcohol abuse
Chronic severe liver disease
X
X
X
X
Severe obstructive/structural lung disease
Asplenia (anatomic or functional)
Legionella Pneumococcal
UAT
UAT
Blood
culture
X
X
X
X
X
Recent travel (within past 2 weeks)
X
Positive Legionella UAT result
X
Positive pneumococcal UAT result
X
X
Pleural effusion
X
X
NA
NA
X
X
Blood culture 1 : Klebsiella pneumoniae
Blood culture
2 : Klebsiella pneumoniae
Risk
of bacteremia
: 36.7%
Tracheal aspirate : Klebsiella pneumoniae
Inpatients, non‐ICU treatment
A respiratory fluoroquinolone (I) or,
A β‐lactam + a macrolide (I)
Inpatients, ICU treatment
A β‐lactam + azithromycin (II) or,
A β‐lactam + respiratory fluoroquinolone (I)
(for penicillin‐allergic patients, a respiratory fluoroquinolone and aztreonam )
Special concerns
If Pseudomonas is a consideration
An antipneumococcal, antipseudomonal β‐lactam + either ciprofloxacin or levofloxacin
or
The above β‐lactam + an aminoglycoside and azithromycin
or
The above β‐lactam + an aminoglycoside + an antipneumococcal fluoroquinolone
(for penicillin‐allergic patients, substitute aztreonam for above β‐lactam) (III)
If CA‐MRSA is a consideration, add vancomycin or linezolid (III)
Conclusion
 CAP is a leading cause of morbidity & mortality
 Pneumococcus is most common etiology
 Atypical organisms cause 1/3rd cases
 Severity scores i.e. CURB 65 or PSI are helpful for
admission decision & prediction of mortality
 Etiological diagnosis is important to guide treatment
Conclusion
 For OPD treatment lactam/macrolide/levofloxacin are
equally good
 Combination treatment preferred for severe pneumonia
 Fluoroquinolone use to be restricted in India
 Immunization has role to prevent CAP in high risk
patients.
 The Abbreviated Mental Test (each question scores 1
mark, total 10 marks)
 Age
 Date of birth
 Time (to nearest hour)
 Year
 Hospital name
 Recognition of two persons (e.g. doctor, nurse)
 Recall address (e.g. 42 West Street)
 Date of First World War
 Name of monarch
 Count backwards 20 to 1
 < 8 is confusion