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ANTIBIOTIC IN LUNG DISEASES -
COMMUNITY ACQUIRED PNEUMONIA
-OLD ENEMY & RECENT FOE
Dr. Md. Sayedul Islam
Consultant
pulmonologist & intensivist
King Saud Chest Hospital
DEFINITION
►An acute infection of the pulmonary parenchyma that is
associated with at least some symptoms of acute
infection,
►accompanied by the presence of an acute infiltrate on a
chest radiograph, or auscultatory findings consistent
with pneumonia,
►in a patient not hospitalized or residing in a long term
care facility for > 14 days before onset of symptoms.
Bartlett. Clin Infect Dis 2000;31:347-82.
Adeel A. Butt, MD
EPIDEMIOLOGY
EPIDEMIOLOGY
Current CAP burden
6Th leading cause of death.
60 60
50
45
40
35
30
20
15
10
0
CID 2007: 44 (supl 2), s27
Hospital
ICU
Mortality
DRSP
ETIOLOGY
Pneumococcal burden
PATHOLOGY
PATHOLOGY
Assessment of pneumonia
Pneumonia with complication
Pneumonia with co morbid illness
Pneumonia with risk factors
Pneumonia with unstable vital sign
Complication of Pneumonia
Parapneumonic effusion
Pneumothorax
Lung abscess/Metastasis abscess
Septicemia /ARDS
Hepatitis, pericarditis, Myocarditis,
meningoencephalitis.
Co morbid illness
COPD
 Congestive heart failure
 Malignancy
 Diabetes Mellitus
 Hepatic or renal disease

Risk factors
Risk factors for DRSP
Age>65years
Recent antibiotics within 1 months (DRSP)
Immunosupressive therapy within 3 months
HIV/ Immunocompromized patient
Unstable Vital sign
Altered level of conciousness
Heart rate >125
Respiratory rate >30/m
Systolic BP<90 mmHg
Temperature <35 or >400 C
Maximize the outcome of CAP
Site of care decision
Time of first antibiotics
Proper choice of antibiotics
SITE OF CARE
PORT PEDICTION RULE
CURB- 65
FINE”S PSI SCORING
PORT Prediction Rule
Items
Score
Neoplastic disease
30
CLD
20
CCF
10
CVD
10
Renal
10
Altered mentation
20
Respiratory rate >30/m
20
Systolic BP <90mmHg
20
Temperature <35ºC
15
Patients outcome research team
PORT Prediction Rule-contd
Items
Score
Na+
10
PH <7.35
30
Urea ≥ 30mg/dl
20
Glucose >250 mg/dl
10
HCT < 30
10
Pao2 <60 mmHg
10
Pleural effusion
10
PORT Prediction Rule - contd
Mod
Low
Risk class
high

Class
Predictor level
I
II
III
IV
Absence of predictor
V
Mortality rate
0.1- 0.4
≤ 70
71- 90
91- 130
0.6-0.7
0.9-2.8
8.2-9.3
> 130
29-31
CMD: 2005
Pneumonia severity scoring index
system (CURB-65 scoring)
CURB-65 score (Updated 2004.)
Confusion*
Urea > 7 mmol/l
Respiratory rate ≥ 30/min
Blood pressure (SBP < 90mmHg or DBP 60mmHg)
Age ≥ 65 years
Score 1 point for each feature present
Pneumonia severity scoring index
system (Fine`s PSI scoring)



Age
Co morbidity
Unstable vital sign
Group-I = No to all, Low mortality risk,
eligible for OPD management of CAP
Group-II = Yes to 1-2 of three questions,
Intermediate mortality risk, close
monitoring or hospitalization for up to
48 hours,
Group III = Yes to all, Moderate to high mortality
risk, proceed to hospitalization
DIAGNOSTIC TOOLS
HISTORY
PHYSICAL EXAMINATION
IMAGING- CXR, CT
LABORATORY
CAP EARLY
Diagnosis
Does this patient
have CAP?
CAP after 12 hours
CAP AFTER 12 HOURS
X-ray Swine flu
LAB Evaluation
SPUTUM CULTURE
BLOOD CULTURE
ANTIGEN DETECTION
ACUTE PHASE SEROLOGY
PCR
LAB Evaluation
Bacteriological
40%
Dx Estb
Not Estb
60%
CID 2003: 37(1 December)
PNEUMONIA IN ER
Sign & clinical symptoms
suggestive of pneumonia
Risk stratification
Yes
Low
Mod/High
OPD
Inpatient
Obtain CXR
Infiltration suggestive pneumonia ?
No
Out of guideline
Empirical Rx of CAP
ATS- Guideline
OPD
Evidence Level- I
Young & otherwise healthy
Macrolide
Alternative
Doxycycline
(Evidence level-Ⅲ)
Comorbid illness or risk factor
C
2nd Ceph +
Macrolide
Res FLQ.
(Evidence level-II)
CID 2007:44 (1supl 2) ;s27
Empirical Rx of CAP- ATS
Guideline
Hospitalized patient
Evidence level- I
Ordinary cases
Alternative
2nd/ Ceph +Macrolide B-lactam + Doxy
(Evidence level- III)
Suspected aspiration
3rd/ cepha+clinda Clinda +macrolide
(Evidence level –III)
With bronchiactesis
CID 2003:37 (1 December)
Anti-Pseudomonal
RFQ + macrolide
3rd/4th ceph +macrolide (Evidence level- II)
Empirical Rx of CAP
Therapeutic Guideline
Severe Pneumonia (ICU)
First line
Alternative
No pseudomonas
risk
3rdCeph+macrolide Carbipenem+
Macrolide
Pseudomonas risk
Antipseudomonas AntiPseudomonal
3rdceph+aminogly+ pencilline+
macrolide
aminogly+macrolid
CID 2003:37 (1 December)
Head to head comparison of first line Abx
MOXIRAPID study group
86.60%
For adult hospitalized Patient with
CAP, MxF therapy is clinically
equivalent to high dose Ctrx +clari
86.40%
86.20%
86.00%
85.80%
Ctrx+Clar
MxF
85.60%
85.40%
85.20%
Clin Infect Dis.2005 Dec 15; 41(12):1697-705
PROBLEM OF CAP
DRSP
MDRSP
EPIDEMIC AND PANDEMIC FLU
De-Escalation
De- Escalation is use of EITHER OR
BOTHFewer drugs,
Narrower spectrum
De Escalation reduced drug resistance
and decrease mortality
VACCINE
INFLUENZA VACCINE
PNEUMOCOCCAL VACCINE
Conclusion
S. pneumonae and H. influenzae are important pathogens
in CAP
Resistant in S. pneumoae is increasing worldwide.
-Fatal pandemic H1N1 cases had bacterial coinfection,esp Spn
Risk stratification by prediction scoring, appropriate ABx,
De-excalation may reduce the resistance pattern
Moxifloxacin has excellent activity against typical RTI
pathogene, including PRSP.
Thanks for Your
Attention!
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 ® 1
Duration of treatment
Place/severity or pathogen Duration of treatment (days)
Home treated, not severe (microbiologically undefined)
Hospital treated, not severe (microbiologically undefined)
Hospital treated, severe (microbiologically undefined)
Legionella infection
“Atypical” pathogen
Pneumococcal infection (uncomplicated)
Staphylococcal infection
Gram negative enteric bacilli
7
7
10
14–21
14
7
14–21
14–21
ABx Choice
Drug category




Advanced
macrolide
Clarithromycine
Azithromycine
Roxithromycine
Respiratory quinolones




Moxifloxacine
Gatifloxacine
Gemifloxacin
Levoloxacin
AntiPseudomonal drugs



Antipseudomonal
Ceph
Carbapenem
 Imipenem
Ceftazidime- 3rd
 Meropenem
generation
Cefipime- 4th
generation Antipseudomonal penicillin
 Piperacilline
 Tazocine
 Ticarcilline-Clavulonic acid
Pseudomonas Risk Factor



Severe structural lung disease
(bronchiactesis)
Recent antibiotic therapy
Stay in hospital (ICU)
Importance of guideline of
empirical therapy

Ideally the first dose of antibiotic should be administered
within 6 hours of initial medical assessment to improve the
outcome

CAP is the evolving process and patient may shift between
risk groups. The physician must be responsive to these
changes and can only do so when the patient is managed
in appropriate setting.

Timely therapy can only be given when disease is
recognized & severity is appropriately assessed.
EPIDEMIOLOGY
CAP PRODUCING ORGANISM
Deference between Typical &
Atypical
Features
Typical
Atypical
Cough
Present, productive
May be absent, when
present dry, hacking
Main complain
Fever, chest pain
Fever, body ache
Physical finding
Typical physical
finding
Of consolidation
Feature out of
proportion to
physical finding
culture
60% culture positive
Usually culture –ve/
serology diagnostic
TLC
Usually very high
May be normal
CxR
Lober consolidation
Variable
COMMUNITY ACQUIRED PNEUMONIA
- Old enemy & recent foe
Dr. Md. Sayedul Islam
Consultant
pulmonologist & intensivist
King Saud Chest Hospital
DEFINITION
Commonly defined asAn acute infection of the lower respiratory
tract
In patient who has not resided in a
hospital or health care facilities in the
previous 14 days.
COMMUNITY ACQUIRED PNEUMONIA
Infection is usually spread by droplet
inhalation
Most patients affected are previously well.
-Smoker
-Alcoholic
more susceptible
-Steroid therapy
EPIDEMIOLOGY
EPIDEMIOLOGY
EPIDEMIOLOGY
Current CAP burden
6Th leading cause of death.
60 60
50
45
40
35
30
20
15
10
0
CID 2007: 44 (supl 2), s27
Hospital
ICU
Mortality
DRSP
ETIOLOGY
Pneumococcal burden
AGE DISTRIBUION
PATHOLOGY
PATHOLOGY
PNEUMONIA TYPES
Community Acquired Pneumonia (CAP)
Hospital Acquired Pneumonia (HAP)
Hospitalized community Acquired Pneumonia (HCAP)
Ventilator Associated Pneumonia (VAP)
Pneumonia in immunocompromized patient
Assessment of pneumonia
Pneumonia with complication
Pneumonia with co morbid illness
Pneumonia with risk factors
Pneumonia with unstable vital sign
Complication of Pneumonia
Parapneumonic effusion
Pneumothorax
Lung abscess/Metastasis abscess
Septicemia /ARDS
Hepatitis, pericarditis, Myocarditis,
meningoencephalitis.
Co morbid illness
COPD
 Congestive heart failure
 Malignancy
 Diabetes Mellitus
 Hepatic or renal disease

Risk factors
Risk factors for DSRP




Age>65years
Recent antibiotics within 3 months (DRSP)
Immunosupressive therapy within 3 months
HIV/ Immunocompromized patient
Unstable Vital sign
 Altered level of conciousness
 Heart rate >125
 Respiratory rate >30/m
 Systolic BP<90 mmHg
 Temperature <35 or >400 C
Maximize the outcome of CAP
Site of care decision
Time of first antibiotics
Proper choice of antibiotics
SITE OF CARE
PORT PEDICTION RULE
CURB- 65
FINE,S PSI SCORING
PORT Prediction Rule
Items
Score
Neoplastic disease
30
CLD
20
CCF
10
CVD
10
Renal
10
Altered mentation
20
Respiratory rate >30/m
20
Systolic BP <90mmHg
20
Temperature <35ºC
15
Patients outcome research team
PORT Prediction Rule-contd
Items
Score
Na+
10
PH <7.35
30
Urea ≥ 30mg/dl
20
Glucose >250 mg/dl
10
HCT < 30
10
Pao2 <60 mmHg
10
Pleural effusion
10
PORT Prediction Rule - contd
Mod
Low
Risk class
high

Class
Predictor level
I
II
III
IV
Absence of predictor
V
Mortality rate
0.1- 0.4
≤ 70
71- 90
91- 130
0.6-0.7
0.9-2.8
8.2-9.3
> 130
29-31
CMD: 2005
Pneumonia severity scoring index
system (CURB-65 scoring)
CURB-65 score (Updated 2004.)
Confusion*
Urea > 7 mmol/l
Respiratory rate ≥ 30/min
Blood pressure (SBP < 90mmHg or DBP 60mmHg)
Age ≥ 65 years
Score 1 point for each feature present
Pneumonia severity scoring index
system (Fine`s PSI scoring)



Age
Co morbidity
Unstable vital sign
Group-I = No to all, Low mortality risk,
eligible for OPD management of CAP
Group-II = Yes to 1-2 of three questions,
Intermittent mortality risk, close
monitoring or hospitalization for up to
48 hours,
Group III = Yes to all, Moderate to high mortality
risk, proceed to hospitalization
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 ® 1
Duration of treatment
Place/severity or pathogen Duration of treatment (days)
Home treated, not severe (microbiologically undefined)
Hospital treated, not severe (microbiologically undefined)
Hospital treated, severe (microbiologically undefined)
Legionella infection
“Atypical” pathogen
Pneumococcal infection (uncomplicated)
Staphylococcal infection
Gram negative enteric bacilli
7
7
10
14–21
14
7
14–21
14–21
CAP PRODUCING ORGANISM
Deference between Typical & Atypical
Features
Typical
Atypical
Cough
Present, productive
May be absent, when
present dry, hacking
Main complain
Fever, chest pain
Fever, body ache
Physical finding
Typical physical
finding
Of consolidation
Feature out of
proportion to
physical finding
culture
60% culture positive
Usually culture –ve/
serology diagnostic
TLC
Usually very high
May be normal
CxR
Lober consolidation
Variable
DIAGNOSTIC TOOLS
HISTORY
PHYSICAL EXAMINATION
IMAZING- CXR, CT
LABORATORY
CAP EARLY
CAP AFTER 12 HOURS
X-ray Swine flu
LAB evaluation
SPUTUM CULTURE
BLOOD CULTURE
ANTIGEN DETECTION
ACUTE PHASE SEROLOGY
PCR
LAB evaluation
Bacteriological
40%
Dx Estb
Not Estb
60%
CID 2003: 37(1 December)
PNEUMONIA IN ER
Sign & clinical symptoms
suggestive of pneumonia
Risk stratification
Yes
Low
Mod/High
OPD
Inpatient
Obtain CXR
Infiltration suggestive pneumonia ?
No
Out of guideline
ABx Choice
Antibiotic treatment
Antibiotic should be given as soon as clinical diagnosis of
pneumonia is made.
If possible culture specimen should be sent prior to
starting antibiotic.
Treatment shouldn’t be delayed if – a sputum sample is not
readily available
Empirical Rx of CAP
ATS- Guideline
OPD
Evidence Level- I
Young & otherwise healthy
Macrolide
Alternative
Doxycycline
(Evidence level-Ⅲ)
Comorbid illness or risk factor
C
2nd Ceph +
Macrolide
Res FLQ.
(Evidence level-II)
CID 2007:44 (1supl 2) ;s27
Empirical Rx of CAP- ATS
Guideline
Hospitalized patient
Evidence level- I
Ordinary cases
Alternative
2nd/ Ceph +Macrolide B-lactam + Doxy
(Evidence level- III)
Suspected aspiration
3rd/ cepha+clinda Clinda +macrolide
(Evidence level –III)
With bronchiactesis
CID 2003:37 (1 December)
Anti-Pseudomonal
RFQ + macrolide
3rd/4th ceph +macrolide (Evidence level- II)
Empirical Rx of CAP
Therapeutic Guideline
Severe Pneumonia (ICU)
First line
Alternative
No pseudomonas
risk
3rdCeph+macrolide Carbipenem+
Macrolide
Pseudomonas risk
Antipseudomonas AntiPseudomonal
3rdceph+aminogly+ pencilline+
macrolide
aminogly+macrolid
CID 2003:37 (1 December)
Drug category
Advanced macrolide
Clarithromycine
Azithromycine
Roxithromycine
Respiratory quinolones




Moxifloxacine
Gatifloxacine
Gemifloxacin
Levoloxacin
AntiPseudomonal drugs
Antipseudomonal Ceph

Ceftazidime- 3rd generation

Cefipime- 4th generation
Carbapenem
 Imipenem
 Meropenem
Antipseudomonal penicillin
 Piperacilline
 Tazocine
 Ticarcilline-Clavulonic acid
Pseudomonas Risk Factor



Severe structural lung disease (bronchiactesis)
Recent antibiotic therapy
Stay in hospital (ICU)
Importance of guideline of empirical
therapy

Ideally the first dose of antibiotic should be administered
within 6 hours of initial medical assessment to improve the
outcome

CAP is the evolving process and patient may shift between
risk groups. The physician must be responsive to these
changes and can only do so when the patient is managed
in appropriate setting.

Timely therapy can only be given when disease is
recognized & severity is appropriately assessed.
Head to head comparison of first line Abx
MOXIRAPID study group
86.60%
For adult hospitalized Patient with
CAP, MxF therapy is clinically
equivalent to high dose Ctrx +clari
86.40%
86.20%
86.00%
85.80%
Ctrx+Clar
MxF
85.60%
85.40%
85.20%
Clin Infect Dis.2005 Dec 15; 41(12):1697-705
Moxi-Rapid trial
Days
Fever resolution
5
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
Moxi
Cef+ Mac
ECCMID (European congress of clinical Microbiology and infectious Disease)
CAPRIE study
Cure %of patients
Clinical cure Day 5-21 post therapy
93
92
91
90
89
88
87
86
85
Moxi
Levo
Bacterial co-infection from fatal
pandemic H1N1
 During May - august 2009, 77 us patients with
fatal cases of confirmed H1N1
 Of the 77 cases, > 30 cases had bacterial coinfection--10 cases with S. pneumoniae,
-6 with S. pyogenes,
-7 cases with S. aureus,
-2 with S. mitis, and
-1 with H influenzae,
-rest of the cases were involved with
multiple pathogen.
MMWR,Sep29,2009
Duration of treatment
Uncomplicated pneumonia 7-10 days
Legionella, Staph, Klebsiella needs
14 days or more
Pneumonia with complication needs
treatment for 4wks or longer
De-Escalation
De- Escalation is EITHER OR BOTH
Fewer drugs,
Narrower spectrum
De Escalation reduced drug resistance
and decrease mortality
VACCINE
Conclusion


S. pneumonae and H. influenzae are important pathogens
in CAP
Resistant in S. pneumoae is increasing worldwide
-In Asia, macrolides resistance was higher than in other areas
-Penicilln and macrolides resistance were clinically significant
-Fatal pandemic H1N1 cases had bacterialcoinfection,esp Spn


Prevalence of BLANR in H. influenza bring concern in
Japan.
Moxifloxacin has excellent activity against typical RTI
pathogene, including PRSP.
Pneumonia in ER
Atypical Pneumonia
MRSA -Pneumonia
National Nosocomial Infection Surveys report

1975
: 2-3% of all S. aureus isolation

1997-1999 : Over 34% of all S. aureus

1999
: Incidence of MRSA, CAP is 25% of
all S. aureus
MRSA- Risk Factors (CAP)





Intravenous drug use
Chronic antimicrobial therapy
Hemodialysis
The major route of MRSA spread is direct
patient to patient contact
Via the hand of medical personnel.
Sites of colonization





Anterior nares
Wound, burns or other areas of decrease
skin integrity.
The perineal area
Upper respiratory tract.
Skin adjacent to- invasive device,
gastrostomy tube, tracheostomies.
Hospital Acquired Pneumonia
Occur at least 2 days after admission in
hospital
 Usually developed in patients with
Chronic lung disease
General disability
Receiving assisted ventilation
 Endotracheal Intubation / tracheostomy

 Infected
ventilator
nebulisers
bronchoscops
 Dental or sinus injections
 Intra venous cannula injection
Organism involved
Commonly gram negative organism
Escherichia .
Pseudomonas.
Klebsiella
 Gram positive organism
Staph. aureus commonly
multidrug resistant variety.
 Anaerobic organism are more
common than cap.

Management
Adequate Gram-negative coverage obtained
• third generation cephalosporin – cefotaxime
plus aminoglycoside- gentamycin
• Imipenem or
• Aztreomam plus flucloxacillin.
 Aspiration pneumonia.
• Amoxiclav 1.2g 8-hrly plus metronidazol
500mg 8hrly

Suppurative & Aspirational
Pneumonia (including pulmonary
abscess



Organism involved
If healthy lung tissue
Staph. aureus
Klebsiella Pneumonia
In pulmonary infarct or collapsed lobe.
Step pneumoniae
Staph. Aureaus
Strep pyogenes & H. inflenzae
Antibiotic treatment

Amoxycillin 500mg 6hrly orally plus
Metronidazole 400 mg 8 hrly
If anaerobic infection suspected
 Antibiotic
CS
therapy modified according to
Removal
or treatment of
endobronchial obstruction if
any.
Duration 4-6 weeks.
Pneumonia in
immunocompromised patient
 In AIDS
disease
Disseminated infection
o Cytomegalovirus (CMV) infection
o Bacterial septicemia
o Pneumococcal
o salmonella
Atypical Pneumonia
MRSA -Pneumonia
National Nosocomial Infection Surveys report

1975
: 2-3% of all S. aureus isolation

1997-1999 : Over 34% of all S. aureus

1999
: Incidence of MRSA, CAP is 25% of
all S. aureus
MRSA- Risk Factors (CAP)





Intravenous drug use
Chronic antimicrobial therapy
Hemodialysis
The major route of MRSA spread is direct
patient to patient contact
Via the hand of medical personnel.
Sites of colonization





Anterior nares
Wound, burns or other areas of decrease
skin integrity.
The perineal area
Upper respiratory tract.
Skin adjacent to- invasive device,
gastrostomy tube, tracheostomies.
Hospital Acquired Pneumonia
Occur at least 2 days after admission in
hospital
 Usually developed in patients with
Chronic lung disease
General disability
Receiving assisted ventilation
 Endotracheal Intubation / tracheostomy

 Infected
ventilator
nebulisers
bronchoscops
 Dental or sinus injections
 Intra venous cannula injection
Organism involved
Commonly gram negative organism
Escherichia .
Pseudomonas.
Klebsiella
 Gram positive organism
Staph. aureus commonly
multidrug resistant variety.
 Anaerobic organism are more
common than cap.

Management
Adequate Gram-negative coverage obtained
• third generation cephalosporin – cefotaxime
plus aminoglycoside- gentamycin
• Imipenem or
• Aztreomam plus flucloxacillin.
 Aspiration pneumonia.
• Amoxiclav 1.2g 8-hrly plus metronidazol
500mg 8hrly

Suppurative & Aspirational
Pneumonia (including pulmonary
abscess



Organism involved
If healthy lung tissue
Staph. aureus
Klebsiella Pneumonia
In pulmonary infarct or collapsed lobe.
Step pneumoniae
Staph. Aureaus
Strep pyogenes & H. inflenzae
Antibiotic treatment

Amoxycillin 500mg 6hrly orally plus
Metronidazole 400 mg 8 hrly
If anaerobic infection suspected
 Antibiotic
CS
therapy modified according to
Removal
or treatment of
endobronchial obstruction if
any.
Duration 4-6 weeks.
Pneumonia in
immunocompromised patient
 In AIDS
disease
Disseminated infection
o Cytomegalovirus (CMV) infection
o Bacterial septicemia
o Pneumococcal
o salmonella
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