2. Antibiotic Strategy in CAP
Gamal Rabie Agmy, MD,FCCP
Professor of Chest Diseases, Assiut university

3. Pneumonias – Classification
CAP
HCAP
• Health Care Associated
HAP
• Hospital Acquired
ICUAP
• ICU Acquired
VAP
3
• Community Acquired
• Ventilator Acquired
Nosocomial Pneumonias

4. HCAP
*HCAP: diagnosis made < 48h after
admission with any of the following risk
factors:
(1)hospitalized in an acute care hospital for >
48h within 90d of the diagnosis;
(2) resided in a nursing home or long-term
care facility;
(3) received recent IV antibiotic therapy,
chemotherapy, or wound care within the 30d
preceding the current diagnosis; and
(4) attended a hospital or hemodialysis
clinic

5. Definition of CAP
Infection of the lung parenchyma in a
person who is not hospitalized or living
in a long-term care facility for ≥ 2
weeks. This pneumonia develops in
the outpatient setting or within 48
hours of admission to a hospital.

6. The clinical diagnosis of CAP
Symptoms:
• Respiratory: Cough dry or productive,
mucopurulent sputum , sometimes
rusty, dyspnea, sometimes pleuritic
chest pain
• Non-respiratory: Fever, body aches,
altered mental state, vomiting or
diarrhea.

7. The clinical diagnosis of CAP
Signs:
Generally:
Fever,
sometimes
hypothermia, tachycardia, tachypnea.
Local: signs of consolidation

8. CAP – The Two Types of Presentations
Classical
•
•
•
•
•
•
•
Sudden onset of CAP
High fever, shaking chills
Pleuritic chest pain, SOB
Productive cough
Rusty sputum, blood tinge
Poor general condition
High mortality up to 20% in
patients with bacteremia
• S.pneumoniae causative
8
Atypical
•
•
•
•
•
Gradual & insidious onset
Low grade fever
Dry cough, No blood tinge
Good GC – Walking CAP
Low mortality 1-2%; except
in cases of Legionellosis
• Mycoplasma, Chlamydiae,
Legionella, Ricketessiae,
Viruses are causative

9. The Bacteriological Diagnosis of CAP
Sputum Gram stain:
is a rapid and inexpensive test that can
help a lot:
• Differentiate Gm –ve from Gm +ve
bacteria.
• Excess pus cells without organism
suspect atypical infection.

10. The Bacteriological Diagnosis of CAP
Cultures to identify the causative
organism:
Sputum cultures are not recommended in
cases of CAP except in certain occasions:
• Patients admitted in hospital or ICU.
• Patients who do not respond to
empirical antibiotic therapy.
• Suspection of resistant strains of
S.pneumoniae.

11. The Bacteriological Diagnosis of CAP
Blood Culture:
Recommended for all patients with
moderate and high severity CAP,
preferably before antibiotic therapy is
commenced.
Examination
of
Mycobacterium TB
sputum
for

12. CAP – Pathogenesis
Inhalation
Aspiration
Hematogenous
12

14. Clinical Parameter
Scoring
Clinical Parameter
Age in years
Example
Clinical Findings
For Men (Age in yrs)
50
Altered Sensorium
20 points
For Women (Age -10)
(50-10)
Respiratory Rate > 30
20 points
NH Resident
10 points
SBP < 90 mm
20 points
Temp < 350 C or > 400 C
15 points
Pulse > 125 per min
10 points
Co-morbid Illnesses
Neoplasia
30 points
Liver Disease
20 points
CHF
10 points
CVD
10 points
Renal Disease (CKD)
10 points
PORT Scoring – PSI
Pneumonia Patient Outcomes
Research Team (PORT)
14
Scoring
Investigation Findings
Arterial pH < 7.35
30 points
BUN > 30
20 points
Serum Na < 130
20 points
Hematocrit < 30%
10 points
Blood Glucose > 250
10 points
Pa O2
10 points
X Ray e/o Pleural Effusion 10 points

15. Classification of Severity - PORT
Class
I
Predictors
Absent
Class
IV
15
Class
II
91 - 130
 70
Class
V
Class
III
> 130
71 – 90

16. CAP – Management based on PSI Score
PORT Class
PSI Score
Mortality %
Treatment Strategy
Class I
No RF
0.1 – 0.4
Out patient
Class II
 70
0.6 – 0.7
Out patient
Class III
71 - 90
0.9 – 2.8
Brief hospitalization
Class IV
91 - 130
8.5 – 9.3
Inpatient
Class V
> 130
27 – 31.1
IP - ICU
16

17. CURB 65 Rule – Management of CAP
CURB 65
Confusion
BUN > 30
RR > 30
BP SBP <90
DBP <60
Age > 65
17
CURB 0 or 1
Home Rx
CURB 2
Short Hosp
CURB 3
Medical Ward
CURB 4 or 5
ICU care

19. CAP – Criteria for ICU Admission
Major criteria
 Invasive mechanical ventilation required
 Septic shock with the need of vasopressors
Minor criteria (least 3)
 Confusion/disorientation
 Blood urea nitrogen ≥ 20 mg%
 Respiratory rate ≥ 30 / min;
 Core temperature < 36ºC
 Severe hypotension;

PaO2/FiO2 ratio ≤ 250
 Multi-lobar infiltrates
 WBC < 4000 cells;
19 
Platelets <100,000

20. The Radiological Diagnosis
of CAP

21. CAP – Value of Chest Radiograph
• Usually needed to establish diagnosis
• It is a prognostic indicator
• To rule out other disorders
• May help in etiological diagnosis
J Chr Dis 1984;37:215-25
21

22. Infiltrate Patterns and Pathogens
CXR Pattern
Possible Pathogens
Lobar
S.pneumo, Kleb, H. influ, Gram Neg
Patchy
Atypicals, Viral, Legionella
Interstitial
Viral, PCP, Legionella
Cavitatory
Anerobes, Kleb, TB, S.aureus, Fungi
Large effusion
Staph, Anaerobes, Klebsiella
22

23. Normal CXR & Pneumonic Consolidation
23

24. Lobar Pneumonia – S.pneumoniae
24

25. CXR – PA and Lateral Views
25

26. Lobar versus Segmental - Right Side
26

27. Lobar Pneumonia
27

28. Special forms of Consolidation
28

29. Round Pneumonic Consolidation
29

30. Special Forms of Pneumonia
30

31. Special Forms of Pneumonia
31

32. Complications of Pneumonia
32

33. Empyema
33

34. Mycoplasma Pneumonia
34

35. Mycoplasma Pneumonia
35

36. Chlamydia Trachomatis
36

37. Rare Types of Pneumonia
37

38. 38

42. Pneumonia
Posterior intercostal scan shows a hypoechoic
consolidated area that contains multiple
echogenic lines that represent an air
bronchogram.

43. Post-stenotic pneumonia
Posterior intercostal scan shows a hypoechoic
consolidated area that contains anechoic,
branched tubular structures in the bronchial tree
(fluid bronchogram).

44. Contrast-enhanced ultrasonography
of pneumonia
A: Baseline scan shows
a
hypoechoic
consolidated area
B: Seven seconds after
iv bolus of contrast
agent, the lesion shows
marked
and
homogeneous
enhancement
C: The lesion remains
substantially unmodified
after 90 s.

45. The Treatment of CAP

46. ANTIMICROBIAL DRUGS

47. MECHANISMS OF ACTION OF
ANTIBACTERIAL DRUGS

Mechanism of action
include:





Inhibition of cell wall
synthesis
Inhibition of protein
synthesis
Inhibition of nucleic acid
synthesis
Inhibition of metabolic
pathways
Interference with cell
membrane integrity

48. EFFECTS OF
COMBINATIONS OF DRUGS
Sometimes the chemotherapeutic effects of
two drugs given simultaneously is greater than
the effect of either given alone.
 This is called synergism. For example,
penicillin and streptomycin in the treatment
of bacterial endocarditis. Damage to
bacterial cell walls by penicillin makes it
easier for streptomycin to enter.


49. EFFECTS OF
COMBINATIONS OF DRUGS
Other combinations of drugs can be
antagonistic.
 For example, the simultaneous use of penicillin
and tetracycline is often less effective than
when wither drugs is used alone. By stopping
the growth of the bacteria, the
bacteriostatic drug tetracycline interferes
with the action of penicillin, which requires
bacterial growth.


50. EFFECTS OF
COMBINATIONS OF DRUGS

Combinations of antimicrobial drugs should
be used only for:
1.
2.
3.
To prevent or minimize the emergence of
resistant strains.
To take advantage of the synergistic effect.
To lessen the toxicity of individual drugs.

51. Patterns of Microbial Killing
Concentration dependent
– Higher concentration
greater killing
Aminoglycosides, Flouroquinolones, Ketolides,
metronidazole, Ampho B.
Time-dependent killing
– Minimal concentration-dependent killing (4x
MIC)
– More exposure
more killing
Beta lactams, glycopeptides, clindamycin,
macrolides, tetracyclines, bactrim

52. The Ideal Drug*
1. Selective toxicity: against target pathogen but
not against host
 LD50 (high) vs. MIC and/or MBC (low)
2. Bactericidal vs. bacteriostatic
3. Favorable pharmacokinetics: reach target site
in body with effective concentration
4. Spectrum of activity: broad vs. narrow
5. Lack of “side effects”
 Therapeutic index: effective to toxic dose ratio
6. Little resistance development

53. Resistance
Physiological Mechanisms
1. Lack of entry – tet, fosfomycin
2. Greater exit
 efflux pumps
 tet (R factors)
3. Enzymatic inactivation
 bla (penase) – hydrolysis
 CAT – chloramphenicol acetyl transferase
 Aminogylcosides transferases
REVIEW

54. Resistance
Physiological Mechanisms
(cont’d)
4. Altered target




RIF – altered RNA polymerase (mutants)
NAL – altered DNA gyrase
STR – altered ribosomal proteins
ERY – methylation of 23S rRNA
5. Synthesis of resistant pathway
 TMPr plasmid has gene for DHF reductase;
insensitive to TMP
REVIEW

55. Empirical Treatment is the
recommended
strategy
in
treatment
of
CAP
and
shouldn’t be delayed.

56. CAP – Special Features – Pathogen wise
Typical – S.pneumoniae, H.influenza, M.catarrhalis
Blood tinged sputum - Pneumococcal, Klebsiella, Legionella
H.influenzae
CAP has associated of pleural effusion:S.Pneumoniae –
commonest – penicillin resistance problem
S.aureus, K.pneumoniae, P.aeruginosa
S.aureus causes CAP in post-viral influenza; Serious CAP
K.pneumoniae primarily in patients of chronic alcoholism
P.Aeruginosa causes CAP in pts with CSLD or CF, Nosocom
Aspiration CAP only is caused by multiple pathogens
Extra pulmonary manifestations only in Atypical CAP
56

57. Recommendations for the Empirical Treatment:
Outpatient treatment:
Oral Respiratory Fluroquinolones
OR Oral B-Lactam/ B-Lactamase + Oral
New Macrolide
OR IM 3rd Generation Cefalosporines +
New Macrolide

58. Recommendations for the Empirical Treatment:
In-patient treatment: Non-ICU:
Intravenous ( IV )Respiratory fluoroquinolone
OR IV B-Lactam/ B-Lactamase + IV New
Macrolide
OR IV 3rd Generation Cephalosporin + IV
New Macrolide

59. Recommendations for the Empirical Treatment:
In-patient treatment: ICU:
No Monotherapy.
IV Respiratory fluoroquinolone + 3rd or
4th generation cephalosporin
OR IV Imipenem + IV New Macrolide

60. Recommendations for the Empirical Treatment:
In-patient treatment: ICU:
No Monotherapy.
IV Respiratory fluoroquinolone + 3rd or
4th generation cephalosporin
OR IV Imipenem + IV New Macrolide

61. Recommendations for the Empirical Treatment:
Special entities in ICU:
Aspiration:
As Before + i.v. Clindamycin OR Metronidazole
Risk of Pseudomonas Infection:
Antipseudomonal beta-lactam (3rd or 4th generation
cephalosporin OR Piperacillin-tazobactam OR
carbapenem)
Plus
(aminoglycoside
OR
antipseudomonal fluoroquinolone)
For
community-acquired
methicillin-resistant
Staphylococcus aureus infection (MRSA):
Add Teicoplanin OR linezolid Alternative: Vancomycin
(considering its renal side effects)

62. Duration of Therapy
• Minimum of 5 days
• Afebrile for at least 48 to 72 h
• No > 1 CAP-associated sign of clinical instability
• Longer duration of therapy
If initial therapy was not active against the identified
pathogen or complicated by extra pulmonary infection
62

63. Strategies for Prevention of CAP
• Cessation smoking
• Influenza Vaccine It offers 90% protection and
reduces mortality by 80%
• Pneumococcal Vaccine (Pneumonia shot)
It protects against 23 types of Pneumococci
70% of us have Pneumococci in our RT
It is not 100% protective but reduces mortality
Age 19-64 with co morbidity of high for pneumonia
Above 65 all must get it even without high risk
63
• Starting first dose of antibiotic within 4 h & O2 status

64. Switch to Oral Therapy
 Four criteria




Improvement in cough, dyspnea & clinical signs
Afebrile on two occasions 8 h apart
WBC decreasing towards normal
Functioning GI tract with adequate oral intake
 If overall clinical picture is otherwise favorable,
hemodynamically stable; can switch to oral
therapy while still febrile.
64

65. Management of Poor Responders
 Consider non-infectious illnesses
 Consider less common pathogens
 Consider serologic testing
 Broaden antibiotic therapy
 Consider bronchoscopy
65

66. CAP – Complications
 Hypotension and septic shock
 3-5% Pleural effusion; Clear fluid + pus cells
 1% Empyema thoracis pus in the pleural space
 Lung abscess – destruction of lung - CSLD
 Single (aspiration) anaerobes, Pseudomonas
 Multiple (metastatic) Staphylococcus aureus
 Septicemia – Brain abscess, Liver Abscess
 Multiple Pyemic Abscesses
66

67. CAP – So How Best to Win the War?
 Early antibiotic administration within 4-6 hours
 Empiric antibiotic Rx. as per guidelines (IDSA / ATS)
 PORT – PSI scoring and Classification of cases
 Early hospitalization in Class IV and V
 Change Abx. as per pathogen & sensitivity pattern
 Decrease smoking cessation - advice / counseling
 Arterial oxygenation assessment in the first 24 h
 Blood culture collection in the first 24 h prior to Abx.
 Pneumococcal & Influenza vaccination; Smoking
67 cessation