Community Acquired Pneumonia(CAP) 
Gamal Rabie Agmy, MD,FCCP 
Professor of Chest Diseases, Assiut university
3 
Pneumonias – Classification •Community Acquired CAP •Health Care Associated HCAP •Hospital Acquired HAP •ICU Acquired ICUAP •Ventilator Acquired VAP Nosocomial Pneumonias
*HCAP: diagnosis made < 48h after hospitalization 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 
HCAP
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. 
Definition 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. 
The clinical diagnosis of CAP
Signs: 
Generally: Fever, sometimes hypothermia, tachycardia, tachypnea. 
Local: signs of consolidation 
The clinical diagnosis of CAP
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 
•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 Atypical
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. 
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. 
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 sputum for Mycobacterium TB 
The Bacteriological Diagnosis of CAP
12 
CAP – Pathogenesis Inhalation Aspiration Hematogenous
14 PORT Scoring – PSI 
Clinical Parameter 
Scoring 
Age in years 
Example 
For Men (Age in yrs) 
50 
For Women (Age -10) 
(50-10) 
NH Resident 
10 points 
Co-morbid Illnesses 
Neoplasia 
30 points 
Liver Disease 
20 points 
CHF 
10 points 
CVD 
10 points 
Renal Disease (CKD) 
10 points 
Clinical Parameter 
Scoring 
Clinical Findings 
Altered Sensorium 
20 points 
Respiratory Rate > 30 
20 points 
SBP < 90 mm 
20 points 
Temp < 350 C or > 400 C 
15 points 
Pulse > 125 per min 
10 points 
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 Pneumonia Patient Outcomes Research Team (PORT)
15 Classification of Severity - PORT Predictors Absent Class I  70 Class II 71 – 90 Class III 91 - 130 Class IV > 130 Class V
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
17 
CURB 65 Rule – Management of CAP CURB 65 Confusion BUN > 30 RR > 30 BP SBP <90 DBP <60 Age > 65 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; 
Platelets <100,000
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
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
23 
Normal CXR & Pneumonic Consolidation
24 
Lobar Pneumonia – S.pneumoniae
25 CXR – PA and Lateral Views
26 
Lobar versus Segmental - Right Side
27 
Lobar Pneumonia
28 
Special forms of Consolidation
29 Round Pneumonic Consolidation
30 Special Forms of Pneumonia
31 
Special Forms of Pneumonia
32 
Complications of Pneumonia
33 
Empyema
34 Mycoplasma Pneumonia
35 
Mycoplasma Pneumonia
36 Chlamydia Trachomatis
37 
Rare Types of Pneumonia
S Curve of Golden 
When there is a mass adjacent to a fissure, the fissure takes the shape of an "S". The proximal convexity is due to a mass, and the distal concavity is due to atelectasis. Note the shape of the transverse fissure. 
This example represents a RUL mass with atelectasis
THE BAT VIEW Chest wall 
Pleural line
THE BAT VIEW 
Chest wall 
Pleural line
41
Pneumonia 
Posterior intercostal scan shows a hypoechoic consolidated area that contains multiple echogenic lines that represent an air bronchogram.
Post-stenotic pneumonia 
Posterior intercostal scan shows a hypoechoic consolidated area that contains anechoic, branched tubular structures in the bronchial tree (fluid bronchogram).
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.
The Treatment of CAP
ANTIMICROBIAL DRUGS
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
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.
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.
EFFECTS OF COMBINATIONS OF DRUGS 
Combinations of antimicrobial drugs should be used only for: 
1.To prevent or minimize the emergence of resistant strains. 
2.To take advantage of the synergistic effect. 
3.To lessen the toxicity of individual drugs.
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
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
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
Resistance Physiological Mechanisms 
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 
(cont’d) REVIEW
Empirical Treatment is the recommended strategy in treatment of CAP and shouldn’t be delayed.
59 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
Outpatient treatment: Oral Respiratory Fluroquinolones OR Oral B-Lactam/ B-Lactamase + Oral New Macrolide OR IM 3rd Generation Cefalosporines + New Macrolide Recommendations for the Empirical Treatment:
In-patient treatment: Non-ICU: 
Intravenous ( IV )Respiratory fluoro- quinolone OR IV B-Lactam/ B-Lactamase + IV New Macrolide OR IV 3rd Generation Cephalosporin + IV New Macrolide 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 
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) Recommendations for the Empirical Treatment:
64 Duration of Therapy 
•Minimum of 5 days 
•Afebrile for at least 48 to 72 h 
•Longer duration of therapy 
If initial therapy was not active against the identified pathogen or complicated by extra pulmonary infection
65 
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 
•Starting first dose of antibiotic within 4 h & O2 status
66 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.
67 Management of Poor Responders 
Consider non-infectious illnesses 
Consider less common pathogens 
Consider serologic testing 
Broaden antibiotic therapy 
Consider bronchoscopy
68 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
69 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 cessation
Broncho-Vaxom is an extract of different bacterial species frequently responsible of respiratory infections. It stimulates the immune system in order to increase the body’s natural defences against a wide spectrum of respiratory pathogens. BRONCHO-VAXOM 
Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
Broncho-Vaxom prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular sinusitis, rhinopharyngitis and middle ear infection, in adults and children. BRONCHO-VAXOM 
Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
Immunostimulating agent In animals, an increased resistance towards experimental infections, a stimulation of macrophages and B lymphocytes as well as an increase in immunoglobulins secreted by the respiratory mucosal cells have been reported. BRONCHO-VAXOM 
Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
Immunostimulating agent In humans, an increase in the rate of circulating T lymphocytes, in salivary IgA, in the non-specific response to polyclonal mitogens and in the mixed lymphocyte reaction have been observed. BRONCHO-VAXOM 
Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
Safety Extensive toxicity studies have not revealed any toxic effect. Effects on ability to drive and use machines: 
Broncho-Vaxom is presumed to be safe and unlikely to produce an effect. 
BRONCHO-VAXOM 
Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
Safety Reproduction studies in animals have not demonstrated any risk to the fetus, but controlled studies in pregnant women are not available. As regards breast-feeding, no specific studies have been performed and no data have been reported up to now. BRONCHO-VAXOM 
Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
Side effects The overall incidence of adverse effects in clinical trials lies between 3 and 4%. Gastrointestinal troubles (nausea, abdominal pain, vomiting), dermatologic reactions (rash, urticaria), and respiratory disorders (coughing, dyspnea, asthma), as well as generalized problems (fever, fatigue, allergic reactions) are the most frequent complaints reported. BRONCHO-VAXOM 
Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
Interaction No drug interaction is known up to now.. BRONCHO-VAXOM 
Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
CAP

CAP

  • 2.
    Community Acquired Pneumonia(CAP) Gamal Rabie Agmy, MD,FCCP Professor of Chest Diseases, Assiut university
  • 3.
    3 Pneumonias –Classification •Community Acquired CAP •Health Care Associated HCAP •Hospital Acquired HAP •ICU Acquired ICUAP •Ventilator Acquired VAP Nosocomial Pneumonias
  • 4.
    *HCAP: diagnosis made< 48h after hospitalization 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 HCAP
  • 5.
    Infection of thelung 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. Definition of CAP
  • 6.
    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. The clinical diagnosis of CAP
  • 7.
    Signs: Generally: Fever,sometimes hypothermia, tachycardia, tachypnea. Local: signs of consolidation The clinical diagnosis of CAP
  • 8.
    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 •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 Atypical
  • 9.
    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. The Bacteriological Diagnosis of CAP
  • 10.
    Cultures to identifythe 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. The Bacteriological Diagnosis of CAP
  • 11.
    Blood Culture: Recommendedfor all patients with moderate and high severity CAP, preferably before antibiotic therapy is commenced. Examination of sputum for Mycobacterium TB The Bacteriological Diagnosis of CAP
  • 12.
    12 CAP –Pathogenesis Inhalation Aspiration Hematogenous
  • 14.
    14 PORT Scoring– PSI Clinical Parameter Scoring Age in years Example For Men (Age in yrs) 50 For Women (Age -10) (50-10) NH Resident 10 points Co-morbid Illnesses Neoplasia 30 points Liver Disease 20 points CHF 10 points CVD 10 points Renal Disease (CKD) 10 points Clinical Parameter Scoring Clinical Findings Altered Sensorium 20 points Respiratory Rate > 30 20 points SBP < 90 mm 20 points Temp < 350 C or > 400 C 15 points Pulse > 125 per min 10 points 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 Pneumonia Patient Outcomes Research Team (PORT)
  • 15.
    15 Classification ofSeverity - PORT Predictors Absent Class I  70 Class II 71 – 90 Class III 91 - 130 Class IV > 130 Class V
  • 16.
    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
  • 17.
    17 CURB 65Rule – Management of CAP CURB 65 Confusion BUN > 30 RR > 30 BP SBP <90 DBP <60 Age > 65 CURB 0 or 1 Home Rx CURB 2 Short Hosp CURB 3 Medical Ward CURB 4 or 5 ICU care
  • 19.
    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; Platelets <100,000
  • 20.
  • 21.
    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
  • 22.
    22 Infiltrate Patternsand 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
  • 23.
    23 Normal CXR& Pneumonic Consolidation
  • 24.
    24 Lobar Pneumonia– S.pneumoniae
  • 25.
    25 CXR –PA and Lateral Views
  • 26.
    26 Lobar versusSegmental - Right Side
  • 27.
  • 28.
    28 Special formsof Consolidation
  • 29.
    29 Round PneumonicConsolidation
  • 30.
    30 Special Formsof Pneumonia
  • 31.
    31 Special Formsof Pneumonia
  • 32.
  • 33.
  • 34.
  • 35.
  • 36.
  • 37.
    37 Rare Typesof Pneumonia
  • 38.
    S Curve ofGolden When there is a mass adjacent to a fissure, the fissure takes the shape of an "S". The proximal convexity is due to a mass, and the distal concavity is due to atelectasis. Note the shape of the transverse fissure. This example represents a RUL mass with atelectasis
  • 39.
    THE BAT VIEWChest wall Pleural line
  • 40.
    THE BAT VIEW Chest wall Pleural line
  • 41.
  • 45.
    Pneumonia Posterior intercostalscan shows a hypoechoic consolidated area that contains multiple echogenic lines that represent an air bronchogram.
  • 46.
    Post-stenotic pneumonia Posteriorintercostal scan shows a hypoechoic consolidated area that contains anechoic, branched tubular structures in the bronchial tree (fluid bronchogram).
  • 47.
    Contrast-enhanced ultrasonography ofpneumonia 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.
  • 48.
  • 49.
  • 50.
    MECHANISMS OF ACTIONOF 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
  • 51.
    EFFECTS OF COMBINATIONSOF 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.
  • 52.
    EFFECTS OF COMBINATIONSOF 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.
  • 53.
    EFFECTS OF COMBINATIONSOF DRUGS Combinations of antimicrobial drugs should be used only for: 1.To prevent or minimize the emergence of resistant strains. 2.To take advantage of the synergistic effect. 3.To lessen the toxicity of individual drugs.
  • 54.
    Patterns of MicrobialKilling 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
  • 55.
    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
  • 56.
    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
  • 57.
    Resistance Physiological Mechanisms 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 (cont’d) REVIEW
  • 58.
    Empirical Treatment isthe recommended strategy in treatment of CAP and shouldn’t be delayed.
  • 59.
    59 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
  • 60.
    Outpatient treatment: OralRespiratory Fluroquinolones OR Oral B-Lactam/ B-Lactamase + Oral New Macrolide OR IM 3rd Generation Cefalosporines + New Macrolide Recommendations for the Empirical Treatment:
  • 61.
    In-patient treatment: Non-ICU: Intravenous ( IV )Respiratory fluoro- quinolone OR IV B-Lactam/ B-Lactamase + IV New Macrolide OR IV 3rd Generation Cephalosporin + IV New Macrolide Recommendations for the Empirical Treatment:
  • 62.
    In-patient treatment: ICU: No Monotherapy. IV Respiratory fluoroquinolone + 3rd or 4th generation cephalosporin OR IV Imipenem + IV New Macrolide Recommendations for the Empirical Treatment:
  • 63.
    Special entities inICU: 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) Recommendations for the Empirical Treatment:
  • 64.
    64 Duration ofTherapy •Minimum of 5 days •Afebrile for at least 48 to 72 h •Longer duration of therapy If initial therapy was not active against the identified pathogen or complicated by extra pulmonary infection
  • 65.
    65 Strategies forPrevention 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 •Starting first dose of antibiotic within 4 h & O2 status
  • 66.
    66 Switch toOral 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.
  • 67.
    67 Management ofPoor Responders Consider non-infectious illnesses Consider less common pathogens Consider serologic testing Broaden antibiotic therapy Consider bronchoscopy
  • 68.
    68 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
  • 69.
    69 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 cessation
  • 70.
    Broncho-Vaxom is anextract of different bacterial species frequently responsible of respiratory infections. It stimulates the immune system in order to increase the body’s natural defences against a wide spectrum of respiratory pathogens. BRONCHO-VAXOM Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
  • 71.
    Broncho-Vaxom prevents and/orreduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular sinusitis, rhinopharyngitis and middle ear infection, in adults and children. BRONCHO-VAXOM Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
  • 72.
    Immunostimulating agent Inanimals, an increased resistance towards experimental infections, a stimulation of macrophages and B lymphocytes as well as an increase in immunoglobulins secreted by the respiratory mucosal cells have been reported. BRONCHO-VAXOM Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
  • 73.
    Immunostimulating agent Inhumans, an increase in the rate of circulating T lymphocytes, in salivary IgA, in the non-specific response to polyclonal mitogens and in the mixed lymphocyte reaction have been observed. BRONCHO-VAXOM Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
  • 74.
    Safety Extensive toxicitystudies have not revealed any toxic effect. Effects on ability to drive and use machines: Broncho-Vaxom is presumed to be safe and unlikely to produce an effect. BRONCHO-VAXOM Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
  • 75.
    Safety Reproduction studiesin animals have not demonstrated any risk to the fetus, but controlled studies in pregnant women are not available. As regards breast-feeding, no specific studies have been performed and no data have been reported up to now. BRONCHO-VAXOM Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
  • 76.
    Side effects Theoverall incidence of adverse effects in clinical trials lies between 3 and 4%. Gastrointestinal troubles (nausea, abdominal pain, vomiting), dermatologic reactions (rash, urticaria), and respiratory disorders (coughing, dyspnea, asthma), as well as generalized problems (fever, fatigue, allergic reactions) are the most frequent complaints reported. BRONCHO-VAXOM Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .
  • 77.
    Interaction No druginteraction is known up to now.. BRONCHO-VAXOM Broncho-Vaxom ® prevents and/or reduces the severity of acute attacks of chronic bronchitis and recurrent infections of the respiratory tract, in particular .