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Antbiotic Strategy in CAP
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Antbiotic Strategy in CAP

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  • 1. Antibiotic Strategy in CAP Gamal Rabie Agmy, MD,FCCP Professor of Chest Diseases, Assiut university
  • 2. Pneumonias – Classification CAP HCAP • Health Care Associated HAP • Hospital Acquired ICUAP • ICU Acquired VAP 3 • Community Acquired • Ventilator Acquired Nosocomial Pneumonias
  • 3. 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
  • 4. 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.
  • 5. 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.
  • 6. The clinical diagnosis of CAP Signs: Generally: Fever, sometimes hypothermia, tachycardia, tachypnea. Local: signs of consolidation
  • 7. 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
  • 8. 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.
  • 9. 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.
  • 10. 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
  • 11. CAP – Pathogenesis Inhalation Aspiration Hematogenous 12
  • 12. 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
  • 13. Classification of Severity - PORT Class I Predictors Absent Class IV 15 Class II 91 - 130  70 Class V Class III > 130 71 – 90
  • 14. 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
  • 15. 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
  • 16. 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
  • 17. The Radiological Diagnosis of CAP
  • 18. 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
  • 19. 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
  • 20. Normal CXR & Pneumonic Consolidation 23
  • 21. Lobar Pneumonia – S.pneumoniae 24
  • 22. CXR – PA and Lateral Views 25
  • 23. Lobar versus Segmental - Right Side 26
  • 24. Lobar Pneumonia 27
  • 25. Special forms of Consolidation 28
  • 26. Round Pneumonic Consolidation 29
  • 27. Special Forms of Pneumonia 30
  • 28. Special Forms of Pneumonia 31
  • 29. Complications of Pneumonia 32
  • 30. Empyema 33
  • 31. Mycoplasma Pneumonia 34
  • 32. Mycoplasma Pneumonia 35
  • 33. Chlamydia Trachomatis 36
  • 34. Rare Types of Pneumonia 37
  • 35. 38
  • 36. Pneumonia Posterior intercostal scan shows a hypoechoic consolidated area that contains multiple echogenic lines that represent an air bronchogram.
  • 37. Post-stenotic pneumonia Posterior intercostal scan shows a hypoechoic consolidated area that contains anechoic, branched tubular structures in the bronchial tree (fluid bronchogram).
  • 38. 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.
  • 39. The Treatment of CAP
  • 40. ANTIMICROBIAL DRUGS
  • 41. 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
  • 42. 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. 
  • 43. 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. 
  • 44. 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.
  • 45. 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
  • 46. 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
  • 47. 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
  • 48. 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
  • 49. Empirical Treatment is the recommended strategy in treatment of CAP and shouldn’t be delayed.
  • 50. 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
  • 51. 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
  • 52. 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
  • 53. 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
  • 54. 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
  • 55. 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)
  • 56. 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
  • 57. 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
  • 58. 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
  • 59. Management of Poor Responders  Consider non-infectious illnesses  Consider less common pathogens  Consider serologic testing  Broaden antibiotic therapy  Consider bronchoscopy 65
  • 60. 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
  • 61. 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

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