pharma lab resp

Macrolides: Mechanism of Action

Bind irreversibly to 50S ribosomal subunit inhibiting translocation.

MRSA Treatment: Moderate-Severe (Hospitalized/IV)

Vancomycin (most common), Daptomycin, Linezolid, Ceftaroline.

Empirical Treatment: HCAP with MDR pathogens

Triple therapy: 1. Antipseudomonal Beta-lactam (e.g., Ceftazidime, Cefepime, Pip/Tazo) PLUS 2. Second anti-pseudomonal agent (Gentamicin or Ciprofloxacin) PLUS 3. Anti-MRSA agent (Vancomycin)

Jarisch-Herxheimer reaction

Fever and exacerbation of syphilis symptoms after first Penicillin injection due to massive destruction of spirochetes.

CURB-65: What does C stand for?

Confusion (1 point if patient has confusion of new onset).

Case 3: Bronchitis treatment for S. pneumoniae?

1st line: Amoxicillin. If allergic: Azithromycin/Clarithromycin.

Case 3: Bronchitis treatment for M. pneumoniae?

Azithromycin or Fluoroquinolone.

Case 4: Pneumonia, H. influenzae (G- bacilli). Treatment?

Non-B-lactamase: Amoxicillin. B-lactamase producing: 2nd/3rd gen Ceph or Amox-Clav or FQ.

Cephalosporins: Adverse Effects

1. Hypersensitivity (Cross-allergy with Penicillin) 2. Nephrotoxicity (esp with Aminoglycosides) 3. Local irritation/Thrombophlebitis 4. Hypoprothrombinemia & Bleeding (Cefoperazone) 5. Disulfiram-like reaction (Alcohol intolerance)

Aminoglycosides: Mechanism of Action

Bactericidal. Bind to 30S ribosomal subunit causing misreading of mRNA.

Case 7: 64yo, blood-tinged sputum, DVT history. Empirical Treatment?

Combination Macrolide/Doxy + Amox-Clav OR Respiratory Fluoroquinolone (Moxifloxacin/Levofloxacin).

Quinolones: Generations

1st: Nalidixic acid 2nd: Ciprofloxacin, Ofloxacin 3rd: Levofloxacin, Moxifloxacin 4th: Trovafloxacin

Case 1: 37yo, nasal congestion, runny nose, normal vitals. Diagnosis?

Common Cold.

Quinolones: Adverse Effects & Contraindications

Adverse: GIT, Photosensitivity, Arthropathy (Cartilage damage). Contraindications: Pregnancy, Lactation, Patients < 18 years.

General treatment measures for CAP (non-antibiotic)

1. Oxygen 2. IV fluids 3. Bronchodilators (if bronchospasm present) 4. Nutritional support 5. Control of fever

MRSA Treatment: Mild-Moderate (Outpatient/Oral)

Clindamycin, Cotrimoxazole (TMP-SMX), Doxycycline/Minocycline, Linezolid.

Tetracyclines: Mechanism of Action

Bacteriostatic. Compete with RNA on 30S ribosomal subunit to inhibit protein synthesis.

Why is Daptomycin avoided in MRSA Pneumonia?

It is inactivated by pulmonary surfactant.

Case 2: 57yo, maxillary pain, yellow discharge, fever >2 weeks. Diagnosis?

Acute Sinusitis.

Antibiotics Class: Cell wall inhibitors

Penicillins, Cephalosporins, Monobactams, Carbapenems, Vancomycin.

Cephalosporins: Fourth Generation Example & Feature

Cefepime. Excellent penetration of BBB and resistant to Beta-lactamases.

CURB-65: What does B stand for?

Blood Pressure. 1 point if Systolic < 90 mmHg OR Diastolic < 60 mmHg.

Antibiotics Class: Protein synthesis inhibitors

Aminoglycosides, Macrolides, Chloramphenicol, Tetracyclines.

Definition of Hospital-Acquired Pneumonia (HAP)

Pneumonia in a patient who is in the hospital for at least 48-72 hours.

Case 2: Treatment (Failure after 72h)

High-dose Amoxicillin-Clavulanate OR Macrolides.

CURB-65: What is the age criterion?

Age 65 years or older (1 point).

Definition of Pneumonia

An infection of the pulmonary parenchyma.

Penicillins: Major adverse effects

1. Hypersensitivity (Rash, Urticaria, Anaphylaxis) 2. Diarrhea (superinfection) 3. CNS toxicity (if intrathecal) 4. Nephrotoxicity 5. Platelet dysfunction 6. Jarisch-Herxheimer reaction (in Syphilis)

Case 4: Pneumonia, P. aeruginosa. Treatment?

Antipseudomonal Beta-lactam + Ciprofloxacin OR Aminoglycoside.

Case 4: Empirical Pneumonia treatment (Risk factors/Unclear org)

A) Beta-lactam (Cefuroxime/Amox-Clav) + Macrolide/Doxycycline OR B) Antipneumococcal Fluoroquinolone.

CURB-65 Score Interpretation: 2

Moderate risk. Consider hospitalization.

Macrolides: Members

Erythromycin, Clarithromycin, Azithromycin.

Vancomycin: Mechanism of Action

Inhibits cell wall synthesis at an earlier stage than Beta-lactams. Bactericidal.

Vancomycin: Adverse Effects

1. Red Man Syndrome (Histamine release due to rapid infusion) 2. Ototoxicity 3. Nephrotoxicity

Empirical Treatment: HCAP with Non-MDR pathogens

Single agent Beta-lactam (e.g., Ceftriaxone, Ampicillin-sulbactam, or Levofloxacin).

Macrolides: Adverse Effects

1. Epigastric pain & Diarrhea (motility) 2. Cholestatic Jaundice 3. Ototoxicity (esp Azithromycin)

Sulphonamides: Mechanism

Bacteriostatic. Compete with PABA to inhibit Folic Acid Synthase.

Case 4: Pneumonia, S. pneumoniae (G+ diplococci). Treatment?

1st line: Penicillin G or Amoxicillin. 2nd line: Macrolide or Cephalosporin. Resistant: 3rd gen Ceph, FQ, or Vancomycin.

Case 1: Treatment?

Symptomatic: NSAIDs for headache, Decongestants (Oxymetazoline, Pseudoephedrine), Antihistamines, Vitamin C.

Aminoglycosides: Adverse Effects

1. Ototoxicity (Irreversible, auditory & vestibular) 2. Nephrotoxicity 3. Neuromuscular blockade (Curare-like action)

Treatment for MRSA Bacteremia/Endocarditis

1st Line: IV Vancomycin. Alternative: Daptomycin (high dose) or Ceftaroline combination.

Tetracyclines: Adverse Effects

1. GIT irritation 2. Superinfection (Candida) 3. Teeth discoloration & Bone deformities (Calcium chelation) 4. Teratogenicity 5. Photosensitivity 6. Fanconi syndrome (expired drugs)

Definition of Community-Acquired Pneumonia (CAP)

Inflammatory process in the lungs in a person with little contact with the healthcare system.

CURB-65: What does R stand for?

Respiratory Rate. 1 point if >= 30 breaths/min.

Case 2: Treatment (No allergy)

Amoxicillin.

Aminoglycosides: Members

Gentamicin, Amikacin, Streptomycin, Tobramycin, Neomycin.

Quinolones: Mechanism of Action

Inhibit DNA Gyrase. Bactericidal.

Drugs for Penicillin-resistant S. pneumonia (MDR)

1. Macrolides 2. TMP-SMZ (Cotrimoxazole) 3. Clindamycin 4. Tetracyclines 5. Fluoroquinolones (low resistance) 6. Vancomycin (no resistance)

Sulphonamides: Adverse Effects

1. Hypersensitivity (Stevens-Johnson) 2. Hemolysis in G6PD deficiency 3. Crystalluria 4. Kernicterus (displace bilirubin)

Case 2: Causative organisms?

S. pneumoniae, H. influenzae.

Cephalosporins: Second Generation Spectrum & Examples

Spectrum: Less active against Gram +ve, more active against Gram -ve. Do not pass BBB (except Cefuroxime). Examples: Cefaclor, Cefuroxime.

Vancomycin: Uses

1. MRSA infections (Pneumonia, Endocarditis, Osteomyelitis) 2. Severe Staph in Penicillin-allergic patients 3. Pseudomembranous colitis (C. diff)

Classification of Pneumonia

1. Community-acquired pneumonia (CAP) 2. Health care-associated pneumonia (HCAP), including Hospital-acquired (HAP) and Ventilator-associated (VAP).

Cephalosporins: Third Generation Spectrum & Examples

Spectrum: More active on Gram -ve bacilli and anaerobes. Pass BBB. Examples: cefpodoxime

CURB-65: What does U stand for?

Urea (Blood Urea Nitrogen). 1 point if > 19 mg/dl.

Cephalosporins: First Generation Spectrum & Examples

Spectrum: Active mainly against Gram +ve. Do not pass BBB. Examples: Cephradine, Cefadroxil, Cefazolin.

Case 6: HAP (15 days, Late onset). Treatment?

Combination for MDR: 1. Antipseudomonal B-lactam (Pip/Tazo or Cefepime) 2. Aminoglycoside or Ciprofloxacin 3. Vancomycin

Case 4: Pneumonia, S. aureus (G+ cocci clusters). Treatment?

Methicillin-Susceptible: Antistaphylococcal penicillin (Oxacillin) or Cefazolin. MRSA: Vancomycin or Linezolid.

Case 2: Treatment (Penicillin allergy)

Clarithromycin or Azithromycin.

Beta-lactamase inhibitors (Names and Combinations)

Clavulanic acid, Sulbactam, Tazobactam. Combinations: Augmentin (Amox+Clav), Unasyn (Amp+Sulb), Sulperazone (Cefoperazone+Sulb), Zosyn (Pip+Tazo).

CURB-65 Score Interpretation: 0 or 1

Low risk. Treat as outpatient.

CURB-65 Score Interpretation: 3, 4, or 5

High severity/risk. Hospitalization required.

Case 5: HAP (3 days). Treatment?

Single agent: Ceftriaxone OR Levofloxacin OR Ampicillin-Sulbactam.

Cephalosporins 1st & 2nd Gen: Spectrum & Common Drugs?

1st Gen: Mainly Gram +ve. (Ex: Cephradine, Cefadroxil). 2nd Gen: More Gram -ve coverage. (Ex: Cefaclor, Cefuroxime). Neither pass BBB well.

Cephalosporins 3rd & 4th Gen: Spectrum & Common Drugs?

3rd Gen: Gram -ve & Anaerobes. Passes BBB. (Ex: Cefotaxime, Ceftriaxone, Cefoperazone). 4th Gen: Cefepime (Resistant to Beta-lactamase, passes BBB).