Pharmacotherapy I: Pulmonary Antibiotics, TB & Pulm HTN PDF

Pharmacotherapy I: Pulmonary Antibiotics, TB & Pulm HTN Augsburg PA Program, 2024 Mary Ruggeri, MEd, MMSc, PA-C  Learning Objectives 1.Identify the most common bacterial pathogens causing pneumonia. 2.Identify the appropriate, first-line, in-patient, and out-patient...

Pharmacotherapy I: Pulmonary Antibiotics, TB & Pulm HTN Augsburg PA Program, 2024 Mary Ruggeri, MEd, MMSc, PA-C  Learning Objectives 1.Identify the most common bacterial pathogens causing pneumonia. 2.Identify the appropriate, first-line, in-patient, and out-patient treatment approach in an adult and pediatric patient with bacterial pneumonia. 3.Discuss alterations in adult bacterial pneumonia management based on the following: a. No comorbid conditions b. Comorbid conditions including: alcohol abuse, recent antibiotic use, and regional drug resistance (pseudomonas-risk). 4.Describe supportive, symptomatic care for adult and pediatric patients being treated as out-patients for bacterial pneumonia. 5.Know the first-line drugs (isoniazid, rifampin, pyrazinamide, ethambutol) used in the treatment of tuberculosis (TB), including their MOA, and their significant side effects. 6.Identify the duration of treatment for latent and active pulmonary TB infection 7.Identify populations in which TB treatment may be modified or extended. 8.Recognize the pathophysiologic categories and characteristics of pulmonary hypertension. 9.Identify the appropriate pharmacologic management for pulmonary hypertension, based on the disease category. 10.Describe the mechanism of action for vasodilators and their applicability to pulmonary hypertension. 11.For the following representative medications (included on the Unit Representative Medication List), know the medication class, mechanism of action, indications, adverse effects, contraindications, interactions (common), monitoring (if needed), and patient education. a. Amoxicillin/clavulanate b. Doxycycline c. Azithromycin d. Levofloxacin e. Cefdinir f. Ceftriaxone  Patient Case A 42-year-old man presents to the emergency department with complaints of fever, chills, shortness of breath, and productive cough with rust-colored sputum. He reports a two- day history of worsening symptoms, including chest pain on deep breaths and general fatigue. He has a history of hypertension and moderate alcohol use but no other comorbidities.  Patient Case On examination, his temperature is 101.5°F, heart rate is 110 bpm, respiratory rate is 24 breaths per minute, and he has crackles in the right lower lung field. A chest X-ray reveals a right lower lobe infiltrate consistent with  Patient Case Given the most common bacterial causes of pneumonia, what organisms should be considered in this patient's case?  Patient Case Common Bacterial Pathogens in Given the most Community Acquired Pneumonia common bacterial Streptococcus pneumoniae: causes of pneumonia, Most common cause in adults. what organisms should Haemophilus influenzae: be considered in this Especially in older adults and smokers. Mycoplasma pneumoniae: patient's case? Atypical, common in younger patients. Staphylococcus aureus: More severe cases, sometimes post- influenza.  Patient Case Common Bacterial Pathogens in Based on the patient’s Community-Acquired Pneumonia presentation and lack Streptococcus pneumoniae: of significant Most common cause in adults. comorbidities, what Haemophilus influenzae: would be the Especially in older adults and smokers. Mycoplasma pneumoniae: ATY appropriate first-line Atypical, common in younger patients. antibiotic treatment for Staphylococcus aureus: More P an outpatient setting? severe cases, sometimes post- influenza.  Outpatient Management - Adults UpToDate  Outpatient Management - Adults CAP Pneumonia - First-Line Treatment Options: ⚬ Healthy adults, no risk factors: Amoxicillin, doxycycline, or macrolide (azithromycin) if local resistance 3rd Gen Ceph, FQ ⚬ Consider broader-spectrum coverage if aspiration is suspected.  Considerations How do regional How would recent antibiotic resistance antibiotic use within rates (e.g., resistance the past three months to macrolides or a affect your choice of higher prevalence of antibiotics? Pseudomonas) might alter the empiric treatment plan.  Considerations Modifying Treatment Based on Antibiotic Resistance Recent Antibiotic Use (last 3 months): Avoid repeat of same antibiotic class. Macrolide Resistance: If resistance >25%, use a beta-lactam + doxycycline or respiratory fluoroquinolone. Pseudomonas Risk: Consider anti-pseudomonal beta-lactam (e.g., piperacillin-tazobactam) for high-risk cases.  Hospital Acquired Pneumonia Empiric Treatment for Hospital-Acquired Pneumonia (HAP/VAP) Patient Criteria ⚬ No risk factors for multidrug-resistant (MDR) pathogens ⚬ No increased mortality risk in non-ventilated HAP (nvHAP) Recommended Regimen ⚬ Cover Pseudomonas, gram-negative bacilli, and methicillin-susceptible S. aureus (MSSA) Preferred IV Antibiotic Options ⚬ Piperacillin-tazobactam ⚬ Cefepime Pediatric Approach - Bacterial Pneumonia Common Pathogens: ⚬ Infants and Young Children: Streptococcus pneumoniae, Haemophilus influenzae. How would your plan ⚬ Older Children/Adolescents: change if it was a Consider Mycoplasma pediatric patient, age pneumoniae and viral causes. 6, who pressents with Outpatient First-Line: ⚬ Amoxicillin similar symptoms? ⚬ Macrolide (azithro) if atypical pneumonia suspected. Inpatient First-Line: IV ampicillin or ceftriaxone; add macrolide if atypical suspected. ABX Summary of First-Line Recommendations Adults (Outpatient & Inpatient): Tailor to comorbidities, alcohol use, recent antibiotics. Pediatrics: Adjust for common pathogens by age group and severity. Special Situations: Resistance considerations, Pseudomonas risk, aspiration risk in alcohol use.  Supportive and Symptomatic Care Rest and Hydration Adults & Pediatrics: Encourage adequate rest and hydration to support recovery. ⚬ Hydration: Essential for managing fever and preventing dehydration. ⚬ Avoid physical exertion: Reduces stress on respiratory system. Fever and Pain Management Adults: Acetaminophen or NSAIDs (e.g., ibuprofen) to reduce fever, body aches, and chest pain. Pediatrics: Acetaminophen or ibuprofen (age-appropriate dosing); avoid aspirin (risk of Reye’s syndrome).  Supportive and Symptomatic Care Cough Relief Adults: Consider expectorants or antitussives for symptom relief (use with caution to avoid suppressing productive cough). Pediatrics: Warm fluids, humidified air; avoid OTC cough suppressants for children inactivates the antibiotic, making bacteria resistant to it.  Amoxicillin/clavulanate Augmentin (Amoxicillin/Clavulanate) - Gram-positive and gram-negative coverage ⚬ Amoxicillin: Beta-lactam = Inhibits bacterial cell wall synthesis by binding to PBPs --> bacterial lysis. ⚬ Clavulanate: A beta-lactamase inhibitor that protects amoxicillin from degradation by beta-lactamase-producing bacteria, extending its spectrum of activity. ⚬ Broad-spectrum PO antibiotic used for: ￭ Upper respiratory infections (e.g., sinusitis, otitis media). ￭ Lower respiratory infections (e.g., pneumonia). ￭ Skin and soft tissue infections. ￭ UTIs ￭ Bite wounds (animal or human). ⚬ CI/Caution: reduced liver function (rare cases of cholestatic jaundice or hepatitis - especially with prolonged use) ⚬ AE: N/V/D, rash, itchy ABX  Ceftriaxone MOA: beta-lactam (Inhibits bacterial cell wall synthesis by binding to PBPs) ⚬ broader resistance to beta-lactamases. ⚬ 3rd Generation: some gram-pos bacteria, greater gram-neg activity (than previous gen) ⚬ Cephtriaxone (brand: Rocephin) IM/IV- Indications ￭ Broad-spectrum antibiotic for: Community-acquired pneumonia (often more severe/hospitalized) Meningitis (including bacterial meningitis). Urinary tract infections (UTIs). Sepsis. Gonorrhea (single-dose treatment). safe in pregnancy/BF C/I in neonates, avoid with liver dysfunction ⚬ AE: inj-site reaction, eosinophilia, thrombocytosis, ALT/AST elev, leukopenia, DIARRHEA, potential for C.diff ABX  Cefdinir MOA: beta-lactam (Inhibits bacterial cell wall synthesis by binding to PBPs) ⚬ broader resistance to beta-lactamases. ⚬ 3rd Generation - not as broad as Ceftriaxone ⚬ Cefdinir (brand: Omnicef) Indications Community-acquired pneumonia (outpatient treatment) Sinusitis Otitis media ⚬ AE: GI issues, hypersensitivity reaction, diarrhea, potential for C.diff ⚬ Interactions: iron supplements and antacids (don’t take at same time as Cefdinir) Antibiotics Action  Tetracyclines Tetracyclines MOA Bind to the 30S ribosomal subunit of bacteria ⚬ prevents the binding of aminoacyl- tRNA to the mRNA-ribosome complex ⚬ stops the process of protein synthesis, which prevents the bacteria from growing and replicating ⚬ bacteriostatic Examples: ⚬ Doxycycline ⚬ Minocycline ⚬ Tetracycline  Doxycycline Doxycycline - oral cap, tab, susp, INJ - (Vibramycin, Monodox, Targadox) Class: Tetracycline antibiotic MOA: Inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. ⚬ Prevents the addition of amino acids to the growing peptide chain (bacteriostatic). Indications: gram-positive infections + MRSA (adult + kids >8yo) ⚬ Respiratory tract infections (e.g., s. pneumonia). ⚬ Tick-borne diseases ⚬ STIs (e.g., chlamydia, syphilis). ⚬ Acne, rosacea, skin and soft tissue infections (MRSA) ⚬ Malaria prophylaxis. AE: N/V/D, (take with food), GERD Caution: hepatic impairment, stains teeth enamel - don’t give to kids under 8yo (permanent), reversible in adults, photosensitivity Preg/BF: avoid in preg, don’t BF until 5 days after discontinued (short term okay non-lyme, but theoretical risk of enamel stain and abnormal bone development) ABX Antibiotics Action  Macrolides Macrolides MOA Bind to the 50S ribosomal subunit of bacteria ⚬ bind and blocking the new peptide exit ⚬ prevent the enzyme peptidyltransferase from adding the next amino acid to the growing peptide chain ⚬ prevents mRNA from being translated ⚬ bacteriostatic Examples: ⚬ Erythromycin ⚬ Clarithromycin ⚬ Azithromycin  Azithromycin Azithromycin (brand: Zithromax, Z-Pak, Zmax) MOA: Inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, inhibiting bacterial growth (bacteriostatic). Indication (Therapeutic Use) ⚬ Respiratory infections (e.g., community-acquired pneumonia, bronchitis) ⚬ Skin and soft tissue infections ⚬ Some sexually transmitted infections (e.g., chlamydia) ⚬ Certain GI infections (e.g., Campylobacter) AE: GI upset, QT prolongation, HA, dizzy, hepatotoxicity (rare) Caution: pt with known prolonged QT interval Interactions: antacids (use separate), warfarin (inc bleeding risk), other QT- ABX Antibiotics Action  Fluoroquinolones Fluoroquinolones MOA Inhibit the enzymes DNA gyrase and topoisomerase IV, which are essential for bacterial DNA replication ⚬ DNA gyrase converts closed circular DNA into supercoil - if blocked, can’t replicate ⚬ Topoisomerase IV seperates daughter DNA strands for cell division Only direct inhibitors of DNA synthesis; by binding to the enzyme-DNA complex, they stabilize DNA strand breaks Examples: ⚬ Ciprofloxacin ⚬ Moxifloxacin ⚬ Levofloxacin  Levofloxacin Levofloxacin (Levaquin) ⚬ MOA: inhibits DNA gyrase and topoisomerase IV Indications: infections of respiratory tract - pneumonia, urinary tract, GI tract, skinand soft tissues ⚬ avoid 20 mmHg confirms pulmonary hypertension) Pulmonary Capillary Wedge Pressure (PCWP): 12 mmHg (normal; 3 WU indicates pulmonary arterial hypertension) Cardiac Output: 3.5 L/min (low-normal) Interpretation: Findings are consistent with Group 1: Pulmonary Arterial Hypertension (PAH) based on elevated mPAP, normal PCWP, and elevated PVR.  Pulmonary HTN - Management Pharmacologic Therapy ⚬ Phosphodiesterase-5 (PDE-5) Inhibitor --> to pulmonary vasodilation. ⚬ Endothelin Receptor Antagonist (ERA) --> reduce vasoconstriction, and lower pulmonary resistance. ⚬ Consider adding a Prostacyclin Analog if symptoms are severe or low response to other Rx Supportive Care ⚬ Oxygen Therapy: If hypoxemic at rest or during exertion. ⚬ Diuretics --> manage fluid retention and reduce preload if significant peripheral edema Thank You