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Respiratory Infections and Treatments
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Respiratory Infections and Treatments
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What are the objectives of the lecture on Bronchitis, Influenza, Pneumonia, and Tuberculosis?
1. Briefly discuss the pathophysiology of Community Acquired, Hospital Acquired, and Ventilator Associated Pneumonia, Bronchitis (acute and chronic), Influenza, and Tuberculosis. 2. List the goals of therapy and different treatment options for pneumonia, acute and chronic bronchitis, and TB. 3. Identify the mechanisms of action, pharmacokinetic issues, adverse drug reactions, and cautions associated with all antimicrobial agents presented in this lecture. 4. List the most common pathogens encountered in pneumonia and bronchitis. 5. Discuss the role of preventive therapy in tuberculosis, including those patients that would benefit. 6. Given a patient case, develop a treatment plan including agent, duration of treatment, and specific monitoring plan for patients with pneumonia, bronchitis, and TB.
What is Acute Bronchitis?
Acute bronchitis is a self-limiting inflammation of the large airways of the lung characterized by cough WITHOUT pneumonia. It affects approximately 5% of adults annually and is the 9th most common illness among outpatients, with a higher incidence in the fall and winter.
What are the infectious triggers for Acute Bronchitis?
The infectious triggers for Acute Bronchitis include viruses (85-95% of occurrences), such as Influenza, RSV, Parainfluenza, Rhinovirus, Coronavirus, Adenovirus, and less common bacteria like Mycoplasma pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.
What are the environmental triggers for Acute Bronchitis?
The environmental triggers for Acute Bronchitis include air pollution and cigarette smoke.
What is the pathogenesis of Acute Bronchitis?
The pathogenesis involves inflammation of the epithelium of the bronchi in response to infections, largely viral. Infection of the trachea and bronchi causes inflammation-induced hyperemia and edematous mucous membranes, resulting in increased bronchial secretions, destroyed respiratory epithelium, and impaired bronchial mucociliary function.
What diagnostic tests are recommended for Acute Bronchitis?
Extended respiratory viral panel tests for viruses and atypical pathogens; antigen-based PCR tests are beneficial for identifying specific pathogens. Throat/sputum cultures have no role in the routine care of acute bronchitis.
What is the clinical presentation of Acute Bronchitis?
Acute Bronchitis initially presents with non-specific mild upper respiratory symptoms, an acute cough (bothersome and slow to resolve) with or without sputum production, and signs of lower respiratory tract infection. Cough usually lasts about 5 days but can last 2-3 weeks.
What are the treatment options for Viral Acute Bronchitis?
1. Influenza virus - Oseltamivir (Tamiflu) 75 mg PO BID x 5 days. 2. Parainfluenza virus - symptomatic treatment. 3. RSV - symptomatic treatment. 4. Coronavirus - symptomatic treatment. 5. Adenovirus - symptomatic treatment. 6. Rhinovirus - symptomatic treatment.
What are the treatment options for Atypical Bacteria causing Acute Bronchitis?
1. Mycoplasma pneumoniae - Azithromycin x 5 days (500 mg x 1 then 250 mg days 2-5) or Doxycycline 100 mg BID x 5 days. 2. Chlamydophila pneumoniae - Azithromycin x 5 days (500 mg x 1 then 250 mg days 2-5) or Doxycycline 100 mg BID x 5 days.
What is included in the supportive treatment for Acute Bronchitis?
Supportive treatment includes antipyretics (Acetaminophen or Ibuprofen), fluid intake to decrease the viscosity of respiratory secretions, expectorants (Guaifenesin), mist therapy, and occasionally antitussive or mucolytic agents.
What are the key signs and symptoms of Influenza?
Influenza presents with sudden onset of respiratory symptoms, cough, sore throat, difficulty breathing, high-grade fevers (102F-104F), and severe general body aches and pains. Complications can include primary viral illness and secondary bacterial pneumonia.
What is Community-Acquired Pneumonia (CAP)?
Community-Acquired Pneumonia (CAP) is defined as an infection acquired outside of the hospital setting.
What is Hospital-Acquired Pneumonia (HAP)?
Hospital-Acquired Pneumonia (HAP) is defined as an infection that occurs 48 hours after admission and did not appear to be incubating at the time of admission.
What is Ventilator Associated Pneumonia (VAP)?
Ventilator Associated Pneumonia (VAP) is a type of HAP that develops 48 hours after endotracheal intubation.
What are the common signs and symptoms of pneumonia?
Common signs and symptoms of pneumonia include abrupt onset of fever, chills, dyspnea, chest pain/tightness, productive cough (possibly with rust-colored sputum or hemoptysis), pleuritic chest pain, tachypnea, tachycardia, dullness to percussion, increased tactile fremitus, and diminished breath sounds.
What are the inflammatory markers for pneumonia diagnosis?
Inflammatory markers for pneumonia diagnosis include Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin.
What is the recommended treatment duration for most pneumonia patients?
Most patients can be treated for 5 days, as long as they demonstrate clinical stability and improvement within the first 48-72 hours. Patients with atypical pneumonia, MRSA, or Pseudomonas CAP should be treated for 7 days.
What are the key considerations for empiric treatment of Community-Acquired Pneumonia?
Consider the most common bacterial pathogens, the presence of risk factors for MRSA and Pseudomonas, recent hospitalization or antibiotic use, and individual risk factors for multidrug-resistant pathogens.
What are the treatment recommendations for outpatient CAP in healthy individuals?
Outpatient empiric treatment for healthy individuals without comorbidities includes Amoxicillin 1g PO TID, Doxycycline 100 mg PO BID, or a macrolide in areas with macrolide resistance (Azithromycin or Clarithromycin).
What is the dosing regimen for Aztreonam?
2 g IV q8h
What type of antibiotics are Gram-negative antibiotics with antipseudomonal activity?
Non beta-lactam based agents.
What is the dosing regimen for Ciprofloxacin?
400 mg IV q8h
What is the dosing regimen for Levofloxacin?
750 mg IV q24h
What is the dosing regimen for Amikacin?
15-20 mg/kg IV q24h
What is the dosing regimen for Gentamicin?
5-7 mg/kg IV q24h.
What is the dosing regimen for Tobramycin?
5-7 mg/kg IV q24h.
What is the dosing regimen for Colistin?
5 mg/kg IV for a loading dose followed by a maintenance dose of 2.5 mg if CrCl is greater than 30, q12h.
What is the dosing regimen for Polymyxin B?
2.5-3.0 mg/kg divided in 2 daily IV doses.
What is de-escalation of therapy based on?
Clinical improvement and culture results.
What should be done for non-critically ill patients regarding antibiotic therapy?
Transition to oral therapy as soon as possible.
What is the approach if culture results are negative?
Step down therapy can be considered.
When should vancomycin be discontinued based on MRSA nasal screening?
If no MRSA is isolated and nasal screen is negative.
What is the pharmacology overview for Ampicillin?
Available in IV and PO forms.
What is the pharmacology overview for Amoxicillin?
Available in PO form.
What is the pharmacology overview for Ampicillin-sulbactam?
Available in IV and PO forms.
What is the pharmacology overview for Amoxicillin-clavulanate?
Available in PO form.
What are the characteristics of Cefepime?
Great gram-positive coverage (Strep spp and MSSA), great gram-negative coverage, very broad including Pseudomonas.
What are the characteristics of Ceftaroline?
Great gram-positive coverage (Strep spp, MSSA, and MRSA), good gram-negative coverage, same as Ceftriaxone, no coverage for Pseudomonas spp.
What is Ceftolozane-Tazobactam used for?
Targets Multi-Drug Resistant Pseudomonas spp.
What is Ceftazidime-Avibactam used for?
Targets Carbapenem resistant gram-negative organisms.
What is Aztreonam classified as?
Monobactam that is ONLY active against Gram-negative pathogens.
What type of activity does Aztreonam lack?
Gram-positive activity.
When should Aztreonam be reserved for use?
For patients with Type I hypersensitivity reaction to penicillins, i.e., anaphylaxis.
Is there cross-reactivity between Aztreonam and ceftazidime?
Yes, if a patient had a reaction to ceftazidime, do not use aztreonam.
What is the dosing for Vancomycin targeting trough levels?
Dose to a targeted trough of 15-20 mg/L.
What is the dosing for Linezolid?
600 mg IV/PO q12h.
What are the pharmacokinetics of Vancomycin?
Moderate pulmonary distribution.
What are the toxicity concerns for Vancomycin?
Nephrotoxicity, infusion-related reactions.
What are the toxicity concerns for Linezolid?
Hematologic effects and drug interactions with other MAO-inhibitors leading to an increased risk of serotonergic side effects.
What is important to monitor when using Vancomycin and Linezolid?
Trough concentrations and normal laboratory parameters.
What is the resistance level in MRSA?
Very low.
What is the clinical presentation of pneumonia in a patient with fever, cough, and pleuritic chest pain?
Left lower lobe consolidation on chest x-ray.
What is the best appropriate treatment option to treat outpatient non-severe pneumonia?
1. Azithromycin x 5 days 2. Amoxicillin x 5 days 3. Doxycycline x 10 days 4. Ciprofloxacin x 5 days.
What is the most appropriate empiric regimen for a patient suspected of VAP based on the 2016 IDSA guidelines?
1. Aztreonam monotherapy 2. Piperacillin-tazobactam plus vancomycin 3. Moxifloxacin 4. Vancomycin monotherapy.
How is Tuberculosis (TB) transmitted?
TB is transmitted through the air when someone infected coughs, sneezes, shouts, or sings.
Can TB be spread through touch or sharing utensils?
No, TB is NOT spread through touch, blood, food, or sharing utensils.
What is the difference between TB infection and TB disease?
It is possible to be infected with TB and not develop TB disease; about 10% of people with TB infection develop TB disease.
What does latent TB infection (LTBI) refer to?
The period when the immune system contains the TB and prevents progression to disease.
What does active TB disease refer to?
The time when TB is no longer contained by the immune system and causes disease.
What is the first-line treatment for active TB disease?
Initial Phase: RIF, INH, PZA, EMB daily x 8 weeks; Continuation Phase: RIF, INH daily x 18 weeks.
What is the mechanism of action (MOA) of Rifampin (RIF)?
Inhibits RNA polymerase and blocks DNA transcription.
What are some adverse effects of Rifampin?
Rash, hepatitis, flu-like syndrome.
What is important to monitor when using Rifampin?
Liver function.
What is the MOA of Isoniazid (INH)?
Inhibits synthesis of mycolic acid by inhibiting essential enzymes for synthesis necessary for bacterial cell wall synthesis.
What are some drug interactions of Isoniazid?
Food impairs absorption, antacids can interfere, and it inhibits the CYP450 system.
What are adverse effects of Isoniazid?
Hepatotoxicity, peripheral neuropathy, rash, drug fever, lupus-like syndrome.
What is the mechanism of action of Pyrazinamide?
Converted to pyrazinoic acid in susceptible strains of Mycobacterium, which lowers the pH of the environment.
What adverse effects are associated with Pyrazinamide?
Hepatotoxicity, needs dose adjustment for severe renal impairment, myalgias, hyperuricemia.
What is the MOA of Ethambutol (EMB)?
Inhibits synthesis of cell wall by inhibiting arabinosyl transferase.
What are the adverse effects of Ethambutol?
Optic neuritis, decrease in visual acuity, inability to discriminate between red and green.
Which agents are considered second-line TB agents?
Amikacin, Levofloxacin, Moxifloxacin, Linezolid, Streptomycin.
Which drug is most likely to cause peripheral neuropathy when receiving RIPE therapy?
Isoniazid.
What is the clinical presentation of acute bronchitis?
Cough lasting 5 days, mildly ill-appearing, fever present in about one-third of patients.
What are the treatment recommendations for Community-Acquired Pneumonia (CAP) in healthy outpatients?
Amoxicillin 1 g TID, Doxycycline, or Azithromycin in areas with macrolide resistance.
What are the treatment recommendations for CAP in outpatients with comorbidities?
Amoxicillin-clavulanate OR a cephalosporin PLUS a macrolide or doxycycline or Levofloxacin or Moxifloxacin.
What are the treatment recommendations for inpatient CAP non-severe without risk for MRSA or P. aeruginosa?
Beta-lactam (ampicillin-sulbactam or ceftriaxone) PLUS macrolide or doxycycline.
What are the treatment recommendations for inpatient CAP severe without risk factors for MRSA or P. aeruginosa?
Beta-lactam PLUS macrolide or doxycycline or beta-lactam PLUS Levofloxacin.
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