Lower Respiratory Tract Infections 2025 PDF

Upper & Lower Respiratory Tract Infections Objectives Describe the following for each infection:  Etiology  Pathophysiology  Signs & Symptoms  Treatment List the following for each medication:  MOA  Adverse effects  Drug-drug interactions...

Upper & Lower Respiratory Tract Infections Objectives Describe the following for each infection:  Etiology  Pathophysiology  Signs & Symptoms  Treatment List the following for each medication:  MOA  Adverse effects  Drug-drug interactions  Contraindications  Expectations of therapy (e.g., formulation, dosing, renal dosing, duration and others) Bronchitis Bronchitis Etiology  Viral  Smoking Pathophysiology  Inflammation of the epithelium of the large airways resulting from infection or exposure to irritating environmental triggers  Hyperemic and edematous mucous membranes with an increase in bronchial secretions Clinical presentation  Cough  Fever < 102.2°F  Normal chest radiography Bronchitis Treatment  Antipyretics / analgesics  No benefit from aerosolized β2-receptor agonists  No benefit from oral or aerosolized corticosteroids  Antitussive – use caution when cough is productive  Dextromethorphan  Codeine / Guaifenesin  Medicare does not cover cough suppressants  Expectorants – clinical effectiveness has not been well established  Guaifenesin  H2O???  Antibiotics  Healthy patients who exhibit persistent fever or respiratory symptoms for more than 5 to 7 days or for predisposed patients (e.g., elderly/frail, COPD, and immune compromised)  Azithromycin  Levofloxacin or moxifloxacin Chronic Bronchitis There are differences with IDSA and GOLD guidelines Use GOLD guidelines… will discuss more during COPD lecture Chronic Bronchitis Etiology  Smoking  Exposure to occupational dusts, fumes, and environmental pollution Pathophysiology  Bronchial wall is thickened, and the number of mucus-secreting goblet cells on the surface epithelium of both larger and smaller bronchi is increased markedly Diagnosis  Chronic cough productive of sputum lasting more than 3 consecutive months of the year for 2 consecutive years without an underlying etiology of bronchiectasis or tuberculosis Chronic Bronchitis Treatment  Smoking cessation  Nicotine replacement therapy (NRT), bupropion (Wellbutrin) or varenicline (Chantix)  United Kingdom: National Health Service (NHS) supports the use of e-cigarettes  Pulmonary rehabilitation  Resistance and aerobic exercise  Chest physiotherapy  Aerosolized mucolytic aerosols  N-acetylcysteine (NAC)  Cleaves the disulfide bonds of mucus, decreasing its viscosity What else is NAC used for? Use GOLD guidelines Chronic Bronchitis Treatment  Short-acting β2-agonist bronchodilator  Albuterol  Combination long-acting β-receptor agonist (LABA) and a corticosteroid  Salmeterol-fluticasone  Formoterol-mometasone  Anticholinergics  Ipratropium  Tiotropium  Phosphodiesterase 4 inhibitors (PDE-4)  Roflumilast (Daliresp) Chronic Bronchitis Treatment  Antibiotics  Anthonisen criteria  Two of the following three criteria  Increase in shortness of breath  Increase in sputum volume  Production of purulent sputum  Duration of therapy  5 – 7 days CB  Diagnosis o Chronic cough productive of sputum lasting more than 3 consecutive months of the year for 2 consecutive years o Change in baseline symptoms  Two of the following three criteria  Increase in shortness of breath  Increase in sputum volume  Production of purulent sputum  Antibiotics o Simple CB – no risk factors  Azithromycin 500mg PO Qday (PAE; five days of therapy acceptable)  Amox/clav. 875mg BID  Doxycycline 100mg BID  Levofloxacin 500mg Qday o Complicated CB  Risk factors: Age > = 65, chronic COPD, > 4 exacerbations / year, heart disease, home oxygen use, abx use in past 3 months, corticosteroid use in past month  Amox/clav. 875mg BID  Doxycycline 100mg BID  Levofloxacin 500mg Qday o Inpatient Complicated CB  > 2 risk factors or FEV1< 35% predicted  Levofloxacin 750mg IV daily (empirically covering P. aeruginosa)  Duration of therapy o 5 to 7 days Bronchiolitis Bronchiolitis Affects approximately 50% of children during the first year of life and 100% by age 2 years 75% of cases due to respiratory syncytial virus (RSV) Bronchiolitis – American Academy of Pediatrics Recommended Not Routinely Recommended Nebulized hypertonic saline Aerosolized β2-agonists Systemically administered corticosteroids Ribavirin  Synthetic nucleoside Bronchiolitis Prevention  Abrysvo – vaccine  Adults ≥60-75 years of age and pregnant patients 32 through 36 weeks' gestation: IM: ~0.5 mL as a single dose.  Arexvy – vaccine  Adults ≥60-75 years of age: IM: 0.5 mL as a single dose.  Palivizumab (Synagis)  Monoclonal antibody  Man-made proteins that act like human antibodies  Nirsevimab (Beyfortus)  Monoclonal antibody  Preferred over Synagis per AAP  https://downloads.aap.org/AAP/PDF/Nirsevemab-Visual-Guide.pdf Influenza Influenza Etiology  Influenza A – seasonal flu  Influenza B – typically associated with sporadic outbreaks (i.e., nursing homes)  Antigenic drift – point mutations in surface antigens that leads to the variability of seasonal influenza  Antigenic shift – genetic reassortment culminating in novel surface antigens that leads to a new influenza variant (e.g., avian flu & swine flu) Pathophysiology  Influenza A antigens  Hemagglutinin (H1 – H16)  Allows the influenza virus to enter host cells by attaching to sialic acid receptors  Neuraminidase (N1 – N9)  Allows the release of new viral particles from host cells by catalyzing the cleavage of linkages to sialic acid  Transmission via person-to-person inhalation of respiratory droplets  1 – 7 days incubation period (average of 2 days)  Infectious period is 1 day before symptom onset and up to 7 days after symptom onset; children may be infectious for up to 10 days after onset Schematic diagram of the life cycle of influenza virus. After receptor-mediated endocytosis, the viral ribonucleoprotein complexes are released into the cytoplasm and transported to the nucleus, where replication and transcription take place (1). Messenger RNAs are exported to the cytoplasm for translation. (2) Early viral proteins required for replication and transcription, including nucleoprotein (NP) and a polymerase protein (PB1), are transported back to the nucleus. RNA polymerase activity of the PB1 protein synthesizes positive single-stranded RNA (ssRNA) from genomic negative single-stranded RNA (–ssRNA) molecules. (3) These +ssRNA templates are copied by the RNA polymerase activity of the PB1 protein. (4) Some of these new genome segments serve as templates for the synthesis of more viral mRNA. Later in the infection, they become progeny genomes. Viral mRNA molecules transcribed from some genome segments encode structural proteins such as hemagglutinin (HA) and neuraminidase (NA). These messages are translated by endoplasmic reticulum-associated ribosomes and delivered to the cell membrane (5). Viral genome segments are packaged as progeny virions bud from the host cell (6). ER, endoplasmic reticulum. (Reproduced with permission from Willey JM, Sherwood LM, Woolverton CJ (eds): Prescott, Harley, & Klein’s Microbiology. McGraw-Hill, 2008, p. 457. © McGraw-Hill Education.) Influenza Signs and symptoms  Fever, myalgia, headache, malaise, nonproductive cough, sore throat, and rhinitis  Primary viral pneumonia – usually occurs in pregnant women of those with underlying cardiovascular disease  Secondary bacterial pneumonia  Typically, flu and pneumonia are combined as the 8th leading cause of death in the US  9th leading cause in 2020; not in top 10 all cause mortality for 2021, 2022, 2023  Typically, this makes flu and pneumonia the deadliest infectious disease in the US per total mortality Diagnosis  Gold standard for diagnosis of influenza is reverse-transcription polymerase chain reaction (RT-PCR)  1 – 6 hours for results  Rapid influenza molecular assays (RIMAs)  90 – 95% sensitive  55 – 99% specific  15 – 30 minutes for results  Rapid influenza diagnostic tests  Enzyme immunoassay  Differentiates between influenza A & B but it cannot be used for subtyping  10 – 15 minutes for results  Immunofluorescence assay  15 minutes – 4 hours for results Influenza Prevention  Influenza vaccine  Booster dose at least 4 weeks after the initial dose in children between 6 months and less than 9 years of age if no previous vaccination  High dose if age > = 65 years old or solid organ transplant  Safe during any trimester of pregnancy  Immunocompromised patients (e.g., HIV) may benefit from high dose vaccine regardless of age Post-exposure prophylaxis  Postexposure prophylaxis should not be given if >48 hours has elapsed since exposure  Oseltamivir  FDA approved for the treatment of influenza in individuals 14 days and older, and for chemoprophylaxis in individuals 1 year and older  CDC, the American Academy of Pediatrics (AAP), and the Pediatric Infectious Diseases Society (PIDS) provide an expanded recommendation for treatment in those less than 14 days, and chemoprophylaxis in those 3 months and older  Zanamivir Influenza Criteria for prophylaxis therapy  Persons at high risk of serious illness and/or complications who are exposed to an infectious person and cannot be vaccinated.  Persons at high risk of serious illness and/or complications who are vaccinated but exposed to an infectious person during the first 2 weeks following vaccination. The development of sufficient antibody titers after vaccination takes approximately 2 weeks.  Persons with severe immune deficiency or who may have an inadequate response to vaccination (e.g., advanced human immunodeficiency virus [HIV] disease, persons receiving immunosuppressive medications), after exposure to an infectious person.  Long-term care facility residents, regardless of vaccination status, when an outbreak has occurred in the institution.  Should be administered as soon as possible after exposure, ideally no later than 48 hours after exposure  *** ***For control of outbreaks in long-term care facilities and hospitals, give for a minimum of 2 weeks, and continue up to 1 week after the last known case (guideline dosage); up to 6 weeks during a community outbreak (FDA dosage) Influenza Treatment  Antihistamines  Antipyretics  Throat lozenges  Adamantanes – no longer recommended  Amantadine and rimantadine  Cap-dependent endonuclease inhibitor  Baloxavir  NA inhibitors  Oseltamivir  Zanamivir  Peramivir Influenza Cap-dependent endonuclease inhibitor  Baloxavir (Xofluza)  Interferes with viral RNA transcription and blocks virus replication  Approved for patients 12 years and older with chronic condition(s)  Asthma, heart disease and diabetes  Drug interactions – chelation – avoid co-administration of baloxavir with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives or antacids, or oral supplements (e.g., calcium, iron, magnesium or zinc)  Not recommended for patients that are pregnant or breast feeding  Side effects – diarrhea, bronchitis, nausea, nasopharyngitis, and increased liver enzymes Influenza Neuraminidase inhibitors  Without NA, release of the virus from infected cells is impaired, and, thus, viral replication is decreased  Observational studies have reported clinical benefit of NA inhibitors in hospitalized patients, including reduction in duration of hospitalization and risk of death, including in ICU patients  Community setting: may reduce the duration of illness by approximately 1 day versus placebo  Neuropsychiatric complications consisting of delirium, seizures, hallucinations, and self-injury in pediatric patients (mostly from Japan) have been reported following treatment with oseltamivir and peramivir  Influenza Oseltamivir Zanamivir Peramivir NA Inhibitors (Tamiflu) (Relenza) (Rapivab) FDA - approved treatment age ≥ 2 weeks ≥ 7 years ≥ 2 years Renal Dose Yes No Yes GI & Bronchospasms & GI & Side effects neuropsychiatric neuropsychiatric neuropsychiatric Formulation Capsule and solution Diskhaler IV Treatment duration 5 days 5 days 1 day Pregnancy & lactation Preferred drug - - Influenza  Diagnosis o Rapid diagnostic test  Antivirals o Treatment – begin w/in 48 hours of symptom onset  Oseltamivir  75mg BID x 5 days  Weight-based dose for pediatrics  CrCl 30 – 60 mL / min: 30 mg BID x 5 days  CrCl 10 – 30 mL / min: 30 mg Qday x 5 days o Prophylaxis – begin w/in 48 hours of exposure  Oseltamivir  75mg Qday x 10 days  Weight-based dose for pediatrics  CrCl 30 – 60 mL / min: 30 mg Qday x 10 days  CrCl 10 – 30 mL / min: 30 mg QOD x 10 days  End-stage renal disease (ESRD) dosing available for dialysis treatments Antitussives Antitussives Benzonatate (Tessalon Perles) MOA – Suppresses cough by topical anesthetic action on the respiratory stretch receptors 100 mg to 200 mg tid for patients 10 years and older No hepatic, renal or geriatric dose adjustments Adverse effect: Oral mucosa anesthesia may occur if capsules are chewed or dissolved in the mouth Opioids* – suppresses Hydrocodone 10 mg / Hydrocodone 5 mg / Codeine 10 mg / cough in medullary Chlorpheniramine 8 mg Homatropine 1.5 mg / 5 Guaifenesin 100mg / 5 center / 5 mL ER (Tussionex) mL (Hydromet) mL (Cheratussin AC) Schedule CII (Rx) CII (Rx) CV (OTC) 5 mL every 12 hours 5 mL every 4 to 6 hours as 15 mL every 4 to 6 hours Dose (maximum: 10 mL per needed (maximum: 30 mL (maximum: 90 mL per 24 day) per 24 hours) hours) Side effects Nausea, itching, constipation and respiratory depression Drug interactions Additive and synergistic CNS depression will occur with concomitant CNS depressants The FDA in January 2018 recommended against routine use of Pediatrics codeine/hydrocodone-containing cough/cold products for patients 2 criteria o Confusion o Uremia (BUN > 20 mg/dL [7.1 mmol/L]) o Respiratory rate ≥30 breaths/min o Blood pressure (systolic 20 mg/dL [7.1 mmol/L])  Respiratory rate ≥30 breaths/min  Hypotension requiring fluid resuscitation  Pao2/Flo2 < = 250  Multilobar infiltrates  WBC < 4,000 cells / µl  Thrombocytopenia ( 48 hours of hospitalization  HAP (No hospitalization or IV abx in past 90 days / not intubated / no septic shock) o Piperacillin / tazobactam 4.5 g IV q 6 H o Cefepime 2 grams IV q 8 h o Better Acinetobacter spp. coverage compared to pip/tazo. o Levofloxacin 750 mg IV daily  HAP (Hospitalization or IV abx in past 90 days, prior MRSA infection, > 20% MRSA isolates) o Cefepime 2 grams IV q 8 h + vancomycin 15–20 mg/kg IV Q 12 H or linezolid 600 mg IV or PO Q 12 H o Levofloxacin 750 mg IV daily + vancomycin 15–20 mg/kg IV Q 12 H or linezolid 600 mg IV or PO Q 12 H  HAP (Hospitalization or IV abx in past 90 days, high risk mortality [intubated or septic shock] or structural lung disease [bronchiectasis or cystic fibrosis]) o Cefepime 2 grams IV q 8 h + amikacin 15-20 mg/kg IV q 24 h + vancomycin 15–20 mg/kg IV Q 12 H or linezolid 600 mg IV or PO Q 12 H  Duration of therapy 7 to 14 days VAP  Diagnosis o S/Sx after > 48 hours of intubation  Antibiotics o No MDR / MRSA / P. aeruginosa risk factors o Piperacillin / tazobactam 4.5 g IV q 6 H o Cefepime 2 grams IV q 8 h o Levofloxacin 750 mg IV daily MDR risk factors: IV antibiotic use within the previous 90 days, septic shock at the time of VAP, ARDS preceding VAP, ≥5 days hospitalization prior to the occurrence of VAP, acute renal replacement therapy prior to VAP onset Cefepime 2 grams IV q 8 h + amikacin 15-20 mg/kg IV q 24 h + vancomycin 15–20 mg/kg IV Q 12 H or linezolid 600 mg IV or PO Q 12 H MRSA risk factors: >10 – 20% MRSA isolates or IV abx in past 90-days Cefepime 2 grams IV q 8 h + amikacin 15-20 mg/kg IV q 24 h + vancomycin 15–20 mg/kg IV Q 12 H or linezolid 600 mg IV or PO Q 12 H P. aeruginosa risk factors: >10% of gram-negative isolates are resistant to an agent being considered for monotherapy, structural lung disease (i.e., bronchiectasis or cystic fibrosis) or IV abx in past 90-days Cefepime 2 grams IV q 8 h + amikacin 15-20 mg/kg IV q 24 h + vancomycin 15–20 mg/kg IV Q 12 H or linezolid 600 mg IV or PO Q 12 H  Duration of therapy 7 to 14 days Therapeutic Drug Monitoring Aminoglycosides Traditional or extended interval dosing High peak serum concentrations are necessary to obtain microbiologically active concentrations in the alveoli Concentration-dependent (Cmax:Min) Vancomycin May use loading dose of 25 – 30 mg / kg for severe illness Target trough is 15 – 20 mg / mL COVID-19 What about COVID-19? IDSA has several guidelines  Prone positioning?  Dexamethasone? Lots of changes still going on  FDA Statement January 24, 2022  Coronavirus (COVID-19) Update: FDA Limits Use of Certain Monoclonal Antibodies to Treat COVID-19 Due to the Omicron Variant  Mortality benefit vs. morbidity benefit with vaccination  Paxlovid and Lagevrio  Dose packs  Need to start within 5 days post symptom onset EUA for therapies Endemic? Yes “Right-to-Try” or “Snake Oil?”  Hydroxychloroquine, azithromycin and ivermectin  In vivo or in vitro studies?  Are the studies observational and only show an association and not a causation? January 24, 2023 – FDA plans to convert COVID shots to annual recommendation Will continue monitoring … COVID-19 Nirmatrelvir/ritonavir (Paxlovid)  Preferred over Lagevrio due to efficacy  MOA: Peptidomimetic and protease inhibitor  Dose: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all 3 tablets taken together twice daily for 5 days  Dose reduction for moderate renal impairment (eGFR ≥30 to