drugs for resp DSA Flashcards
Antivirals
a) Oseltamivir
Antifungals
fluconazole
voriconazole
amphotericin B
Acute Bronchitis
a) Epidemiology: occurs during winter months; cold, damp climates and high concentrations of irritating substances (e.g., pollution, cigarette smoke) may precipitate attacks.
b) Etiology: respiratory viruses; common cold viruses (rhinovirus and coronavirus) and lower respiratory tract pathogens (influenza and adenovirus) account for majority of cases.
c) General approach to treatment: symptomatic and supportive (reassurance and antipyretics).
i) Routine use of antibiotics is not recommended.
ii) May consider antibiotics (azithromycin or levofloxacin) in those with suspected concurrent bacterial infection – those with persistent fever or respiratory symptoms for more than 4-6 days or for predisposed patients (e.g., elderly, immunocompromised).
iii) During influenza outbreaks, consider early/prompt antiviral therapy (zanamivir, oseltamivir).
Chronic Bronchitis (CB)
a) Epidemiology: component of chronic obstructive pulmonary disease (COPD), generally affects adults.
b) Etiology: cigarette smoke predominant factor in etiology of chronic bronchitis; occupational dust, chemicals, or air pollution may also contribute.
c) General approach to treatment: attempt to reduce patient exposure to irritants (e.g., cigarette smoke, workplace pollution), assist with pulmonary hygiene (i.e., clear secretions/mucus), continue/modify COPD regimen (e.g., B2-agonists, inhaled corticosteroids, inhaled anticholinergics, PDE4 inhibitors), and provide antibiotics if appropriate (variable activity against: H. influenzae, S. pneumoniae, M. catarrhalis, and M. pneumonia).
i) During an acute exacerbation of chronic bronchitis (AECB), the patient will likely benefit from antibiotic therapy if two of the following three criteria are met – increased shortness of breath, increased sputum volume, production of purulent sputum.
Bronchiolitis
a) Epidemiology: affects ~50% of children in first year of life and 100% by age 2 years; peaks in winter months and persists through early spring.
b) Etiology: respiratory syncytial virus (RSV) accounts for up to 75% of cases; others include: parainfluenza, adenovirus, and influenza; bacteria are secondary pathogens in minority of cases.
c) General approach to treatment: almost all otherwise healthy babies may be treated as outpatients with reassurance, antipyretics, and adequate fluid intake.
i) Respiratory failure and marked dehydration requires hospitalization; underlying cardiac and pulmonary diseases potentiates these conditions; may consider aerosolized ribavirin.
ii) In infants with pulmonary or cardiovascular disease, prophylaxis with palivizumab (monoclonal antibody for RSV) may be indicated.
Pneumonia
a) Epidemiology: occurs in all ages; clinical manifestations most severe in very young, the elderly, and the chronically ill. Most common cause of sepsis and infectious cause of death in children and adults in the U.S. Mortality rate: 30-40%.
b) Microorganism access to the respiratory tract:
i) Aspiration of oropharyngeal contents
ii) Inhalation of aerosolized particles
iii) Entrance to the lung via bloodstream from extrapulmonary site
c) Goals of therapy: eradicate infecting organism, resolve clinical disease.
d) Antibiotic selection: depends on causative organism and susceptibility.
i) Empirical regimens based on most likely infecting pathogen(s) and local susceptibility patterns.
ii) Specific factors help determine which potential pathogens are likely involved: present clinical status (severity of illness), underlying disease(s), patient age, previous and current medication history, and major organ function.
iii) Once organism identified and susceptibility determined, therapy should be narrowed to cover specific pathogens.
Community-Acquired Pneumonia (CAP)
1) Site-of-Care Decisions
a) Initial assessment of severity provides the framework for all major decisions regarding management of CAP (includes diagnostic and treatment issues).
i) Hospital vs. outpatient; intensive care unit vs. general ward.
b) Severity of illness scores (CURB-65 and the Pneumonia Severity Index (PSI)), along with clinical judgement, may assist the physician in determining whether the patient should be admitted to the hospital or receive treatment as an outpatient.
2) Etiology: wide variety of pathogens.
b) May consider other etiologic pathogens based on disease state.
i) Underlying bronchopulmonary disease:
(1) H. influenzae
(2) Moraxella catarrhalis
(3) + S. aureus during an influenza outbreak
ii) Chronic oral steroids or severe bronchopulmonary disease, alcoholism, frequent antibiotic use:
(1) Enterobacteriaceae
(2) Pseudomonas aeruginosa
iii) Classic aspiration pleuropulmonary syndrome in alcohol/drug overdose or in seizures with gingival disease or esophageal motility disorders:
(1) Anaerobes
c) Potential viral causes: influenza (predominant viral cause), RSV, adenovirus, parainfluenza virus.
i) Less common viruses: human metapneumovirus, herpes simplex virus (HSV), varicella-zoster (VSV), SARS-associated coronavirus, measles virus.
d) Other potential etiologic agents occurring at a frequency of ≤ 3% (exception, endemic fungi in appropriate geographic distribution):
i) M. tuberculosis, Chlamydophila psittaci (psittacosis), Coxiella burnetii (Q fever), Francisella tularensis (tularemia), Bordetella pertussis (whooping cough), and endemic fungi (Histoplasma capsulatum, Coccidioides immitis, Cryptococcus neoformans, and Blastomyces hominis).
e) **Drug Resistant Streptococcus pneumoniae (DRSP)
i) Risk factors:
(1) **Medication history – B-lactam use within previous 3 months
(2) Age < 2 years or > 65 years
(3) Alcoholism
(4) Immunosuppressive illness or therapy
(5) Exposure to child at day care
Community-Acquired Pneumonia Empiric Antimicrobial Coverage
i) Outpatient Recommendations
(1) Previously healthy
(a) Macrolide PO (azithromycin, clarithromycin)
- OR-
(b) Doxycycline PO
(2) At risk for DRSP (comorbidities, age > 65 years, use of antimicrobials within 3 months)
(a) Respiratory fluoroquinolone PO (levofloxacin, moxifloxacin)
- OR-
(b) B-lactam PO [high dose amoxicillin or amoxicillin-clavulanate preferred (alternates: ceftriaxone, cefuroxime)] PLUS a macrolide PO
ii) Inpatient, Non-Intensive Care Unit
(1) Respiratory FQ IV or PO (levofloxacin, moxifloxacin)
- OR-
(2) B-lactam IV (ceftriaxone, cefotaxime, or ampicillin preferred) PLUS macrolide IV (azithromycin)
iii) Inpatient, Intensive Care Unit
(1) B-lactam IV (ceftriaxone, cefotaxime, or ampicillin/sulbactam preferred) PLUS azithromycin IV
- OR-
(2) B-lactam IV (ceftriaxone, cefotaxime, or ampicillin/sulbactam preferred) PLUS a respiratory FQ (levofloxacin, moxifloxacin)
Modifying Empiric Regimen
CAP: Pseudomonas aeruginosa
(1) Risk factors:
(a) Structural lung disease (bronchiectasis)
(b) Repeated COPD exacerbations (frequent corticosteroid and/or antibiotic use)
(c) Prior antibiotic therapy
(2) Treatment:
(a) Antipseudomonal B-lactam IV (piperacillin-tazobactam, cefepime, imipenem, meropenem) PLUS either ciprofloxacin or levofloxacin
-OR-
(b) Antipseudomonal B-lactam PLUS aminoglycoside (gentamicin) AND azithromycin
-OR-
(c) Antipseudomonal B-lactam PLUS aminoglycoside AND antipneumococcal fluoroquinolone
ii)
Modifying Empiric Regimen: CAP MRSA
Community-acquired methicillin-resistant Staphylococcus aureus (MRSA)
(1) Risk factors:
(a) End-stage renal disease (dialysis)
(b) Injection drug abuse
(c) Prior influenza
(d) Prior antibiotic use (especially FQ)
(2) Treatment:
(a) Add vancomycin IV or linezolid
(b) Panton-Valentine leucocidin necrotizing pneumonia: add clindamycin or use linezolid
CAP Duration of Therapy
a) Minimum of 5 days (most patients receive 7-10 days).
b) Must be afebrile for 48-72 hours.
c) Exception: Pseudomonas – an 8-day course led to more relapse compared to 15-day course.
Empiric Therapy for VAP (ventilator assisted pneumonia)
a) Risk factors for MDR pathogens:
i) IV antibiotic use within the previous 90 days
ii) Septic shock at the time of VAP
iii) ARDS preceding VAP
iv) ≥ 5 days of hospitalization prior to the occurrence of VAP
v) Acute renal replacement therapy prior to VAP onset
vi) Treatment in an ICU in which > 10% of gram-negative isolates are resistant to an agent being considered for monotherapy
vii) Treatment in an ICU in which local antimicrobial susceptibility rates are not known
viii) Treatment in a unit in which > 10-20% of S. aureus isolates are methicillin-resistant
ix) Treatment in a unit in which the prevalence of MRSA is not known
b) For patients WITHOUT risk factors, one of the following agents may be used:
i) Piperacillin-tazobactam -OR- cefepime -OR- imipenem -OR- meropenem -OR- levofloxacin
c) For patients WITH risk factors, patient should receive two agents with activity against P. aeruginosa and one agent with activity against MRSA:
i) Choose one: antipseudomonal B-lactam (piperacillin-tazobactam, cefepime, ceftazidime, imipenem, meropenem, aztreonam)
ii) Choose one: antipseudomonal fluoroquinolone (ciprofloxacin, levofloxacin) -OR- an aminoglycoside (gentamicin, tobramycin) -OR- polymyxin (colistin)
iii) Choose one: MRSA coverage (linezolid -OR- vancomycin)
d) For patients WITHOUT risk factors i-vii above but WITH risk factors for MRSA (risk factors viii or ix), patient should receive one agent with gram-negative coverage and one with MRSA coverage:
i) Choose one: antipseudomonal B-lactam (piperacillin-tazobactam, cefepime, ceftazidime, imipenem, meropenem, aztreonam)
ii) Choose one: MRSA coverage (linezolid -OR- vancomycin)
Empiric Therapy for HAP
a) Risk factors:
i) Increased mortality – ventilatory support for HAP, septic shock
ii) MDR Pseudomonas, other gram-negative bacilli, and MRSA – IV antibiotics within the past 90 days
iii) MDR Pseudomonas and other gram-negative bacilli – structural lung disease, respiratory specimen with numerous and prominent gram-negative bacilli
iv) MRSA – treatment in a unit in which > 20% of S. aureus isolates are methicillin-resistant, treatment in a unit in which the prevalence of MRSA is not known
b) For patients WITHOUT MDR risk factors or increased risk of mortality, choose one:
i) Piperacillin-tazobactam -OR- cefepime -OR- imipenem -OR- meropenem -OR- levofloxacin
c) For patients WITH MDR risk factors and/or increased risk of mortality, patient should receive two agents with activity against P. aeruginosa and one agent with activity against MRSA:
i) Choose one: antipseudomonal B-lactam (piperacillin-tazobactam, cefepime, ceftazidime, imipenem, meropenem, aztreonam)
ii) Choose one: antipseudomonal fluoroquinolone (ciprofloxacin, levofloxacin) -OR- an aminoglycoside (gentamicin, tobramycin) -OR- polymyxin (colistin)
iii) Choose one: MRSA coverage (linezolid -OR- vancomycin)
iv) If risk factors for MRSA are not present, eliminate MRSA coverage from the above regimen. If there are risk factors for MRSA but not MDR Pseudomonas, only one agent with activity against P. aeruginosa is required (piperacillin-tazobactam -OR- cefepime -OR- imipenem -OR- meropenem -OR- levofloxacin) plus one agent with MRSA coverage.
duration of therapy for VAP or HAP
a) For patients with VAP or HAP, a 7-day course of antibiotics is recommended.
b) However, there are situations with necessitate shorter or longer course depending on rate of improvement of clinical, radiologic, and laboratory parameters.
Neurominidase Inhibitors MOA etc.
a) MOA: analogs of sialic acid, interferes with release of progeny influenza virus from infected cells.
e) Therapeutic Use: influenza prophylaxis (household and institutional), influenza treatment.
f) ADRs:
i) Oseltamivir (approved for children ≥ 1 year) – nausea, vomiting, abdominal pain (5-10%), headache, fever, diarrhea, neuropsychiatric effects.
ii) Zanamivir (approved for children ≥ 7 years) – cough, bronchospasm, decrease in pulmonary function (reversible), nasal/throat discomfort, not recommended in underlying airway disease.
iii) Peramivir (approved for adults) – diarrhea, increased serum glucose, neutropenia, insomnia.
