Infectious Diseases I PDF

Infectious Diseases I I. RESPIRATORY TRACT INFECTIONS A. Pneumonia 1. Pneumonia is the most common cause of death attributable to infectious diseases (very high mortality rate in older adults) and in the top 10 causes of death in the United States. 2. Hospital-acquired pneumonia (HAP) is...

Infectious Diseases I I. RESPIRATORY TRACT INFECTIONS A. Pneumonia 1. Pneumonia is the most common cause of death attributable to infectious diseases (very high mortality rate in older adults) and in the top 10 causes of death in the United States. 2. Hospital-acquired pneumonia (HAP) is the second most common nosocomial infection (0.6%–1.1% of all hospitalized patients). There is a higher incidence in patients in the intensive care unit recovering from thoracic or upper abdominal surgery and in older adults. 3. Mortality rates a. Community-acquired pneumonia (CAP) without hospitalization: Less than 1% b. CAP with hospitalization: About 14% c. Ventilator-associated pneumonia (VAP): About 20%–50% B. Community-Acquired Pneumonia 1. Definition: Acute infection of the pulmonary parenchyma, accompanied by an acute infiltrate consistent with pneumonia on chest radiograph or auscultatory findings, acquired in the community. 2. Symptoms of CAP are listed below. Older adults often have fewer and less severe findings (mental status changes are common). a. Fever or hypothermia b. Rigors c. Sweats d. New cough with or without sputum (90%) e. Chest discomfort (50%) f. Onset of dyspnea (66%) g. Fatigue h. Myalgias i. Abdominal pain j. Anorexia k. Headache 3. Hospitalization should be based on a clinical prediction rule for prognosis (e.g., Pneumonia Severity Index [PSI] – Table 1 and Table 2). ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-194 Infectious Diseases I Table 1. Pneumonia Severity Index Scoring Risk Factor Men Women Nursing home resident Neoplasm Liver disease Heart failure Stroke Renal failure Altered mental status Respiratory rate ≥ 30 breaths/min Systolic blood pressure < 90 mm Hg Temperature < 95°F (35°C) or ≥ 104°F (40°C) Heart rate ≥ 125 beats/min Arterial pH < 7.35 BUN > 30 mg/dL Na < 130 mmol/L Glucose ≥ 250 mg/dL Hct < 30% Pao2 < 60 mm Hg Pleural effusion Points Age (yr) Age minus 10 (yr) +10 +30 +20 +10 +10 +10 +20 +20 +20 +15 +10 +30 +20 +20 +10 +10 +10 +10 Table 2. Pneumonia Severity Index Location of Therapy Risk Low Low Low Medium High Class I II III IV V Score < 51 51–70 71–90 91–130 > 130 Mortality (%) 0.1 0.6 0.9 9.5 26.7 Recommendation Outpatient Outpatient Outpatient Inpatient Inpatient ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-195 Infectious Diseases I 4. ICU or general medicine floor should be based on a clinical prediction rule for prognosis (e.g., 2007 Infectious Diseases Society of America/American Thoracic Society [IDSA/ATS] criteria for defining severe community-acquired pneumonia – Table 3). Table 3. 2007 IDSA/ATS Criteria for Defining Severe Community-Acquired Pneumoniaa Major Criteria Septic shock with need for vasopressors Respiratory failure requiring mechanical ventilation Minor Criteria Respiratory rate > 30 breaths/min Pao2/Fio2 ratio < 250 Multilobar infiltrates Confusion/disorientation Uremia (BUN ≥ 20 mg/dL) Leukopenia (WBC < 4.0 × 103 cells/mm3) Thrombocytopenia (Plt < 100,000/mm3) Hypothermia (temperature < 36°C) Hypotension requiring aggressive fluid resuscitation Higher level of care if either one major criterion or three or more minor criteria. Fio2 = fraction of inspired oxygen. a C. HAP and VAP 1. HAP: Pneumonia in a nonventilated patient that occurs 48 hours or more after admission and was not incubating at the time of admission 2. VAP: Pneumonia that arises more than 48 hours after endotracheal intubation 3. Risk factors for hospital-acquired pneumonia a. Intubation and mechanical ventilation b. Supine patient position c. Enteral feeding d. Oropharyngeal colonization e. Stress ulcer prophylaxis f. Blood transfusion g. Hyperglycemia h. Immunosuppression or corticosteroids i. Surgical procedures: thoracoabdominal, upper abdominal, thoracic j. Immobilization k. Nasogastric tubes l. Previous antibiotic therapy m. Admission to the intensive care unit n. Advanced age o. Underlying chronic lung disease ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-196 Infectious Diseases I D. Microbiology (Table 4) Table 4. Incidence of Pneumonia by Organism Community Acquired (%) Unidentifiable 40–60 Mycoplasma pneumoniae 13–37 Streptococcus pneumoniae 9–20 Haemophilus influenzae 3–10 Chlamydia pneumoniae 1–17 Legionella pneumophila 0.7–13 Viruses Common Others: Uncommon Staphylococcus aureus Moraxella catarrhalis Anaerobes Gram-negative bacilli (e.g., Klebsiella pneumoniae) Hospital Acquired (%) Unidentifiable S. aureus Pseudomonas aeruginosa Enterobacter spp. K. pneumoniae Candida spp. Acinetobacter spp. Serratia marcescens Escherichia coli S. pneumoniae 50 10 8 5 4 3 2 2 2 1 Specific populations in community-acquired pneumonia: Issues in hospital-acquired pneumonia: Alcoholism: S. pneumoniae, oral anaerobes, gram-negative bacilli (e.g., Klebsiella) P. aeruginosa is transmitted by health care workers’ hands or respiratory equipment Nursing home: S. pneumoniae, H. influenzae, gram-negative bacilli, S. aureus S. aureus is transmitted by health care workers’ hands COPD: S. pneumoniae, H. influenzae, M. catarrhalis Postinfluenza: H. influenzae, S. aureus, S. pneumoniae Exposure to water: Legionella Poor oral hygiene: oral anaerobes HIV infection: Pneumocystis jirovecii, S. pneumoniae, M. pneumoniae, Mycobacterium Enterobacteriaceae endogenously colonize hospitalized patients’ airways (healthy people seldom have gram-negative upper airway colonization) Stress changes respiratory epithelial cells so that gram-negative organisms can adhere Up to 70% of patients in the intensive care unit have gram-negative upper airway colonization, and 25% of them become infected through aspiration COPD = chronic obstructive pulmonary disease; HIV = human immunodeficiency virus. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-197 Infectious Diseases I Patient Case 1. R.L. is a 68-year-old man who presents to the emergency department with coughing and shortness of breath. His symptoms, which began 4 days ago, have worsened during the past 24 hours. He is coughing up yellow-green sputum, and he has chills, with a temperature of 102.4°F (39°C). His medical history includes coronary artery disease with a myocardial infarction 5 years ago, congestive heart failure, hypertension, and osteoarthritis. He rarely drinks alcohol and has not smoked since his myocardial infarction. He lives at home with his wife. His medications on admission include lisinopril 10 mg/day, hydrochlorothiazide 25 mg/day, and acetaminophen 650 mg four times/day. On physical examination, he is alert and oriented, with the following vital signs: temperature 101.8°F (38°C), heart rate 100 beats/minute, respiratory rate 32 breaths/minute, and blood pressure 142/94 mm Hg. His laboratory results are normal except for blood urea nitrogen (BUN) 32 mg/dL (serum creatinine [SCr] 1.23 mg/dL). A chest radiograph reveals infiltrates in the right lower lobe. A sputum specimen is not available. If R.L. were hospitalized, which would be the best empiric therapy for him? A. Ampicillin/sulbactam 1.5 g intravenously every 6 hours. B. Piperacillin/tazobactam 4.5 g intravenously every 6 hours plus gentamicin 180 mg intravenously every 12 hours. C. Ceftriaxone 1 g intravenously every 24 hours plus azithromycin 500 mg intravenously every 24 hours. D. Doxycycline 100 mg intravenously every 12 hours. E. Therapy: Pneumonia 1. CAP a. Empiric treatment of nonhospitalized patients i. No comorbidities or risk factors for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (a) Amoxicillin (dosing 1 g three times daily) (b) Doxycycline (c) Macrolide (clarithromycin or azithromycin) if local pneumococcal resistance to macrolides is less than 25%. ii.  Comorbidities (chronic obstructive pulmonary disease [COPD], diabetes mellitus, alcoholism, chronic renal or liver failure, congestive heart failure, malignancy, asplenia, or immunosuppression) (a) Respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin dosing 750 mg once daily) (b) Macrolide or doxycycline with amoxicillin/clavulanate or cefpodoxime or cefuroxime b. Empiric treatment of hospitalized patients with non-severe pneumonia (may need to add other antibiotics if the patient has risk factors for Pseudomonas aeruginosa or MRSA) i. Respiratory fluoroquinolone (moxifloxacin or levofloxacin) ii. β-Lactam (ampicillin/sulbactam, ceftriaxone, or ceftaroline) plus a macrolide (or doxycycline) c. Empiric treatment of hospitalized patients with severe pneumonia necessitating intensive care unit treatment (may need to add other antibiotics if the patient has risk factors for P. aeruginosa or methicillin-resistant S. aureus [MRSA]) i. Ampicillin/sulbactam plus either a respiratory fluoroquinolone or a macrolide ii. Ceftriaxone plus either a respiratory fluoroquinolone or a macrolide iii. Ceftaroline plus either a respiratory fluoroquinolone or a macrolide d. Treatment duration: At least 5 days; duration should be guided by a validated measure of clinical stability (resolution of vital sign abnormalities, ability to eat, and normal mentation) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-198 Infectious Diseases I 2. CAP and Risk Factors for MRSA or P. aeruginosa a. Treat with CAP guideline regimens. b. Additional antibiotics with MRSA activity i. Include if prior respiratory isolation of MRSA ii. Include if patient has severe pneumonia and locally validated risk factors for MRSA (especially hospitalization and parenteral antibiotics given in past 90 days) iii. Vancomycin or linezolid. c. Additional antibiotics with Pseudomonas activity i. Include if prior respiratory isolation of P. aeruginosa ii. Include if patient has severe pneumonia and locally validated risk factors for P. aeruginosa (especially hospitalization and parenteral antibiotics given in past 90 days). iii. Piperacillin/tazobactam, cefepime, ceftazidime, imipenem, meropenem, or aztreonam d. In lieu of locally validated risk factors, can use the Drug Resistance in Pneumonia (DRIP) score e. Therapy with additional antibiotics should be de-escalated on the basis of culture results, nasal PCR for MRSA, and clinical improvement. Patient Case 2. B.P. is a 66-year-old woman who underwent a two-vessel coronary artery bypass graft 8 days ago and has been on a ventilator in the surgical intensive care unit since then. Her temperature is now rising and her chest radiograph reveals a new infiltrate in the right lower lobe. Her medical history includes coronary artery disease with a myocardial infarction 2 years ago, COPD, and hypertension. All antipseudomonal antibiotics in the institution are active against at least 90% of strains. B.P. has no known drug allergies. Which is the best empiric therapy for B.P.? A. C  eftriaxone 1 g intravenously every 24 hours plus gentamicin 7 mg/kg intravenously every 24 hours plus linezolid 600 mg intravenously every 12 hours. B. Piperacillin/tazobactam 4.5 g intravenously every 6 hours. C. Levofloxacin 750 mg intravenously every 24 hours plus linezolid 600 mg intravenously every 12 hours. D. C  efepime 2 g intravenously every 8 hours plus tobramycin 7 mg/kg intravenously every 24 hours plus vancomycin 15 mg/kg intravenously every 12 hours. 3. VAP a. Empiric regimen should include antibiotics with activity against S. aureus (MSSA), P. aeruginosa, and other gram-negative organisms. b. Options for single agents: Piperacillin/tazobactam, cefepime, levofloxacin, imipenem, or meropenem. c. Two antibiotics with activity against P. aeruginosa should be included if the patient has risk factors for MDR organisms (see below) or if P. aeruginosa resistance in the hospital unit to the antibiotic considered for monotherapy is greater than 10%. In addition, use two agents for patients with structural lung disease (bronchiectasis or cystic fibrosis). i. Options for first agent: Antipseudomonal β-lactam (ceftazidime, cefepime, imipenem, meropenem, piperacillin/tazobactam, or aztreonam). Ceftazidime and aztreonam only if an antibiotic with MRSA activity is also being used. ii. Options for second agent: Aminoglycoside, fluoroquinolone (ciprofloxacin, levofloxacin) or colistin (aztreonam may be used with another β-lactam if no other second option is available) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-199 AL GRAWANY Infectious Diseases I d. Risk factors for MDR organisms i. Intravenous antibiotic therapy within the past 90 days ii. Hospitalization of 5 days or more (VAP only) iii. Septic shock at time of VAP (VAP only) iv. Acute respiratory distress syndrome preceding VAP (VAP only) v. Acute renal replacement therapy before VAP (VAP only) e. An antibiotic with activity against MRSA should be included if the patient has risk factors for MDR organisms (see below) or if MRSA incidence in the hospital unit is greater than 10%–20%. Note: In locations where the prevalence of MRSA respiratory infections is low (< 10%), a negative MRSA nasal screen suggests that MRSA antibiotics are unnecessary empirically. Locations with a high prevalence of MRSA respiratory infections should follow the rule above. i. Options if MRSA activity necessary: Vancomycin or linezolid ii. If a MRSA agent is used, then ceftazidime and aztreonam are potential alternative choices for the antipseudomonal agent. f. Ideally, dose antibiotics based on pharmacokinetic/pharmacodynamic data, including antibiotic serum concentrations, extended infusions of β-lactams and weight-based dosing of aminoglycosides g. Antibiotics should be de-escalated on the basis of culture results. Antibiotic therapy for P. aeruginosa can be de-escalated to one active agent on the basis of culture and sensitivity results. Antibiotic therapy for MRSA can be de-escalated/discontinued on the basis of nasal PCR for MRSA results. h. Treatment duration: 7-day course is recommended for most infections. 4. HAP a. Empiric regimen should include antibiotics with activity against S. aureus (MSSA), P. aeruginosa, and other gram-negative organisms. b. Options for single agents: Piperacillin/tazobactam, cefepime, levofloxacin, imipenem, or meropenem. c. Two antibiotics with activity against P. aeruginosa should be included if the patient has received antibiotics in the past 90 days or has a high risk of mortality (indicated by the need for ventilator support or septic shock due to HAP). In addition, use two agents for patients with structural lung disease (bronchiectasis or cystic fibrosis). i. Options for first agent: Antipseudomonal β-lactam (ceftazidime, cefepime, imipenem, meropenem, piperacillin/tazobactam, or aztreonam) ii. Options for second agent: Aminoglycoside, fluoroquinolone (ciprofloxacin, levofloxacin), or colistin (aztreonam may be used with another β-lactam if no other second option is available) iii. Aminoglycosides should not be used as monotherapy. d. An antibiotic with activity against MRSA should be included if the patient has risk factors for MDR organisms, if MRSA incidence in the hospital unit is greater than 10%–20%, or if the patient is at a high mortality risk. See statement in VAP section regarding MRSA nasal screening. i. Options if MRSA activity necessary: Vancomycin or linezolid ii. If a MRSA agent is used, then ceftazidime and aztreonam are potential alternative choices for the antipseudomonal agent. iii. Use oxacillin, nafcillin, or cefazolin for proven MSSA infections. e. Ideally, dose antibiotics according to pharmacokinetic/pharmacodynamic data, including antibiotic serum concentrations, extended infusions of β-lactams, and weight-based dosing of aminoglycosides. f. Antibiotics should be de-escalated according to culture results. Antibiotic therapy for P. aeruginosa can be de-escalated to one active agent on the basis of culture and sensitivity results. Antibiotic therapy for MRSA can be de-escalated/discontinued on the basis of nasal PCR for MRSA results. g. Treatment duration: A 7-day course is recommended for most infections. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-200 Infectious Diseases I F. Antibiotic Resistance 1. Innate resistance – Based on characteristics of the microorganism (e.g., P. aeruginosa has innate resistance to vancomycin) 2.  Acquired resistance a. Mutations – Chromosomal alterations passed to daughter cells only b.  Horizontal gene transfer i. Plasmids – Extrachromosomal DNA that codes for resistance; mobile; can code for resistance to multiple antibiotics ii. Transposons – Resistance genes transferred within or between chromosomal DNA or plasmids iii. Integrons – DNA component that contains a site where a gene cassette that codes for resistance can be integrated into the bacterial DNA 3. Mechanisms of resistance a.  Decreased uptake i. β-Lactams ii.  Fluoroquinolones iii.  Aminoglycosides (especially Pseudomonas) b. Enzyme modification and degradation i. β-Lactamases (see Table 5) ii.  Aminoglycoside hydrolytic enzymes (e.g., acetyltransferase, phosphotransferase, adenyl transferase) – Enteric gram-negative bacteria c. Altered target site i. β-Lactams (e.g., altered penicillin-binding proteins (PBPs), mecA) – Staphylococcus, Streptococcus, and Enterococcus ii.  Glycopeptides (e.g., vanA and vanB) – Vancomycin resistance in Enterococcus iii.  Fluoroquinolones (e.g., gyrA and parC mutations) iv. Ribosomal mutations (e.g., macrolides, tetracyclines) v. Sulfonamides (e.g., altered genes encoding dihydropteroate synthase) vi. Trimethoprim (e.g., altered genes encoding dihydrofolate reductase or overproduction of dihydrofolate reductase) d. Efflux pumps i. Macrolides (e.g., mef-encoded efflux in Streptococcus) ii. Carbapenems iii. Fluoroquinolones iv. Tetracyclines ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-201 Infectious Diseases I Table 5. β-Lactamases Molecular Category Class Name A Serine β-lactamases B C D Metallo β-lactamases Serine β-lactamases Serine β-lactamases Target Penicillins, cephalosporins, aztreonam, carbapenems Carbapenems Cephalosporins Extended-spectrum cephalosporins, carbapenems Examples CARB; TEM family; SHV family; CTX-M family; most ESBLs; CRE (KPC) IMP family, VIM family; CRE (NDM-1) Amp C CRE (OXA family) Effective Inhibitors Avibactam, relebactam, vaborbactam ±clavulanic acid, ±sulbactam, ±tazobactam None Avibactam, relebactam, vaborbactam Avibactam CARB = carbenicillin-hydrolysing β-lactamases; CRE = carbapenem-resistant Enterobacteriaceae; CTX-M = cefotaximase, Munich; ESBL = extended-spectrum β-lactamase; IMP = imipenemase; KPC = Klebsiella pneumoniae carbapenemase; NDM = New Delhi metallo-β-lactamase; OXA = oxacillinase; VIM = Verona integron-encoded metallo-β-lactamase. G. Influenza 1. Characteristics of influenza infection a. Epidemic with significant mortality b. Epidemics begin abruptly → peak in 2–3 weeks → resolve in 5–6 weeks. c. Occurs almost exclusively in the winter d. Average overall attack rates of 10%–20% e. Mortality greatest in those older than 65 years, with 80% of influenza-related deaths attributed to this age group. Patients with heart and lung disease are at the highest risk. 2. Is it influenza, COVID-19, or the common cold? (Table 6) Table 6. Differentiating the Symptoms of Influenza, COVID-19, and the Common Cold Signs and Symptoms Onset Temperature Influenza Sudden Characteristic, high (> 101°F [38°C]) of 3–4 days’ duration Dry; can become severe Common, but not consistently present Dry with mucus; can become severe Hacking Headache Myalgia (muscle aches and pains) Tiredness and weakness Extreme exhaustion Chest discomfort Stuffy nose Prominent Usual; often severe Occasional Usual; can be severe Occasional Slight Can last 2–3 weeks Early and prominent Common Sometimes Can last 2–3 weeks Common Common Common (especially with recent variants) Very mild Never Mild to moderate Common Sneezing Sometimes Common (especially with recent variants) Usual Sore throat Sometimes Common (especially with recent variants) Common Loss of taste/smell Never Common Never Cough COVID-19 Common Cold Gradual Occasional ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-202 Infectious Diseases I 3. Pathophysiology a. Type A i. Influenza further grouped by variations in hemagglutinin and neuraminidase (e.g., H1N1, H3N2) ii. Changes through antigenic drift or shift (a) Drift: Annual, gradual change caused by mutations, substitutions, and deletions (b) Shift: Less common dramatic change leading to pandemics iii. Causes epidemics every 1–3 years b. Type B i. Type B influenza carries one form of hemagglutinin and one form of neuraminidase, both of which are less likely to mutate than the hemagglutinin and neuraminidase of type A influenza. ii. Changes through antigenic drift (minor mutations from year to year); when enough drifts occur, an epidemic is likely. iii. Causes epidemics every 5 years 4. Therapy a. Treatment with neuraminidase inhibitors indicated in patients with confirmed or suspected influenza and the following conditions: i. Hospitalized patients ii. Outpatients with severe or progressive illness iii. Outpatients at high risk of influenza complications (a) Patients younger than 2 years or 65 years and older (b) Patients with chronic disease states: Pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematologic (including sickle cell disease), metabolic disorders (including diabetes mellitus), or neurologic and neurodevelopment conditions (c) Immunosuppressed patients (d) Pregnant women and those within 2 weeks postpartum (e) Patients younger than 19 years who are receiving long-term aspirin therapy (f) American Indians and Alaska Natives (g) Patients who are morbidly obese (h) Residents of nursing homes and other long-term care facilities iv. Treatment may be considered for those without risk factors including: (a) Outpatients with illness onset less than 48 hours (b)  Symptomatic outpatients who are household contacts of individuals at high risk of complications (c) Symptomatic health care providers who are caregivers for individuals at high risk of complications, including: (1) Outpatients with illness onset less than 48 hours (2) Symptomatic outpatients who are household contacts of individuals at high risk of complications (3) Symptomatic health care providers who are caregivers for individuals at high risk of complications b. Adamantanes i. Amantadine, rimantadine ii. Inhibit viral uncoating and release of viral nucleic acid by inhibiting M2 protein (a) Never effective against influenza B virus (b) Not recommended for treatment because of current universal resistance in influenza A c. Neuraminidase inhibitors i. Oseltamivir, zanamivir, peramivir ii. Inhibit neuraminidase; symptoms resolve 1–1.5 days sooner ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-203