1 Lower respiratory tract infection N B THERAPEUTICS

1 Lower respiratory tract infection N. B THERAPEUTICS 2 COURSE

ACUTE BRONCHITIS an acute, self-limiting respiratory illness of the upper bronchi accompanied by cough for more than 5 days that can last up to 3 weeks. occurs most commonly during the winter months Respiratory viruses are by far the most common infectious agents associated with acute bronchitis. The common cold viruses (rhinovirus and coronavirus) and lower respiratory tract pathogens (influenza virus and adenovirus) account for the majority of cases. Chronic bronchitis (CB) is defined as having daily symptoms of sputum production on most days for more than 3 or more consecutive months for greater than 2 successive years N. B 2

CLINICAL PRESENTATION Cough lasting for more than 5 days is the hallmark sign of AB. Sputum production occurs in up to 50% of cases, but does not indicate bacterial infection. N. B Fever is unusual in most cases, but when present should lead to investigation for influenza during appropriate seasons or pneumonia if other clinical signs are present. rarely exceeds 39°C (102. 2°F) Dyspnea, cyanosis, or signs of airway obstruction are observed rarely unless the patient has underlying pulmonary disease, such as emphysema or COPD. 3

It is important to distinguish AB from pneumonia with chest radiograph or other imaging tests when fever, tachycardia, tachypnea, rales, hypoxemia or mental status changes (especially in the elderly) are present. Tachycardia (heart rate >100 beats/min) Tachypnea (respiratory rate >24 breaths/ min) Fever (oral temperature >38 °C) Abnormal findings on a chest examination (rales, egophony, or tactile fremitus) Microbiological tests: For patients with moderate- or highseverity community-acquired pneumonia: ü Blood cultures Sputum cultures Consider pneumococcal and legionella urinary antigen tests. ü ü N. B 4

PHARMACOLOGIC THERAPY Bronchodilators (if asthma or COPD) or antitussives depending on symptoms. (antitussives should be used cautiously when the cough is productive) Mild analgesic–antipyretic therapy often is helpful in relieving the associated lethargy, malaise, and fever. In children, aspirin should be avoided and acetaminophen used as the preferred agent. Caution should be exercised in the administration of ibuprofen for patients younger than 6 months, elderly patients, and individuals with poor renal function. N. B 5

Although not recommended for routine use, persistent, mild cough, which may be bothersome, can be treated with dextromethorphan. N. B Antibiotic for: persistent fever or respiratory symptoms for more than 4 to 6 days predisposed patients (e. g. , immunocompromised, elderly, ) the possibility of a concurrent bacterial infection should be suspected. anticipated respiratory pathogen ex: S. pneumoniae 6

1. 2. N. B 3. Antibiotics: Azithromycin IF bacterial infection Fluoroquinolones (ex: levofloxacin): active against suspected pathogens. Zanamivir and oseltamivir: are active against both influenza A and B viral infections and may reduce the severity and duration of the influenza episode if administered promptly during the onset of the viral infection and are the preferred treatment…. . Problem is Resistance 7

CASE EXAMPLE A. R. is a 30 -year-old woman presenting with a chief complaint of cough. Her symptoms have persisted for 10 days, and she now produces yellow sputum with each cough. She has had no recent illnesses; however, her 2 -year-old daughter in day care has experienced recent colds. She denies nausea, vomiting, or emesis or fever and chills. A review of systems reveals fatigue and difficulty sleeping because of cough. Past medical history includes ulcerative colitis managed with mesalamine and generalized anxiety disorder for which she takes sertraline. N. B 8

Vital signs review indicates a temperature of 37. 1◦C, heart rate of 70 beats/minute, blood pressure of 130/70 mm Hg, and respiratory rate of 18 breaths/minute with accompanying oxygen saturations of 98% on room air. Her physical examination is positive for coarse breath sounds that clear with coughing, but is otherwise normal. What signs and symptoms in A. R. are consistent with AB? What are the most likely causes of A. R. ’s case of AB? Should A. R. be provided an antimicrobial agent for her AB? Should a chest radiograph be ordered for A. R. ? What other illnesses may be considered as the cause of her symptoms? N. B 9

Pneumonia is an infection of the lung parenchyma Community-Acquired Pneumonia (CAP): pneumonia acquired outside of the hospital or extended-care facility in patients without recent exposure to the health care system. Hospital-acquired pneumonia (HAP): pneumonia that occurs at least 48 hours after admission and is not incubating at the time of hospitalization. Ventilator-associated pneumonia (VAP): pneumonia that arises 48 to 72 hours after endotracheal intubation. N. B 10

Healthcare-Associated Pneumonia(HCAP): which is defined as pneumonia occurring in any patient hospitalized for at least 2 days within 90 days of the onset of the infection; residing in a nursing home or longterm care facility; received IV antibiotic therapy, wound care, or chemotherapy within the last 30 days prior to the onset of the infection; or having attended a hemodialysis clinic Atypical Pneumonia: Pneumonia caused by atypical pathogens may be more difficult to treat with antibiotics than “typical” pathogens N. B 11

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PNEUMONIA CLASSIFICATIONS AND RISK FACTORS N. B 13

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GENERAL APPROACH TO TREATMENT Oxygen or, in severe cases, mechanical ventilation administration of bronchodilators (albuterol) when bronchospasm is present. adequate hydration (IV if necessary) optimal nutritional support control of fever. N. B 15

ANTIBIOTIC CONCENTRATIONS Penetration into pulmonary secretions: large, unionized form of drug and lipid solubility also appears to favor drug penetration. Patient age, previous and current medication history, underlying disease(s), major organ function, and present clinical status. the fluoroquinolone antibiotics represent important treatment tools based on their highly favorable PK (tissue and intracellular distribution) and PD (potency, broad spectrum) characteristics combined with ease of administration (IV, oral) and patient tolerability. N. B 16

COMMUNITY-ACQUIRED PNEUMONIA S. pneumoniae is the most common community-acquired bacterial pneumonia in adult and pediatric patients. In preschool-aged children, viral pathogens more commonly cause CAP compared with bacterial pathogens. N. B 17

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LAB AND MICROBIAL TESTS The WBC Sputum Gram stain: should demonstrate the presence of WBCs and the absence of squamous epithelial cells. Sputum culture Bronchoscopy may be performed to improve the ability to diagnose pneumonia. Serology (Ig. M and Ig. G) is useful in determining the presence of atypical organisms such as Mycoplasma and Chlamydia. Polymerase chain reaction (PCR) is being used more frequently to detect the DNA of respiratory pathogens N. B 20

MICROBIOLOGICAL TESTS For patients with moderate- or high-severity communityacquired pneumonia: take blood and sputum cultures and consider pneumococcal and legionella urinary antigen tests. Done for moderate to severe cases N. B The chest radiograph: white spots in the lungs (called infiltrates) that identify an infection 21

TREATMENT The CURB-65, developed by the British Thoracic Society, is a simple tool that makes five assessments: confusion (owing to pneumonia), uremia (BUN >19 mg/d. L), respiratory rate of at least 30 breaths/minute, blood pressure of less than 90 mm Hg systolic or 60 mm Hg or less diastolic, and age of at least 65 years. N. B 0– 1 = outpatient, 2 = admission to ward, ≥ 3 = ICU care. 22

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The IDSA/ATS guidelines recommend treatment for a minimum of 5 days, and patients should be a febrile for 48 to 72 hours before therapy is discontinued. In addition, patients should not have therapy discontinued if they meet two or more CAP-associated signs of clinical instability, including: temperature of greater than 37. 8◦C heart rate of greater than 100 beats/minute respiratory rate of greater than 24 breaths/minute systolic blood pressure of less than 90 mm Hg arterial oxygen saturation of less than 90% or Pao 2 of less than 60 mm. Hg on room air, inability to maintain oral intake, or abnormal mental status N. B 25

PATIENT INFORMATION most people can expect that by: 1 week: fever should have resolved 4 weeks: chest pain and sputum production should have substantially reduced 6 weeks: cough and breathlessness should have substantially reduced 3 months: most symptoms should have resolved but fatigue may still be present 6 months: most people will feel back to normal. N. B 26

The remainder of the physical examination is notable for orientation to person but not place or time and for diffuse crackles bilaterally, which are most apparent on the right side. Laboratory results include the following: WBC count, 15, 500 cells/μL Hematocrit, 29. 3% Sodium, 133 mmol/L Potassium, 3. 8 mmol/L BUN, 23 mg/d. L SCr, 0. 8 mg/d. L Glucose 148, mg/d. L p. H 7. 42 PO 2, 61 mm Hg PCO 2, 46 mm Hg HCO 3, 28 m. Eq/L A test for human immunodeficiency virus is negative. Chest radiograph reveals a right lower lobe infiltrate. N. B 27

CASE EXAMPLE 65 -year-old man presents to your ED complaining of difficulty breathing and shortness of breath. PMH: Hypertension for 8 years, COPD for 5 years, currently controlled FH: Father died of lung cancer at the age of 68 years; mother died of natural causes SH: Denies alcohol use, smokes 1 pack per day for 15 years. Lives alone and has 2 children. He is 5’ 8” (173 cm) and weighs 140 lb (63. 6 kg) Allergies: NKDA Meds: Hydrochlorothiazide 25 mg orally once daily; fluticasone propionate/salmeterol 250/50 mcg one inhalation twice daily; albuterol inhaler 1 to 2 inhalations every 4 hours as needed for shortness of breath N. B 28

ROS: (+) difficulty breathing and shortness of breath; (–) chest pain, change in appetite PE: VS: BP 120/80, P 82, RR 22, T 38. 6°C (101. 5°F) CV: RRR, normal S 1, S 2; no murmurs, rubs, or gallops Lungs: Decreased breath sounds on the left side compared with the right with rales and crackles in the left lower lobe Abd: Soft, nontender, nondistended; (+) bowel sounds, no hepatosplenomegaly, heme (–) stool Neuro: Oriented to name and place, confused N. B 29

Diagnostic Tests: Chest x-ray: left lower lobe infiltrates; oxygen saturation 84% (0. 84) on room air Labs: WBCs 14. 2 × 103/mm 3 (14. 2 × 109/L) with a cell differential of 70% (0. 70) neutrophils, 2% (0. 02) bands, 20% (0. 20) lymphocytes, and 8% (0. 08) monocytes; BUN 9 mg/d. L (3. 2 mmol/L), SCr 0. 9 mg/d. L (80 μmol/L), glucose 90 mg/d. L (5. 0 mmol/L); sputum Gram stain: moderate gram-positive cocci, few gram-negative bacilli, many WBCs; sputum culture is pending What is the possible disgnosis ? What organisms should you include in your list of potential pathogens? What pharmacologic agents are available for treating this patient? N. B 30

CASE EXAMPLE N. B M. R. is a 33 -year-old man presenting to the ED with fevers, chills, and chest pain. His symptoms have persisted for 3 days, and he has a productive cough with rusty-colored sputum and dyspnea with exertion. He has had no recent illnesses and no known sick contacts, but he was recently released from a 2 -year period of incarceration. He has tried ibuprofen to alleviate his fever and chest pain. Past medical history is positive for asthma, for which he is prescribed fluticasone and albuterol, and depression, for which he takes sertraline. Vital signs reveal a temperature of 40. 1◦C, heart rate of 128 beats/minute, blood pressure of 130/76 mm Hg, and respiratory rate of 32 breaths/minute with accompanying oxygen saturations of 85% on 5 L of oxygen by nasal cannula. 31

HOSPITAL-ACQUIRED PNEUMONIA HAP is seen most commonly in critically ill patients and usually caused by bacteria. Factors: the severity of illness, duration of hospitalization, supine positioning, witnessed aspiration, coma, acute respiratory distress syndrome, patient transport, and prior antibiotic exposure. The strongest predisposing factor, is mechanical ventilation (intubation). The length of stay for hospital admissions is increased, on average, by 7 to 9 days for patients who develop HAP N. B 32

The organisms most commonly associated with HAP are S. aureus and enteric (e. g. , K. pneumoniae or E. coli) and nonenteric (e. g. , P. aeruginosa) gram-negative bacilli. Patients with longer lengths of hospital admission prior to the development of HAP are more likely to have MDR organisms presence of a new infiltrate on chest radiograph, fever, worsening respiratory status, and the appearance of thick, neutrophil-laden respiratory secretions. N. B 33

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CASE EXAMPLE N. B A. S. is a 37 -year-old woman with poorly controlled type 1 diabetes and resultant end-stage renal disease who is on intermittent hemodialysis. She completed a course of meropenem for a catheter-associated bloodstream infection 2 weeks ago. A. S. presents to the ED from her home with a 3 -day history of dyspnea, cough with purulent sputum production, and intermittent fever. Examination reveals decreased breath sounds over the right middle and lower lobes consistent with chest radiograph findings of dense consolidation throughout the same areas. Her blood pressure is 159/63 mm Hg, pulse is 88 beats/minute, respiration is 26 breaths/minute, and temperature is 38. 3◦C. Significant laboratory findings include the following: WBC, 15, 000 cells/μL Differential polymorphonuclear neutrophil cells, 89% Bands, 9% Lymphocytes, 30% 36

CASE EXAMPLE N. B M. L. is a 71 -year-old man admitted to the hospital for a deep vein thrombosis. His past medical history is significant for chronic kidney disease, diabetes mellitus, COPD, GERD, hypertension, and a recent diagnosis of non–small cell lung cancer for which he is not currently receiving chemotherapy. M. L. ’s home medications include lisinopril, famotidine, aspirin, insulin glargine, insulin aspart, tiotropium, fluticasone/salmeterol, and asneeded albuterol. What characteristics does M. L. exhibit that place him at risk for HAP? 37

N. B Six days after admission, M. L. exhibits a fever to 39. 3◦C. He has since been intubated and has increasing secretions coming from his endotracheal tube, an elevated WBC count, and new infiltrate on his daily chest radiograph. Sputum cultures are sent, and the decision is made to start M. L. on antibiotics. How should antimicrobial therapy be managed for M. L. ? 38

VENTILATOR-ASSOCIATED PNEUMONIA pneumonia occurring >48 hours post–endotracheal intubation. The risk for developing pneumonia in the hospital increases by 6 to 21 times after a patient is intubated. N. B migration of upper respiratory tract organisms into the lower tract Is exacerbated by the wide use of acid-reducing drugs (e. g. , H 2 - receptor blocking agents, proton pump inhibitors) in the intensive care unit, which increases the p. H of gastric secretions and may promote the proliferation of microorganisms in the 39 upper GI tract.

Pneumonia that develops within 4 days of hospitalization is more likely to be caused by an antibiotic sensitive organism such as S. pneumoniae. infections developing later are more likely to be MDR (e. g. , P. aeruginosa, MRSA) new or persistent infiltrates are found on chest radiograph along with ≥ 2 of the following: purulent tracheal secretions, leukocytosis or leucopenia, and body temperature >38. 3°C (>100. 94°F) N. B 40

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ATYPICAL PNEUMONIA Legionella species, Mycoplasma species, Chlamydia species, viruses, and fungi Fluoroquinolones or Azithromycin for bacterial Oseltamivir for H 1 N 1 influenza N. B 42

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PNEUMONIA IN CHILDREN N. B 44

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REFERENCES Pharmacotherapy, Principles & Practice, 4 th ed, 2016 Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of Physicians and the Centers for Disease Control and Prevention, American collage of physicians, 2016 Pneumonia : Diagnosis and management of community- and hospitalacquired pneumonia in adults , National Clinical Guideline Centre, 2014 Pharmacotherapy, physiological approach, 2014, Chapter 85 Applied therapeutics, 2013, Chapters 64 N. B 47