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ACUTE BRONCHITIS

Acute bronchitis is a commonly encountered clinical diagnosis exhibited

by cough for more than 5 days and generally does not require treatment

with antimicrobial agents.

Case 67-1 (Questions 1 and

3)

ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE

PULMONARY DISEASE

Antibiotics should be provided to patients with acute exacerbations of

chronic obstructive pulmonary disease (AECOPD) if three primary

symptoms (increased dyspnea, increased sputum volume, and increased

sputum purulence) are present, if two primary symptoms are present

and increased sputum purulence is one of the symptoms, or with

required mechanical ventilation.

Case 67-2 (Question 4)

Hospitalized patients with AECOPD should both be optimally treated,

and their COPD management be assessed to decrease the likelihood of

readmission. Baseline COPD medications should be examined and

adjusted based on disease severity. Additionally, an assessment of

patients’ understanding of the role of medications (maintenance therapy

vs. rescue medications), ability to use inhalers correctly, access to

prescribed medications, and discussions regarding pulmonary

rehabilitation should take place. Consideration for pharmacologic venous

thromboembolism prophylaxis should also be made in this high-risk

population.

Case 67-2 (Question 6)

Vaccinations to prevent influenza and Streptococcus pneumoniae in

patients with COPD or previous pneumonia reduce disease-associated

morbidity.

Case 67-2 (Question 7)

COMMUNITY-ACQUIRED PNEUMONIA

The first decision after a diagnosis of community-acquired pneumonia

(CAP) is to determine the need for hospitalization. Several predictive

rules including the pneumonia severity index (PSI) and CURB-65

(confusion, uremia, increased respiratory rate, low blood pressure, and

age ≥65 years) have been developed to facilitate site-of-care decision

making.

Case 67-3 (Question 2)

The most frequently isolated bacterial pathogen causing CAP, regardless

of epidemiologic factors and severity of illness, is S. pneumoniae.

Case 67-3 (Question 4)

The most important consideration when selecting empiric therapy is to

identify patients at risk for infection with drug-resistant S. pneumoniae

(DRSP).

Case 67-3 (Question 5)

Patients who continue to have a positive laboratory test result for

influenza more than 48 hours after the onset of illness are at high risk of

requiring hospitalization, or who are not improving should also be

treated.

Case 67-4 (Question 2)

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HOSPITAL-ACQUIRED, VENTILATOR-ASSOCIATED, AND

HEALTH CARE–ASSOCIATED PNEUMONIA

Hospital-acquired pneumonia (HAP) is defined as pneumonia that

occurs at least 48 hours after hospital admission. Ventilator-associated

pneumonia (VAP) refers to pneumonia that arises 48 to 72 hours after

endotracheal intubation. Health care–associated pneumonia (HCAP) is

diagnosed in any patient who has been hospitalized in an acute-care

hospital for 2 or more days within 90 days of infection; resided in a

nursing home or long-term care facility; received intravenous antibiotic

therapy, chemotherapy, or wound care within the past 30 days of the

current infection; lived in close contact with a person with a multidrugresistant (MDR) pathogen; or attended a hospital or hemodialysis clinic.

Case 67-5 (Question 1)

The major difference in the bacteriology between CAP and

HAP/HCAP/VAP is a shift to gram-negative pathogens, MDR

pathogens, and methicillin-resistant Staphylococcus aureus (MRSA) in

HAP/HCAP/VAP.

Case 67-5 (Question 1)

Risk factors for pneumonia caused by MDR pathogens include

antimicrobial therapy in the previous 90 days, current hospitalization of 5

days or more, immunosuppressive disease or therapy, or any risk factor

for HCAP.

Case 67-5 (Question 1)

Patients with early-onset pneumonia (<5 days) and no MDR risk factors

can be treated with a single agent, including a non-antipseudomonal

third-generation cephalosporin or ertapenem, ampicillin/sulbactam, or an

antipneumococcal fluoroquinolone. Empiric therapy in those with lateonset pneumonia (≥5 days) or MDR risk factors should include a

combination of antibiotics active against Pseudomonas aeruginosa. This

regimen usually includes an antipseudomonal β-lactam, plus either an

aminoglycoside or ciprofloxacin/levofloxacin. Vancomycin or linezolid

should be added if MRSA risk factors are present or if there is a high

incidence at the health care facility.

Case 67-6 (Question 2)

ACUTE BRONCHITIS

Definition and Incidence

Acute bronchitis (AB) is defined as 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.

1–3 AB may be associated with or without purulent sputum production, and

fever is rare.

2 Patients can be diagnosed with AB when there is no evidence of

pneumonia and when acute asthma, an acute exacerbation of chronic obstructive

pulmonary disease (AECOPD), or the common cold have been ruled out as the cause

of cough.

3 While the true incidence of AB is unknown, it is considered to be one of

the most common conditions encountered in clinical practice, accounting for more

than 6.7 million outpatient visits per year.

4

Pathophysiology and Epidemiology

AB is characterized by the inflammatory response to infection in the epithelium of the

bronchi. Further progression of this inflammation leads to thickening of the tracheal

mucosa.

1

,

2 Sloughing of cells from the tracheobronchial epithelium and inflammatory

mediators causes bronchospasm and reduced forced expiratory volume in 1 second

(FEV1

) that usually improves after 5 weeks. Spread of pathogen and inflammatory

response correlate with patient symptoms. Although bacteria can be isolated from

sputum, bacterial invasion of the bronchial tree rarely occurs, and the role of

bacterial pathogens in AB is limited.

5 The vast majority of cases of AB are presumed

to be caused by viruses.

2

,

5–7

Clinical Presentation

Cough lasting for more than 5 days is the hallmark sign of AB. Although the illness is

self-limited, cough can last for up to 3 weeks (typical duration 10–20 days). Sputum

production occurs in up to 50% of cases, but it does not indicate bacterial infection.

3

Fever is unusual in most cases; when present, it should prompt investigation for

influenza (during appropriate seasons) or for pneumonia (if other clinical signs are

present).

Overview of Drug Therapy

Antimicrobials do not significantly reduce symptoms of AB, and their use increases

the risk of adverse drug events and antimicrobial resistence.

8 Expert guidelines in the

United States and abroad recommend against the use of antimicrobial agents for the

treatment of AB.

3

,

6

,

7

,

9 Despite the evidence refuting their use, greater than 70% of AB

cases are treated with antibiotics in the United States. Furthermore, the agents used

for AB are increasingly broad-spectrum drugs, further exacerbating bacterial

resistance pressure.

10 Non-antimicrobial treatment considerations include

bronchodilators or antitussives depending on symptoms, even though evidence to

support the use of many of these modalities is limited.

3

,

11

,

12

Clinical Presentation

CASE 67-1

QUESTION 1: A.R. is a 50-year-old man presenting with a chief complaint of cough. His symptoms have

persisted for 8 days, and he now produces yellow sputum with each cough. He has had no recent illnesses;

however, his 14-year-old son in high school has experienced recent mild colds. A.R. denies nausea, vomiting, or

fever and chills. A review of systems reveals fatigue and difficulty sleeping because of cough. Past medical

history includes hypertension managed with lisinopril and hyperlipidemia for which he takes atorvastatin. He

also takes low-dose aspirin for stroke prevention. Vital signs indicate a temperature of 37.1°C, heart rate of 70

beats/minute,

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blood pressure of 130/70 mm Hg, and respiratory rate of 18 breaths/minute with accompanying oxygen

saturation of 98% on room air. His physical examination is positive for coarse breath sounds that clear with

coughing, but it is otherwise normal. What signs and symptoms in A.R. are consistent with AB?

Persistent cough in the absence of other symptoms including fever or myalgia is

typical with AB.

3 Cough can last up to 3 weeks and is usually self-limited. The

typical duration of symptoms in AB is 5 to 14 days.

2 Pneumonia must be ruled out;

however, normal oxygen saturation and lack of focal signs on pulmonary physical

examination makes this diagnosis less likely. Sputum production is common, although

not present in all cases of AB. Symptoms can be present at night, contributing to

A.R.’s symptoms of fatigue.

Microbiology

CASE 67-1, QUESTION 2: What are the most likely causes of A.R.’s case of AB?

The causative agent for AB is identified in a minority of cases; however, when

pathogens are isolated, they are usually of viral etiology.

2

,

5–7 A limited number of

bacterial pathogens are associated with AB and should primarily be considered in

patients with underlying COPD, mechanical ventilation (tracheobronchitis), or in

cases of outbreaks and exposures (e.g., Bordetella pertussis). A list of common

pathogens with their specific symptoms is included in Table 67-1.

2

Sick contacts, duration of incubation (2–7 days for viruses vs. weeks for atypical

bacteria), and previous exposures should be considered when determining the

etiologic agent responsible for AB. Specific symptoms reveal infection caused by

specific pathogens, such as an inspiratory whoop and post-tussive emesis (B.

pertussis), pharyngitis and cough lasting longer than 4 weeks (Mycoplasma

pneumoniae), hoarseness with low-grade fever (Chlamydophila pneumoniae), or

cough with fever and myalgias (influenza).

2 Given A.R.’s lack of sick contacts with

bacterial infections (his son’s recent colds are most likely of viral etiology), time

course of present illness, and absence of symptoms suggestive of influenza, a viral

etiology (other than influenza) is most likely to be the cause of his symptoms.

Clinical Diagnosis and Treatment

CASE 67-1, QUESTION 3: Should A.R. be provided an antimicrobial agent for his AB?

Antibiotics have not been shown to substantially reduce the duration of illness in

AB.

8 Thus, guidelines recommend against the routine use of antimicrobial therapy for

AB.

3

,

6

,

7

,

9 Despite these recommendations, antimicrobials are frequently prescribed

for this condition.

10

Inappropriate use of antimicrobial therapy is a public health

concern because it may lead to adverse events and antimicrobial resistance. One

exception to avoidance of antimicrobial therapy in AB is if B. pertussis infection

(whooping cough) is suspected. In these cases, antibiotic therapy with a macrolide

antibiotic is recommended, and patients should remain in isolation for the first 5 days

of treatment to prevent disease transmission.

3

In A.R.’s case, no antimicrobial agent

is warranted.

CASE 67-1, QUESTION 4: Should a sputum culture be obtained from A.R.? What other diagnostics should

be considered?

Obtaining a sputum sample for culture to determine the presence of the causative

agent or diagnostic screening for atypical pathogens is not routinely indicated for AB.

The rationale is that most of the identified pathogens have no specific treatment (viral

illnesses), and the isolated organisms often are not true pathogens. Diagnostic

screening, however, should be performed during influenza season or during outbreaks

of B. pertussis or other atypical pathogens for infection control purposes. The use of

biomarkers for the diagnosis of bacterial infection, such as procalcitonin or Creactive protein (CRP), may decrease inappropriate antimicrobial use in AB, but

their widespread use cannot be recommended at this time.

13

,

14

CASE 67-1, QUESTION 5: What symptom-guided therapies should be offered to A.R.?

Table 67-1

Causes of Acute Bronchitis

Pathogen Comments

Viruses

Influenza Quick onset with fever, chills, headache, and cough. Myalgias are common and may be

accompanied by myopathy.

Parainfluenza Epidemics in autumn. Outbreaks may occur in nursing homes. Croup in child at home

suggests presence of the organism.

Respiratory syncytial

virus

About 45% of family members exposed to infant with bronchiolitis become infected.

Outbreaks prominent in winter or spring. Twenty percent of adults have ear pain.

Coronavirus Can cause severe respiratory symptoms in elderly. Epidemics present in military recruits.

Adenovirus Similar presentation as influenza; abrupt onset of fever.

Rhinovirus Fever is uncommon and infection generally mild.

Atypical Bacteria

Bordetella pertussis Incubation period of 1–3 weeks. Whooping occurs in a minority of patients, and fever is

uncommon. Marked leukocytosis with lymphocytic predominance can occur.

Mycoplasma

pneumoniae

Incubation period is 2–3 weeks. Outbreaks in military personnel and students have been

reported.

Chlamydophila

pneumoniae

Incubation period is 3 weeks. Onset of symptoms, which include hoarseness before

cough, is gradual. Outbreaks reported in nursing homes, college students, and military

personnel.

Source: Wenzel RP, Fowler AA 3rd. Clinical practice. Acute bronchitis. N EnglJ Med. 2006;355:2125.

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Symptom-guided therapies include the use of inhaled β-agonists (albuterol) for

shortness of breath, particularly in patients with underlying reactive airway disease;

inhaled or systemic steroids for persistent cough; nonsteroidal anti-inflammatory

drugs (NSAIDs), aspirin, or acetaminophen to alleviate myalgias or fever; or

antihistamines (brompheniramine), antitussives (codeine, dextromethorphan, or

benzonatate), or mucolytics (guaifenesin) for cough. These symptom-guided

treatments, however, are not backed by strong evidence demonstrating a clear benefit

in patients with AB.

1–3,11,12 As such, each of these treatments should be approached

with an appropriate consideration of the balance between perceived benefit and risk

of adverse events. Given A.R.’s troublesome cough that has kept him up at night, a

trial of an antitussive such as dextromethorphan is a reasonable first option. NSAIDs

should be avoided given his concurrent aspirin use and lack of clear indication. An

inhaled β-agonist or steroid is also not necessary at this time.

12

,

15

CASE 67-1, QUESTION 6: Should a chest radiograph be ordered for A.R.? What other illnesses may be

considered as the cause of his symptoms?

It is important to distinguish AB from pneumonia with chest radiograph or other

imaging tests when fever, tachycardia, tachypnea; physical examination findings such

as egophony or rales; or hypoxemia or mental status changes (especially in the

elderly) are present.

2

,

3 Clinical differentiation of AB fromAECOPD, postnasal drip,

gastroesophageal reflux disorder (GERD), and asthma must also be made (discussed

separately in this chapter and in Chapter 23 Upper Gastrointestinal Disorders, and in

Chapter 18 Asthma, respectively). In A.R.’s case, no signs of pneumonia are seen on

physical examination or on reviewing symptomatology; therefore, no chest

radiograph is warranted. Frequent symptoms over time or risk factors for COPD

would warrant an investigation for chronic bronchitis. Wheezing or frequent AB

outbreaks and GERD symptoms would guide evaluations for asthma or

gastrointestinal disorders, respectively.

Patient Education

CASE 67-1, QUESTION 7: What education would you provide to A.R. to dissuade his perceived need for an

antibiotic?

An evaluation of A.R.’s expectations for therapy is important to alleviate concerns

about the decision to not to prescribe antimicrobials. Overuse of antibiotics in AB is

often driven by either prescriber knowledge or patient request. Communication is key

with each patient to provide insight into the potential causative agents of AB, the

natural course of the disease, the role of symptomatic relief, and reasons for avoiding

prescriptions for antibiotics.

ACUTE EXACERBATION OF CHRONIC

OBSTRUCTIVE PULMONARY DISEASE

Definition, Incidence, and Epidemiology

According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD),

Chronic Obstructive Pulmonary Disease (COPD) is a persistent and progressive

reduction in airflow that results from repeated exposure to noxious particles. The

chronic inflammation in the lungs results in a narrowing of the small airways,

destruction of alveoli, and loss of elastic recoil. Of note, COPD may or may not be

accompanied by increased sputum production and chronic cough. This disease is also

characterized by acute exacerbations (AECOPD), which is defined as a worsening of

symptoms that is more severe than the typical day-to-day variations that patients

experience during the stable phase of their disease. Acute exacerbations of COPD

typically require a change in medication to relieve symptoms and improve

outcomes.

16 Maintenance therapy for COPD (discussed separately in Chapter 19

Chronic Obstructive Pulmonary Disease) is often targeted to reduce the severity and

frequency of AECOPD.

COPD is associated with high health care expenditures, decreased quality of life,

significant morbidity, and high mortality around the world. AECOPD is responsible

for most of this burden. In the United States and Canada, COPD is the third and fourth

leading cause of death, respectively. In 2009 in the United States, 1.5 million

emergency department visits and 715,000 hospitalizations were attributable to

COPD.

17 Direct health care costs associated with COPD in 2010 were estimated to

be $29.5 billion in the United States.

17 AECOPD is associated with a decrease in

quality-of-life measurements and an increase in the rate of decline in lung function,

particularly if not treated early.

16

The primary precipitating factors for AECOPD are infection of the bronchial tree

and air pollution.

16

,

18–20 As many as one-third of the cases of AECOPD do not have a

cause identified.

Pathophysiology

Bacteria, viruses, and pollutants lead to inflammatory responses.

20 Airway

inflammation, associated with increases in interleukin-8, tumor necrosis factor-α, and

neutrophils, contributes to pulmonary remodeling, decreased ciliary clearance of

mucus, worsening airflow obstruction, and the respiratory symptoms associated with

AECOPD.

Viruses have been identified as the etiologic cause of AECOPD in up to one-third

of the cases, while bacteria have been identified in up to one-half of cases.

20 The

micro-organisms most commonly associated with AECOPD include Haemophilus

influenza, Streptococcus pneumoniae, and Moraxella catarrhalis. In patients with

GOLD 3 (severe) or GOLD 4 (very severe) COPD, Pseudomonas aeruginosa is more

prevalent.

16 Many patients with COPD are also colonized with bacteria during the

stable phase of their illness.

21 Evidence suggests that either an increased burden of

the same colonizing microorganism(s) or acquisition of a new bacterial species may

be associated with exacerbating COPD symptoms.

16

,

21 Decreases in adaptive immune

responses occur as COPD disease progresses, making patients susceptible to more

frequent exacerbations caused by bacterial pathogens. Additionally, pathogens

associated with exacerbations tend to increase in virulence and antimicrobial

resistance as the underlying disease progresses.

16

,

19

,

20

,

22 A possible mechanism for

prolonged infection and colonization in patients with COPD is suggested by

interactions between both viruses and bacteria altering immune respone.

20

Clinical Presentation and Diagnosis

Common features of AECOPD include the following: breathlessness, increased

cough, increased sputum volume, and increased sputum purulence. In contrast to AB,

purulent sputum in AECOPD is associated with an acute bacterial infection.

22 Other

less specific symptoms include insomnia, fatigue, tachycardia, tachypnea, and a

decrease in exercise tolerance. Patients often report a decrease in ability to conduct

activities of daily living.

16

Diagnostic considerations in the evaluation of patients with AECOPD include

pulse oximetry and arterial blood gases, electrocardiogram, and complete blood

count including white blood cell (WBC) differential. Chest radiographs are helpful to

rule out

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p. 1408

pneumonia, pneumothorax, or pleural effusion. An assessment of comorbidities,

such as the presence of heart failure or lung diseases (e.g., asthma or lung cancer),

should be performed to aid in both prognosis and diagnosis.

16

,

18 Collection of sputum

samples for Gram stain and culture are not generally recommended, but it may be

helpful if patients are failing initial therapies.

Overview of Treatment

Pharmacotherapy directed at AECOPD includes bronchodilators and supplemental

oxygen, antimicrobial therapy to decrease the burden of microorganisms, and

corticosteroids targeting the inflammatory response.

16

,

18 Methylxanthines

(aminophylline or theophylline) are rarely used owing to conflicting and limited

evidence of efficacy and concerns about toxicity.

16 Nonpharmacologic AECOPD

treatment considerations include decisions regarding the site-of-care and the level of

respiratory support. These nondrug considerations are not discussed in detail in this

chapter but are available in the GOLD Guidelines.

16

Disease Severity

CASE 67-2

QUESTION 1: T.H. is an 81-year-old white woman presenting to the emergency department (ED) because

she “cannot catch my breath.” At baseline she is on 4 L of oxygen continuously via nasal cannula. However,

during the last week she has experienced worsening dyspnea necessitating help with daily activities including

bathing and feeding. Her daughter had contacted T.H.’s primary-care physician who directed the patient to the

ED when T.H. seemed “out of it” and was difficult to arouse. T.H.’s daughter indicates that T.H. has been

“having a cold” with increased sputum that is more yellow than in the past with frequent coughing spells. Past

medical history is significant for very severe COPD, atrial fibrillation, depression, obstructive sleep apnea,

morbid obesity, and a left humerus fracture. No medication allergies are noted. Medications at home include

aspirin 81 mg PO daily, citalopram 20 mg PO daily, diltiazem extended-release capsule 240 mg PO daily,

salmeterol–fluticasone dry powdered inhaler 50/250 one puff twice daily, and albuterol inhaler four puffs every

6 hours as needed for shortness of breath. Social history is significant for a greater than 80-pack-year history of

cigarette smoking, but she quit 4 to 5 years ago. In the ED she was afebrile, heart rate was 96 beats/minute,

respiratory rate was 23 breaths/minute, blood pressure was 135/75 mm Hg, and oxygen saturation was 60% on

4 L of oxygen. T.H. is in some distress, alert and oriented times two, and is using accessory muscles for

breathing. Initial physical examination was significant for distant breath sounds and decreased air movement

bilaterally, a noted absence of lower extremity edema, and an irregularly irregular heartbeat. Laboratory

findings are as follows:

Arterial blood gases: pH, 7.34, PCO2

, 60 mm Hg, PO2

, 72 mm Hg

WBC, 9.8 × 10

3

/μL (neutrophils 71%)

Hemoglobin, 12 g/dL

Platelets, 319 × 10

3

/μL

Sodium, 135 mmol/L

Potassium, 3.7 mmol/L

Chloride, 91 mmol/L

Bicarbonate, 39 mmol/L

Blood urea nitrogen (BUN), 15 mg/dL

Serum creatinine (SCr), 1.21 mg/dL

Glucose, 104 mg/dL

Brain natriuretic peptide, 66 pg/mL

Troponin, <0.07 ng/mL

Thyrotropin, 1.63 micro-international units/mL

Chest radiograph indicated small pleural effusions, but it was otherwise negative for infiltrates or

consolidation. An electrocardiogram indicated the presence of atrial fibrillation. Pulmonary function tests

(obtained 1 year ago) indicated an FEV1

to forced vital capacity ratio of 0.39 and an FEV1

of 37% predicted.

How would you stage the severity of this exacerbation for T.H.?

T.H. has several risk factors for a poor outcome, including the presence of atrial

fibrillation and severe COPD defined by her home oxygen requirement and low

baseline FEV1

.

16

Clinical signs and symptoms consistent with a severe exacerbation include the use

of accessory respiratory muscles, paradoxical chest wall movements, worsening or

new cyanosis, peripheral edema, hemodynamic compromise, signs of right heart

failure, and alterations in mental status. T.H. has two of these factors: reduced

alertness and use of accessory muscles.

16

,

18

Disease Prevention

CASE 67-2, QUESTION 2: Which therapies should be made available to T.H. to alleviate her shortness of

breath?

Supplemental oxygen to alleviate hypoxemia is a foundation of treatment for

AECOPD. Controlled provision of oxygen should be implemented to provide an

oxygen saturation of greater than 90% or a Pao2 of greater than 60 mm Hg. Hypoxia

that is not easily reversible warrants further examination for venous

thromboembolism, pneumonia, or other causes. A repeat arterial blood gas should be

obtained within 1 hour of initiation of supplemental oxygen to assess for carbon

dioxide retention or acidosis.

The use of short-acting bronchodilators should be initiated promptly in all patients

with AECOPD. β-Agonists, such as albuterol, with or without an anticholinergic

agent (ipratropium), are the preferred agents.

16

If the patient does not respond, a

methylxanthine (theophylline or aminophylline) may be considered as second-line

therapy. There is no role for long-acting bronchodilators in AECOPD at this time.

CASE 67-2, QUESTION 3: Does T.H. need to be treated with antimicrobial therapy?

The “cardinal” symptoms of AECOPD include increases in sputum purulence,

sputum volume, and dyspnea.

23 The use of cardinal symptoms as a method of staging

AECOPD severity has been used in several prospective studies and is recommended

in the GOLD guidelines.

16

,

24

Experts advocate for the use of antibiotics for AECOPD, particularly when two or

three cardinal symptoms are present.

16

,

18 Specifically, the GOLD Guidelines

recommend antibiotics for patients with three cardinal symptoms (increased dyspnea,

increased sputum volume, and increased sputum purulence); when two cardinal

symptoms are present if increased sputum purulence is one of the symptoms; or in all

patients requiring mechanical ventilation for their AECOPD.

16

T.H. is exhibiting all three of the cardinal symptoms and therefore should receive

antibiotics. Likely benefits would be enhanced treatment success, prevention of

relapse, decreased risk for rehospitalization, improvement in pulmonary function,

and reduction of the severity of her exacerbation.

CASE 67-2, QUESTION 4: Which antimicrobial agent should be selected for treating T.H.? What duration

of treatment would be recommended?

p. 1408

p. 1409

Given T.H.’s history, diminished mental status, and risk factors for poor outcomes,

intravenous (IV) administration seems appropriate for the initial antibiotic

administration. Potential risk factors for P. aeruginosa should be evaluated. If T.H.

demonstrates risk factors for P. aeruginosa, an anti-pseudomonal β-lactam, such as

cefepime, would be an appropriate initial agent. If no risk factors for P. aeruginosa

exist, a β-lactam/β-lactamase inhibitor such as ampicillin/sulbactam, a thirdgeneration cephalosporin such as ceftriaxone, or a respiratory fluoroquinolone such

as moxifloxacin or levofloxacin should be selected. All these therapies are active

against drug-resistant S. pneumoniae (DRSP). If T.H. improves on one of these

parenteral agents and is ready for discharge, T.H. could transition to an oral

respiratory fluoroquinolone or high doses of amoxicillin/clavulanate.

Another important consideration for initial selection of antimicrobials is an

evaluation of antibiotic history. Alternative antimicrobials from another class should

be considered if patients have been previously treated in the last 3 months.

16

Additionally, if no improvements in symptoms occur within 72 hours, consider

obtaining a sputum sample for directed therapy.

16

The duration of treatment of antibiotics for AECOPD suffers from lack of solid

evidence-based recommendation. Given findings from CB investigations, a duration

of 5 to 10 days has been suggested, but this is an area in need of further research.

16

CASE 67-2, QUESTION 5: Should T.H. be treated with corticosteroids? If so, which dose and duration

would be selected?

In the setting of AECOPD, systemic corticosteroids help to improve lung function,

shorten recovery time, and prevent relapses. Based on available evidence, the GOLD

Guidelines recommend a corticosteroid regimen of 40 mg/day of prednisone for 5

days in patients with AECOPD.

16 This regimen would be appropriate for T.H.,

although an equivalent intravenous regimen could be considered if she was not able

to take an oral regimen. Higher doses and longer durations of therapy have not been

found to confer a clinical advantage, and intravenous and oral regimens are

considered equally effective.

25

,

26

In those patients receiving more than 3 weeks of

steroids or multiple course of steroids in the previous months, tapering the dose

should be considered. Although it is more expensive, nebulized budesonide may be

considered as an alternative to oral corticosteroids for treatment of AECOPD.

16

Enhancing Patient Outcomes

CASE 67-2, QUESTION 6: What factors should be assessed for T.H. during her hospitalization, and what

follow-up should be planned to help assure she recovers fully and is not readmitted for COPD?

Hospitalized patients with AECOPD should both be optimally treated, and their

COPD management be assessed to decrease the likelihood of readmission. T.H.’s

baseline COPD medications should be examined and adjusted based on disease

severity (see Chapter 19 Chronic Obstructive Pulmonary Disease for details).

Additionally, an assessment of her understanding of the role of medications

(maintenance therapy vs. rescue medications), ability to use inhalers correctly,

access to her prescribed medications, and discussions regarding pulmonary

rehabilitation should take place.

16

,

17 Consideration for pharmacologic venous

thromboembolism prophylaxis (see Chapter 11 Thrombosis) should also be made in

this high-risk population.

16

,

27

PREVENTION OF COMMON RESPIRATORY

INFECTIONS BY VACCINATION

CASE 67-2, QUESTION 7: Which vaccines should be considered for T.H. as part of her COPD

management?

Vaccination records for influenza and S. pneumoniae should be evaluated in T.H.

Annual influenza vaccination is recommended for all patients ≥6 months with COPD,

and it has been shown to reduce the risk of AECOPD.

16

,

17 Vaccination against S.

pneumoniae with the 23-valent polysaccharide vaccine is recommended for patients

≥19 years old with COPD. Unlike the influenza vaccine, however, vaccination

against S. pneumoniae has not been clearly linked with a reduced risk of AECOPD.

The pneumococcal vaccine is recommended by guidelines, however, as part of the

overall health plan of the patient.

COMMUNITY-ACQUIRED PNEUMONIA

Definition, Incidence, and Epidemiology

Pneumonia is an infection of the lung parenchyma. Community- acquired pneumonia

(CAP) refers to pneumonia acquired in the absence of health care system exposure

(i.e., hospital, long-term care, chronic antibiotic exposure). Diagnosis is dependent

upon clinical features and radiologic evidence of an infiltrate, but it may be further

supported by physical examination and/or hypoxemia.

Current estimates show that CAP accounts for 24.8 cases per 10,000 discharges in

the US adult population with the elderly being primarily affected (65–79 years:

63/10,000; ≥80 years: 164.3/10,000).

28

In the pediatric population, CAP accounts for

15.7 cases per 10,000 discharges, with infants and young children showing increased

risk (<2 years: 62.2/10,000).

29 The overall mortality rate for patients ≥65 years is

5.6% and is more pronounced in hospitalized patients (8.5%) compared to

outpatients (3.8%).

30 Seventeen percent of older patients who develop CAP will

suffer cardiac complications.

31

Pathophysiology

Development of CAP occurs through the inhalation of infectious particles via

droplets or aerosols, or the aspiration of oral flora. Rarely, hematogenous spread of

bacteria from distant sources into the lungs may occur, as well as direct extension of

infection to the lung from contiguous areas, such as the pleural or subdiaphragmatic

spaces.

Once bacteria reach the tracheobronchial tree, defects in local pulmonary defenses

facilitate infection. Contributing factors include inflammation-mediated injury to

bronchial epithelium leading to depressed mucociliary clearance and a blunted

cellular and humoral response. Patients with underlying or acquired

immunodeficiencies are at an increased risk.

Clinical Presentation and Diagnosis

In the majority of CAP cases, patients present acutely with high fever, chills,

tachypnea, tachycardia, and productive cough. Physical examination findings are

usually localized to a specific lung zone and can include crackles, rhonchi, bronchial

breath sounds,

p. 1409

p. 1410

dullness, or egophony. On rare occasions, CAP exhibits a subacute presentation with

fever, nonproductive cough, constitutional symptoms, and absent or diffuse findings

on lung examination. Children with CAP may present with vomiting.

A chest radiograph or other imaging technique revealing an infiltrate is required

for the diagnosis of CAP.

32 Radiographic manifestations of diseases such as

congestive heart failure and malignancy can obscure the infiltrate, reinforcing the

need to utilize both clinical and chest radiographic findings.

Pretreatment blood cultures and a respiratory sample (expectorated or induced

sputum or endotracheal aspirate in intubated patients) should be obtained for culture

and Gram stain. Although these cultures are often negative, when they are positive,

they allow fine-tuning of the empirical antibiotic selection.

Overview of Drug Therapy

Antibiotic therapy for CAP is empirical in the majority of cases and should always

be based on the most likely pathogen(s), underlying patient characteristics, and the

severity of disease. Based on these variables, clinicians can triage patients for risk of

infection caused by antibiotic-resistant pathogens and appropriately tailor therapy.

CLINICAL PRESENTATION

CASE 67-3

QUESTION 1: J.T. is a 45-year-old woman presenting to the ED with fevers, chills, and chest pain. Her

symptoms have persisted for 4 days, and she has a productive cough with rusty-colored sputum and dyspnea on

exertion. She has had no recent illnesses and no known sick contacts, but she was recently released from a 2-

year period of incarceration. She has tried acetaminophen to alleviate her fever and chest pain. Past medical

history is positive for asthma, for which she is prescribed fluticasone and albuterol, and depression, for which

she takes paroxetine. 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 saturation of 85% on 5

L of oxygen by nasal cannula. 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/dL

SCr, 0.8 mg/dL

HCO3

, 28 mEq/L

Glucose 148, mg/dL

Arterial blood gases: pH 7.42, PO2

, 61 mm Hg, PCO2

, 46 mm Hg

A test for human immunodeficiency virus is negative. Chest radiograph reveals a right lower lobe infiltrate.

What signs, symptoms, and tests are consistent with CAP in J.T.?

In the majority of cases, patients with CAP present with cough with sputum

production, dyspnea, and pleuritic chest pain.

33 Patients may show signs of the

systemic inflammatory response syndrome, including tachycardia, tachypnea, fever,

and an abnormal WBC count.

34 Auscultatory examination often reveals decreased

breath sounds, crackles or rhonchi, or egophony in patients with consolidation. Signs

and symptoms associated with severe pneumonia are grouped into minor and major

criteria defined by the Infectious Disease Society of America (IDSA)/American

Thoracic Society (ATS) Guidelines for CAP.

32 Minor criteria include respiratory

rate greater than 30 breaths/minute at admission; ratios of the Pao2

to fraction of

inspired oxygen (FIO2

) (Pao2

/FIO2

) less than 250 mm Hg; systolic blood pressure

(SBP) less than 90 mm Hg, or diastolic blood pressure (DBP) less than 60 mm Hg;

confusion; multilobar infiltrates; SBP less than 90 mm Hg despite aggressive fluid

resuscitation; BUN of at least 20 mg/dL; leukopenia; thrombocytopenia; and

hypothermia. Major criteria include requirement of mechanical ventilation and

requirement of vasopressors for more than 4 hours.

32

Clinical findings and a positive infiltrate by chest radiograph or other imaging

technique is required for the diagnosis of pneumonia.

32 Patients who are hospitalized

based on clinical symptoms absent of positive imaging should have repeat imaging

performed 24 to 48 hours post-admission.

Disease Severity

CASE 67-3, QUESTION 2: Given the clinical condition of J.T. in the ED, where should her care be

continued?

The first decision after a diagnosis of CAP is to determine whether the patient

requires hospitalization. Several predictive rules have been developed to facilitate

site-of-care decision making. The two best-studied tools that are endorsed by the

IDSA/ATS guidelines are the pneumonia severity index (PSI) and the CURB-65 rule.

The PSI uses individually scored demographic characteristics (age, gender,

nursing home residence), comorbidities (liver disease, CHF, renal disease,

neoplasm), physical examination findings (mental status, RR, SBP, temp, HR), and

laboratory data (Na

+

, glucose, Hct, BUN); the total PSI score categorizes patients

into one of five classes that are associated with an escalating risk of death (Table 67-

2).

35 The CURB-65, developed by the British Thoracic Society, is a simple tool that

focuses on five assessments: confusion (owing to pneumonia), uremia (BUN >19

mg/dL), respiratory rate of at least 30 breaths/minute, SBP less than 90 mm Hg

systolic or DBP less than 60 mm Hg, and age of at least 65 years.

36 Each criteria

receives one point, and the cumulative score is associated with a specific (rising

with higher score) 30-day mortality risk. Based on the score, subsequent care should

be as follows: 0–1 = outpatient; 2 = admission to ward; ≥3 = ICU care. Both scales

identify patients at low risk of death, but the CURB-65 has been found to be more

discerning of patients who need ICU care and with the highest risk of death.

37 The

need for ICU admission can be subjective; however, the IDSA/ATS guidelines

recommend that patients with three or more minor criteria, or at least one major

criteria for severe CAP, be admitted to the ICU.

32

CASE 67-3, QUESTION 3: What testing should be performed to obtain a microbiologic diagnosis in J.T.?

Patient J.T. can be assessed as follows using the PSI: 45-year-old woman (35

points [45 for age – 10 for gender female]), respiratory rate greater than 30

breaths/minute (20 points), heart rate greater than 125 beats/minute (20 points),

temperature greater than 40°C (15 points), hematocrit less than 30% (10 points), and

altered mental status (20 points). A total score of 120 points places J.T. in risk strata

IV (30-day mortality risk: 9.3%–27%), and she should be admitted to the hospital,

potentially to the ICU. Using the CURB-65, J.T. has a score of 3 (30-day mortality of

9.2%) based on uremia, confusion, and increased respiratory rate, and she should be

admitted to the ICU.

Microbiologic testing is optional for outpatients with CAP. However, the

IDSA/ATS guidelines recommend attempting to make a microbiologic diagnosis in

patients with CAP who are hospitalized.

32 Microbiologic diagnosis (via sputum or

endotracheal aspirate) can help guide empiric therapy as well as identify rare and

usual etiologies and cluster cases.

p. 1410

p. 1411

Table 67-2

Predicted Pneumonia Mortality and Recommended Site of Care

System and Score Predicted 30-Day Mortality (%) Recommended Site of Care

PSI strata I–II (≤70) 0.1–0.7 Outpatient

PSI strata III (71–90) 0.9–2.8 Admit to hospital ward

PSI strata IV–V (≥91) 9.3–27 Admit to hospital; consider ICU

CURB-65 score 0–1 0.7–2.1 Outpatient

CURB-65 score 2 9.2 Admit to hospital ward

CURB-65 score ≥3 14.5–57 Admit to ICU

CURB-65, confusion, uremia, increased respiratory rate, low blood pressure, and age ≥65 years; ICU, intensive

care unit; PSI, pneumonia severity index.

Source: Fine MJ et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N EnglJ

Med. 1997;336:243.

Urine antigen tests for pneumococcus and Legionella pneumophila serogroup 1 are

available for patients with severe CAP. Both tests are sensitive (>80%) and specific

(>90%), and have the advantage of detecting pathogens after antibiotics have been

administered.

The IDSA/ATS guidelines recommend consideration of influenza testing during

traditional “flu season” and during times of an outbreak.

32 Detection of influenza

should be via reverse transcriptase polymerase chain reaction (RT-PCR), which is

the most sensitive and specific method, with a quick turnaround time for results (4–6

hours).

38 Rapid influenza antigen detection tests may be used, but because of lower

sensitivity and specificity RT-PCR is recommended to confirm negative test results

reported by the rapid antigen test. Viral isolation in standard cell culture should be

routinely performed with respiratory specimens during the influenza season.

Microbiology

CASE 67-3, QUESTION 4: What pathogens are most likely in J.T.?

The major pathogens for CAP are summarized in Table 67-3. The most frequently

isolated bacterial pathogen, regardless of epidemiologic factors and severity of

illness, accounting for approximately 27% of CAP worldwide, is S. pneumoniae.

32

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