Oxford Medicine: The Brigham Intensive Review of Internal Medicine

Pneumonia and Respiratory Infections
Oxford Medicine
The Brigham Intensive Review of Internal Medicine

Edited by Ajay K. Singh and Joseph Loscalzo
Publisher: Oxford University Press Print Publication Date: Jul 2014
Print ISBN-13: 9780199358274 Published online: Jul 2014
DOI: 10.1093/med/9780199358274.001.0001

Chapter: Pneumonia and Respiratory Infections
Author(s): Joel T. Katz
DOI: 10.1093/med/9780199358274.003.0001
Respiratory symptoms are among the most frequent reasons for patients to seek medical
attention. Seventy percent of patients presenting with a new cough will be diagnosed with
acute bronchitis. Other common causes of a new cough include pneumonia, cough-variant
asthma, congestive heart failure, postnasal drip, rhinosinusitis, and aspiration of oral contents.
Among patients presenting to their primary care provider with a cough, clinical predictors of
the 10–15% who will have pneumonia are advanced patient age (odds ratio [OR] 4.6),
shortness of breath (2.4), fever (5.5), tachycardia (3.8), and localizing chest auscultation
findings such as focal respiratory crackles (23.8) or rhonchi (14.6). The etiology, treatment,
and prognosis of upper and lower respiratory tract infections are highly varied and are
reviewed in this chapter.
Acute Bronchitis
Acute bronchitis (AB) is a common seasonal (winter peak) infection of the upper respiratory
tract that is generally viral in origin and does not require antibiotic therapy. The incidence of
AB is 30–170 cases/100,000 per year. The most common causes are rhinoviruses, respiratory
syncytial virus, influenza, parainfluenza, and adenovirus. These are highly contagious
Page 1 of 11
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pathogens that spread rapidly through exposure to respiratory secretions or indirectly through
shared environmental fomites. AB is generally a self-limited condition that lasts no more than
1–2 weeks. When symptoms last more than 2 weeks, one should consider “atypical” bacteria,
such as Bordetella pertussis or Mycoplasma pneumoniae infections, or alternative diagnoses
such as postnasal drip syndrome from conditions of the nose and sinuses, asthma,
gastroesophageal reflux disease, chronic bronchitis caused by cigarette smoking or other
irritants, bronchiectasis, eosinophilic bronchitis, or the use of an angiotensin converting
enzyme inhibitor. At least nine randomized trials and a number of subsequent meta-analyses
have addressed the benefit of antibiotics in AB. There is modest or no benefit to prescribing
antibiotics in AB, and this must be weighed against the significant cost and adverse
consequences of these medications. Overtreatment of AB leads directly to increasing rates of
antimicrobial resistance in the general population, and it is estimated to be responsible for
spending in excess of $300 million yearly on unnecessary antibiotics.
A small subset of patients with AB merit treatment, including those with episodes that occur
during documented B. pertussis outbreaks, chronic bronchitis (lasting more than 2 weeks), or
individuals with underlying lung disease (chronic obstructive pulmonary disease, asthma, or
heavy tobacco use). The incidence of pertussis (whooping cough) and a clinically
indistinguishable parapertussis have risen recently in the United States. In such settings a
second-generation macrolide, such as clarithromycin or azithromycin, is the ideal agent.
Community-Acquired Pneumonia
Despite major advances in understanding its pathophysiology and management over the
century since Sir William Osler declared it the “[c]aptain of the men of death,” pneumonia
remains the leading infectious cause of death in the United States and in the world. Three
major incremental reductions in community-acquired pneumonia (CAP) mortality have resulted
from the introduction of antipneumococcal serum therapy (discovered 1895, widely adopted
by the 1920s), antibiotics (discovered 1928, widely adopted by the 1940s), and mechanical
ventilation (discovered in 1952, widely adopted in the 1960s). Pneumococcal vaccination has
added only marginal survival benefit compared to these other advances. Annually, about 4
million cases of CAP are reported in the United States (approximately 6 cases per 1000
persons per year), leading to 1 million hospitalizations and 45,000–50,000 deaths. Mortality in
all hospitalized patients with CAP ranges from 2% to 30%, and those patients who are assigned
to the intensive care unit for their initial care have a mortality as high as 40%. In contrast,
mortality in outpatients ranges from <1% to 3%.
CAP is defined as an acute infection of the lung parenchyma accompanied by a new infiltrate
on chest radiography or compatible auscultatory findings in a patient who is not hospitalized or
living in a long-term facility for at least 2 weeks prior to the onset of symptoms. CAP symptoms
usually include at least two of the following features: fever or hypothermia, sweats, rigors,
pleurisy, and new cough with or without sputum production or change in color of respiratory
secretions. The absence of mucoid sputum production is associated with “atypical” pathogens
(M. pneumoniae, Chlamydophila pneumoniae, Legionella species, B. pertussis).
As was the case in Osler’s day, Streptococcus pneumoniae is the leading identifiable cause of
CAP (table 1.1). “Atypical” pathogens are increasingly recognized as the cause of both
outpatient and inpatient CAP, and these pathogens should be covered with empirical antibiotics
Page 2 of 11
in all cases. Despite thorough investigation, the etiological cause of CAP cannot be identified in
half of all cases. The high rate of culture-negative CAP may be attributed to antibiotic
pretreatment, inability to produce sputum for analysis, viral causes, or emerging pathogens
that remain to be elucidated.
Table 1.1 Etiology of Cap (%) by Site of Initial Triage
OUTPATIENT (n INPATIENT (n = INTENSIVE CARE (n =

= 457) 6152) 1415)
Unknown 64.4 48.3 39.7
S. pneumoniae 4 20.3 22.5
H. influenzae 4 6 5.3
M. pneumoniae 15.3 3.9 1.9
C. pneumoniae 4.5
Legionella spp. 0.9 3.4 5.9
S. aureus 1.8 2.5
GNR 3.2 10
Pneumocystis 1.3 1.6

jiroveci
Influenza 3.5 2.8
Polymicrobial 1.5 8.6 5.4
In the appropriate clinical situation the diagnosis of CAP is established by demonstration of

focal pulmonary findings, either by lung auscultation or by chest radiograph. Chest
radiographs should be done in all patients with suspected CAP, because this test is useful in
excluding complications (e.g., pleural effusions) and because associated findings may predict
the pathogen (e.g., lymphadenopathy) or suggest alternative diagnoses (e.g., lung mass, lung
abscess). When examined in a blinded fashion, the radiographic pattern does not reliably
differentiate specific pathogens. This is particularly true among the elderly and
immunocompromised patients, who may have unusual or no infiltrate in the setting of CAP.
Radiographic improvement lags behind clinical response, and routine serial chest radiographs
are not recommended unless the patient is not improving; however, all tobacco smokers and
patients over the age of 65 should have follow-up chest radiographs 3–6 months after an
episode of pneumonia in order to exclude an occult lung nodule.
Page 3 of 11
Various risk-stratification methods have been developed and validated to predict which
patients are at sufficiently low mortality risk to justify home therapy, which costs 20-fold less
than an inpatient stay. The easy-to-use CURB-65 risk score can be calculated on the basis of
five simple features, including the presence of confusion (1 point), blood urea nitrogen (BUN)
>30 mg/dL (1 point), respiratory rate ≥ 30 breaths per minute (1 point), systolic blood pressure
<90 mm Hg or diastolic blood pressure <60 mm Hg (1 point), and patient age 65 or older (1
point). The risk of death or ICU admission increases with increasing CURB-65 scores (table
1.2).
Table 1.2 Mortality and ICU Admission Based on CURB-65 Score
POINTS MORTALITY/ICU
0 0.7
1 3.2
2 13
3 17
4 41.5
5 57
Source: Adapted from Lim WS, et al. Thorax, 2001;56:296–301.
The Pneumonia Severity Index (PSI) is a validated risk stratification method that considers the
risk contributions of patient demographic features (age having the greatest influence) and key
physical examination and laboratory findings (table 1.3). Of note, other than a measurement of
arterial oxygenation all laboratory testing is left up to the discretion of the healthcare provider.
Patients in risk class I or II can be safely cared for at home. Risk class III can generally be
cared for at home, but an inpatient observation is reasonable. Patients in risk classes IV and V
should be admitted to the hospital (table 1.4). All CAP patients with unexplained or a high
degree of hypoxemia should be admitted to the hospital. Clinical judgment should supersede
the recommendations of clinical prediction rules.
Page 4 of 11
Table 1.3 Pneumonia Severity Index Point Assignments
CHARACTERISTIC OR DEMOGRAPHIC FACTOR POINTS ASSIGNED
Age
Men Age (yr)

Women Age (yr) – 10 +
Nursing home resident 10
Coexisting illness
Cancer 30
Liver disease 20
Congestive heart failure 10
Cerebrovascular disease 10
Renal disease 10
Physical examination findings
Altered mental status 20

Respiratory rate >30 breaths/min 20
Systolic blood pressure <90 mm Hg 20
Temperature <35 or ≥40o C 15
Pulse >125 10
Laboratory and radiographic findings
Arterial pH <7.35 30
BUN >30 mg/dL 20
Sodium <130 mmol/L 30
Glucose >250 mg/dL 10
Hematocrit <30% 10
Partial pressure of arterial oxygen <60 mm Hg 10
Pleural effusion 10
Source: Fine MJ, et al. NEJM 1997;336:243–250.
Table 1.4 PSI Risk Classification and Recommendation
CLASS POINTS MORTALITY (%) RECOMMENDATION*
I ** 0.1 Home antibiotics
Page 5 of 11
II <70 0.6 Home antibiotics
III 71–90 0.9 Consider short hospitalization
IV 91–130 9.3 Hospitalize
V >130 27 Hospitalize
* If the patient can be cared for at home (social).
** Risk class I requires age <50, lacking PSI comorbidities and abnormal vital signs (table
1.3).
Source: Fine MJ, et al. NEJM 1997;336:243–250.
Key principles of pharmacotherapy for CAP include the following: (1) once the diagnosis is
established, delays in administering antibiotics are associated with increased mortality; (2) all
patients with CAP should be covered for “atypical” pathogens; and (3) recent antibiotic
exposure should be considered when choosing empirical antibiotics. Clinicians should seek
specific environmental exposures that may suggest an unusual pathogen (table 1.5).
Table 1.5 Epidemiological Conditions Related to Specific Pathogens in Patients with Selected
CAP
CONDITION COMMONLY ENCOUNTERED PATHOGEN(S)
Alcoholism Streptococcus pneumoniae and anaerobes
COPD and/or smoking S. pneumoniae, Haemophilus influenzae, Moraxella

catarrhalis, and Legionella species
Nursing home residency S. pneumoniae, gram-negative bacilli, H. influenzae,

Staphylococcus aureus, anaerobes, and Chlamydia
pneumoniae
Poor dental hygiene Anaerobes
Epidemic Legionnaires’ Legionella species

disease
Exposure to bats or soil Histoplasma capsulatum

enriched with bird droppings
Exposure to birds Chlamydia psittaci
Page 6 of 11
Exposure to rabbits Francisella tularensis
HIV infection (early stage) S. pneumoniae, H. influenzae, and Mycobacterium

tuberculosis
HIV infection (late stage) Above plus P. carinii, Cryptococcus, and Histoplasma
species
Travel to southwestern Coccidioides species

United States
Exposure to farm animals or Coxiella burnetii (Q fever)

parturient cats
Influenza active in Influenza, S. pneumoniae, S. aureus, Streptococcus

community pyogenes, and H. influenzae
Suspected large-volume Anaerobes (chemical pneumonitis, obstruction)

aspiration
Structural disease of lung Pseudomonas aeruginosa, Burkholderia (Pseudomonas)

(bronchiectasis, cystic cepacia, and S. aureus
fibrosis, etc.)
Injection drug use S. aureus, anaerobes, M. tuberculosis, and S.

pneumoniae
Airway obstruction Anaerobes, S. pneumoniae, H. influenzae, and S. aureus
A summary of the Infectious Diseases Society of America (IDSA) and American Thoracic
Society (ATS) combined recommendations is given in table 1.6. Once a specific organism has
been identified, antibiotics should be narrowed to cover this agent with the least overlap in
spectrum and additional cost. Indications for transition to oral antibiotics and for hospital
discharge are reviewed by File (2003).
Page 7 of 11
Table 1.6 IDSA/ATS Treatment Guidelines for CAP
INITIAL TREATMENT
TRIAGE
Outpatients Macrolides or doxycycline

Fluoroquinolones may be preferred for older patients or in individuals
with underlying chronic illnesses (heart, liver, renal, diabetes,
alcoholism, malignancy, immunosuppressive medications)
Generally avoid antibiotic classes that have been administered in the
past 3 months
Hospitalized Extended-spectrum cephalosporin or beta-lactam/beta-lactamase

(general inhibitor plus a macrolide; or fluoroquinolone (alone)
medical ward)
Hospitalized Extended-spectrum cephalosporin or a beta-lactam/beta-lactamase

(ICU) inhibitor plus either a macrolide or fluoroquinolone
Special Antipseudomonal agents (piperacillin, piperacillin-tazobactam,

considerations carbapenem, or cefepime) plus a fluoroquinolone
Individuals with structural lung disease
Beta-lactam Fluoroquinolone +/– clindamycin

allergy
Suspected Add vancomycin or linezolid

community-
associated
MRSA
Suspected Fluoroquinolone +/– clindamycin, metronidazole, or a beta-lactam/beta

aspiration lactamase inhibitor
SOURCE: Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of
America/American Thoracic Society consensus guidelines on the management of
community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:S27–S72. Also available
online at: http://cid.oxfordjournals.org/content/44/Supplement_2/S27.full.
Increasingly, healthcare providers and facilities are being graded publicly by their adherence
to established quality measures. The current Agency for Healthcare Research and Quality CAP
quality measures are:
1. Measurement of oxygen saturation on admission

2. Blood cultures before antibiotics
Page 8 of 11
3. Appropriate antibiotics within 6 hours of presentation

4. Tobacco cessation counseling if appropriate
5. Documentation of pneumococcal vaccine before discharge
Finally, a number of vaccines are available for the prevention of S. pneumoniae and influenza
virus infections. One adult pertussis vaccine dose (Tdap) is recommended by the US Centers
for Disease Control and Prevention for all adults, effective 2013. Hospitalization for other
problems should not be overlooked as an opportunity to protect unvaccinated patients by
administering these vaccines. Updated adult vaccine recommendations are available at
http://www.cdc.gov/vaccines/schedules/index.html.
Additional Reading
Advisory Committee on Immunization Practices. Recommended adult immunization schedule:
United States, 2013. Ann Intern Med. 2013 Feb 5;158(3):191–199.
Carratalà J, Garcia-Vidal C. An update on Legionella. Curr Opin Infect Dis. 2010;23(2):152–

157.
File TM Jr. Case studies of lower respiratory tract infections: Community- acquired pneumonia.
Am J Med. 2010;123(4 Suppl):S4–S15.
Hoare Z, Lim WS. Pneumonia: Update on diagnosis and management. BMJ. 2006;332:1077–
1079.
Kabra SK, Lodha R, Pandey RM. Antibiotics for community-acquired pneumonia in children.
Cochrane Db Syst Rev. 2010;3: CD004874.
Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American
Thoracic Society consensus guidelines on the management of community-acquired
pneumonia in adults. Clin Infect Dis. 2007;44:S27–S72.
Smith SM, Fahey T, Smucny J, Becker LA. Antibiotic treatment for people with a clinical
diagnosis of acute bronchitis. Cochrane Summaries. April 18, 2012. Available online at
http://summaries.cochrane.org/CD000245/antibiotic-treatment-for-people-with-a-clinical-
diagnosis-of-acute-bronchitis.
Talwar A, Lee H, Fein A. Community-acquired pneumonia: What is relevant and what is not?
Curr Opin Pulm Med. 2007;13(3):177–185.
Torres A, Rello J. Update in community-acquired and nosocomial pneumonia 2009. Am J Respir

Crit Care Med. 2010;181(8):782–787.
Yu VL. Guidelines for hospital-acquired pneumonia and healthcare-associated pneumonia: a

vulnerability, a pitfall and a fatal flaw. Lancet Inf Dis. 2011;11:248–252.
Questions
Page 9 of 11
QUESTION 1. A 77-year-old man with well-controlled diabetes mellitus and chronic renal failure
(serum creatinine baseline 1.6 mg/dL) presents with 3 days of fevers, chills, and a cough
productive of green sputum. Physical examination reveals temperature 102.9°F, respiratory
rate 16 breaths per minute, and focal crackles in the right lung base. Initial laboratory
evaluation should include all of the following EXCEPT:
A. Measurement of arterial oxygen saturation by pulse oximetry

B. Pneumococcal urinary antigen
C. Blood cultures
D. Serum electrolytes
E. Chest radiograph
QUESTION 2. Which of the following oral antibiotics should NOT be used as a single agent in the
empirical coverage of outpatient community-acquired pneumonia?
A. Levofloxacin
B. Amoxicillin-clavulanic acid
C. Clarithromycin
D. Doxycycline
E. Azithromycin
QUESTION 3. A 32-year-old woman presents to the emergency department with fever, chills, and
a progressive and persistent dry cough. She tells you that she had been seen approximately 1
week earlier in an emergency room while on her vacation in Florida with fever, chills, and a dry
cough. She says that she was told that the chest x-ray was normal. She was prescribed
amoxicillin and was sent home. She has a past medical history of lupus nephritis and is being
treated with mycophenolate mofetil (MMF) at a dose of 1 g twice daily for the past 2 years. On
physical examination, she is in moderate distress with a respiratory rate of 34 breaths per
minute using accessory muscles. Blood pressure is 142/74 mm Hg, heart rate 110 beats per
minute. Lung examination reveals moist crackles at the right base. Arterial blood gases: pH
7.48, PCO2 28 mm Hg, PO2 62 mm Hg on 100% FIO2 with a nonrebreather mask. Chest x-ray
shows a lobar infiltrate at the right base. Blood and sputum cultures are sent.
Which of the following is the most appropriate initial management for this patient?
A. Switch antibiotic treatment to ceftriaxone

B. Switch antibiotic treatment to azithromycin and ceftriaxone
C. Withhold antibiotics pending sputum culture results
D. Switch antibiotic treatment to vancomycin, ciprofloxacin, and Zosyn (piperacillin and
tazobactam injection)
Answers
1. B
2. B
3. D
Page 10 of 11
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Pneumonia and Respiratory Infections

The Brigham Intensive Review of Internal Medicine

Pneumonia and Respiratory Infections

Table 1.1 Etiology of Cap (%) by Site of Initial Triage

OUTPATIENT (n INPATIENT (n = INTENSIVE CARE (n =

Unknown 64.4 48.3 39.7

S. pneumoniae 4 20.3 22.5

M. pneumoniae 15.3 3.9 1.9

Legionella spp. 0.9 3.4 5.9

S. aureus 1.8 2.5

Pneumocystis 1.3 1.6

Influenza 3.5 2.8

Polymicrobial 1.5 8.6 5.4

In the appropriate clinical situation the diagnosis of CAP is established by demonstration of

Table 1.2 Mortality and ICU Admission Based on CURB-65 Score

Source: Adapted from Lim WS, et al. Thorax, 2001;56:296–301.

Table 1.3 Pneumonia Severity Index Point Assignments

CHARACTERISTIC OR DEMOGRAPHIC FACTOR POINTS ASSIGNED

Men Age (yr)

Physical examination findings

Altered mental status 20

Laboratory and radiographic findings

Source: Fine MJ, et al. NEJM 1997;336:243–250.

Table 1.4 PSI Risk Classification and Recommendation

CLASS POINTS MORTALITY (%) RECOMMENDATION*

I ** 0.1 Home antibiotics

II <70 0.6 Home antibiotics

III 71–90 0.9 Consider short hospitalization

IV 91–130 9.3 Hospitalize

* If the patient can be cared for at home (social).

Source: Fine MJ, et al. NEJM 1997;336:243–250.

CONDITION COMMONLY ENCOUNTERED PATHOGEN(S)

Alcoholism Streptococcus pneumoniae and anaerobes

COPD and/or smoking S. pneumoniae, Haemophilus influenzae, Moraxella

Nursing home residency S. pneumoniae, gram-negative bacilli, H. influenzae,

Poor dental hygiene Anaerobes

Epidemic Legionnaires’ Legionella species

Exposure to bats or soil Histoplasma capsulatum

Exposure to birds Chlamydia psittaci

Exposure to rabbits Francisella tularensis

HIV infection (early stage) S. pneumoniae, H. influenzae, and Mycobacterium

Travel to southwestern Coccidioides species

Exposure to farm animals or Coxiella burnetii (Q fever)

Influenza active in Influenza, S. pneumoniae, S. aureus, Streptococcus

Suspected large-volume Anaerobes (chemical pneumonitis, obstruction)

Structural disease of lung Pseudomonas aeruginosa, Burkholderia (Pseudomonas)

Injection drug use S. aureus, anaerobes, M. tuberculosis, and S.

Airway obstruction Anaerobes, S. pneumoniae, H. influenzae, and S. aureus

Table 1.6 IDSA/ATS Treatment Guidelines for CAP

Outpatients Macrolides or doxycycline

Hospitalized Extended-spectrum cephalosporin or beta-lactam/beta-lactamase

Hospitalized Extended-spectrum cephalosporin or a beta-lactam/beta-lactamase

Special Antipseudomonal agents (piperacillin, piperacillin-tazobactam,

Individuals with structural lung disease

Beta-lactam Fluoroquinolone +/– clindamycin

Suspected Add vancomycin or linezolid

Suspected Fluoroquinolone +/– clindamycin, metronidazole, or a beta-lactam/beta

1. Measurement of oxygen saturation on admission

3. Appropriate antibiotics within 6 hours of presentation

Carratalà J, Garcia-Vidal C. An update on Legionella. Curr Opin Infect Dis. 2010;23(2):152–

Torres A, Rello J. Update in community-acquired and nosocomial pneumonia 2009. Am J Respir

Yu VL. Guidelines for hospital-acquired pneumonia and health- care-associated pneumonia: a