Annals of Internal MedicineT
In the ClinicT
Community-Acquired
Pneumonia
C
ommunity-acquired pneumonia is an important cause of morbidity and mortality. It can
be caused by bacteria, viruses, or fungi and
can be prevented through vaccination with pneumococcal, influenza, and COVID-19 vaccines.
Diagnosis requires suggestive history and physical
findings in conjunction with radiographic evidence
of infiltrates. Laboratory testing can help guide
therapy. Important issues in treatment include
choosing the proper venue, timely initiation of the
appropriate antibiotic or antiviral, appropriate respiratory support, deescalation after negative culture results, switching to oral therapy, and short
treatment duration.
CME/MOC activity available at Annals.org.
Physician Writer
Michael B. Rothberg, MD, MPH
Cleveland Clinic, Cleveland,
Ohio
doi:10.7326/AITC202204190
This article was published at Annals.org on 12 April 2022.
CME Objective: To review current evidence for prevention, diagnosis, treatment,
and practice improvement of community-acquired pneumonia.
Funding Source: American College of Physicians.
Acknowledgment: The author thanks Michael S. Niederman, MD, author of the
previous version of this In the Clinic.
Disclosures: Dr. Rothberg, ACP Contributing Author, reports grants or contracts
from the Agency for Healthcare Research and Quality and the National Institute
on Aging, consulting fees from Health Advances, participation on a data safety
monitoring board or advisory board for BMS, and stock in Moderna. All relevant
financial relationships have been mitigated. Disclosures can also be viewed at
www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-4473.
With the assistance of additional physician writers, the editors of Annals of
Internal Medicine develop In the Clinic using MKSAP and other resources of
the American College of Physicians. The patient information page was written by
Monica Lizarraga from the Patient and Interprofessional Partnership Initiative at
the American College of Physicians.
In the Clinic does not necessarily represent official ACP clinical policy. For ACP
clinical guidelines, please go to https://www.acponline.org/clinical_information/
guidelines/.
© 2022 American College of Physicians
Prevention
Treatment
Diagnosis
Practice Improvement
Community-acquired pneumonia (CAP)
can vary from a mild outpatient illness
to a more severe disease requiring hospital admission or intensive care. In the
United States, CAP together with influenza is the ninth leading cause of death
overall and the leading cause of death
from infectious disease (1). Outpatient
CAP is managed mainly by primary care
physicians, whereas inpatient treatment
often involves hospitalists. The key management decisions related to CAP are
recognition and treatment in a timely
and effective manner, defining the appropriate site of care (home, hospital, or
intensive care unit [ICU]), choosing
effective treatment based on the cause,
limiting antibiotic duration, and prevention. In particular, persons who have
recently been hospitalized and received
parenteral antibiotics and those who
have previously been infected with multidrug-resistant organisms (MDROs) are at
increased risk for resistant infections.
Prevention
Who is at increased risk for CAP?
1. Heron M. Deaths: Leading
Causes for 2019. National
Vital Statistics Reports.
National Center for Health
Statistics; 2021.
2. QuickStats: death rates
from influenza and
pneumonia among
persons aged ≥65 years,
by sex and age group—
National Vital Statistics
System, United States,
2018. MMWR Morb Mortal
Wkly Rep. 2020;69:1470.
[PMID: 33031359]
3. Nuorti JP, Butler JC, Farley
MM, et al. Cigarette smoking and invasive pneumococcal disease. Active
Bacterial Core Surveillance
Team. N Engl J Med.
2000;342:681-9. [PMID:
10706897]
4. Gupta NM, Lindenauer PK,
Yu PC, et al. Association
between alcohol use disorders and outcomes of
patients hospitalized with
community-acquired pneumonia. JAMA Netw Open.
2019;2:e195172. [PMID:
31173120]
5. Patel MS, Patel SB,
Steinberg MB. Smoking
cessation. Ann Intern Med.
2021;174:ITC177-ITC192.
[PMID: 34904907]
6. Kobayashi M, Farrar JL,
Gierke R, et al. Use of 15valent pneumococcal conjugate vaccine and 20-valent
pneumococcal conjugate
vaccine among U.S. adults:
updated recommendations
of the Advisory Committee
on Immunization Practices
—United States, 2022.
MMWR Morb Mortal Wkly
Rep. 2022;71:109-117.
[PMID: 35085226]
7. Moberley S, Holden J,
Tatham DP, et al. Vaccines
for preventing pneumococcal infection in adults.
Cochrane Database Syst
Rev. 2013:CD000422.
[PMID: 23440780]
Persons with comorbid illness and elderly persons are at increased risk for
pneumonia and for having a more
complex course. The death rate from
pneumonia per 100 000 persons increases rapidly with age, from 31.7
among adults aged 65 to 74 years to
377.6 among those aged 85 years or
older (2). Existing respiratory disease,
cardiovascular disease, diabetes mellitus, chronic liver disease, immunosuppression, chronic kidney disease, and
previous splenectomy are associated
with increased incidence of CAP.
Cigarette smoking and alcohol misuse
predispose to severe CAP and to bacteremic pneumococcal infection (3, 4).
Patients should be screened for these
conditions, should be advised to quit,
and should be offered counseling and
pharmacotherapy (5). Other common
comorbid conditions include cancer
and neurologic illnesses that predispose to aspiration, such as seizures and
dementia.
Who should receive pneumococcal
vaccination, and when?
Pneumococcal vaccination is recommended for all persons at increased
risk for pneumococcal infection (Table
1). For persons without high-risk conditions, vaccination should be given at
age 65 years. Patients with risk factors
© 2022 American College of Physicians
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In the Clinic
should be vaccinated when the risk is
first identified.
New recommendations from the Centers
for Disease Control and Prevention
(CDC) vastly simplify the approach to vaccination (6). The 20-valent conjugate vaccine (PCV20) can be given in a single
dose to all patients with risk factors or
those aged 65 years or older. If PCV15
is administered instead, it should be followed by the 23-valent polysaccharide
vaccine (PPSV23) 6 to 12 months later,
or as soon as 8 weeks later for persons
with cochlear implants, cerebrospinal
fluid leaks, or immunosuppressive conditions. Persons who have previously
received only PPSV23 should receive a
dose of PCV15 or PCV20 at least 1 year
later.
A 2013 Cochrane review of pneumococcal vaccination found that it reduces
the frequency of invasive pneumonia in
healthy, immunocompetent adults (7).
There was no evidence of effectiveness
in adults with chronic illness, but there
were very few events and CIs were
wide.
In a subsequent double-blind randomized controlled trial (RCT) of 84 496
adults older than 65 years, PCV13 prevented both bacteremic and nonbacteremic vaccine strain–specific pneumococcal pneumonia and vaccine-type
invasive pneumococcal pneumonia;
Annals of Internal Medicine
April 2022
Table 1. Persons Eligible for Pneumococcal Vaccination
Risk Group
Characteristic or Underlying Medical Condition
Older persons
Immunocompetent persons
Age ≥65 y
Chronic heart disease*
Chronic lung disease†
Diabetes mellitus
Cerebrospinal fluid leak
Cochlear implant
Alcoholism
Chronic liver disease, cirrhosis
Cigarette smoking
Sickle cell disease/other hemoglobinopathy
Congenital or acquired asplenia
Congenital or acquired immunodeficiency‡
HIV infection
Chronic renal failure
Nephrotic syndrome
Leukemia
Lymphoma
Hodgkin disease
Generalized cancer
Iatrogenic immunosuppression§
Solid organ transplant
Multiple myeloma
Persons with functional or anatomic asplenia
Immunocompromised persons
* Includes congestive heart failure and cardiomyopathies but excludes hypertension.
† Includes chronic obstructive pulmonary disease, emphysema, and asthma.
‡ Includes B-lymphocyte (humoral) or T-lymphocyte deficiency, complement deficiencies (particularly
C1, C2, C3, and C4 deficiencies), and phagocytic disorders (excluding chronic granulomatous disease).
§ Diseases requiring treatment with immunosuppressive drugs, including long-term systemic corticosteroids and radiation therapy.
however, it did not reduce all-cause
CAP or mortality (8). Over 4 years, it prevented 41 cases, for a number needed to treat of approximately 1000.
In an RCT of 1006 nursing home residents in Japan, PPSV23 significantly
reduced the frequency and mortality of
pneumococcal pneumonia, as well as
the frequency—but not the mortality—of
all-cause pneumonia (9).
What is the role of influenza
vaccination in the prevention
of CAP and its complications?
Influenza is a common cause of CAP
and may be complicated by bacterial
co-infection (10). By limiting the spread
of influenza, vaccination can reduce the
incidence of CAP and protect vulnerable persons (11). The Advisory Committee on Immunization Practices (ACIP)
recommends yearly influenza vaccine
for all persons older than 6 months.
Although patients with weakened immune systems, older patients, and those
with chronic medical illnesses have the
highest risk for hospitalization and
death, even healthy adults can be hospitalized with influenza and can spread it
to others. Details about specific influenza vaccines were reviewed in a previous In the Clinic article (12).
Prevention... Physicians should screen for tobacco use at every visit; smokers should
be advised to quit, be referred for counseling, and be offered pharmacologic treatment.
Persons at risk for CAP and its complications should be offered pneumococcal and influenza vaccination, and all patients should be encouraged to get COVID-19 vaccination.
CLINICAL BOTTOM LINE
April 2022
Annals of Internal Medicine
In the Clinic
ITC51
8. Bonten MJ, Huijts SM,
Bolkenbaas M, et al.
Polysaccharide conjugate
vaccine against pneumococcal pneumonia in
adults. N Engl J Med.
2015;372:1114-25.
[PMID: 25785969]
9. Maruyama T, Taguchi O,
Niederman MS, et al.
Efficacy of 23-valent pneumococcal vaccine in preventing pneumonia and
improving survival in nursing home residents: double blind, randomised and
placebo controlled trial.
BMJ. 2010;340:c1004.
[PMID: 20211953]
10. Bartley PS, Deshpande A,
Yu PC, et al. Bacterial
coinfection in influenza
pneumonia: rates, pathogens, and outcomes.
Infect Control Hosp
Epidemiol. 2021:1-6.
[PMID: 33890558]
11. Taksler GB, Rothberg MB,
Cutler DM. Association of
influenza vaccination coverage in younger adults
with influenza-related illness in the elderly. Clin
Infect Dis. 2015;61:1495503. [PMID: 26359478]
12. Uyeki TM. Influenza. Ann
Intern Med. 2021;174:
ITC161-ITC176. [PMID:
34748378]
© 2022 American College of Physicians
Diagnosis
CAP accounts for only about 5% of respiratory complaints in the ambulatory
setting. History and physical examination can help suggest the presence of
pneumonia; predict the cause, which
dictates treatment; and define severity,
which determines the site of care.
13. Rowe TA, Jump RLP,
Andersen BM, et al.
Reliability of nonlocalizing
signs and symptoms as
indicators of the presence
of infection in nursinghome residents. Infect
Control Hosp Epidemiol.
2020:1-10. [PMID:
33292915]
14. Metlay JP, Kapoor WN,
Fine MJ. Does this patient
have community-acquired
pneumonia? Diagnosing
pneumonia by history
and physical examination.
JAMA. 1997;278:1440-5.
[PMID: 9356004]
15. Wipf JE, Lipsky BA,
Hirschmann JV, et al.
Diagnosing pneumonia
by physical examination:
relevant or relic. Arch
Intern Med.
1999;159:1082-7. [PMID:
10335685]
16. Metlay JP, Waterer GW,
Long AC, et al. Diagnosis
and treatment of adults
with community-acquired
pneumonia. An official
clinical practice guideline
of the American Thoracic
Society and Infectious
Diseases Society of
America. Am J Respir Crit
Care Med. 2019;200:e45e67. [PMID: 31573350]
17. Graffelman AW, le Cessie
S , Knuistingh Neven A ,
et al. Can history and
exam alone reliably predict pneumonia. J Fam
Pract. 2007;56:465-70.
[PMID: 17543257]
18. Hersh AL, King LM,
Shapiro DJ, et al.
Unnecessary antibiotic
prescribing in US ambulatory care settings, 20102015. Clin Infect Dis.
2021;72:133-7. [PMID:
32484505]
19. Hopstaken RM, Witbraad
T, van Engelshoven JM,
et al. Inter-observer variation in the interpretation
of chest radiographs for
pneumonia in community-acquired lower respiratory tract infections. Clin
Radiol. 2004;59:743-52.
[PMID: 15262550]
20. Claessens YE, Debray MP,
Tubach F, et al. Early chest
computed tomography
scan to assist diagnosis
and guide treatment decision for suspected community-acquired pneumonia. Am J Respir Crit Care
Med. 2015;192:974-82.
[PMID: 26168322]
How is the diagnosis made?
CAP usually presents with both respiratory and systemic symptoms, particularly in young and immunocompetent
persons. It should be suspected when
the patient has cough, purulent sputum, pleuritic chest pain, dyspnea,
fever, and chills. Among older patients
and those with chronic illness, the disease may go unrecognized because
fever may be absent or the patient may
have nonrespiratory symptoms, such as
confusion, weakness, lethargy, falling,
poor oral intake, or decompensation of
a chronic illness (for example, congestive heart failure [CHF]) (13). Most
patients present acutely with symptoms
for 1 to 2 days, but symptoms may be
present for longer in older persons.
Physical findings suggestive of pneumonia include fever or hypothermia,
tachypnea, hypoxia, and rales or bronchial breath sounds on auscultation.
Unfortunately, no single symptom or
finding is sufficiently sensitive or specific
to diagnose or rule out pneumonia, and
prediction rules that combine several
findings have failed to outperform physician judgment (14). Moreover, physicians' agreement on findings is often
poor, and the prognostic value of the
finding varies from one physician to the
next (15). Thus, clinical diagnosis of
pneumonia is often inaccurate, with
overall sensitivity ranging from 70% to
90% and specificity ranging from 40%
to 70% (16, 17). A chest radiograph
(CXR) can confirm the diagnosis and
identify certain complications.
When signs and symptoms from history
(cough, fever, dyspnea, pleuritic pain)
and physical examination (focal crackles,
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In the Clinic
temperature ≥38 C) were used to predict the presence of radiographic pneumonia in a study of 129 patients with
lower respiratory tract infection (26 with
pneumonia), no combination of signs
and symptoms was highly accurate. The
positive predictive value of each varied
from 17% to 43% (17).
When should clinicians obtain a CXR?
In general, when CAP is suspected, a
CXR should be obtained. However, for
otherwise healthy outpatients with clinical features strongly suggestive of
CAP, it is reasonable to forego CXR,
bearing in mind that prescribing antibiotics without a CXR may contribute to
overuse, which is already a major issue
in the United States (18). It is important
to maintain a strong index of suspicion
because elderly and immunosuppressed patients can have radiographic
evidence of pneumonia without clinical
features.
It is especially important to obtain a
CXR if the diagnosis is questionable or
if pleural effusion, lung abscess, necrotizing pneumonia, or multilobar illness
is suspected. Radiographs can aid
patient management if findings of
severe illness are present (bilateral,
multilobar, or rapidly expanding infiltrates), but patterns rarely suggest a
specific cause (for example, tuberculosis, Pneumocystis jirovecii). Radiologists
frequently disagree on the presence of
an infiltrate; thus, a negative study is
more likely to rule out pneumonia than
a positive one is to rule it in (19).
However, if the patient has a convincing history and focal physical findings,
pneumonia may be present even in the
absence of a radiographic infiltrate. In
this setting, computed tomography
(CT) scans may be helpful. One singlecenter study found that routine CT
scanning affected treatment in about
25% of cases (20). Another prospective
study of older patients with suspected
pneumonia found that 30% had their
Annals of Internal Medicine
April 2022
Table 2. Organisms That Commonly Cause Community-Acquired Pneumonia*
Organisms
Frequency, %†
Bacteria
Streptococcus pneumoniae
Staphylococcus aureus
Pseudomonas
Escherichia coli
Klebsiella
Mycoplasma pneumoniae
Chlamydophila pneumoniae
Legionella pneumophila
Haemophilus influenzae
Other Streptococcus species
Mycobacterium tuberculosis
14.0
5.1
1.6
<1
1.4
<1
1.9
<1
1.4
<1
<1
<1
Viruses
Human rhinovirus
Influenza A or B
Adenovirus
Human metapneumovirus
Respiratory syncytial virus
Parainfluenza virus
Coronavirus
27.0
8.6
5.8
1.4
3.9
3.0
3.0
2.3
Fungi
Histoplasma
Coccidioides
1.0
<1
<1
* Adapted from reference 22.
† No discernible cause is found in 62% of patients.
treatment downgraded, and another
15% had it upgraded (21). The economic implications of routine CT scans
for pneumonia diagnosis have not
been established. However, because of
the high cost and radiation exposure, it
should be reserved for cases in which
the diagnosis remains in doubt after
CXR.
viral–bacterial co-infection. The most commonly identified pathogens were human
rhinovirus, influenza, and Streptococcus
pneumoniae (pneumococcus); other
common bacterial pathogens included
Mycoplasma pneumoniae, Staphylococcus aureus, Legionella, and Enterobacteriaceae. Control patients had few
or none of these pathogens.
How is the cause determined?
History and physical examination cannot determine the cause of pneumonia,
which requires laboratory testing. However, the history can identify risk factors
for MDROs, such as hospitalization with
intravenous antibiotic therapy in the
previous 90 days. This is important
because treatment is usually empirical.
History can also identify risk factors for
less common causes of pneumonia,
such as exposure to birds (Chlamydia
psittaci, Cryptococcus neoformans) or
bats (Histoplasma capsulatum) or travel
to the southwestern United States
CAP can be caused by viruses, bacteria, or fungi (Table 2).
A prospective population-based surveillance study conducted at 3 hospitals
in Chicago, Illinois, and 2 in Nashville,
Tennessee, before the COVID-19 pandemic found that despite comprehensive diagnostic testing, a causative
organism was isolated in only 38% of
cases (22). Viruses were present in 27%
of patients, bacteria in 14%, and fungi
in 1%. Three percent of patients had
April 2022
Annals of Internal Medicine
In the Clinic
ITC53
21. Prendki V, Scheffler M,
Huttner B, et al. Low-dose
computed tomography
for the diagnosis of pneumonia in elderly patients:
a prospective, interventional cohort study. Eur
Respir J. 2018;51. [PMID:
29650558]
22. Jain S, Self WH,
Wunderink RG, et al; CDC
EPIC Study Team.
Community-acquired
pneumonia requiring hospitalization among U.S.
adults. N Engl J Med.
2015;373:415-27.
[PMID: 26172429]
© 2022 American College of Physicians
(endemic fungi, such as coccidioidomycosis). This information is useful
if patients do not respond to usual
therapy.
23. Klompas M, Imrey PB, Yu
PC, et al. Respiratory viral
testing and antibacterial
treatment in patients hospitalized with communityacquired pneumonia.
Infect Control Hosp
Epidemiol. 2021;42:81725. [PMID: 33256870]
24. Schimmel JJ, Haessler S,
Imrey P, et al.
Pneumococcal urinary
antigen testing in United
States hospitals: a missed
opportunity for antimicrobial stewardship. Clin
Infect Dis. 2020;71:142734. [PMID: 31587039]
25. Self WH, Balk RA, Grijalva
CG, et al. Procalcitonin as
a marker of etiology in
adults hospitalized with
community-acquired
pneumonia. Clin Infect
Dis. 2017;65:183-90.
[PMID: 28407054]
26. Upadhyay S, Niederman
MS. Biomarkers: what is
their benefit in the identification of infection, severity assessment, and
management of community-acquired pneumonia.
Infect Dis Clin North Am.
2013;27:19-31. [PMID:
23398863]
27. Christ-Crain M, Stolz D,
Bingisser R, et al.
Procalcitonin guidance of
antibiotic therapy in community-acquired pneumonia: a randomized trial.
Am J Respir Crit Care
Med. 2006;174:84-93.
[PMID: 16603606]
28. Vaughn VM, Flanders SA,
Snyder A, et al. Excess antibiotic treatment duration
and adverse events in
patients hospitalized with
pneumonia: a multihospital cohort study. Ann
Intern Med.
2019;171:153-63. [PMID:
31284301]
What is the role of laboratory tests?
For outpatients, no tests are needed
beyond pulse oximetry and a rapid
influenza test during influenza season
(12). For inpatients, additional testing
may be required to define disease severity and identify the cause. Clinicians
should measure pulse oximetry in all
patients and arterial blood gases if carbon dioxide retention is suspected.
Even with extensive diagnostic testing,
a specific cause is found in fewer than
half of patients (22). Blood culture
results are positive in only about 10%
of patients with CAP, and in low-risk
patients (hospitalized without severe illness), the incidence of false-positive
results may exceed the incidence of
true-positive results, leading to potential overtreatment (16). Thus, blood cultures should not be ordered routinely.
In patients with severe pneumonia and
patients suspected of being infected
with an MDRO or an unusual pathogen,
2 sets of blood cultures should be collected before therapy is started, and
sputum should be collected if a goodquality sample can be obtained. Urine
should be tested for Legionella and
pneumococcal antigens.
Serologic tests for viruses and atypical
pathogens are not useful because they
require convalescent titers in 6 to 8
weeks to identify infection. Rapid diagnostic tests for viral pathogens, such as
rapid antigen testing, direct fluorescent
antibody, or polymerase chain reaction
(PCR), are available and should be considered, especially during local outbreaks (for example, during influenza
season or a COVID-19 outbreak). The
role of these tests in managing patients
with CAP and in guiding antibiotic
selection is not yet established, although some studies have shown that
they may reduce unnecessary antibiotic
use and increase antiviral prescribing,
especially when results are positive for
influenza (23). Similarly, testing for
© 2022 American College of Physicians
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In the Clinic
COVID-19 can inform isolation and
treatment. Other rapid diagnostic testing, such as streptococcal and Legionella urinary antigen testing, can reduce the use of overly broad empirical
antibiotic coverage and promote antimicrobial stewardship (24).
Measurement of serum procalcitonin
has been proposed to differentiate
between bacterial and viral infections.
Levels are usually elevated with bacterial and Legionella infection, but not
always with other atypical pathogens
and not with viral infections (25). In prospective studies, however, the sensitivity is too low to reliably identify patients
who do not require antibiotics, so procalcitonin is not recommended for this
purpose. Alternatively, among hospitalized patients with an initially elevated
procalcitonin level, serial measurements may help determine when to
stop antibiotic therapy (26).
A randomized trial of 302 patients hospitalized with CAP compared those
managed with usual care versus those
managed with an algorithm recommending antibiotics and the duration of
therapy. The algorithm was based on
serial measurement of procalcitonin
levels on admission and after 6 to 24
hours, 4 days, 6 days, and 8 days. The
procalcitonin-guided group had significantly less antibiotic use, and the duration of therapy was reduced from 12 to
5 days with similar clinical success (27).
What other disorders should
clinicians consider in patients
suspected of having CAP?
Most CAP responds to empirical antibiotics within 48 to 72 hours (28). If the
patient does not respond within this
window, clinicians should consider the
possibility of a resistant bacterium; a
virus; or unusual bacterial pathogens,
such as Mycobacterium tuberculosis
(which may be masked by a partial
response to empirical quinolone therapy
for CAP) or endemic fungi (histoplasmosis, coccidioidomycosis, blastomycosis).
Clinicians should also consider noninfectious possibilities, such as bronchiolitis
Annals of Internal Medicine
April 2022
obliterans with organizing pneumonia,
pulmonary vasculitis, hypersensitivity
pneumonitis, interstitial diseases, lung
cancer, lymphangitic carcinoma, bronchoalveolar cell carcinoma, lymphoma,
or CHF. If the patient's condition
deteriorates after an initial response to
therapy, clinicians should consider pulmonary embolus; antibiotic-induced colitis; and the pneumonia complications
of empyema, meningitis, and endocarditis.
Diagnosis... History is valuable for defining risk factors for specific pathogens, and
physical findings help define disease severity. Clinical findings are less dramatic in elderly persons. Clinicians should confirm the diagnosis of CAP with a CXR, or a CT scan if
the CXR is negative and suspicion is high. Laboratory testing can also help to define severity and identify complications. Diagnosing specific pathogens early can help to guide
antiviral therapy and empirical antibiotic selection. If the patient does not respond to initial therapy, a specialist should be consulted.
CLINICAL BOTTOM LINE
Treatment
What is the overall approach to
treatment, and how should clinicians
determine whether a patient with
CAP requires outpatient, inpatient,
or ICU care?
Treatment decisions are based on severity of illness. The first step is determining the appropriate site of care—
outpatient, hospital, or ICU—and the
second is choosing the appropriate
treatment. Hospitalization decisions
can be facilitated with the Pneumonia
Severity Index (PSI) or the British
Thoracic Society (BTS) rule (Figures 1
and 2), which predict risk for death.
Patients at high risk are generally managed in the hospital. The PSI stratifies
patients into 5 categories based on
age, comorbid illness, physical examination findings, and laboratory data. In
general, patients in classes I and II are
treated as outpatients, those in class III
require careful clinical assessment to
determine the site of care, and those in
classes IV and V are admitted to the
hospital. The BTS rule, or “CURB-65,”
evaluates patients for the presence of
Confusion, blood Urea nitrogen level
above 7.0 mmol/L (>19.6 mg/dL),
Respiratory rate of 30 breaths/min or
higher, systolic Blood pressure below
April 2022
Annals of Internal Medicine
90 mm Hg or diastolic blood pressure
of 60 mm Hg or lower, and age 65
years or older. Patients meeting at least
2 of these criteria are usually hospitalized (16, 29, 30). For select patients, a
hospital-at-home program can substitute for inpatient care, reduce costs,
and prevent readmissions (31).
A prospective study of 3181 patients
seen in 32 emergency departments
compared the PSI with the CURB-65 criteria and found that both approaches
accurately identified low-risk patients.
CURB-65 was better for predicting mortality in high-risk patients (29). In another
prospective study of 1651 patients,
measurement of serum procalcitonin
levels supplemented data obtained by
prognostic scoring, and patients who
had low procalcitonin levels had low
mortality, regardless of PSI class or
CURB-65 score (30).
The PSI and CURB-65 were not developed to predict need for ICU care.
Current guidelines recommend ICU care
if the patient requires assisted ventilation, has septic shock requiring vasopressors, or has at least 3 of the
following: respiratory rate of 30 breaths/
min or higher, PaO2–FiO2 ratio of 250 or
In the Clinic
ITC55
29. Aujesky D, Auble TE, Yealy
DM, et al. Prospective
comparison of three validated prediction rules for
prognosis in communityacquired pneumonia. Am
J Med. 2005;118:38492. [PMID: 15808136]
30. Huang DT, Weissfeld LA,
Kellum JA, et al; GenIMS
Investigators. Risk prediction with procalcitonin
and clinical rules in community-acquired pneumonia. Ann Emerg Med.
2008;52:48-58.e2.
[PMID: 18342993]
31. Levine DM, Ouchi K,
Blanchfield B, et al.
Hospital-level care at
home for acutely ill
adults: a randomized controlled trial. Ann Intern
Med. 2020;172:77-85.
[PMID: 31842232]
© 2022 American College of Physicians
Figure 1. Pneumonia Severity Index for evaluating severity of illness in community-acquired
pneumonia.
Factor
Demographic Factors
Age
Female sex
Nursing home resident
Comorbid Illnesses
Neoplastic disease
Liver disease
Congestive heart failure
Cerebrovascular disease
Renal disease
Physical Examination Findings
Altered mental status
Respiratory rate ≥30 breaths/min
Systolic blood pressure <90 mm Hg
Temperature <95 °F or ≥104 °F
Pulse ≥125 beats/min
Laboratory and Radiographic Findings
Arterial pH <7.35
BUN level ≥30 mg/dL
Sodium level <130 mEq/L
Glucose level ≥250 mg/dL
Hematocrit <30%
PaO2 <60 mm Hg or oxygen saturation <90%
Pleural effusion
Score
<51
51–70
71–90
91–130
>130
Risk Class
I
II
III
IV
V
Points
1 per year
-10
+10
+30
+20
+10
+10
+10
+20
+20
+20
+15
+10
+30
+20
+20
+10
+10
+10
+10
Interpretation
Mortality
0.1%
0.6%
0.9%
9.3%
27.0%
Recommendation
Outpatient
Outpatient
Careful assessment
Inpatient
Inpatient
BUN = blood urea nitrogen.
lower, multilobar infiltrates, confusion or
disorientation, blood urea nitrogen level
of 7.1 mmol/L (20 mg/dL) or higher, leukocyte count below 4 109 cells/L, platelet count below 100 109 cells/L,
temperature below 36 C, and hypotension requiring aggressive fluid resuscitation (16).
Figure 2. CURB-65 score for evaluating severity
of illness in community-acquired pneumonia.
32. Gupta V, Yu KC, Schranz
J, et al. A multicenter
evaluation of the US prevalence and regional variation in macrolide-resistant
S. pneumoniae in ambulatory and hospitalized
adult patients in the
United States. Open
Forum Infect Dis. 2021;8:
ofab063. [PMID:
34250183]
Factor
Confusion
Blood Urea nitrogen level >19 mg/dL
Respiratory rate ≥30 breaths/min
Systolic Blood pressure <90 mm Hg or
diastolic Blood pressure ≤60 mm Hg
Age ≥65 y
Total
Score
0 or 1
2
≥3
© 2022 American College of Physicians
Points
1
1
1
1
1
_____
Interpretation
Mortality
Recommendation
1.5%
Outpatient
9.2%
Inpatient
22%
Inpatient
ITC56
In the Clinic
Which antibiotics should be
prescribed for outpatients?
For patients without cardiopulmonary
disease or factors that increase risk for
infection with MDROs, the American
Thoracic Society/Infectious Diseases
Society of America (ATS/IDSA) guidelines recommend high-dose amoxicillin, doxycycline, or a macrolide (azithromycin, clarithromycin, or erythromycin), with macrolides appropriate
only in areas where fewer than 25% of
pneumococcal isolates are resistant to
macrolides (Table 3; Appendix Table,
available at Annals.org). In most of the
United States, macrolide resistance
now exceeds 30% (32). For outpatients
with cardiopulmonary disease or factors that increase risk for infection with
drug-resistant S pneumoniae (DRSP) or
enteric gram-negative bacteria, treatment should include a respiratory
Annals of Internal Medicine
April 2022
Table 3. Initial Treatment Strategies for Inpatients With CAP, by Level of Severity and Risk for Drug Resistance
Level of Severity
Standard Regimen
Prior Respiratory Isolation
of MRSA
Prior Respiratory Isolation
of Pseudomonas
aeruginosa
Recent Hospitalization and
Parenteral Antibiotics and
Locally Validated Risk
Factors for MRSA
Recent Hospitalization and
Parenteral Antibiotics and
Locally Validated Risk
Factors for P aeruginosa
Nonsevere inpatient
pneumonia*
b-Lactam þ macrolide† or Add MRSA coverage§ and Add coverage for
Obtain cultures but withObtain cultures but
respiratory
obtain cultures/nasal PCR P aeruginosa|| and obtain hold MRSA coverage
initiate coverage for
fluoroquinolone‡
to allow deescalation or
cultures to allow deescala- unless culture results are
P aeruginosa only if
confirmation of need for
tion or confirmation of
positive
culture results are positive
continued therapy
need for continued
If rapid nasal PCR is availtherapy
able, add coverage if PCR
result is positive and
obtain cultures
Severe inpatient
pneumonia*
b-Lactam þ macrolide† or Add MRSA coverage§ and Add coverage for
Add MRSA coverage§ and Add coverage for
b-lactam þ fluoroquinoobtain cultures/nasal PCR P aeruginosa|| and
obtain nasal PCR and cul- P aeruginosa|| and obtain
lone‡
to allow deescalation or
obtain cultures to allow
tures to allow deescalation cultures to allow deescalaconfirmation of need for
deescalation or confirma- or confirmation of need
tion or confirmation of
continued therapy
tion of need for continued for continued therapy
need for continued
therapy
therapy
ATS = American Thoracic Society; CAP = community-acquired pneumonia; HAP = hospital-acquired pneumonia; IDSA = Infectious
Diseases Society of America; MRSA = methicillin-resistant Staphylococcus aureus; PCR = polymerase chain reaction; VAP = ventilatorassociated pneumonia.
* As defined by the 2007 ATS/IDSA CAP severity criteria guidelines.
† Ampicillin þ sulbactam, 1.5 to 3 g every 6 hours; cefotaxime, 1 to 2 g every 8 hours; ceftriaxone, 1 to 2 g/d; or ceftaroline, 600 mg
every 12 hours, and azithromycin, 500 mg/d, or clarithromycin, 500 mg twice daily.
‡ Levofloxacin, 750 mg/d, or moxifloxacin, 400 mg/d.
§ Per the 2016 ATS/IDSA HAP/VAP guidelines: vancomycin (15 mg/kg every 12 hours, adjust on basis of levels) or linezolid (600 mg
every 12 hours).
|| Per the 2016 ATS/IDSA HAP/VAP guidelines: piperacillin–tazobactam (4.5 g every 6 hours), cefepime (2 g every 8 hours), ceftazidime (2 g every 8 hours), imipenem (500 mg every 6 hours), meropenem (1 g every 8 hours), or aztreonam (2 g every 8 hours). Does
not include coverage for extended-spectrum b-lactamase–producing Enterobacteriaceae, which should be considered only on the
basis of patient or local microbiological data.
fluoroquinolone (levofloxacin or moxifloxacin) or a combination of a b-lactam
(amoxicillin–clavulanate, cefpodoxime,
or cefuroxime) with a macrolide or doxycycline. If the patient has received an
antibiotic in the previous 3 months, antibiotics of the same class should be
avoided.
How long should outpatients continue
antibiotic treatment?
In general, it is important to keep antibiotic courses as short as possible to
avoid adverse drug events and antibiotic resistance. The duration of therapy
should be based on the patient's clinical response, severity of illness, and
probable pathogen. Outpatients with
mild to moderate CAP can be treated
for as few as 3 to 5 days if clinical
response is good, there has been no
fever for 48 to 72 hours, and there are
no signs of extrapulmonary infection
(33). Persistent cough and sputum production are not reasons to prolong antibiotic therapy.
April 2022
Annals of Internal Medicine
How should clinicians follow patients
during outpatient treatment?
Up to 10% of patients initially managed
at home do not respond to therapy
and require hospitalization (34). The
evidence base for home therapy is limited, but prudence dictates the need
for careful follow-up. Patients should
be told to measure their temperature
orally every 8 hours and to report if it
exceeds 38.3 C (101 F) or does not
fall below 37.2 C (99 F) after 48 hours.
Patients should be encouraged to drink
1 to 2 quarts of liquid daily and report if
they cannot achieve this goal. Clinicians should instruct patients to report
chest pain, severe or increasing shortness of breath, or lethargy.
A follow-up visit, either in person or virtually, should be arranged in 24 to 48
hours to confirm the response to therapy. If the response is satisfactory, the
patient should return for an examination in 10 to 14 days. At that time,
In the Clinic
ITC57
33. Dinh A, Ropers J, Duran
C, et al; Pneumonia Short
Treatment (PTC) Study
Group. Discontinuing
b-lactam treatment after
3 days for patients with
community-acquired
pneumonia in non-critical
care wards (PTC): a double-blind, randomised,
placebo-controlled, noninferiority trial. Lancet.
2021;397:1195-203.
[PMID: 33773631]
34. Tillotson G, Lodise T,
Classi P, et al. Antibiotic
treatment failure and
associated outcomes
among adult patients
with community-acquired
pneumonia in the outpatient setting: a real-world
US insurance claims database study. Open Forum
Infect Dis. 2020;7:
ofaa065. [PMID:
32195289]
© 2022 American College of Physicians
pneumococcal and influenza vaccinations should be administered if they
have not been previously. For patients
whose symptoms resolve within 5 to 7
days, a follow-up CXR is not necessary
(16). For smokers concerned about
underlying lung cancer, routine screening with low-dose CT is appropriate. If
the pneumonia is not resolving, additional imaging, laboratory testing, and
microbiological work-up are indicated.
35. Centers for Medicare &
Medicaid Services.
Hospital Quality Initiative
Overview. July 2008.
36. Meehan TP, Fine MJ,
Krumholz HM, et al.
Quality of care, process,
and outcomes in elderly
patients with pneumonia.
JAMA. 1997;278:2080-4.
[PMID: 9403422]
37. Kanwar M, Brar N, Khatib
R, et al. Misdiagnosis of
community-acquired
pneumonia and inappropriate utilization of antibiotics: side effects of the 4h antibiotic administration
rule. Chest.
2007;131:1865-9. [PMID:
17400668]
38. Horita N, Otsuka T,
Haranaga S, et al. Betalactam plus macrolides or
beta-lactam alone for
community-acquired
pneumonia: a systematic
review and meta-analysis.
Respirology.
2016;21:1193-200.
[PMID: 27338144]
39. Martínez JA, Horcajada
JP, Almela M, et al.
Addition of a macrolide to
a beta-lactam-based empirical antibiotic regimen
is associated with lower
in-hospital mortality for
patients with bacteremic
pneumococcal pneumonia. Clin Infect Dis.
2003;36:389-95. [PMID:
12567294]
40. Lujan M, Gallego M,
Fontanals D, et al.
Prospective observational
study of bacteremic pneumococcal pneumonia:
effect of discordant therapy on mortality. Crit Care
Med. 2004;32:625-31.
[PMID: 15090938]
41. Yu VL, Chiou CC, Feldman
C, et al; International
Pneumococcal Study
Group. An international
prospective study of pneumococcal bacteremia: correlation with in vitro
resistance, antibiotics
administered, and clinical
outcome. Clin Infect Dis.
2003;37:230-7. [PMID:
12856216]
What is the approach to antibiotic
therapy for patients hospitalized with
CAP outside the ICU?
Patients should receive initial antibiotic
therapy as soon as possible after diagnosis. Although therapy within 4 hours
of arrival in the emergency department
has been associated with reduced mortality, an undue emphasis on early therapy may lead to unnecessary use of
antibiotics and associated complications (35, 36). In 1 study, the final diagnosis of pneumonia in patients suspected of having it in the emergency
department decreased from 75.9% to
58.9% after initiation of a program to
give patients antibiotics within 4 hours
of arrival in the emergency department
(37).
Specific therapies should be guided by
the diagnosis. Patients at risk for infection with methicillin-resistant S aureus
(MRSA), DRSP, and resistant gram-negative organisms require extendedspectrum empirical therapy. Many risk
factors have been identified for each of
these infections, but they tend to be
only weakly associated and should not
be relied on when choosing therapy.
Importantly, the previous designation
of health care–associated pneumonia
has been abandoned because it was
not particularly associated with resistant infections and led to increased use
of extended-spectrum antibiotics. The
2 consistently strong risk factors are
previous isolation of the resistant organism, especially from the respiratory
tract, and hospitalization within 90 days
with administration of antibiotics. Despite multiple attempts to create models
© 2022 American College of Physicians
ITC58
In the Clinic
to identify resistant organisms based
on patient risk factors, none have been
sufficiently validated for use in clinical
practice. Such validation is important
because the prevalence of resistant
organisms is low and varies among
hospitals. Recognizing this fact, the
ATS/IDSA guidelines recommend that
hospitals validate their own local risk
factors or else treat patients on the basis of a history of resistant infections or
recent hospitalization with antibiotics. If
available, rapid nasal PCR for MRSA
can be used to guide empirical therapy. Patients with influenza pneumonia
should receive treatment with a neuraminidase inhibitor, even if they have
been sick for more than 48 hours (12).
Because co-infection is common, they
should also receive antibiotics, at least
until culture results are available. Such
patients are at increased risk for S aureus infection but not for MRSA and
may therefore be treated with standard
antibiotics (10).
For patients without risk factors for resistant bacteria, guidelines recommend
treatment with either an intravenous or
oral quinolone (levofloxacin, 750 mg/d,
when renal function is normal, or
moxifloxacin, 400 mg/d) or the combination of a b-lactam (cefotaxime,
ceftriaxone, ampicillin–sulbactam, or
high-dose ampicillin, but not cefuroxime) plus a macrolide or doxycycline
(16). The addition of a macrolide to a
b-lactam has been associated with
reduced mortality, although this benefit may be limited to patients with
severe pneumonia (38). Even those
with bacteremic pneumococcal pneumonia seem to benefit from added
macrolide coverage (39). Specific
b-lactams, such as ceftriaxone and
cefotaxime, are preferred if DRSP is
suspected because they are effective
at mean inhibitory concentrations up
to 2 mg/L (40). However, 1 study
showed increased mortality when
cefuroxime was used in patients with
bacteremic DRSP (41).
An international study of 4337 hospitalized patients with CAP showed that
approximately 20% had evidence of
Annals of Internal Medicine
April 2022
atypical pathogen infection and that
therapy directed against these organisms decreased time to clinical stability,
length of stay, and both total and CAPrelated mortality (42). Another study of
2209 hospitalized Medicare patients
with bacteremic pneumonia found that
therapy directed at atypical pathogens
reduced 30-day mortality and 30-day
readmission rate, but the benefits
occurred only with macrolides and not
with fluoroquinolones (43).
Patients who have had a resistant organism in the past should receive therapy
directed at the previously isolated organism. Therapy for suspected MRSA
includes vancomycin (15 mg/kg every
12 hours, with adjustment based on
levels) or linezolid (600 mg every 12
hours) but may be withheld if nasal
PCR results are negative. Therapy for
suspected gram-negative infections
includes piperacillin–tazobactam (4.5 g
every 6 hours), cefepime (2 g every 8
hours), ceftazidime (2 g every 8 hours),
imipenem (500 mg every 6 hours), meropenem (1 g every 8 hours), or aztreonam (2 g every 8 hours). If culture
results are negative at 48 hours and
the patient is clinically stable, the antibiotic regimen may be deescalated. Although there are no randomized trials
of deescalation after negative culture
results, there is a strong evidence base
from observational studies.
A study of 165 U.S. hospitals found that
among 14 170 patients who received
extended-spectrum antibiotics, only
13% had them deescalated by hospital
day 4. Deescalation seemed to be safe
and was associated with lower odds of
subsequent transfer to the ICU (adjusted odds ratio, 0.38 [95% CI, 0.18 to
0.79]), shorter hospital stay, and lower
costs in propensity-matched analyses.
Importantly, hospital deescalation rates
ranged from 2% to 35%, and even hospitals in the top quartile of deescalation
failed to deescalate more than 50% of
their lowest-risk patients, leaving ample
room for improvement (44).
April 2022
Annals of Internal Medicine
Patients whose only risk factor is recent
hospitalization with antibiotic administration should have cultures obtained, but
antibiotics against MRSA or Pseudomonas
should be withheld unless culture results
are positive or the patient's condition
deteriorates.
Which antibiotics should be given to
patients admitted to the ICU?
Patients in the ICU should receive empirical therapy with at least 2 antibiotics
(16). Clinicians should assess for risk
factors for Pseudomonas aeruginosa
and treat those without risk factors with
intravenous ceftriaxone or cefotaxime
plus either azithromycin or a respiratory quinolone. Patients with risk factors should be treated with an
intravenous, antipseudomonal b-lactam (cefepime, piperacillin–tazobactam, imipenem, meropenem) plus an
intravenous quinolone effective against
P aeruginosa (ciprofloxacin or highdose levofloxacin). Alternatively, an intravenous, antipseudomonal b-lactam
combined with an aminoglycoside
(amikacin, gentamicin, or tobramycin)
plus either an intravenous macrolide
(azithromycin or erythromycin) or an intravenous antipneumococcal quinolone (levofloxacin or moxifloxacin)
should be used. In studies of patients
admitted to the ICU with severe CAP,
mortality was reduced when combination therapy was used; monotherapy, even with a quinolone, was not as
effective.
A 2012 meta-analysis of 28 observational studies involving nearly 10 000 critically ill patients found that macrolide
use (generally in a combination regimen) was associated with an 18%
reduction in mortality compared with
nonmacrolide regimens and that a
b-lactam–macrolide combination had a
trend toward reduced mortality compared with a b-lactam–quinolone regimen (45). In patients with bacteremic
pneumococcal pneumonia and critical
illness, studies have found that mortality
was lower with combination therapy
than with monotherapy (46).
In the Clinic
ITC59
42. Arnold FW, Summersgill
JT, Lajoie AS, et al;
Community-Acquired
Pneumonia Organization
(CAPO) Investigators. A
worldwide perspective of
atypical pathogens in
community-acquired
pneumonia. Am J Respir
Crit Care Med.
2007;175:1086-93.
[PMID: 17332485]
43. Metersky ML, Ma A,
Houck PM, et al.
Antibiotics for bacteremic
pneumonia: improved
outcomes with macrolides
but not fluoroquinolones.
Chest. 2007;131:466-73.
[PMID: 17296649]
44. Deshpande A, Richter SS,
Haessler S, et al. De-escalation of empiric antibiotics following negative
cultures in hospitalized
patients with pneumonia:
rates and outcomes. Clin
Infect Dis. 2021;72:131422. [PMID: 32129438]
45. Sligl WI, Asadi L, Eurich
DT, et al. Macrolides and
mortality in critically ill
patients with communityacquired pneumonia: a
systematic review and
meta-analysis. Crit Care
Med. 2014;42:420-32.
[PMID: 24158175]
46. Baddour LM, Yu VL,
Klugman KP, et al;
International
Pneumococcal Study
Group. Combination antibiotic therapy lowers mortality among severely ill
patients with pneumococcal bacteremia. Am J
Respir Crit Care Med.
2004;170:440-4. [PMID:
15184200]
© 2022 American College of Physicians
47. Girou E, Schortgen F,
Delclaux C, et al.
Association of noninvasive
ventilation with nosocomial infections and survival in critically ill
patients. JAMA.
2000;284:2361-7. [PMID:
11066187]
48. Stern A, Skalsky K, Avni T,
et al. Corticosteroids for
pneumonia. Cochrane
Database Syst Rev.
2017;12:CD007720.
[PMID: 29236286]
49. Horby P, Lim WS,
Emberson JR, et al;
RECOVERY Collaborative
Group. Dexamethasone in
hospitalized patients with
Covid-19. N Engl J Med.
2021;384:693-704.
[PMID: 32678530]
50. Belforti RK, Lagu T,
Haessler S, et al.
Association between initial route of fluoroquinolone administration and
outcomes in patients hospitalized for communityacquired pneumonia. Clin
Infect Dis. 2016;63:1-9.
[PMID: 27048748]
51. Fishbane S, Niederman
MS, Daly C, et al. The
impact of standardized
order sets and intensive
clinical case management
on outcomes in community-acquired pneumonia.
Arch Intern Med.
2007;167:1664-9. [PMID:
17698690]
52. Ciarkowski CE, Timbrook
TT, Kukhareva PV, et al. A
pathway for communityacquired pneumonia with
rapid conversion to oral
therapy improves health
care value. Open Forum
Infect Dis. 2020;7:
ofaa497. [PMID:
33269294]
53. Graham WG, Bradley DA.
Efficacy of chest physiotherapy and intermittent
positive-pressure breathing in the resolution of
pneumonia. N Engl J
Med. 1978;299:624-7.
[PMID: 355879]
54. Yang M, Yan Y, Yin X, et
al. Chest physiotherapy
for pneumonia in adults.
Cochrane Database Syst
Rev. 2013:CD006338.
[PMID: 23450568]
55. Stefan MS, Priya A, Pekow
PS, et al. The comparative
effectiveness of noninvasive and invasive ventilation in patients with
pneumonia. J Crit Care.
2018;43:190-6. [PMID:
28915393]
What are the other components of
ICU care for CAP?
Hydration should be ensured and supplemental oxygen should be given to
maintain oxygen saturation above 90%.
Chest physiotherapy should be considered. Intubation and mechanical ventilation are required in patients with
oxygen saturation below 90% on maximal mask oxygen, inability to clear
secretions, inability to protect the airway, or hypercarbia. If the patient has
only hypoxemia or hypercarbia and is
alert and cooperative, noninvasive positive-pressure ventilation should be
considered. This therapy is associated
with fewer complications than endotracheal intubation, including ventilatorassociated pneumonia (47). Studies of
steroids in CAP tend to be small and
heterogeneous in nature (48). Many
are subject to bias and report problematic outcomes, such as length of stay.
Therefore, routine use of systemic corticosteroids is not recommended, but
patients with refractory septic shock
(16) or COVID-19 requiring ventilator
support may benefit from steroids (49).
When can clinicians transition
hospitalized patients from
intravenous to oral antibiotics?
Switching to oral antibiotics is indicated
once cough, sputum production, and
dyspnea improve; the patient is afebrile on 2 occasions 8 hours apart; and
they are able to take oral medications.
This switch can be made as early as 24
to 48 hours after admission and can be
done safely even if pneumococcal bacteremia has been documented. Longer
durations of therapy are usually
needed for patients infected with P aeruginosa or S aureus and for those with
extrapulmonary complications, such as
empyema or meningitis, but should be
individualized to specific patient situations. An oral regimen that covers all
organisms isolated in blood or sputum
cultures and corresponds to the intravenous therapy should be selected.
For some patients, this means a blactam–macrolide combination or qui-
© 2022 American College of Physicians
ITC60
In the Clinic
nolone monotherapy. Patients who
have responded to a b-lactam–macrolide combination can be continued on
macrolide monotherapy unless culture
results justify dual therapy. Quinolones
have excellent oral bioavailability. For
patients with a working gastrointestinal
tract, there is little added benefit to intravenous quinolones (50).
To facilitate a switch to oral therapy,
hospitals should consider using a
standing order set supplemented by
antibiotic stewardship. Such programs
have been shown to reduce the number of days patients receive intravenous therapy and shorten hospital stay
(51). Gains seem to be maintained
even after stewardship efforts are
reduced, and the program can save
money (52).
What is the role of nondrug therapies?
In outpatients, nondrug therapy consists of oral hydration. For hospitalized
patients, nondrug therapies include intravenous hydration and oxygen for hypoxemia. Chest physiotherapy has not
been widely studied but can improve
outcomes in patients with pneumonia
who have more than 30 mL of sputum
per day and impaired clearance of
secretions (53).
A 2013 meta-analysis of 6 randomized
trials involving 434 patients evaluated
the following 4 types of chest physiotherapy: conventional chest physiotherapy, active cycle breathing, osteopathic
manipulation, and positive expiratory
pressure. No method reduced mortality, but osteopathic manipulation and
positive expiratory pressure reduced
the duration of hospital stay by 2.02
and 1.4 days, respectively (54).
In severely ill patients, nondrug therapy
can include noninvasive ventilatory
support and mechanical ventilation for
those with respiratory failure. One
observational study found that noninvasive ventilation was associated with
lower mortality, but only for patients
with comorbid chronic obstructive pulmonary disease (COPD) or CHF (55).
Annals of Internal Medicine
April 2022
When should a consultation be
requested for hospitalized patients,
and which types of specialists or
subspecialists should be consulted?
An infectious disease consultation is
appropriate if there are questions
about initial antibiotic therapy or when
the patient does not respond to initial
therapy. Questions about appropriate
site of care or the need for vasopressors or ventilatory support are appropriate indications for critical care
consultation. Pulmonary or thoracic
surgical consultation is appropriate for
placement of a chest tube if a complicated parapneumonic effusion or empyema is found on thoracentesis
because early therapy can reduce hospital stay and avoid complications.
Cardiology consultation may be needed in cases of ischemia or CHF.
In a study of 170 patients with pneumococcal pneumonia, 19.4% had at least 1
major cardiac event, including 12 with
acute myocardial infarction, 8 with newonset atrial fibrillation or ventricular
tachycardia, and 13 with newly diagnosed or worsening heart failure without
other cardiac complications. Patients
with cardiac events had significantly
higher mortality (27.3% vs. 8.8%) (56).
When can patients be discharged from
the hospital, and how long should
antibiotics be continued?
Patients can be discharged once they are
clinically stable (temperature ≤37.8 C,
heart rate <100 beats/min, respiratory
rate <24 breaths/min, oxygen saturation
≥90%, systolic blood pressure ≥90 mm
Hg, and normal mental status) (57).
Therapy may be continued after discharge, but the total duration should not
exceed 5 to 7 days. In some cases, 3
days may be sufficient (33). Excess treatment is common, particularly after discharge, and is associated with increased
incidence of adverse drug events (28). If
switching to oral therapy, it is not necessary to observe the response in the
April 2022
Annals of Internal Medicine
hospital. In one study, clinically stable
patients were observed on oral therapy before discharge, and no deterioration occurred (58). Another study
compared patients who remained in
the hospital for 1 day after the switch
with those discharged on the same
day and found no differences in mortality or 14-day readmission rate (59).
Patients may be discharged on intravenous antibiotics as long as they are
clinically stable; consultation with an
infectious disease specialist can ensure that the duration and route of
outpatient therapy are appropriate
(60). Programs directed by infectious
disease specialists seem to produce
better outcomes at lower costs (61).
What are the indications for followup CXR after discharge?
Routine CXR before discharge is
unnecessary, but patients who do not
achieve clinical stability and those who
deteriorate despite therapy require
an aggressive evaluation, including
CXR. As with outpatient pneumonia, if
the patient has a good clinical response to therapy, CXR need not be
repeated.
How can patients prevent recurrent
CAP?
Patients should receive pneumococcal
and influenza vaccinations; avoid
smoking; and optimize treatment of
comorbid illnesses, such as CHF and
COPD. They should be evaluated for
medical conditions that could predispose them to recurrent infection. One
study found that 6% of patients with
CAP had a new comorbid condition,
including diabetes mellitus, cancer,
COPD, and HIV infection (62). If pneumonia recurs in the same location, the
possibility of bronchiectasis, aspirated
foreign body, or endobronchial obstruction should be considered. Recurrent pneumonia or pneumonia with
an unusual pathogen may signal
immunodeficiency.
In the Clinic
ITC61
56. Musher DM, Rueda AM,
Kaka AS, et al. The association between pneumococcal pneumonia and
acute cardiac events. Clin
Infect Dis. 2007;45:15865. [PMID: 17578773]
57. Mandell LA, Wunderink
RG, Anzueto A, et al;
Infectious Diseases
Society of America.
Infectious Diseases
Society of America/
American Thoracic Society
consensus guidelines on
the management of community-acquired pneumonia in adults. Clin Infect
Dis. 2007;44 Suppl 2:
S27-72. [PMID:
17278083]
58. Rhew DC, Hackner D,
Henderson L, et al. The
clinical benefit of in-hospital observation in ‘lowrisk’ pneumonia patients
after conversion from parenteral to oral antimicrobial therapy. Chest.
1998;113:142-6. [PMID:
9440581]
59. Nathan RV, Rhew DC,
Murray C, et al. In-hospital observation after antibiotic switch in
pneumonia: a national
evaluation. Am J Med.
2006;119:512.e1-7.
[PMID: 16750965]
60. Sharma R, Loomis W,
Brown RB. Impact of mandatory inpatient infectious
disease consultation on
outpatient parenteral antibiotic therapy. Am J Med
Sci. 2005;330:60-4.
[PMID: 16103785]
61. Shah A, Petrak R,
Fliegelman R, et al.
Infectious diseases specialty intervention is associated with better
outcomes among privately insured individuals
receiving outpatient parenteral antimicrobial therapy. Clin Infect Dis.
2019;68:1160-5. [PMID:
30247512]
62. Falguera M, Martín M,
Ruiz-González A, et al.
Community-acquired
pneumonia as the initial
manifestation of serious
underlying diseases. Am
J Med. 2005;118:37883. [PMID: 15808135]
© 2022 American College of Physicians
In a 2014 review of 12 studies, the 30-day
readmission rate for patients with CAP varied from 16.8% to 20.1% (63). Pneumonia
caused the readmission only 17.9% to
29.4% of the time; other common causes
were exacerbations of CHF or COPD.
Treatment... The most important clinical decisions in the treatment of CAP include
determining the site of care, selecting antibiotic therapy, delivering supportive care, and
determining the need for ventilatory support. Antibiotic therapy differs by site of care.
However, all patients should receive timely empirical therapy directed at pneumococcus, atypical pathogens, and other organisms depending on risk factors. The PSI and
the CURB-65 score aid decisions about hospital admission. Patients should be managed
in the ICU if they require ventilatory or vasopressor support or close observation.
Consultation should occur in cases of severe disease and when patients do not respond
to initial therapy or have complications. Broad-spectrum empirical antibiotics should be
deescalated promptly after negative culture results, and patients can be transitioned to
oral antibiotics and discharged once they are clinically stable. Routine follow-up CXR is
unnecessary if the patient is responding well. Patients should be offered pneumococcal,
COVID-19, and influenza vaccinations and should be encouraged to avoid smoking.
CLINICAL BOTTOM LINE
Practice Improvement
What measures do stakeholders use to
measure the quality of care?
63. Prescott HC, Sjoding MW,
Iwashyna TJ. Diagnoses of
early and late readmissions after hospitalization
for pneumonia. A systematic review. Ann Am
Thorac Soc.
2014;11:1091-100.
[PMID: 25079245]
64. Werner RM, Bradlow ET.
Relationship between
Medicare's Hospital
Compare performance
measures and mortality
rates. JAMA.
2006;296:2694-702.
[PMID: 17164455]
65. Lee RA, Centor RM,
Humphrey LL, et al;
Scientific Medical Policy
Committee of the
American College of
Physicians. Appropriate
use of short-course antibiotics in common infections: best practice advice
from the American
College of Physicians. Ann
Intern Med.
2021;174:822-7. [PMID:
33819054]
66. Centers for Disease
Control and Prevention.
Core Elements of Hospital
Antibiotic Stewardship
Programs. Accessed at
www.cdc.gov/antibioticuse/core-elements/
hospital.html on 10
January 2022.
Process measures for pneumonia quality of care, including measurement of
oxygenation, prompt initiation of appropriate antibiotics, drawing of blood cultures before antibiotic administration,
providing smoking cessation counseling, and administration of influenza and
pneumococcal vaccine, are no longer
collected or publicly reported by the
Centers for Medicare & Medicaid
Services (CMS). Pneumonia is not one
of the conditions for which CMS
requires core measures. Instead, CMS
reports risk-standardized mortality, readmission, and excess days in acute
care for patients with pneumonia.
Although attention to the previous
© 2022 American College of Physicians
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In the Clinic
process measures represents good
care, it may not affect these outcomes
(64), which are influenced by various
medical and social conditions.
What do professional organizations
recommend with regard to
prevention and treatment?
The ATS and IDSA issue joint guidelines on the treatment of CAP (16). The
American College of Physicians has
issued a guideline on appropriate use
of short-course antibiotics, which includes treatment of CAP (65). The CDC
publishes the ACIP recommendations
for influenza, COVID-19, and pneumococcal vaccination and Core Elements
of Antibiotic Stewardship (66). The recommendations in this article reflect
these guidelines.
Annals of Internal Medicine
April 2022
Tool Kit
Community-Acquired
Pneumonia
Patient Information
https://medlineplus.gov/pneumonia.html
https://medlineplus.gov/languages/
pneumonia.html
Information and handouts in English and
other languages from the National
Institutes of Health's MedlinePlus.
www.nhlbi.nih.gov/health/pneumonia
www.nhlbi.nih.gov/health-topics/espanol/
neumonia
Information in English and Spanish from
the National Heart, Lung, and Blood
Institute.
www.cdc.gov/pneumococcal/index.html
www.cdc.gov/pneumococcal/index-sp.
html
Information on pneumococcal disease in
English and Spanish from the Centers for
Disease Control and Prevention.
Information for Health Professionals
www.atsjournals.org/doi/full/10.1164/
rccm.201908-1581ST
2019 clinical practice guideline on diagnosis
and treatment of adults with communityacquired pneumonia from the American
Thoracic Society and the Infectious
Diseases Society of America.
www.cdc.gov/vaccines/vpd/pneumo/hcp/
index.html
Pneumococcal vaccination information and
resources from the Centers for Disease
Control and Prevention.
www.cdc.gov/pneumococcal/clinicians/
index.html
Information on pneumococcal disease in
English and Spanish from the Centers for
Disease Control and Prevention.
April 2022
Annals of Internal Medicine
In the Clinic
ITC63
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In the Clinic
© 2022 American College of Physicians
In the Clinic
Annals of Internal Medicine
WHAT YOU SHOULD KNOW
ABOUT PNEUMONIA
What Is Pneumonia?
Pneumonia is a serious infection of the lungs.
Community-acquired pneumonia is when you
develop pneumonia outside a hospital or nursing home. Pneumonia can be caused by bacteria, viruses, or fungi and can range from mild to
severe. It is important that pneumonia be identified and treated quickly.
What Are the Symptoms?
Fever or chills
A cough that produces a lot of mucus
Chest pain that is worse with deep breathing
Shortness of breath
Feeling tired and weak
Confusion
What Are the Risk Factors?
• Being age 65 years or older
• Having other health conditions, like diabetes or
lung, heart, liver, or kidney disease
Drinking alcohol
Smoking cigarettes
Having the flu or COVID-19
Having a weakened immune system
Pneumonia can be prevented by quitting smoking
and by receiving vaccines. The pneumococcal,
influenza, and COVID-19 vaccines have all been
shown to prevent pneumonia and its
complications.
•
•
•
•
How Is It Diagnosed?
• Your doctor will take a history; check your vital
signs, including your oxygen level; and perform a
physical examination.
• You might be given a flu test or a COVID-19 test.
• You might have other tests. A chest x-ray may be
helpful to confirm the diagnosis. You may need
to have a chest CT scan. Tests of the sputum (the
mucus you produce when coughing) or urine
may help your doctor learn what type of bacteria
is causing your pneumonia. Blood tests may help
determine the severity of the infection.
How Is It Treated?
• Treatment depends on how severe your pneu-
•
•
•
•
•
monia is. Your doctor will determine whether you
can be treated at home or in the hospital.
Most patients can be treated at home. Some who
are very ill or have a risk for complications might
need to stay in the hospital. If you have to stay in
the hospital, your doctor will monitor your heart
and breathing rates, and you might be given IV
fluids or medicine.
If your pneumonia is caused by bacteria, your
doctor will prescribe antibiotics. Symptoms usually start to go away within 2 to 3 days of starting
medicine. It is important to finish all of your antibiotics, even if you are feeling better.
Follow up with your doctor 1 to 2 days after starting antibiotics to make sure you are responding
well.
Drink plenty of fluids and stay hydrated.
Get plenty of rest. Feeling tired and coughing
may last for a month or longer.
Questions for My Doctor
•
•
•
•
•
Should I be treated at home or in the hospital?
What medicine do I need to take?
What can I do to help relieve my symptoms?
When should I have a follow-up visit?
How can I prevent another episode of
pneumonia?
For More Information
American Lung Association
www.lung.org/lung-health-diseases/lung-disease-lookup/
pneumonia
MedlinePlus
https://medlineplus.gov/pneumonia.html
© 2022 American College of Physicians
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Annals of Internal Medicine
April 2022
Patient Information
•
•
•
•
•
•
Appendix Table. Drug Treatments for CAP
Agent
Mechanism of Action
Dosage
Benefits
Adverse Effects
Notes
Linezolid (Zyvox)
Bacteriostatic; binds to
50S ribosomal subunit to inhibit bacterial protein synthesis
600 mg PO or IV every
12 h
Penetrates well into the
lung and is active
against MRSA
Myelosuppression, particularly thrombocytopenia, vomiting,
diarrhea, seizures,
hypoglycemia
Drug interactions may
lead to serotonin syndrome
Do not use with tricyclic antidepressants,
monoamine oxidase
inhibitors, or selective
serotonin reuptake
inhibitors
Monitor blood
pressure
Clindamycin*
(Cleocin)
Bacteriostatic; binds to
50S ribosomal subunit to inhibit bacterial protein synthesis
600 mg PO every 8 h
Can inhibit toxin production by MRSA
Diarrhea, esophagitis,
hypersensitivity
Can cause
Clostridioides difficile–
associated diarrhea
Caution with asthma,
severe hepatic
disease
Vancomycin
(Vancocin)
Bactericidal; inhibits
cell wall and RNA
synthesis
15–20 mg/kg IV every
8–12 h
Active against MRSA,
with extensive clinical
experience
Is not therapy for
methicillin-susceptible Staphylococcus
aureus
Ototoxicity, nephrotoxicity, neutropenia,
nausea, hypokalemia
Avoid rapid infusion
(causes histamine
release)
Avoid optimal extravasation
Monitor trough concentrations
In chronic kidney disease, individualize
dose
Bactericidal; interferes
with peptidoglycan
cross-linking and prevents formation of the
bacterial cell wall
Piperacillin–tazobactam: 3.375 mg IV
every 4–6 h
Cefepime: 1–2 g IV
every 12 h
Imipenem: 1 g IV every
8h
Meropenem: 1 g IV
every 8 h
Active against pneumococci and
Pseudomonas
aeruginosa
Anaphylaxis, rash, nausea, vomiting, diarrhea, phlebitis,
seizures (high doses),
hypokalemia (high
doses), elevated liver
enzymes, prolonged
prothrombin time
(especially if patient is
using coumadin)
Seizure potential
greater with imipenem than
meropenem
Only use for patients
with pseudomonal
risk factors, although
generally active
against DRSP
Can dose daily if
patient has renal
insufficiency
Bactericidal; interferes
with peptidoglycan
cross-linking and prevents formation of the
bacterial cell wall
Cefuroxime: 500 mg
PO twice daily
Cefpodoxime: 400 mg
PO twice daily
Ceftriaxone: 1–2 g
every 12–24 h (usually
every 24 h)
Cefotaxime: 1 g every
8h
Active against pneumococci and Haemophilus
influenzae, including
b-lactamase–producing
organisms
Anaphylaxis, rash,
nausea, vomiting,
diarrhea, elevated
liver function test
results, interstitial nephritis, altered coagulation, pseudomembranous colitis
Not to be used alone
in CAP
Combine with a macrolide
Although cefuroxime
can be used as oral
therapy, it should not
be used IV because it
is not as active
against DRSP as other
cephalosporins
Antibiotics for
community-acquired
MRSA
Antipseudomonal
b-lactams
Piperacillin–
tazobactam
Cefepime
Imipenem
Meropenem
Cephalosporins
Cefuroxime
Cefpodoxime
Ceftriaxone
Cefotaxime
Continued on following page
April 2022
Annals of Internal Medicine
In the Clinic
© 2022 American College of Physicians
Appendix Table—Continued
Agent
Mechanism of Action
Dosage
Benefits
Adverse Effects
Notes
Bacteriostatic; binds to
30S ribosomal subunit to inhibit bacterial protein synthesis
100 mg IV initially, then
50 mg IV every 12 h
Infuse over 30–60 min
Can be used for CAP,
but only when there
are no other options
Penetrates well into respiratory secretions;
active against pneumococcus and atypical pathogens, but
not P aeruginosa
Vomiting, diarrhea,
hepatotoxicity, pancreatitis, anemia
Increase in all-cause
mortality
Avoid with pregnancy
With severe hepatic
disease, use 25 mg
for maintenance
infusion
Bacteriostatic; binds to
50S ribosomal subunit and inhibits bacterial protein synthesis
Azithromycin: 500 mg
IV or PO on day 1, followed by 500 mg IV
or PO for 7–10 d for
hospitalized patients
(250 mg on days 2–5
for outpatients)
Azithromycin in the
microspheres oral
extended-release formulation: 2 g PO on
day 1 without followup dosing for outpatients
Clarithromycin: 500
mg PO twice daily,
or 1000 mg/d PO
(extended-release
preparation) for
outpatients
Covers pneumococcus,
atypical pathogens,
and H influenzae
Nausea, vomiting, diarrhea, QT prolongation, dyspepsia
(clarithromycin)
Use as monotherapy
only in patients without cardiopulmonary
disease or modifying
factors; otherwise,
combine with a
b-lactam
Erythromycin is less expensive but is not recommended because
of the need for more
frequent dosing,
more intestinal upset,
and no coverage of
H influenzae
Bactericidal; interferes
with peptidoglycan
cross-linking and prevents formation of the
bacterial cell wall
Amoxicillin–clavulanate: 875 mg PO
twice daily
Ampicillin: 500–1000
mg PO 3 times daily
Ampicillin–sulbactam:
1–2 g IV every 6 h
Active against pneumococci and b-lactamase–producing
H influenzae
High doses (1 g 3 times
daily) active against
DRSP
Anaphylaxis, rash,
nausea, vomiting, diarrhea, phlebitis, seizures (high doses),
hypokalemia (high
doses), elevated liver
enzymes, prolonged
prothrombin time
(especially if patient is
using warfarin)
Do not use alone in
CAP
Combine with a
macrolide
Bactericidal; interferes
with bacterial DNA
gyrase
Kills bacteria in a
concentrationdependent fashion
Ciprofloxacin: 400 mg
IV every 8 h
Levofloxacin: 500–750
mg/d IV or PO
Moxifloxacin: 400
mg/d IV or PO
Active against P aeruginosa, atypical pathogens, and
H influenzae
Levofloxacin and moxifloxacin are the “respiratory quinolones,”
with activity against
DRSP, H influenzae,
and atypical
pathogens
Seizures, hypersensitivity, photosensitivity,
tendon rupture, nausea, vomiting, diarrhea, QT
prolongation
Only use ciprofloxacin
in severe CAP
Not always reliable
against pneumococci,
and should be combined with other
agents if DRSP is possible
If used in severe CAP,
do not use as
monotherapy
Bacteriostatic; binds to
30S ribosomal subunit and interferes
with bacterial protein
synthesis
100 mg IV or PO twice
daily
Active against key
bacterial and atypical
pathogens
Nausea, vomiting, diarrhea, photosensitivity
Not always fully reliable against
pneumococci
Glycylcycline
Tigecycline*
(Tygacil)
Macrolides
Azithromycin
Clarithromycin
Penicillins
Amoxicillin–
clavulanate
Ampicillin
Ampicillin–
sulbactam
Quinolones
Ciprofloxacin
Levofloxacin
Moxifloxacin
Tetracyclines
Doxycycline
CAP = community-acquired pneumonia; DRSP = drug-resistant Streptococcus pneumoniae; IV = intravenously; MRSA = methicillinresistant Staphylococcus aureus; PO = orally.
* Black box warning.
© 2022 American College of Physicians
In the Clinic
Annals of Internal Medicine
April 2022