Download NEUMONIA ADQUIRIDA EN LA COMUNIDAD (NAC)

NEUMONIA ADQUIRIDA EN
LA COMUNIDAD
(NAC)
Dr. Carlos Fernando Estrada Garzona
Departamento de Farmacología
Universidad de Costa Rica
OBJETIVOS
GENERALIDADES
SEVERIDAD
TRATAMIENTO
EMPIRICO
ESPECIFICO
NEUMONIA COMPLICADA
NAC
GENERALIDADES caused by Legionella infection. The clinical presentation
of CAP is often more subtle in older patients, and many
of these patients do not exhibit classic symptoms.1 They
often present with weakness and decline in functional
and mental status.
The patient history should focus on detecting symptoms
consistent with CAP, underlying defects in host defenses,
and possible exposure to specific pathogens. Persons with
chronic obstructive pulmonary disease or human immunodeficiency virus infection have an increased incidence
tachypnea (LR+ = 3.5). Asymmetric breath sounds,
pleural rubs, egophony, and increased fremitus are relatively uncommon, but are highly specific for pneumonia
(LR+ = 8.0); these signs help rule in pneumonia when
present, but are not helpful when absent.8 Rales or bronchial breath sounds are helpful, but much less accurate
than chest radiography.10 Tachypnea is common in older
patients with CAP, occurring in up to 70 percent of those
older than 65 years.11 Pulse oximetry screening should
be performed in all patients with suspected CAP.12
Table 1. Common Etiologies of Community-Acquired Pneumonia
Etiology
Outpatients
Mycoplasma pneumoniae
Respiratory viruses
Streptococcal pneumoniae
Chlamydophila pneumoniae
Legionella species
Haemophilus influenzae
Unknown
Frequency
(median
percentage)
Frequency
(median
percentage)
Etiology
16
15
14
12
2
1
44
Inpatients not admitted to ICU
S. pneumoniae
25
Respiratory viruses
10
M. pneumoniae
6
H. influenzae
5
C. pneumoniae
3
Legionella species
3
Unknown
37
Etiology
Frequency
(median
percentage)
Inpatients admitted to ICU
S. pneumoniae
17
Legionella species
10
Gram-negative bacilli
5
Staphylococcus aureus
5
Respiratory viruses
4
H. influenzae
3
Unknown
41
ICU = intensive care unit.
Information from references 1 through 3.
1300 American Family Physician
www.aafp.org/afp
Volume 83, Number 11
Am Fam Physi-­‐ cian. 2011;83(11):1299-­‐1306 ◆
June 1, 2011
Hotel or cruise ship stay in previous 2 weeks
Legionella species
Travel to or residence in southwestern United States
Travel to or residence in Southeast and East Asia
Coccidioides species, Hantavirus
Burkholderia pseudomallei, avian influenza, SARS
Influenza active in community
Influenza, S. pneumoniae, Staphylococcus aureus,
H. influenzae
Downloaded from http://cid.oxfordjournals.org/ at Universidad de Costa Rica on August 31, 2014
acquired pneumonia (CAP) has been the f
different organizations, and several hav
guidelines for management of CAP. Two
widely referenced are those of the Infect
Table 8. Epidemiologic conditions and/or risk factors related to specific pathogens in community-acquired
Society of America (IDSA) and the Ameri
pneumonia.
Condition
Commonly Society
encountered pathogen(s)
(ATS). In response to confusion r
Alcoholism
Streptococcus pneumoniae, oral anaerobes, Klebsiella
pneumoniae, Acinetobacter species, Mycobacterium
ferences between their respective guidelin
tuberculosis
COPD and/or smoking
Haemophilus influenzae, Pseudomonas aeruginosa,
Legionella species, S.
pneumoniae,
and
theMoraxella
ATScararconvened a joint committee
rhalis, Chlamydophila pneumoniae
Aspiration
Gram-negative enteric pathogens, oral anaerobes
unified
CAP
guideline document.
Lung abscess
CA-MRSA, oral anaerobes,
endemic fungal
pneumonia,
M. tuberculosis, atypical mycobacteria
Exposure to bat or bird droppings
Histoplasma capsulatum The guidelines are intended primaril
Exposure to birds
Chlamydophila psittaci (if poultry: avian influenza)
Exposure to rabbits
Francisella tularensis
emergency medicine physicians, hospital
Exposure to farm animals or parturient cats
Coxiella burnetti (Q fever)
HIV infection (early)
S. pneumoniae, H. influenzae, M. tuberculosis
mary
care
practitioners; however, the ext
HIV infection (late)
The pathogens listed for
early infection
plus Pneumocystis jirovecii, Cryptococcus, Histoplasma, Aspergillus,
atypical mycobacteria (especially Mycobacterium
ture evaluation suggests that they are al
kansasii), P. aeruginosa, H. influenzae
Reprints or correspondence: Dr. Lionel A. Mandell, Div. of
McMaster University/Henderson Hospital, 5th Fl., Wing
Pseudomonas aeruginosa, Burkholderia cepacia, S. aureus
St.,
Hamilton, Ontario L8V 1C3, Canada (lmandel
Injection drug use
S. aureus, anaerobes, Concession
M. tuberculosis, S.
pneumoniae
Endobronchial obstruction
Anaerobes, S. pneumoniae, H. influenzae, S. aureus
This official statement of the Infectious Diseases Society
In context of bioterrorism
Bacillus anthracis (anthrax), Yersinia pestis (plague),
Francisella tularensisand
(tularemia)
the American Thoracic Society (ATS) was approved by
NOTE. CA-MRSA, community-acquired methicillin-resistant Staphylococcus aureus; COPD,
chronic
pulmonary dis- 2006 and the ATS Board of Directo
Directorsobstructive
on 5 November
ease; SARS, severe acute respiratory syndrome.
2006.
a
Committee cochairs.
for pneumonia is uncertain, and few well-controlled studies
Antibiotic Resistance Issues
Cough 12 weeks with whoop or posttussive
vomiting
Structural lung disease (e.g., bronchiectasis)
Resistance to commonly used antibiotics for CAP presents another major consideration in choosing empirical therapy. Resistance patterns clearly vary by geography. Local antibiotic
prescribing patterns are a likely explanation [179–181]. However, clonal spread of resistant strains is well documented.
Bordetella pertussis
have examined the impact of in vitro resistance on clinical
Clinical Infectious Diseases 2007; 44:S27–72
outcomes of CAP. Published studies are limited by small sample
! 2007
by the design,
Infectious
Society of America.
sizes, biases inherent
in observational
and theDiseases
relative
infrequency of isolates
exhibiting high-level resistance [183–
1058-4838/2007/4405S2-0001$15.00
185]. Current levels of b-lactam resistance do not generally
All r
NAC
SEVERIDAD evel monitoring unit
of the minor criteria
oderate recommen-
vere CAP is 4-fold:
mizes use of limited
ory failure or delayed
2
2
3
3
Septic shock with the need for vasopressors
Downloaded from http://cid.oxfordjournals.
whether to place the
ing unit rather than
10% of hospitalized
n [68–70], but the
s, physicians, hospime of the variability
ability of high-level
ropriate for patients
e respiratory failure
to the ICU, simple
he criteria for a highere CAP. One of the
for ICU care is the
[68–72]. However,
evere CAP were pre-
acquired pneumonia (CAP) has been the f
different organizations, and several hav
guidelines for management of CAP. Two
Table 4. Criteria for severe community-acquired pneumonia.
widely referenced are those of the Infect
Society of America (IDSA) and the Ameri
Minor criteriaa
Society (ATS). In response to confusion r
Respiratory rateb !30 breaths/min
PaO /FiO ratiob "250
ferences between their respective guidelin
Multilobar infiltrates
and the ATS convened a joint committee
Confusion/disorientation
Uremia (BUN level, !20 mg/dL)
unified CAP guideline document.
c
Leukopenia (WBC count, !4000 cells/mm )
The guidelines are intended primaril
Thrombocytopenia (platelet count, !100,000 cells/mm )
emergency medicine physicians, hospital
Hypothermia (core temperature, !36!C)
Hypotension requiring aggressive fluid resuscitation mary care practitioners; however, the ext
Major criteria
ture evaluation suggests that they are al
Invasive mechanical ventilation
NOTE. BUN, blood urea nitrogen; PaO2/FiO2, arterial oxygen pressure/fraction of inspired oxygen; WBC, white blood cell.
Reprints or correspondence:
Dr. Lionel A. Mandell, Div. of
Other criteria to consider include hypoglycemia (in nondiabetic
patients),
McMaster
University/Henderson Hospital, 5th Fl., Wing
acute alcoholism/alcoholic withdrawal, hyponatremia, unexplained metabolic
Concession St., Hamilton, Ontario L8V 1C3, Canada (lmandel
acidosis or elevated lactate level, cirrhosis, and asplenia.
b
Thisrate
official
statement of the Infectious Diseases Society
A need for noninvasive ventilation can substitute for a respiratory
130
and the American Thoracic Society (ATS) was approved by
breaths/min or a PaO2/FiO2 ratio !250.
c
As a result of infection alone.
Directors on 5 November 2006 and the ATS Board of Directo
2006.
a
Committee cochairs.
a
admission include the initial ATS definition of severe CAP [5]
Clinical Infectious Diseases 2007; 44:S27–72
and its subsequent modification [6, 82], the CURB !
criteria
[39,
2007 by
the Infectious Diseases Society of America. All r
45], and PSI severity class V (or IV and V) [42].
However,
1058-4838/2007/4405S2-0001$15.00
D E N T I F Y LOW- R I S K PAT I E N TS W I T H C O M M U N I T Y- AC Q U I R E D P N E U M O N I A
ation of each of these
mortality in each of
nd among the three
ality was low for risk
om 0.1 to 0.4 percent
cent for class II, and
ass III. There was no
5) in the area under
ristic curves between
ohort (0.84) and the
rt (0.83). Although
gnificantly greater in
(0.89) than in either
P"0.001), the absoinimal.
ORT patients in the
died (1 in class I, 3 in
nly 4 of these deaths
patients with terminal
obstructive pulmonary
rition. None of these
n preventable.
on between risk class
outcomes evaluated in
Table 4). Among outhospitalization within
t for class I patients to
001). None of the 62
ho were subsequently
was admitted to an inoutpatients in classes
TABLE 2. POINT SCORING SYSTEM FOR STEP 2 OF THE PREDICTION
RULE FOR ASSIGNMENT TO RISK CLASSES II, III, IV, AND V.
CHARACTERISTIC
Demographic factor
Age
Men
Women
Nursing home resident
Coexisting illnesses†
Neoplastic disease
Liver disease
Congestive heart failure
Cerebrovascular disease
Renal disease
Physical-examination findings
Altered mental status‡
Respiratory rate #30/min
Systolic blood pressure "90 mm Hg
Temperature "35°C or #40°C
Pulse #125/min
Laboratory and radiographic findings
Arterial pH "7.35
Blood urea nitrogen #30 mg/dl
(11 mmol/liter)
Sodium "130 mmol/liter
Glucose #250 mg/dl (14 mmol/liter)
Hematocrit "30%
Partial pressure of arterial oxygen
"60 mm Hg§
Pleural effusion
POINTS
ASSIGNED*
Age (yr)
Age (yr)$10
%10
%30
%20
%10
%10
%10
%20
%20
%20
%15
%10
%30
%20
%20
%10
%10
%10
%10
*A total point score for a given patient is obtained by summing the patient’s age in years (age minus 10 for women) and the points for each applicable characteristic. The points assigned to each predictor variable were
based on coefficients obtained from the logistic-regression model used in
step 2 of the prediction rule (see the Methods section).
†Neoplastic disease is defined as any cancer except basal- or squamouscell cancer of the skin that was active at the time of presentation or diagnosed within one year of presentation. Liver disease is defined as a clinical
or histologic diagnosis of cirrhosis or another form of chronic liver disease,
N Engl J Med 1997;336:243-­‐50. The New England Journal of Medicine
TABLE 3. COMPARISON
RISK CLASS
(NO. OF
POINTS)†
MEDISGROUPS
DERIVATION COHORT
OF
RISK-CLASS–SPECIFIC MORTALITY RATES
AND VALIDATION COHORTS.*
MEDISGROUPS
VALIDATION COHORT
DERIVATION
PNEUMONIA PORT VALIDATION COHORT
INPATIENTS
I
II ("70)
III (71–90)
IV (91–130)
V (#130)
Total
IN THE
OUTPATIENTS
no. of
patients
%
who died
no. of
patients
%
who died
no. of
patients
%
who died
no. of
patients
%
who died
1,372
2,412
2,632
4,697
3,086
14,199
0.4
0.7
2.8
8.5
31.1
10.2
3,034
5,778
6,790
13,104
9,333
38,039
0.1
0.6
2.8
8.2
29.2
10.6
185
233
254
446
225
1343
0.5
0.9
1.2
9.0
27.1
8.0
587
244
72
40
1
944
0.0
0.4
0.0
12.5
0.0
0.6
ALL PATIENTS
no. of
%
patients who died
772
477
326
486
226
2287
0.1
0.6
0.9
9.3
27.0
5.2
*There were no statistically significant differences in overall mortality or mortality within risk class among patients in
the MedisGroups derivation, MedisGroups validation, or overall Pneumonia PORT validation cohort. The P values for
the comparisons of mortality across risk classes are as follows: class I, P$0.22; class II, P$0.67; class III, P$0.12; class
IV, P$0.69; and class V, P$0.09.
†Inclusion in risk class I was determined by the absence of all predictors identified in step 1 of the prediction rule.
Inclusion in risk classes II, III, IV, and V was determined by a patient’s total risk score, which was computed according
to the scoring system shown in Table 2.
N Engl J Med 1997;336:243-­‐50. TABLE 4. MEDICAL OUTCOMES IN THE PNEUMONIA PORT COHORT
ACCORDING TO RISK CLASS.
MEDICAL OUTCOME
Outpatient
CLASS I
CLASS II
CLASS III
CLASS IV
CLASS V
TOTAL
P VALUE
Defining CAP severity on presentation to hospital
Table 3 Multivariate analysis using CURB as a
binary variable (2 or more features = severe) to
identify other factors that are independently associated
with mortality (n=637)
Clinical feature
RESPIRATORY
Albumin <30 g/dl
INFECTION
Age >65 years
Temperature <37°C
CURB score >2 (severe CAP)
Table 5
prediction
and valida
OR
95% CI
p value377
Rule
4.7
3.5
1.9
5.2
2.5 to 8.7
1.6 to 8.0
1.01 to 3.6
2.7 to 10.3
<0.001
0.003
0.047
<0.001
Derivation s
CURB
Defining community acquired pneumonia severity on
resentation to hospital: an international derivation and
alidation study
CURB-65
W S Lim, M M van der Eerden, R Laing, W G Boersma, N Karalus, G I Town, S A Lewis,
T Macfarlane
The univariate association between 30 day mortality and
each potential predictor variable, includingThorax
the2003;58:377–382
CURB score
and each of the components of the CURB score, was analysed
Background: In the assessment
of severity in community acquired pneumonia (CAP), the modified Brit2
test.
To avoid
associations
arising
from
using
a
χ
ish Thoracic Society (mBTS) rule identifies
patientsspurious
with severe pneumonia
but not patients
who might
be suitable for home management. A multicentre study was conducted to derive and validate a practimultiple statistical tests, 12 predictor variables selected from
cal severity assessment model for stratifying adults hospitalised with CAP into different management
groups.the current literature as most consistently important in
Methods: Data from three prospective studies of CAP conducted in the UK, New Zealand,
and the
3–5 7 11–19
predicting
prognosis
in comprising
CAP were
examined.
Netherlands
were combined.
A derivation cohort
80% of the
data was used to develop theThis
..........................................................................................................................
e end of article for
hors’ affiliations
....................
CRB-65
All patients were treated with empirical antimicrobial
agents according to local hospital guidelines. This usually
comprised a β-lactamase stable β-lactam in combination with
a macrolide. Dutch patients were randomised within 2 hours
CURB score of 2 or more—in the derivation cohort was 75%
(95% CI 72 to 78) and 69% (95% CI 66 to 72), respectively.
Corresponding values in the validation cohort were 74% (95%
CI 68 to 80) and 73% (95% CI 67 to 79).
≥
≤
≥
377
RESPIRATORY INFECTION
Defining community acquired pneumonia severity on
presentation to hospital: an international derivation and
validation study
assessment in a hospital setting: the CURB-65 score. One step strategy for stratifying patients with CAP into risk groups
W S Lim,Figure
M 2MtoSeverity
van
der Eerden,
R the
Laing,
WG
N Karalus, G I Town, S A Lewis,
according
risk of mortality
at 30 days when
results of blood
ureaBoersma,
are available.
J T Macfarlane
.............................................................................................................................
www.thoraxjnl.com
Thorax 2003;58:377–382
Background: In the assessment of severity in community acquired pneumonia (CAP), the modified British Thoracic Society (mBTS) rule identifies patients with severe pneumonia but not patients who might
be suitable for home management. A multicentre study was conducted to derive and validate a practical severity assessment model for stratifying adults hospitalised with CAP into different management
Defining CAP severity on presentation to hospital
381
≥
≤
≥
377
RESPIRATORY INFECTION
Defining community acquired pneumonia severity on
presentation to hospital: an international derivation and
validation study
Figure 3 Clinical severity assessment in the community setting: the CRB-65 score. Strategy for stratifying patients with CAP into risk groups in
the community using only clinical observations (when blood urea results not available).
W S Lim, M M van der Eerden, R Laing, W G Boersma, N Karalus, G I Town, S A Lewis,
J T Macfarlane
Based on the results of the multivariate analysis, age >65
Although the profiles of the three cohorts are very similar
. . . . . . . . . . . . . . . . .years
. . . . .was
. . . .added
. . . . . .as
. . another
. . . . . . . .adverse
. . . . . . .prognostic
. . . . . . . . . feature
. . . . . . .to
. .the
. . . . . . .(table
. . . . . 1),
. . .there
. . . . .may
. . . .be
. . other
. . . . . potential
. . . . . . . . differences
. . . . . . . . . . between
. . . . . . . .the
.
cohorts which may not be obvious. This represents a limitation
CURB score resulting in a six point score (CURB-65, range
Thorax 2003;58:377–382
of the study.
0–5) which allowed patients to be stratified according to
The importance of mental confusion, low blood pressure,
increasing risk of mortality ranging from 0.7% (score 0) to
raised respiratory rate, and raised urea as “core” adverse prog40% (score 4; table 4) The numbers with a score of 5 (highest)
Background: In the assessment of severity in community
acquired pneumonia (CAP), the modified Britnostic features in patients admitted to hospital with CAP is
were small; of the seven patients, only one (14%) died.
ish
Thoracic
Society
(mBTS)
rule
identifies
patients
with
severe
but not
who might
underlined. Thispneumonia
study confirmed
our patients
previous finding
in the
However, three (43%) others required mechanical ventilation
be
suitable
for
home
management.
A
multicentre
study
was
conducted
to
derive
and
validate
a practiUK subset of patients that a simple severity scoring
system
in an intensive care setting and survived. A further model
severityfeatures
assessment
model
stratifying
hospitalised
with
CAPprognostic
into different
management
based
on these four
adverse
features
(CURB score)
based onlycal
on clinical
available
from afor
clinical
assess- adults
See end of article forment without
correlates well with mortality.6
groups.
laboratory results (confusion, respiratory rate,
authors’ affiliations
NAC
COMPLICADA are major causes of apparent antibiotic failure. Therefore, the
first response to nonresponse or deterioration is to reevaluate
the initial microbiological results. Culture or sensitivity data
not available at admission may now make the cause of clinical
failure obvious. In addition, a further history of any risk factors
for infection with unusual microorganisms (table 8) should be
taken if not done previously. Viruses are relatively neglected as
a
Fluoroquinolone therapy
Concordant therapy
Discordant therapy
b
0.5
…
…
…
…
…
…
…
0.61
…
…
2.51
urnals.org/ at Universidad de Costa Rica on August 31, 2014
acquired pneumonia (CAP) has been the f
different organizations, and several hav
guidelines for management of CAP. Two
widely referenced are those of the Infect
Society of America (IDSA) and the Ameri
Table 12. Factors associated with nonresponding pneumonia.
Society (ATS). In response to confusion r
Overall failure
Early failure
ferences
between their respective guidelin
Risk factor
Decreased risk Increased risk Decreased risk Increased risk
Older age (165 years)
…
…
0.35and the …
ATS convened a joint committee
COPD
0.60
…
…
…
Liver disease
…
2.0
… unified CAP
…
guideline document.
Vaccination
0.3
…
…
…
Pleural effusion
…
2.7
…
…
The guidelines
are intended primaril
Multilobar infiltrates
…
2.1
…
1.81
medicine physicians, hospital
Cavitation
…
4.1
… emergency
…
Leukopenia
…
3.7
…
…
mary
care
PSI class
…
1.3
…
2.75 practitioners; however, the ext
Legionella pneumonia
…
…
…
2.71
ture
evaluation
suggests that they are al
Gram-negative pneumonia
…
…
…
4.34
CAP. Although in the original study only 8 (16%) of 49 cases
could not be classified [101], a subsequent prospective multicenter trial found that the cause of failure could not be determined in 44% [84].
Management of nonresponding CAP. Nonresponse to antibiotics in CAP will generally result in !1 of 3 clinical responses: (1) transfer of the patient to a higher level of care, (2)
Reprints or correspondence: Dr. Lionel A. Mandell, Div. of
McMaster University/Henderson Hospital, 5th Fl., Wing
Concession St., Hamilton, Ontario L8V 1C3, Canada (lmandel
This official statement of the Infectious Diseases Society
and the American Thoracic Society (ATS) was approved by
Directors on 5 November 2006 and the ATS Board of Directo
2006.
a
Committee cochairs.
NOTE. Data are relative risk values. COPD, chronic obstructive pulmonary disease; PSI, Pneumonia Severity
Index.
a
b
From [84].
From [81].
S58 • CID 2007:44 (Suppl 2) • Mandell et al.
Clinical Infectious Diseases 2007; 44:S27–72
! 2007 by the Infectious Diseases Society of America. All r
1058-4838/2007/4405S2-0001$15.00
practice
M.P.H.,
eM.D.,
w e ng
l a n d jEditor
o u r na l
of
m e dic i n e
uired Pneumonia
ciated Pneumonia.
Table 3. Clinical Features Suggesting CommunityAcquired MRSA Pneumonia.*
CavitaryM.B.,
infiltrate or
necrosisPh.D.
Grant
W.
B.S.,
e previous 90
daysWaterer,
ded-care facility
Rapidly increasing pleural effusion
Gross hemoptysis (not just blood-streaked)
home,
including
ette highlighting
aConcurrent
commoninfluenza
clinical problem.
sented, followed byNeutropenia
a review of formal guidelines,
the authors’ clinicalErythematous
recommendations.
rash
days
ant pathogen
Skin pustules
py† disease who
Young,
healthy
patient of proFrom the Division of Pulmonary and Criter’s
haspreviously
a 2-day
history
Severe pneumonia during summer months
sion is transferred
from a nursing home to ical Care Medicine, Northwestern Unie previous 90 days
versity Feinberg School of Medicine, Chi*
MRSA
denotes
methicillin-resistant
Staphylococcus
the
she has had no recent cago (R.G.W., G.W.W.); and the University
days transfer records,
aureus.
c agents. Her temperature is 38.4°C (101°F), of Western Australia, Perth (G.W.W.). Address reprint requests to Dr. Wunderink
espiratory ratepulmonary
is 30 breaths
minute,
thereceived
disease per
[COPD])
who have
at [email protected].
multiple
courses
of
outpatient
antibiotics;
the
he
oxygen
saturation
is
91%
while
she
is
s
frequency of P. aeruginosa infection is particularly
N Engl J Med 2014;370:543-51.
in both lower increased
lung fields.
She
is
oriented
to
13
in this population.
DOI: 10.1056/NEJMcp1214869
n Thoracic Society
28
Whereas
is sodium
commonly level
identifiedCopyright
in
er cubic
millimeter,
theMRSA
serum
merica.
© 2014 Massachusetts Medical Society
original criteria but patients with risk factors for health care–associitrogen
is 25 mg per deciliter (9.0 mmol per
s of health care–
ated pneumonia, a community-acquired strain of
NAC
TRATAMIENTO acquired pneumonia (CAP) has been the f
different organizations, and several hav
guidelines
for management
ofcatarrhalis,
CAP. Two
andgenerally
Moraxella
gen
Table 7.empirical
Recommended
antibiotics and
for communityMoraxella catarrhalis,
in patients
who have
Table 7. Recommended
antibioticsempirical
for communityacquired pneumonia.
acquired pneumonia.
widely bronchopulmonary
referencedderlying
aredisease,
those
ofS.the
Infect
bronchopulmonary
derlying
and
aureus,
esped
during
an of
influenza
outbreak.
Risks
for
infection
with E
during
an influenza
Society
America
(IDSA)
and
theoutbreak
Ameri
Outpatient treatment
Outpatient treatment
obacteriaceae species and
P. aeruginosaspecies
as etiologies
fora
obacteriaceae
and P.
1. Previously healthy
and no use healthy
of antimicrobials
within
1. Previously
and no use
of the
antimicrobials
within
the
Society
(ATS).
In
response
to
confusion
r
are chronic oral steroidare
administration
or steroid
severe under
previous 3 months
chronic
oral
adm
previous 3 months
bronchopulmonary
disease,
alcoholism,
and frequent
antib
A macrolide (strong recommendation; level I evidence)
ferences between
their
respective
guidelin
bronchopulmonary
disease,
al
A macrolide (strong recommendation; level I evidence)
therapy [79, 131], whereas recent hospitalization would d
Doxycyline (weak recommendation; level III evidence)
therapy a[79,
131],committee
whereas rec
Doxycyline (weak recommendation; level III evidence)
and asthe
ATSLess
convened
joint
cases
HCAP.
common causes
of pneumonia inc
2. Presence of comorbidities such as chronic heart, lung, liver
casesto,as
HCAP. Less
common
2. Presence
of comorbidities
as chronic heart,
liver
or renal disease;
diabetes mellitus;
alcoholism;such
malignanbut
arelung,
by no
means
limited
Streptococcus
pyogenes,
Nei
unified
CAP
guideline
document.
or renal disease;conditions
diabetesormellitus;
cies; asplenia; immunosuppressing
use of alcoholism; malignanbut
are
by
no
means
limited
to
meningitidis, Pasteurella multocida, and H. influenzae typ
immunosuppressing
drugs;
or use immunosuppressing
of antimicrobials withinconditionsThe
cies;
asplenia;
or useguidelines
of
are intended
primaril
meningitidis,
Pasteurella
multo
The “atypical”
the previous 3 months
(in which case an drugs;
alternative
fromofa antimicrobials
immunosuppressing
or use
within organisms, so called because they are
different class should
selected)
Thecultivatable
“atypical”onorganisms,
emergency
medicine
physicians,
hospital
detectable
on
Gram
standard
ba
the be
previous
3 months (in which case an alternative
from
a stain or
A respiratory fluoroquinolone
different(moxifloxacin,
class shouldgemifloxacin,
be selected)or
ologic media, include M.detectable
pneumoniae,
pneumoniae,
Le
on C.Gram
stain
or
mary
care
practitioners;
however,
the
ext
levofloxacin [750 mg]) (strong recommendation; level I
A respiratory fluoroquinolone (moxifloxacin, gemifloxacin,
or respiratory
ella species, and
viruses.
With
the exception
o
ologic
media,
include
M. pneu
evidence)
levofloxacin [750 mg]) (strong recommendation;
level
I
ture evaluation
suggests
thatarethey
arecaus
alvi
gionella
species, these microorganisms
common
A b-lactam plus a macrolide (strong recommendation; level I
ella species, and
respiratory
evidence)
evidence)
pneumonia, especially among outpatients. However, these
gionella species, these microo
A
b-lactam
plus
a
macrolide
(strong
recommendation;
level I
3. In regions with a high rate (125%) of infection with high-level
ogens are not often identified in clinical practice because,
evidence)
pneumonia, especially among
(MIC !16 mg/mL) macrolide-resistant
Streptococcus pneua
few
exceptions,
such
as
L. pneumophila and influenza v
moniae, consider
of alternative
listed
above of
in infectionReprints
3. Inuse
regions
with a agents
high rate
(125%)
with high-level
or correspondence:
Dr.are
Lionel
Mandell,
Div. of
ogens
notA.
often
identified
no
specific,
rapid,
or
standardized
tests
for
their
detection
(2) for patients without
comorbidities
(moderate
recommen(MIC !16 mg/mL) macrolide-resistant Streptococcus
McMaster pneuUniversity/Henderson
Hospital, 5thsuch
Fl., as
Wing
a fewthe
exceptions,
L.
dation; level III evidence)
influenza
remains
predominant viral
caup
moniae, consider use of alternative agentsAlthough
listed above
in
Concession St., Hamilton, Ontario L8V 1C3, Canada (lmandel
Inpatients, non-ICU treatment
no specific,
rapid,viruses
or standardi
(2) for patients without comorbidities (moderate
CAP
inrecommenadults, statement
other commonly
recognized
include
This
official
of
the
Infectious
Diseases
Society
A respiratory fluoroquinolone
recommendation;
level I
dation;(strong
level III
evidence)
Although
influenza
remains
[107],
adenovirus,
and
parainfluenza
virus,
as
well
as
and the American Thoracic Society (ATS) was approvedless
by
evidence)
Inpatients, non-ICU treatment
mon
viruses,
including
human
metapneumovirus,
herpes
CAP
in
adults,
other
commonl
Directors on 5 November 2006 and the ATS Board of Directo
A b-lactam plus a macrolide (strong recommendation; level I
A
respiratory
fluoroquinolone
(strong
recommendation;
level I
plex
virus,adenovirus,
SARS-associated
coronav
evidence)
[107],
and parainfl
2006.virus, varicella-zoster
evidence)
anda measles
virus.
In a recent
of immunocompetent
Inpatients, ICU treatment
Committee
cochairs.
mon study
viruses,
including human
A
b-lactam
plus
a
macrolide
(strong
recommendation;
level
I
A b-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam)
patients admitted to the hospital with CAP, 18% had evid
plex virus,
viru
Clinical Infectious Diseases
2007;varicella-zoster
44:S27–72
evidence)
plus either azithromycin
(level II evidence) or a respiratory
of a viral etiology, and, in 9%, a respiratory virus was the
! 2007 by the Infectiousand
Diseases
Society
of America.
All rs
fluoroquinolone
(level I ICU
evidence)
(strong recommendation)
measles
virus.
In a recent
Inpatients,
treatment
pathogen
identified
[176].
Studies
that
include
outpatient
(for penicillin-allergic patients, a respiratory fluoroquinolone
1058-4838/2007/4405S2-0001$15.00
A b-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam)
patients admitted to the hosp
levofloxacin [750 mg]) (strong recommendation; level I
evidence)
acquired ella
pneumonia
(CAP) viruses.
has been
species, and respiratory
With the
the exf
gionella species, these microorganisms are comm
A b-lactam plus a macrolide (strong recommendation;different
level I
organizations, and several hav
evidence)
pneumonia, especially among outpatients. Howev
3. In regions with a high rate (125%) of infection with high-level
guidelinesogens
foraremanagement
CAP.practice
Two
not often identifiedof
in clinical
and
Moraxella catarrhalis, generally in patients who have
Table 7. Recommended(MIC
empirical
antibiotics
for community!16 mg/mL)
macrolide-resistant
Streptococcus
pneua few exceptions, such as L. pneumophila and in
in
acquired pneumonia. moniae, consider use of alternative agents listed above
widely
referenced
aredisease,
thoseand
ofS.the
Infect
derlying
bronchopulmonary
aureus,
espe
no specific, rapid, or standardized tests for their d
(2) for patients without comorbidities (moderate recommenduring
an of
influenza
outbreak.
Risks
for
infection
with E
dation; level III evidence)
Although
influenza
remains
the
predominant
Society
America
(IDSA)
and
the
Ameri
Outpatient treatment
Inpatients, non-ICU treatment
obacteriaceaeCAP
species
and other
P. aeruginosa
etiologiesviruse
for
in adults,
commonlyasrecognized
1. Previously healthy and no use of antimicrobials within the
Society
(ATS).
In
response
to
confusion
A respiratory fluoroquinolone (strong recommendation; are
level chronic
I
oral steroid
administration
or severe
[107],
adenovirus,
and parainfluenza
virus,under
as wer
previous 3 monthsevidence)
bronchopulmonary
disease,
alcoholism,
frequent
antib
mon viruses,
including
humanand
metapneumoviru
A macrolide (strong
recommendation;
level(strong
I evidence)
ferences
between
their
respective
guidelin
A b-lactam
plus a macrolide
recommendation; level
I
varicella-zoster
virus, SARS-associated
therapy [79, plex
131],virus,
whereas
recent hospitalization
would d
evidence)
Doxycyline (weak recommendation;
level III evidence)
and
the
ATS
convened
a
joint
committee
and measles
virus. In causes
a recent of
study
of immunoco
Inpatients, ICUsuch
treatment
cases as HCAP.
Less common
pneumonia
inc
2. Presence of comorbidities
as chronic heart, lung, liver
A
b-lactam
(cefotaxime,
ceftriaxone,
or
ampicillin-sulbactam)
or renal disease; diabetes mellitus; alcoholism; malignanpatients
admitted
to Streptococcus
the
hospital with
CAP, 18%
but
are by no
means
limited to,
pyogenes,
Nei
unified
CAP
guideline
document.
plus either azithromycin
(level or
II evidence)
cies; asplenia; immunosuppressing
conditions
use of or a respiratory
of
a
viral
etiology,
and,
in
9%,
a
respiratory
viru
meningitidis, Pasteurella multocida, and H. influenzae typ
fluoroquinolone
I evidence) (strong
recommendation)
immunosuppressing
drugs; or use(level
of antimicrobials
within
The guidelines
are so
intended
primaril
pathogen
identified
[176].
Studies
that
include
ou
(for penicillin-allergic
a respiratory
The “atypical”
organisms,
called
because
they are
the previous 3 months
(in which casepatients,
an alternative
from afluoroquinolone
and be
aztreonam
are recommended)
viral pneumonia rates as high as 36% [167]. The
different class should
selected)
emergency
medicine
physicians,
hospital
detectable
on Gram
stain or cultivatable
on standard
ba
Special concerns
other
etiologic
agents—for
example,
M.
tubercu
A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or
ologic media, include M. pneumoniae, C. pneumoniae, Le
Pseudomonas
is arecommendation;
consideration
mary caredophila
practitioners;
however,
the ext
psittaci (psittacosis),
Coxiella burnetii
(Q
levofloxacin If[750
mg]) (strong
level I
ella
species,
and
respiratory
viruses.
With
the
exception
o
An
antipneumococcal,
antipseudomonal
b-lactam
(piperacillinevidence)
cisella tularensis (tularemia), Bordetella pertuss
tazobactam, cefepime, imipenem, or meropenem)
plus
ture evaluation
suggests
that(Histoplasma
they
arecapsu
al
gionella
species,
theseand
microorganisms
common
caus
A b-lactam plus a macrolide (strong recommendation; level I
cough),
endemic fungi are
either ciprofloxacin or levofloxacin (750 mg)
evidence)
pneumonia, dioides
especially
among
outpatients.
However,and
these
immitis,
Cryptococcus
neoformans,
Bla
or
3. In regions with a The
highabove
rate (1b-lactam
25%) ofplus
infection
with
high-level
ogens are notinis)—is
often identified
in clinical
because,
largely determined
bypractice
the epidemiologic
an aminoglycoside and azithromycin
(MIC !16 mg/mL) macrolide-resistant Streptococcus pneuor
a few exceptions,
L. pneumophila
and[113,
influenza
v
8) butsuch
rarelyasexceeds
2%–3% total
177]. T
moniae, consider use of alternative agents listed above in
Reprints
or
correspondence:
Dr.
Lionel
A.
Mandell,
Div.
of
The above b-lactam plus an aminoglycoside and an antipneumay be
fungitests
in the
geog
no specific, rapid,
or endemic
standardized
forappropriate
their detection
(2) for patients without
comorbidities (moderate recommenMcMaster University/Henderson Hospital, 5th Fl., Wing
mococcal fluoroquinolone (for penicillin-allergic patients,
dation; level III evidence)
bution [100].
Although influenza
remains the predominant viral cau
substitute aztreonam for above b-lactam)
Concession St., Hamilton, Ontario L8V 1C3, Canada (lmandel
Inpatients, non-ICU treatment
The
need
for specific
anaerobicviruses
coverage
for CA
CAP
in official
adults, statement
other
commonly
recognized
include
(moderate recommendation; level III evidence)
This
of
the
Infectious
Diseases
Society
A respiratory fluoroquinolone
recommendation;
level I or linezolid
overestimated.
Anaerobic bacteria
cannot
de
If CA-MRSA(strong
is a consideration,
add vancomycin
[107],
adenovirus,
and parainfluenza
virus,
asapproved
well asbe
less
and
the
American
Thoracic
Society
(ATS)
was
by
evidence)
(moderate recommendation; level III evidence)
agnostic techniques in current use. Anaerobic cov
mon
viruses,
including
human
metapneumovirus,
herpes
Directors
on
5
November
2006
and
the ATS
Board ofpleuropu
Directo
A b-lactam plus a macrolide (strong recommendation; level I
indicated
only
in
the
classic
aspiration
NOTE. CA-MRSA, community-acquired methicillin-resistant Staphylococplex
evidence) cus aureus; ICU, intensive care unit.
2006.virus, varicella-zoster virus, SARS-associated coronav
drome in patients with a history of loss of cons
anda measles
virus.
In a recent study of immunocompetent
Inpatients, ICU treatment
Committee
cochairs.
result
of alcohol/drug overdose or after seizures in
A b-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam)
patients admitted
to the gingival
hospitaldisease
with CAP,
18% had mot
evid
concomitant
or esophogeal
SARS-associated
continually increases
the Infectious
Clinical
Diseases 2007;
44:S27–72
plus either azithromycin
(levelcoronavirus
II evidence)[170],
or a respiratory
of a viral etiology,
and,trials
in 9%,
virus was
the
Antibiotic
havea respiratory
not
demonstrated
a need
challenge
appropriate
management.
! 2007 by the
Infectious
Diseases
Society
of America.
All r
fluoroquinolone
(level for
I evidence)
(strong
recommendation)
pathogen
identified
[176].
Studies in
that
outpatient
treat these
organisms
theinclude
majority
of CAP
(for penicillin-allergic
respiratory
fluoroquinolone
Table 6patients,
lists the amost
common
causes of CAP, in decreasing
1058-4838/2007/4405S2-0001$15.00
Table 9. Recommended antimicrobial therapy for specific pathogens.
Organism
Preferred antimicrobial(s)
acquired pneumonia (CAP) has been the f
different organizations, and several hav
guidelines for management of CAP. Two
widely referenced are those of the Infect
Society of America (IDSA) and the Ameri
Society (ATS). In response to confusion r
ferences between their respective guidelin
and the ATS convened a joint committee
unified CAP guideline document.
The guidelines are intended primaril
emergency medicine physicians, hospital
mary care practitioners; however, the ext
ture evaluation suggests that they are al
Alternative antimicrobial(s)
Streptococcus pneumoniae
Penicillin G, amoxicillin
Macrolide, cephalosporins (oral [cefpodoxime, cefprozil, cefuroxime, cefdinir, cefditoren] or parenteral [cefuroxime, ceftriaxone, cefotaxime]), clindamycin,
doxycyline, respiratory fluoroquinolonea
Penicillin resistant; MIC !2 mg/mL
Agents chosen on the basis of susceptibility, including cefotaxime, ceftriaxone,
fluoroquinolone
Vancomycin, linezolid, high-dose amoxicillin
(3 g/day with penicillin MIC "4 mg/mL)
Amoxicillin
Fluoroquinolone, doxycycline, azithromycin,
clarithromycinb
Second- or third-generation cephalosporin,
amoxicillin-clavulanate
Fluoroquinolone, doxycycline, azithromycin,
b
clarithromycin
Mycoplasma pneumoniae/Chlamydophila
pneumoniae
Legionella species
Chlamydophila psittaci
Coxiella burnetii
Macrolide, a tetracycline
Fluoroquinolone
Fluoroquinolone, azithromycin
A tetracycline
A tetracycline
Doxycyline
Macrolide
Macrolide
Francisella tularensis
Yersinisa pestis
Doxycycline
Streptomycin, gentamicin
Gentamicin, streptomycin
Doxycyline, fluoroquinolone
Bacillus anthracis (inhalation)
Ciprofloxacin, levofloxacin, doxycycline
(usually with second agent)
Other fluoroquinolones; b-lactam, if
susceptible; rifampin; clindamycin;
chloramphenicol
Enterobacteriaceae
Third-generation cephalosporin, carbapenemc (drug of choice if extended-spectrum b-lactamase producer)
b-Lactam/b-lactamase inhibitor,
fluoroquinolone
Pseudomonas aeruginosa
Burkholderia pseudomallei
Antipseudomonal b-lactam plus (ciproflox- Aminoglycoside plus (ciprofloxacin or
f
f
acin or levofloxacin or aminoglycoside)
levofloxacin )
Carbapenem, ceftazadime
Fluoroquinolone, TMP-SMX
Acinetobacter species
Carbapenem
Haemophilus influenzae
Non–b-lactamase producing
b-Lactamase producing
e
d
Cephalosporin-aminoglycoside, ampicillinsulbactam, colistin
Staphylococcus aureus
Downloaded from http://cid.oxfordjournals.org/ at Universidad de Costa Rica on August 31, 2014
Penicillin nonresistant; MIC !2 mg/mL
Reprints or correspondence: Dr. Lionel A. Mandell, Div. of
Bordetella pertussis
Macrolide
TMP-SMX
McMaster University/Henderson Hospital, 5th Fl., Wing
Carbapenem
Anaerobe (aspiration)
b-Lactam/b-lactamase inhibitor,
clindamycin
Concession St., Hamilton, Ontario L8V 1C3, Canada (lmandel
Influenza virus
Oseltamivir or zanamivir
Mycobacterium tuberculosis
Isoniazid plus rifampin plus ethambutol
Refer to [243] for specific This official statement of the Infectious Diseases Society
plus pyrazinamide
recommendations
Coccidioides species
For uncomplicated infection in a normal
Amphotericin B
and the American Thoracic Society (ATS) was approved by
host, no therapy generally recommended; for therapy, itraconazole,
Directors on 5 November 2006 and the ATS Board of Directo
fluconazole
Histoplasmosis
Itraconazole
Amphotericin B
2006.
Blastomycosis
Itraconazole
Amphotericin B
a
cochairs.
NOTE. Choices should be modified on the basis of susceptibility test results and advice from local specialists. Refer to local referencesCommittee
for appropriate
Methicillin susceptible
Antistaphylococcal penicilling
Methicillin resistant
Vancomycin or linezolid
Cefazolin, clindamycin
TMP-SMX
d
doses. ATS, American Thoracic Society; CDC, Centers for Disease Control and Prevention; IDSA, Infectious Diseases Society of America; TMP-SMX,
trimethoprim-sulfamethoxazole.
a
Clinical Infectious Diseases 2007; 44:S27–72
! 2007 by the Infectious Diseases Society of America. All r
1058-4838/2007/4405S2-0001$15.00
Levofloxacin, moxifloxacin, gemifloxacin (not a first-line choice for penicillin susceptible strains); ciprofloxacin is appropriate for Legionella and most
gram-negative bacilli (including H. influenza).
b
Azithromycin is more active in vitro than clarithromycin for H. influenza.
c
Imipenem-cilastatin, meropenem, ertapenem.
d
Piperacillin-tazobactam for gram-negative bacilli, ticarcillin-clavulanate, ampicillin-sulbactam or amoxicillin-clavulanate.
e
Ticarcillin, piperacillin, ceftazidime, cefepime, aztreonam, imipenem, meropenem.
f
750 mg daily.
Systematic review
%
Study
ID
OR (95% CI)
Weight
0.73 (0.60, 0.89)
20.07
Dudas 2000
0.42 (0.14, 1.26)
0.71
Houck 2001
0.65 (0.49, 0.86)
10.34
Waterer 2001
0.33 (0.13, 0.84)
0.98
Martinez 2003
Garcia Vazquez 2005
0.40 (0.17, 0.94)
0.50 (0.31, 0.81)
1.17
3.66
Aspa 2006
0.98 (0.55, 1.75)
2.53
Dwyer 2006
1.09 (0.41, 2.90)
0.89
Metersky 2007
Paul 2007
0.61 (0.43, 0.87)
0.69 (0.32, 1.49)
6.70
1.44
Rodriguez 2007
0.58 (0.36, 0.93)
3.75
Blasi 2008
Bratzler 2008
0.40 (0.23, 0.70)
0.70 (0.57, 0.86)
2.74
18.58
Tessmer 2009
0.53 (0.30, 0.94)
2.60
Naucler 2013
0.24 (0.03, 1.92)
0.20
Rodrigo 2013
Overall (I2 = 2.7%, P = 0.422)
0.72 (0.60, 0.86)
23.64
0.67 (0.61, 0.73)
100.00
NOTE: Weights are from random effects analysis
.03
.1
.3
1
3.3
10
30
Figure 2. Comparison of the effects of BLM dual therapy and BL monotherapy on reduction in mortality. The vertical line shows the point of no difference
between the two therapies, squares show ORs, the diamond shows the pooled OR for all studies and horizontal lines show the 95% CIs.
Table 2. Subgroup analyses of mortality risk
Test of association
Characteristics
All studies
Site
ward
Downloaded from http://jac.oxfordjournals.org/ at Universidad de Costa Rica on Augus
Gleason 1999
J Antimicrob Chemother 2014; 69: 1441 – 1446
doi:10.1093/jac/dku033 AdvanceHeterogeneity
Access publication 16 February 2014
No. of studies
OR (95% CI)a
Z
P
16
0.66 (0.61–0.73)
8.60
,0.001
8
0.64 (0.55–0.73)
6.28
Model
x2
P
I 2 (%)
R
15.47
0.42
3.0
b-Lactam/macrolide
dual
therapy
versus b-la
treatment
of 11.46
community-acquired
pneumon
,0.001
R
0.12
39.0
of adverse
3%) of 256
72 patients
he 750-mg
up were evluable popnts (33.8%)
le 3).
oth the ITT
oportion of
I class III/
nt arm and
sided Fish-
nt, the clination were
and 91.1%
CI, "7.0 to
rates were
ponse rates
ble 6.
erapy visits
of 166 patients in the 500-mg group were initially thought to
have experienced clinical relapses
(P p .10
, bythe
2-sided
Fisher’s of drug-resistan
etiologies
and
emergence
exact test). Upon detailed examination, 5 patients were con-
Streptococcus pneumoniae has long been iden
most important pathogen among adults wi
Table 5. Clinical success rates for the clinically evaluable population at the 7–14-day posttherapy
according to the Pneulowed visit,
by Haemophilus
influenzae, Moraxella
monia Severity Index (PSI) score.
and Staphylococcus aureus [1–4]. However, re
a
n/N
(%)
have documented an increased incidence of
750-mg groupb 500-mg groupc
due to (n“atypical”
(e.g.,
Patient category
(n p 198)
p 192)
95% CIdLegionella pneumop
Evaluable patients 183/198 (92.4) 175/192 (91.1) "7.0 to 4.4
Stratum Ie
Total
69/76 (90.8)
PSI class IIIf
44/49 (89.8)
44/51
to 10.2
Received
25 (86.3)
February "17.2
2003; accepted
g
PSI class IV
h
PSI class V
i
Stratum II
a
73/86 (84.9)
25/27 (92.6)
27/32 (84.4)
August 2003.
0/0 (0.0)
2/3 (66.7)
"16.5 to 4.7
2 May 2003; electronic
"26.1 to 9.6
Not applicable
Financial support: Ortho-McNeil Pharmaceutical.
114/122 (93.4) 102/106 (96.2) "3.4 to 9.0
Reprints or correspondence: Dr. Alan Tennenberg, Ortho-McNe
No. of patients in the category with clinically successful treatment/no. of
1000 Rt. 202 S, Raritan, NJ 08869-0602 ([email protected].
patients in the category (%).
b
Levofloxacin, 750 mg q.d. iv Clinical
or po for 5Infectious
days.
Diseases 2003; 37:752–60
c
Levofloxacin, 500 mg q.d. iv or po for 10 days.
d
! 2003
by the
Infectious
Diseases
Society of America. All righ
Two-sided 95% CI around the
difference
(10-day
levofloxacin
regimen
minus 5-day levofloxacin regimen).
1058-4838/2003/3706-0002$15.00
e
PSI classes III, IV, and V combined.
f
P
ct of the intervention
eat population. Solid
g rank, 0.60; hazard
P 5 0.44.
anically ventilated
ary and secondary
de in 118 (55.4%)
he most frequently
n of the pathogens
e 5. Patients with
nia Severity Index.
Measurements and Main Results: We enrolled 213 patients. Fifty-four
(25.4%) patients had a CURB-65 score greater than 2, and 93
(43.7%) patients were in Pneumonia Severity Index class IV-V.
Clinical cure at Days 7 and 30 was 84/104 (80.8%) and 69/104
(66.3%) in the prednisolone group and 93/109 (85.3%) and 84/109
979 group (P 5 0.38 and P 5 0.08). Patients on
(77.1%) in the placebo
prednisolone had faster defervescence and faster decline in serum
C-reactive protein levels compared with placebo. Subanalysis of
patients with severe pneumonia did not show differences in clinical
outcome. Late failure (.72 h after admittance) was more common in
the prednisolone group (20 patients, 19.2%) than in the placebo
group (10 patients, 6.4%; P 5 0.04). Adverse events were few and not
different between the two groups.
Conclusions: Prednisolone (at 40 mg) once daily for a week does not
improve outcome in hospitalized patients with CAP. A benefit in
more severely ill patients cannot be excluded. Because of its
association with increased late failure and lack of efficacy prednisolone should not be recommended as routine adjunctive treatment
in CAP.
Clinical trial registered with www.clinicaltrials.gov (NCT 00170196).
Keywords: community-acquired pneumonia; corticosteroids; infection
(Received in original form May 29, 2009; accepted in final form February 1, 2010)
Supported by an unrestricted grant from Astra Zeneca.
Some of the results of these studies have been previously reported in the form of
an abstract at the 2009 annual ATS conference (Snijders D, de Graaff CS, van der
Werf TS, Boersma WG. Clinical efficacy of prednisolone in patients with
4. Defervescence in patients with community-acquired
pneucommunity-acquired
pneumonia, a randomized clinical trial [abstract A6116].
Presented
at the 2009 ATS International Conference, May 15–20.).
treated with prednisolone or placebo. Diamonds
5 pednisolone;
Figure
monia
and requests
squares 5 placebo. Data are presented as mean 6 Correspondence
SD. * P , 0.01.
for reprints should be addressed to Dominic
Snijders, M.D., Department of Pulmonary Diseases, Medical Centre Alkmaar,
Wilhelminalaan 15, 1812 JD Alkmaar, The Netherlands. E-mail: [email protected]
This article has an online supplement, which is accessible from this issue’s table of
patients hospitalized with CAP; clinical cure was
equal
in both
contents
at www.atsjournals.org
groups at Day 7. A trend toward a higher clinical
cure
rate
Am J Respir
Crit Care
MedinVol 181. pp 975–982, 2010
Originally Published in Press as DOI: 10.1164/rccm.200905-0808OC on February 4, 2010
the placebo group was observed. The overall Internet
clinical
cure rate
address: www.atsjournals.org
(83% at Day 7 and 71.8% at Day 30) is in concordance with
other studies (15). Our findings contrast with the findings in
other recent studies. In experimental studies a benefit has been
found with the combination of hydrocortisone and antibiotics
Citation:
thors have declared that no competing interests
exist.Nie W, Zhang Y, Cheng J, Xiu Q (2012) Corticosteroids in the Treatment of Community-Acquired Pneumonia
e47926. doi:10.1371/journal.pone.0047926
Editor: Miguel Santin, Barcelona University Hospital, Spain
qually to this work.
Received May 31, 2012; Accepted September 18, 2012; Published October 24, 2012
Copyright: ! 2012 Nie et al. This is an open-access article distributed under the terms of the Creative Commons Attr
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was supported by grant no. 81170025 from the National Natural Science Foundation of China an
and Development" from the National Ministry of Science and Technology (no. 2011ZX09302-003-001). The funders h
Corticosteroids for CAP
and analysis, decision to publish, or preparation of the manuscript.
with antibiotics attenuated local inflammatory response and
Competing
Interests: The
authors haveburden
declared that
competing
interests exist. model of severe
decreased
bacterial
innothe
experimental
eumonia (CAP) is a common and* E-mail: pneumonia
[email protected]
[5]. In a mouse pneumonia model, Li et al. [6] found
authors contributed equally to this work.
associated with high morbidity and. These that
hydrocortisone decreased inflammatory response significantly.
eading cause of death and the most
In addition, Salluh et al. [7] reported that relative adrenal
death worldwide [1]. Despite effective
Introduction
insufficiency occurred in most of the patientswith
withantibiotics
severe attenuate
CAP,
decreased
bacterial
burden
12–36% patients admitted to theCommunity-acquired
suggesting underlying
benefits
corticosteroids
treatment
in
these
pneumonia (CAP)
is aofcommon
and
pneumonia [5]. In a mouse
th severe CAP die within a short time
serious infectious
disease
associated
with
high
morbidity
and
that hydrocortisone
decreas
patients. Taken together, these facts indicated
a potential
mortality.
It
is
the
sixth
leading
cause
of
death
and
the
most
In addition, Salluh et al
ment of an efficacious treatment has
beneficial
effect
of worldwide
corticosteroids
in effective
pneumonia.
common infectious
cause
of death
[1]. Despite
insufficiency occurred in m
educing the high mortality.
antibiotic therapy,
about a12–36%
patients randomized
admitted to thecontrolled
Recently,
multicenter
(RCT)
suggestingtrial
underlying
bene
intensive
care
unit
(ICU)
with
severe
CAP
die
within
a
short
time
onia, inflammatory cytokines, such as
patients.
together
performed by Confalonieri et al. [8] demonstrated
thatTaken
hydrocor[2]. Therefore, the development of an efficacious treatment has
beneficial effect of corticos
IL-10 acted as acute phase proteins
treatment
incorticosteroids.
severe
was associated Recently,
with a significant
importanttisone
implications
for reducing
the high CAP
mortality.
Figure 2. Meta-analysis for the association
between
mortality
and
a multicenter
that the excess
of IL-6 and IL-10 wasDuringreduction
doi:10.1371/journal.pone.0047926.g002
infectious pneumonia,
inflammatory
cytokines,
such
as
in mortality. A retrospective study conducted
byConfalonieri
Garciaperformed by
interleukin
(IL)-6,
IL-8
and
IL-10
acted
as
acute
phase
proteins
ality rate in CAP [4]. Corticosteroids
tisone
in who
severe
Vidal
etshowed
al.
[9]that
found
thatofmortality
decreased
in thetreatment
patients
[3]. Ainrecent
study
themetabolic
excess
IL-6 and gastroduodenal
IL-10
was
disorders,
bleeding,
muscle
weakness,
replacement therapy might be effective
critical
illness,
including
reduction in mortality. A re
widely usedsevere
anti-inflammatory
drugs.
and
Previous
study Vidal
found ettreatment
that
corticosteroids
CAP. In subgroup analysis
by the duration
corticosteassociated
with a of
high
mortality rate
in superinfection.
CAP [4].
Corticosteroids
received
systemic
steroids
along
with antibiotic
al. [9]
found for
that m
increased
the
risk
of
hyperglycemia
and
hypernatremia
[23].
In
roids
treatment,
we
found
that
prolonged
corticosteroids
treatment
are the most
effective
and
widely
used
anti-inflammatory
drugs.
ed the association of glucocorticoids
received
systemic
steroids
severe
CAP.
Moreover,
results
from
a
systematic
review
showed
addition, there was no evidence for an increased risk of bleeding,
(.5 days) was associated with a greater benefit compared with
g
An early study demonstrated the association of glucocorticoids
severe CAP. Moreover, re
superinfection, or neuromuscular weakness [23]. In our metaanalysis, treatment with corticosteroids in CAP was associated with
an increased risk of hyperglycemia,
was not associated Octob
with
17 but
October
2012
|
Volume
|
Issue
10
|
e47926
gastroduodenal bleeding and superinfection. However, we could
not address the association between treatment with corticosteroids
and risk of hypernatremia or neuromuscular weakness. It was due
to insufficient information can be extracted from primary
publications. Further studies should be designed to analyze these
issues. Hyperglycemia occurred frequently in corticosteroids
treatment courses less than 5 days. Recently, Annane et al. [23]
assessed the use of corticosteroids for severe sepsis and septic shock
in a systematic review. They showed
that hydrocortisone
for a
PLOS ONE
| www.plosone.org
1
prolonged duration (.5 days) may improve survival in severe
sepsis and septic shock [23]. Moreover, a study on acute
respiratory distress syndrome (ARDS) suggested that more than
7 days corticosteroids strategy led to reduction in markers of
inflammation, duration of mechanical ventilation, and intensive
care unit stay [31]. Therefore, the beneficial effect of prolonged
on. For these and other
a specific time window
ould be recommended.
therapy should be addiagnosis is considered
dicated that antibiotic
as also associated with
re even more concerns
biotic when the patient
2
NOTE. Criteria are from [268, 274, 294]. pO2, oxygen partial pressure.
a
Important for discharge or oral switch decision but not necessarily for
determination of nonresponse.
Reprints or correspondence: Dr. Lionel A. Mandell, Div. of
McMaster University/Henderson Hospital, 5th Fl., Wing
at a predetermined time, regardless of the clinical
response
Concession
St., Hamilton, Ontario L8V 1C3, Canada (lmandel
This was
official
statement of the Infectious Diseases Society
[269]. One study population with nonsevere illness
ranand intravenous
the American Thoracic Society (ATS) was approved by
domized to receive either oral therapy alone or
Directors on 5 November 2006 and the ATS Board of Directo
therapy, with the switch occurring after 72 h without fever. The
2006.
study population with severe illness was randomized
to receive
a
Committee
cochairs.
Downloaded from http://cid
apy has adverse consey ill, hemodynamically
should be encouraged,
s recommendation. Deing the transition from
ith the frequent use of
d communication issues
tibiotics for 18 h after
that the best and most
the initial dose be given
acquired pneumonia (CAP) has been the f
different organizations, and several hav
guidelines for management of CAP. Two
widely referenced are those of the Infect
Society of America (IDSA) and the Ameri
Society (ATS). In response to confusion r
Table 10. Criteria for clinical stability.
ferences between their respective guidelin
and the ATS convened a joint committee
Temperature !37.8!C
unified CAP guideline document.
Heart rate !100 beats/min
Respiratory rate !24 breaths/min
The guidelines are intended primaril
Systolic blood pressure "90 mm Hg
emergency
Arterial oxygen saturation "90% or pO "60 mm Hg
on room air medicine physicians, hospital
Ability to maintain oral intakea
mary care practitioners; however, the ext
a
Normal mental status
ture evaluation suggests that they are al
either intravenous therapy with a switch to oral therapy after
Clinical Infectious Diseases 2007; 44:S27–72
2 days or a full 10-day course of intravenous antibiotics.
! 2007 by Time
the Infectious Diseases Society of America. All r
to resolution of symptoms for the patients with1058-4838/2007/4405S2-0001$15.00
nonsevere ill-
NAC
PREVENCION 250
PCV-7 vaccine
introduced
Age
<1 year
1 year
2 years
3 years
Rate per 100 000 population
200
150
100
50
0
1998
1999
2000
2001
2002
2003
2004
2005
Year
Figure 1: Incidence of pneumococcal disease in children in the USA before and after introduction of the
PCV-7 vaccine
PCV-7=conjugate seven-valent pneumococcal vaccine. Reprinted with permission.17
within urban neighbourhoods. Similar small-scale
outbreaks have been reported in day-care centres, jails,
military bases, and men’s shelters.10–12 Airway colonisation
by pneumococci is readily detectable in about 10% of
healthy adults. 20–40% of healthy children are carriers,
decreased overall incidence
rise in invasive pneumococc
serotypes.18 This pattern see
prompted a renewed in
formulations. Incidence rate
per 100 000 per year in isola
such as Alaskan Eskimos,
the Maoris of New Zealand.
Other recognised risk fa
coccal disease in children a
alcoholism, diabetes mellitu
underlying lung disease, se
and probably other respirato
and complement deficien
compromised states, includi
recent acquisition of a virul
smoking, proton pump in
factors probably contribute
(panel).3,14 Antecedent respi
exposure to antibiotics seem
for colonisation of airways
disease. Antibiotic-induced
inhibitory bacteria (α-ha
particular), release of vira
neuraminidase) that prom
inflammation-induced exp
invasion receptors on host ce
factor receptor21 and CD14,22
colonisation and invasion.
Table 13.
Recommendations for vaccine prevention of community-acquired pneumonia.
Factor
Pneumococcal
polysaccharide vaccine
Inactivated
influenza vaccine
Route of administration
Type of vaccine
Intramuscular injection
Intramuscular injection
Bacterial component (polysaccha- Killed virus
ride capsule)
Recommended groups
All persons !65 years of age
All persons !50 years of age
High-risk persons 2–64 years of
age
High-risk persons 6 months–49
years of age
b
Current smokers
Household contacts of high-risk
persons
Health care providers
Chronic cardiovascular, pulmonary, renal, or liver disease
Diabetes mellitus
Children 6–23 months of age
Chronic cardiovascular or pulmonary disease (including
asthma)
Chronic metabolic disease (including diabetes mellitus)
Cerebrospinal fluid leaks
Alcoholism
Renal dysfunction
Hemoglobinopathies
Asplenia
Immunocompromising conditions/medications
Immunocompromising conditions/medications
Native Americans and Alaska
natives
Long-term care facility residents
Compromised respiratory function or increased aspiration risk
Pregnancy
Residence in a long-term care
facility
a
Downloaded from http://cid.oxfordjournals.org/ at Universidad de Costa Rica on August 31, 2014
Specific high-risk indications for
vaccination
acquired pneumonia (CAP) has been the f
different organizations, and several hav
guidelines for management of CAP. Two
Live attenuated
widely
referenced are those of the Infect
influenza vaccine
Intranasal spray
Live virus
Society of America (IDSA) and the Ameri
Healthy persons 5–49 years of
In response to confusion r
age,Society
including health(ATS).
care
providers and household contacts of high-risk persons
ferences between their respective guidelin
and the ATS convened a joint committee
unified CAP guideline document.
Avoid in high-risk persons
The guidelines are intended primaril
emergency medicine physicians, hospital
mary care practitioners; however, the ext
ture evaluation suggests that they are al
Reprints or correspondence: Dr. Lionel A. Mandell, Div. of
McMaster University/Henderson Hospital, 5th Fl., Wing
Revaccination schedule
One-time revaccination after 5
Annual revaccination
Annual revaccination
Concession St., Hamilton, Ontario L8V 1C3, Canada (lmandel
years for (1) adults !65 years
of age, if the first dose is reThis official statement of the Infectious Diseases Society
ceived before age 65 years; (2)
persons with asplenia; and (3)
and the American Thoracic Society (ATS) was approved by
immunocompromised persons
Directors on 5 November 2006 and the ATS Board of Directo
NOTE. Adapted from the Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention [304].
Avoid use in persons with asthma, reactive airways disease, or other chronic disorders of the pulmonary or cardiovascular systems; persons with other
2006.
underlying medical conditions, including diabetes, renal dysfunction, and hemoglobinopathies; persons with immunodeficiencies
or who receive immunosuppressive therapy; children or adolescents receiving salicylates; persons with a history of Guillain-Barré syndrome; and pregnant women.
a
Committee
cochairs.
Vaccinating current smokers is recommended by the Pneumonia Guidelines Committee but is not currently an indication for vaccine according
to the Advisory
Aspirin therapy in persons "18
years of age
a
b
Committee on Immunization Practices statement.
40. The intranasally administered live attenuated vaccine is
an alternative vaccine formulation for some persons 5–
Clinical Infectious Diseases 2007; 44:S27–72
2007toby
theACIP
Infectious Diseases Society of America. All r
high-risk concurrent diseases, !
according
current
guidelines. (Strong recommendation;
level II evidence.)
1058-4838/2007/4405S2-0001$15.00