Upload
anonymous-so6znlkyw
View
221
Download
0
Embed Size (px)
Citation preview
8/12/2019 Therapeutic Advances in Infectious Disease 2014 Simonetti 3 16
1/15
http://tai.sagepub.com/Therapeutic Advances in Infectious Disease
http://tai.sagepub.com/content/2/1/3The online version of this article can be found at:
DOI: 10.1177/20499361135180412014 2: 3Therapeutic Advances in Infectious Disease
Antonella F. Simonetti, Diego Viasus, Carolina Garcia-Vidal and Jordi CarratalManagement of community-acquired pneumonia in older adults
Published by:
http://www.sagepublications.com
can be found at:Therapeutic Advances in Infectious DiseaseAdditional services and information for
http://tai.sagepub.com/cgi/alertsEmail Alerts:
http://tai.sagepub.com/subscriptionsSubscriptions:
http://www.sagepub.com/journalsReprints.navReprints:
http://www.sagepub.com/journalsPermissions.navPermissions:
http://tai.sagepub.com/content/2/1/3.refs.htmlCitations:
What is This?
- Jan 20, 2014Version of Record>>
by guest on March 6, 2014tai.sagepub.comDownloaded from by guest on March 6, 2014tai.sagepub.comDownloaded from
http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/content/2/1/3.full.pdfhttp://tai.sagepub.com/http://tai.sagepub.com/content/2/1/3http://tai.sagepub.com/content/2/1/3http://tai.sagepub.com/content/2/1/3http://www.sagepublications.com/http://tai.sagepub.com/cgi/alertshttp://tai.sagepub.com/subscriptionshttp://tai.sagepub.com/subscriptionshttp://www.sagepub.com/journalsReprints.navhttp://www.sagepub.com/journalsReprints.navhttp://www.sagepub.com/journalsPermissions.navhttp://tai.sagepub.com/content/2/1/3.refs.htmlhttp://tai.sagepub.com/content/2/1/3.refs.htmlhttp://online.sagepub.com/site/sphelp/vorhelp.xhtmlhttp://online.sagepub.com/site/sphelp/vorhelp.xhtmlhttp://tai.sagepub.com/content/2/1/3.full.pdfhttp://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://online.sagepub.com/site/sphelp/vorhelp.xhtmlhttp://online.sagepub.com/site/sphelp/vorhelp.xhtmlhttp://tai.sagepub.com/content/2/1/3.full.pdfhttp://tai.sagepub.com/content/2/1/3.full.pdfhttp://tai.sagepub.com/content/2/1/3.refs.htmlhttp://www.sagepub.com/journalsPermissions.navhttp://www.sagepub.com/journalsReprints.navhttp://tai.sagepub.com/subscriptionshttp://tai.sagepub.com/cgi/alertshttp://www.sagepublications.com/http://tai.sagepub.com/content/2/1/3http://tai.sagepub.com/8/12/2019 Therapeutic Advances in Infectious Disease 2014 Simonetti 3 16
2/15
Management of community-acquired
pneumonia in older adults
Antonella F. Simonetti, Diego Viasus, Carolina Garcia-Vidal and Jordi Carratala
Abstract:Community-acquired pneumonia (CAP) is an increasing problem among the elderly.Multiple factors related to ageing, such as comorbidities, nutritional status and swallowingdysfunction have been implicated in the increased incidence of CAP in the older population.Moreover, mortality in patients with CAP rises dramatically with increasing age. Streptococcuspneumoniaeis still the most common pathogen among the elderly, although CAP may also becaused by drug-resistant microorganisms and aspiration pneumonia. Furthermore, in theelderly CAP has a different clinical presentation, often lacking the typical acute symptomsobserved in younger adults, due to the lower local and systemic inflammatory response.
Several independent prognostic factors for mortality in the elderly have been identified,including factors related to pneumonia severity, inadequate response to infection, and lowfunctional status. CAP scores and biomarkers have lower prognostic value in the elderly, andso there is a need to find new scales or to set new cut-off points for current scores in thispopulation. Adherence to the current guidelines for CAP has a significant beneficial impact onclinical outcomes in elderly patients. Particular attention should also be paid to nutritionalstatus, fluid administration, functional status, and comorbidity stabilizing therapy in this groupof frail patients. This article presents an up-to-date review of the main aspects of CAP inelderly patients, including epidemiology, causative organisms, clinical features, and prognosis,and assesses key points for best practices for the management of the disease.
Keywords: clinical features, community-acquired pneumonia, elderly, etiology, management,
prognosis, treatment
What is the magnitude of the problem?Community-acquired pneumonia (CAP) is
among the most common infectious diseases
and causes significant morbidity and mortality
[Mandell et al. 2007]. CAP is an increasing prob-
lem among the elderly. CAP rates in older adults
are rising as a consequence of an overall increase
in the elderly population [Centers for Disease
Control and Prevention, 2003]. It has been
reported that CAP is the third most common
reason for hospitalization for persons aged 65
years and over [May et al. 1991], and in fact
nearly 50% of hospitalized patients with CAP
are in this age group [Niederman et al. 1998].
Interestingly, in a prospective cohort of 4534 hos-
pitalized patients with CAP (19952012), we
found that the number of patients aged 80 and
over has increased significantly in the last 17
years (Figure 1).
The incidence of hospitalized CAP is much
higher among elderly patients. In a US
Medicare cohort of patients 65 years, the inci-
dence was 18.3/1000 population and rose more
than fivefold, from 8.4/1000 in those aged 6569
years to 48.5/1000 in those aged 90 years or older
[Kaplanet al.2002]. In a Spanish cohort study of
11,240 inhabitants aged 65 years conducted
from 2002 to 2005, the annual incidence rate of
CAP was 13.9/1000 elderly persons/year [Vila-
Corcoles et al. 2009]. As in the US cohort, the
incidence also increased with age in this popula-
tion (from 9.9% in those aged 6574 years to
16.9% in those aged 7584 years, and to
29.4% in the over 85s) [Ochoa-Gondar et al.
2008].
Furthermore, mortality in hospitalized CAP
patients ranges between 10% and 25%, being
http://tai.sagepub.com 3
Therapeutic Advances in Infectious Disease Review
Ther Adv Infect Dis
(2014) 2(1) 316
DOI: 10.1177/2049936113518041
! The Author(s), 2013.Reprints and permissions:http://www.sagepub.co.uk/
journalsPermissions.nav
Correspondence to:Jordi Carratala, MD, PhD
Department of InfectiousDiseases, HospitalUniversitari de Bellvitge -IDIBELL, LHospitalet deLlobregat, Feixa Llarga
s/n, 08907, LHospitalet deLlobregat, Barcelona,[email protected]
Antonella F. Simonetti,
MD
Department of InfectiousDiseases, HospitalUniversitari de Bellvitge -IDIBELL, LHospitalet deLlobregat, Barcelona,Spain
Diego Viasus, MD, PhD
Department of InfectiousDiseases, HospitalUniversitari de Bellvitge -IDIBELL, LHospitalet deLlobregat, Barcelona,Spain and Spanish
Network for Research inInfectious Diseases(REIPI), Madrid, Spain
Carolina Garcia-Vidal,MD, PhD
Department of InfectiousDiseases, HospitalUniversitari de Bellvitge -IDIBELL, LHospitalet deLlobregat, Barcelona,Spain and SpanishNetwork for Research inInfectious Diseases(REIPI), Madrid, Spain
by guest on March 6, 2014tai.sagepub.comDownloaded from
http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/8/12/2019 Therapeutic Advances in Infectious Disease 2014 Simonetti 3 16
3/15
particularly high in older adults and in patients
with comorbidities [Fernandez-Sabeet al. 2003].
In the Spanish cohort study just mentioned the
30-day case-fatality rate rose dramatically with
increasing age (7.2% in those aged 6574
years, 13.5% in those aged 7584 years and
23.5% in the over-85 s) [Ochoa-Gondar et al.
2008].
Key points
The elderly population is at an increased risk
for acquiring CAP and is more likely to suffer
from severe disease.
In the coming years, rates of CAP in older
adults will rise due to the overall increase in
the elderly population.
CAP in elderly patients is associated with
high morbidity and mortality. The risk of
poor outcome increases with age.
What are the predisposing factors for CAPin older patients?Several factors have been linked with an
increased risk of CAP in the elderly. Even in
healthy ageing without comorbidity, immunity
and lung function may be impaired. In older
patients, nasal mucociliary clearance has been
shown to be less efficient [Ho et al. 2001]. Age-
related effects on pulmonary host defenses have
been reported, such as mechanical barriers,
phagocytic activity, humoral and T-cell immun-
ity, in animal and human models [Meyer, 2001].
Similarly, changes in the immune system asso-
ciated with ageing involve, in particular, a decline
in peripheral antigen-specific T- and B-cell func-
tion. Finally, the function of natural killer cells,
macrophages, and neutrophils also decreases inthe elderly [Meyer, 2001; Renshaw et al. 2002;
Janssens and Krause, 2004].
A variety of methodological approaches have
been tested in attempts to identify independent
risk factors for CAP in the elderly. Jackson and
colleagues identified lung diseases, heart dis-
eases, weight loss, poor functional status,
and smoking as independent predictors for CAP
in older patients [Jackson et al. 2009].
Riquelme and colleagues found that suspicion
of swallowing disorders, large volume aspiration,
malnutrition, hypoproteinemia (7 mmol/l, Respiratory rate
(RR) 30/min, Blood pressure (systolic blood
pressure (BP)
8/12/2019 Therapeutic Advances in Infectious Disease 2014 Simonetti 3 16
8/15
cancer, stroke) performed better than both
CURB-65 and PSI for predicting mortality
[Abisheganaden et al. 2012]. Moreover, it is
known that in advancing age both confusion
and increased urea are common and may be
affected by multiple confounding factors. For
this reason, Myint and colleagues also proposed
a new set of criteria named SOAR (Systolic BP,
Oxygenation, Age and Respiratory rate), for use
in older patients with CAP instead of CURB[Myint et al. 2006]. However, most authors
favor modifying existing scores in order to
improve their prognostic value rather than creat-
ing new tools for elderly patients [Brito and
Niederman, 2010].
Are biomarkers useful for predicting prognosis
in older patients?
Markers such as C-reactive protein (CRP) level,
white blood cell (WBC) count, procalcitonin
level, proadrenomedullin, and natriuretic pep-
tides are increasingly being used to assess the
prognosis of patients with CAP. However, few
studies have explored the value of biomarkers in
the elderly.
Ahkee and colleagues found an inverse relation
between mortality and WBC. In elderly patients
with CAP, the mortality rate was seven times
higher in those without leukocytosis on hospitaladmission than in the group with the condition.
The authors suggest that the lack of a systemic
inflammatory response may be seen as a marker
of an abnormal immune system [Ahkee et al.
1997]. However, a prospective study of 897
patients admitted with CAP found no difference
in interleukin (IL)-6 or in IL-10 levels between
younger patients and those older than 65 years.
This study presents further data rejecting the
Figure 2. Area under receiver operating characteristic curve (95% confidence interval) for predicting mortalityof PSI and CURB-65 scores by age group in 4534 hospitalized cases with community-acquired pneumonia in atertiary teaching hospital in Barcelona, Spain.
PSI, Pneumonia Severity Index; CURB-65, Confusion, Urea >7 mmol/l, Respiratory rate30/min, Blood pres-sure (systolic blood pressure
8/12/2019 Therapeutic Advances in Infectious Disease 2014 Simonetti 3 16
9/15
view that older patients display a muted response
to pneumonia [Kelly et al. 2009].
More recently, the usefulness of other biomarkers
such as CRP and procalcitonin in elderly patients
has been evaluated. An analysis of a retrospectivecohort of 438 patients65 years with CAP did not
reveal any association between CRP or WBC and
mortality, or between CRP or WBC and pneumo-
nia severity [Thiemet al. 2009]. The investigators
stress that the same phenomenon has been iden-
tified for the prognostic value of risk scores. On
the other hand, a recent study [Kim et al. 2013]
reported a good correlation between procalcitonin
level and both PSI and CURB-65 in elderly
patients. However, no relationship was found
between procalcitonin and mortality.
What factors are associated with mortalityin older patients?
Several studies of CAP [Riquelme et al. 1996;
Rello et al. 1996; Garcia-Ordonez et al. 2001]
have failed to associate age alone with a higher
risk of mortality. In a cohort of patients with
severe CAP admitted to the ICU, no difference
in mortality rate was found between patients aged
6575 years and those over 75. This finding
stresses how inappropriate it is to withhold inten-
sive care from elderly patients on account of age,
because more than half may survive the respira-
tory infection and may return to their previous
lifestyle [Rello et al. 1996].
The data regarding the impact of comorbidities
in the outcome of elderly population with CAP
are controversial. Some researchers identify
comorbid illness as one of the most important
prognostic factors [Conte et al. 1999; Ma et al.
2011]. An association has also been found
between certain specific comorbid conditions
and mortality, such as chronic obstructive pul-
monary disease (COPD), cerebrovascular disease
[Neupane et al . 2010], renal disease, and
immunosuppression [Skull et al . 2009].
Nevertheless, many other studies of CAP in theelderly have not found an association between
comorbid illness and mortality [Lim and
Macfarlane, 2001; Janssens et al. 1996; Rello
et al. 1996; Riquelme et al. 1996].
Moreover, several independent prognostic factors
for mortality in the elderly have been identified
(Table 3). Many studies have reported the associ-
ation between mortality and the severity of
pneumonia, as expressed by its extension and
consequent respiratory failure [Riquelme et al.
1997; Garca-Ordonez et al. 2001; Naito et al.2006; Skull et al. 2009]. Another group of prog-
nostic factors for poor outcome is related to an
inadequate response to infection, such as septic
shock at admission, apyrexia, and altered mental
status [Riquelme et al. 1997; Garca-Ordonez
et al. 2001; Fernandez-Sabe et al. 2003]. The
third group of factors related to mortality includes
host characteristics: low functional status, bedrid-
den status, poor nutritional status, and passive or
active smoking have all been related to poor out-
come in elderly patients with CAP [Skull et al.
2009; Naito et al. 2006; Riquelme et al. 1997;
Maet al. 2011; Vecchiarino et al. 2004].
Key points
The accuracy of CURB-65 and PSI for pre-
dicting outcome in CAP decreases with
advancing age.
There are insufficient data to sustain the use-
fulness of biomarkers in older patients.
Severity and extension of pneumonia, inad-
equate response to infection, and low func-
tional status are the principal factors
associated with mortality in older patients.
What treatment should elderly patientswith CAP receive?Antimicrobials are the cornerstone of therapy for
CAP in any population, including the elderly.
The most recently published clinical practice
guidelines for CAP do not recommend different
treatments for elderly patients [Mandell et al.
2007; Woodhead et al. 2011].
Table 3. Factors associated with poor outcome forcommunity-acquired pneumonia in elderly patients.
Severity of pneumonia:3 lobes affectedtachypneasevere hypoxemia
hypercapniaInadequate response to infection:
shock at admissionapyrexiaaltered mental status
Factors related with the host:comorbiditieslow functional statusbedridden statuspoor nutritional statuspassive or active smokers
Therapeutic Advances in Infectious Disease2 (1)
10 http://tai.sagepub.com
by guest on March 6, 2014tai.sagepub.comDownloaded from
http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/8/12/2019 Therapeutic Advances in Infectious Disease 2014 Simonetti 3 16
10/15
According to the IDSA/ATS guidelines, in the
outpatient setting, the recommended empirical
treatment is a macrolide for previously healthy
patients who have not used antimicrobials
within the previous 3 months. However, in
some countries macrolide-resistantS. pneumoniaeare frequent [Jones et al. 2010; European Centre
for Disease Prevention and Control,
20052013]. A respiratory fluoroquinolone or a
beta-lactam plus a macrolide are recommended
for patients with comorbidities. In hospitalized
patients with nonsevere CAP, the recommen-
dation is a respiratory fluoroquinolone or a
beta-lactam plus a macrolide. In severe CAP, a
combination of antibiotics is usually recom-
mended. A beta-lactam plus either azithromycin
or a respiratory fluoroquinolone are preferred. In
patients with predisposing factors for P. aerugi-
nosa or other Gram-negative bacilli an antipneu-mococcal, antipseudomonal beta-lactam plus
either a quinolone or an aminoglycoside and
azithromycin should be considered [Mandell
et al. 2007]. If MRSA is considered as a possible
causative organism, guidelines recommend
adding vancomycin or linezolid.
Importantly, it has been demonstrated that good
adherence to the 2007 IDSA/ATS guidelines for
CAP has a significant beneficial impact on clin-
ical outcomes in elderly patients. In a cohort of
1649 hospitalized CAP patients aged 65 years,
adherence to guidelines was associated with asignificantly shorter time taken to achieve clinical
stability compared with nonadherence.
Adherence to guidelines was also associated
with shorter length of stay (8 days versus 10
days) and decreased overall in-hospital mortality
(8%versus 17%) [Arnoldet al.2009]. Recently, a
Danish study in older patients with CAP
reported that the CAP guidelines were mainly
applied with regard to diagnostic tests and treat-
ment initiation whereas nutrition and mobiliza-
tion were neglected or only sporadically
addressed [Lindhardt et al. 2013].
Several studies have shown that elderly persons
hospitalized for CAP may be at increased risk of
functional loss during hospitalization and after
discharge. A lack of recovery in the first 3
months is associated with an increased risk of
hospital readmission and 1-year mortality [El
Solh et al. 2006]. For this reason, rehabilitation
of elderly patients during hospitalization and
post-discharge should be encouraged [Klausen
et al. 2012]. In addition, in elderly patients
special attention should also be paid to the
global assessment, including aspects such as
nutritional status, fluid therapy, comorbidity sta-
bilizing therapy, and patient information. A ran-
domized, controlled trial demonstrated that
nutritional supplementation in older patientsadmitted for pneumonia achieved a faster and
greater physical recovery [Woo et al. 1994].
Similarly, the use of a three-step critical pathway,
including early mobilization, was safe and effect-
ive in reducing the length of hospital stay for CAP
and did not adversely affect patient outcomes
[Carratala et al. 2012].
Importantly, a recent study showed that in elderly
patients with CAP, the decision to use a do not
resuscitate (DNR) order was taken in nearly 30%
of hospitalized patients [Oshitani et al. 2013]. In
this study physicians were more inclined to pro-pose DNR orders when CAP patients demon-
strated older in age (more than 75 years), poor
performance status, dementia, aspiration, low
albumin, extensive consolidation, and respiratory
failure. The decision to use DNR orders did not
make physicians choose less-intense antimicro-
bial treatments. Nevertheless effort to detect bac-
teria was not made in the DNR group as
elaborately as in the non-DNR g roup.
They also found that the DNR group has
higher 30-day mortality.
Key points
Adherence to guidelines for treatment of
CAP is highly recommended in the elderly.
Risk factors for P. aeruginosa, MRSA, and
other Gram-negative bacilli have to be con-
sidered when selecting antibiotic treatment.
Physicians should pay special attention to
nutrition, early mobilization, and comorbid-
ity-stabilizing therapy in older patients.
Which vaccines should be administered to
elderly patients in order to prevent CAP?Vaccination remains the primary preventive strat-egy for CAP in the elderly. Guidelines recom-
mend immunization against both influenza virus
andS. pneumoniaein patients above the age of 65.
Nevertheless, both vaccinations are substantially
underused in this vulnerable population.
Recent meta-analyses provide evidence support-
ing the recommendation of pneumococcal poly-
saccharide vaccine (PPV) to prevent invasive
AF Simonetti, D Viasus et al.
http://tai.sagepub.com 11
by guest on March 6, 2014tai.sagepub.comDownloaded from
http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/8/12/2019 Therapeutic Advances in Infectious Disease 2014 Simonetti 3 16
11/15
pneumococcal disease in adults, but, with regard
to adults with chronic illness, do not find compel-
ling evidence to support the routine use of PPV
to prevent all-cause pneumonia or mortality
[Moberley et al. 2013; Huss et al. 2009].
However, the 23-valent vaccine preventedpneumococcal pneumonia and reduced mortality
due to pneumococcal pneumonia in nursing-
home residents in a randomized trial
[Maruyamaet al. 2010]. Moreover, in a matched
casecontrol study in patients aged 65 years
and hospitalized with CAP, Domnguez and col-
leagues found an effectiveness of 23.6% for the
PPV for preventing hospitalizations due to pneu-
monia [Domnguezet al. 2010].
Recently, randomized trials have showed that 13-
valent pneumococcal conjugate vaccine (PCV13)
induces a greater functional immune responsethan PPSV23 for the majority of serotypes cov-
ered by PCV13 in adults [Jackson et al. 2013].
Consequently, the United States Food and Drug
Administration approved the use of the PCV13 in
this population. However, studies evaluating the
clinical effectiveness of PCV vaccination in adults
are lacking. Similarly, recently it was suggested
that there is no epidemiological reason to vaccin-
ate older adults with PCV due to the fact that
PCV vaccination of children has also reduced
the incidence of conjugate vaccine-serotype dis-
ease in older adults.
Regarding the impact of influenza vaccination on
CAP, a Cochrane meta-analysis did not find any
effect on hospital admissions, incidence of pneu-
monia, or complication rates between vaccinated
and unvaccinated patients [Jefferson et al. 2010].
However, in the elderly, vaccinations against
influenza and pneumococcus are associated
with reduced risk of hospitalization for heart dis-
ease and acute cardiovascular events. These find-
ings highlight the benefits of vaccination and
support efforts to increase vaccination rates
among the elderly [Nichol et al. 2003;
Lamontagne et al. 2008].
Key points
Current guidelines recommend vaccination
against S. pneumoniae and influenza in all
patients 65 years.
Nevertheless, coverage of both vaccinations
remains low; physicians should promote
their implementation.
ConclusionsThe elderly population is at an increased risk of
acquiring CAP and is more likely to suffer from
severe disease. In the coming years, CAP cases in
older adults will increase as a consequence of the
overall increase in the elderly population. Thespectrum of etiological pathogens in elderly
patients with CAP is diverse and shows substan-
tial variations between studies, butS. pneumoniae
is still the most common pathogen. Moreover,
drug-resistant microorganisms and aspiration
pneumonia should also be borne in mind.
Significantly, the clinical presentation in elderly
patients may be subtle and may lack the typical
acute symptoms, due to the lower local and sys-
temic inflammatory response. This suggests the
need to maintain a high suspicion of CAP in eld-
erly patients, even if they present with atypical
symptoms such as falls, altered mental statusand/or worsening of underlying diseases. The
usefulness of CAP-specific scores and biomarkers
to predict outcomes in elderly population is con-
troversial; we probably need to set different cutoff
points for current scores. New scales developed
recently for assessing severity in elderly patients
with CAP need further evaluation. Antimicrobial
selection for elderly patients with CAP is the
same as for younger adult populations; however,
when choosing the correct treatment, physicians
must carefully check for possible risk factors for
resistant microorganisms and evaluate the possi-
bility of aspiration pneumonia. In addition toantibiotic treatment, special attention should be
paid to the management of older patients, includ-
ing nutrition, rehabilitation, comorbidity stabil-
ization, and early mobilization. Preventive steps
such as pneumococcal and influenza vaccination
and measures aimed at improving nutritional
status may help to reduce CAP incidence.
FundingThis work was supported by the Fondo de
Investigacion Sanitaria de la Seguridad Social
(g rant number 11/01106) and Spains
Ministerio de Economia y Competitividad,
Instituto de Salud Carlos III, cofinanced by the
European Regional Development Fund A way to
achieve Europe and Spanish Network for
Research in Infectious Diseases (grant number
REIPI RD12/0015). Dr Simonetti is the recipient
of a research grant from the IDIBELL, Bellvitge
Biomedical Research Institute. Dr Viasus is the
recipient of a research grant from the REIPI. Dr
Garcia-Vidal is the recipient of a Juan de la
Therapeutic Advances in Infectious Disease2 (1)
12 http://tai.sagepub.com
by guest on March 6, 2014tai.sagepub.comDownloaded from
http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/8/12/2019 Therapeutic Advances in Infectious Disease 2014 Simonetti 3 16
12/15
Cierva research grant from the Instituto de Salud
Carlos III, Madrid, Spain.
Conflict of interest statementNo authors have any conflicts of interest to
disclose.
ReferencesAbisheganaden, J., Ding, Y., Chong, W., Heng, B. andLim, T. (2012) Predicting mortality among olderadults hospitalized for community-acquired pneumo-nia: an enhanced confusion, urea, respiratory rate and
blood pressure score compared with pneumoniaseverity index. Respirology 17: 969975.
Ahkee, S., Srinath, L. and Ramirez, J. (1997)Community-acquired pneumonia in the elderly: asso-
ciation of mortality with lack of fever and leukocytosis.South Med J90: 296298.
Almirall, J., Rofes, L., Serra-Prat, M., Icart, R.,Palomera, E., Arreola, V. et al. (2013) Oropharyngealdysphagia is a risk factor for community-acquired
pneumonia in the elderly. Eur Respir J41: 923928.
Arnold, F., LaJoie, A., Brock, G., Peyrani, P., Rello, J.,Menendez, R. et al. (2009) Improving outcomes inelderly patients with community-acquired pneumoniaby adhering to national guidelines: Community-
Acquired Pneumonia Organization Internationalcohort study results.Arch Intern Med169: 15151524.
Bolotin, S., Pebody, R., White, P., McMenamin, J.,Perera, L., Nguyen-Van-Tam, J. et al. (2012) A newsentinel surveillance system for severe influenza in
England shows a shift in age distribution of hospita-
lised cases in the post-pandemic period.PLoS One7: e30279.
Bont, J., Hak, E., Hoes, A., Macfarlane, J. and Verheij,T. (2008) Predicting death in elderly patients with
community-acquired pneumonia: a prospective valid-ation study reevaluating the CRB-65 severity assess-ment tool. Arch Intern Med168: 14651468.
Brito, V. and Niederman, M. (2010) Predicting mor-
tality in the elderly with community-acquired pneu-monia: should we design a new car or set a new speedlimit? Thorax 65: 944945.
Carratala, J., Garcia-Vidal, C., Ortega, L., Ferna ndez-Sabe, N., Clemente, M., Albero, G.et al.(2012) Effect
of a 3-step critical pathway to reduce duration of
intravenous antibiotic therapy and length of stay incommunity-acquired pneumonia: a randomized con-
trolled trial. Arch Intern Med172: 922928.
Carratala, J., Mykietiuk, A., Fernandez-Sabe, N.,
Suarez, C., Dorca, J., Verdaguer, R. et al. (2007)Health care-associated pneumonia requiring hospitaladmission: epidemiology, antibiotic therapy, and clin-
ical outcomes. Arch Intern Med167: 13931399.
Centers for Disease Control and Prevention (2003)Trends in aging - United States and worldwide.
MMWR Morb Mortal Wkly Rep 52: 101106.
Chen, J., Chang, S., Liu, J., Chan, R., Wu, J., Wang,
W. et al. (2010) Comparison of clinical characteristics
and performance of pneumonia severity score and
CURB-65 among younger adults, elderly and very old
subjects.Thorax 65: 971977.
Chowell, G., Bertozzi, S., Colchero, M., Lopez-Gatell,
H., Alpuche-Aranda, C., Hernandez, M.et al. (2009)Severe respiratory disease concurrent with the circu-
lation of H1N1 influenza.N Engl J Med361: 674679.
Conte, H., Chen, Y., Mehal, W., Scinto, J. and
Quagliarello, V. (1999) A prognostic rule for elderly
patients admitted with community-acquired pneumo-
nia. Am J Med106: 2028.
Domnguez, A., Izquierdo, C., Salleras, L., Ruiz, L.,
Sousa, D., Bayas, J. et al. (2010) Effectiveness of
the pneumococcal polysaccharide vaccine in prevent-
ing pneumonia in the elderly. Eur Respir J
36: 608614.
Donowitz, G. and Cox, H. (2007) Bacterial commu-
nity-acquired pneumonia in older patients. Clin GeriatrMed23: 515534.
El-Solh, A., Sikka, P., Ramadan, F. and Davies, J.
(2001) Etiology of severe pneumonia in the very eld-
erly. Am J Respir Crit Care Med163: 645651.
El Solh, A., Pineda, L., Bouquin, P. and Mankowski,
C. (2006) Determinants of short and long term func-
tional recovery after hospitalization for community-
acquired pneumonia in the elderly: role of inflamma-
tory markers. BMC Geriatr6: 12.
European Centre for Disease Prevention and Control
(20052013) European Antimicrobial Resistance
Surveillance Network. Available at: http://www.ecd-
c.europa.eu/en/healthtopics/antimicrobial_resistance/
database/Pages/map_reports.aspx
Ewig, S., Kleinfeld, T., Bauer, T., Seifert, K., Schafer,
H. and Goke, N. (1999) Comparative validation of
prognostic rules for community acquired pneumonia
in an elderly population.Eur Respir J14: 370375.
Ewig, S., Welte, T., Chastre, J. and Torres, A. (2010)
Rethinking the concepts of community-acquired and
health-care-associated pneumonia. Lancet Infect Dis
10: 279287.
Farr, B., Bartlett, C., Wadsworth, J. and Miller, D.
(2000) Risk factors for community-acquired pneumo-
nia diagnosed upon hospital admission. British
Thoracic Society Pneumonia Study Group. Respir Med
94: 954
963.
Fernandez-Sabe, N., Carratala, J., Roson, B., Dorca,
J., Verdaguer, R., Manresa, F. et al. (2003)
Community-acquired pneumonia in very eld-
erly patients: causative organisms, clinical
characteristics, and outcomes. Medicine (Baltimore)
82: 159169.
Fine, M., Auble, T., Yealy, D., Hanusa, B., Weissfeld,
L., Singer, D. et al.(1997) A prediction rule to identify
low-risk patients with community-acquired pneumo-
nia. N Engl J Med336: 243250.
AF Simonetti, D Viasus et al.
http://tai.sagepub.com 13
by guest on March 6, 2014tai.sagepub.comDownloaded from
http://-/?-http://-/?-http://-/?-http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://-/?-http://-/?-http://-/?-8/12/2019 Therapeutic Advances in Infectious Disease 2014 Simonetti 3 16
13/15
Fung, H. and Monteagudo-Chu, M. (2010)
Community-acquired pneumonia in the elderly. Am J
Geriatr Pharmacother8: 4762.
Garca-Ordonez, M., Garca-Jimenez, J., Paez, F.,
Alvarez, F., Poyato, B., Franquelo, M. et al. (2001)
Clinical aspects and prognostic factors in elderly
patients hospitalised for community-acquired pneu-monia. Eur J Clin Microbiol Infect Dis 20: 1419.
Ho, J., Chan, K., Hu, W., Lam, W., Zheng, L., Tipoe,
G. et al. (2001) The effect of aging on nasal muco-
ciliary clearance, beat frequency, and ultrastructure of
respiratory cilia. Am J Respir Crit Care Med
163: 983988.
Huss, A., Scott, P., Stuck, A., Trotter, C. and Egger,
M. (2009) Efficacy of pneumococcal vaccination in
adults: a meta-analysis. CMAJ180: 4858.
Jackson, M., Nelson, J. and Jackson, L. (2009) Risk
factors for community-acquired pneumonia in
immunocompetent seniors. J Am Geriatr Soc
57: 882
888.
Jackson, L., Gurtman, A., Rice, K., Pauksens, K.,
Greenberg, R., Jones, T. et al. (2013) Immunogenicity
and safety of a 13-valent pneumococcal conjugate
vaccine in adults 70 years of age and older previously
vaccinated with 23-valent pneumococcal polysacchar-
ide vaccine. Vaccine 31: 35853593.
Janssens, J., Gauthey, L., Herrmann, F., Tkatch, L.
and Michel, J. (1996) Community-acquired
pneumonia in older patients. J Am Geriatr Soc
44: 539544.
Janssens, P. and Krause, K. (2004) Pneumonia in the
very old. Lancet Infect Dis 4: 112124.
Jefferson, T., Di Pietrantonj, C., Rivetti, A., Bawazeer,G., Al-Ansary, L. and Ferroni, E. (2010) Vaccines for
preventing influenza in healthy adults. Cochrane
Database Syst Rev 7: CD001269.
Jones, R., Sader, H., Moet, G. and Farrell, D. (2010)
Declining antimicrobial susceptibility of
Streptococcus pneumoniae in the United States:
report from the SENTRY Antimicrobial Surveillance
Program (19982009). Diagn Microbiol Infect Dis
68: 334336.
Juthani-Mehta, M., De Rekeneire, N., Allore, H.,
Chen, S., OLeary, J., Bauer, D. et al. (2013)
Modifiable risk factors for pneumonia requiring hos-
pitalization of community-dwelling older adults: The
Health, Aging, and Body Composition Study. JAGS61: 11111118.
Kaplan, V., Angus, D., Griffin, M., Clermont, G.,
Scott Watson, R. and Linde-Zwirble, W. (2002)
Hospitalized community-acquired pneumonia in the
elderly: age- and sex-related patterns of care and out-
come in the United States. Am J Respir Crit Care Med
165: 766772.
Keipp Talbo, H. and Falsey, A. (2010) The diagnosis
of viral respiratory disease in older adults. Clin Infect
Dis 50: 747751.
Kelly, E., MacRedmond, R., Cullen, G., Greene, C.,McElvaney, N. and ONeill, S. (2009) Community-
acquired pneumonia in older patients: does age influ-ence systemic cytokine levels in community-acquired
pneumonia? Respirology 14: 210216.
Kikuchi, R., Watabe, N., Konno, T., Mishina, N.,
Sekizawa, K. and Sasaki, H. (1994) High incidence ofsilent aspiration in elderly patients with community-
acquired pneumonia. Am J Respir Crit Care Med
150: 251253.
Kim, J., Seo, J., Mok, J., Kim, M., Cho, W., Lee, K.et al. (2013) Usefulness of plasma procalcitonin topredict severity in elderly patients with community-
acquired pneumonia. Tuberc Respir Dis 74: 207214.
Klausen, H., Petersen, J., Lindhardt, T., Bandholm,T., Hendriksen, C., Kehlet, H. et al. (2012) Outcomes
in elderly Danish citizens admitted with community-acquired pneumonia. Regional differences, in a public
healthcare system. Respir Med106: 17781787.
Kothe, H., Bauer, T., Marre, R., Suttorp, N., Welte, T.and Dalhoff, K. (2008) Outcome of community-acquired pneumonia: influence of age, residence status
and antimicrobial treatment.Eur Respir J32: 139146.
Lamontagne, F., Garant, M., Carvalho, J., Lanthier,L., Smieja, M. and Pilon, D. (2008) Pneumococcal
vaccination and risk of myocardial infarction. CMAJ
179: 773777.
Lim, W. and Macfarlane, J. (2001) Defining prognosticfactors in the elderly with community acquired pneu-
monia: a case controlled study of patients aged75 yrs. Eur Respir J17: 200205.
Lim, W., van der Eerden, M., Laing, R., Boersma, W.,Karalus, N., Town, G. et al. (2003) Defining com-
munity acquired pneumonia severity on presentationto hospital: an international derivation and validation
study. Thorax 58: 377382.
Lindhardt, T., Klausen, H., Christiansen, C., Smith,
L., Pedersen, J. and Andersen, O. (2013) Elderlypatients with community-acquired pneumonia are not
treated according to current guidelines. Dan Med J
60: A4572.
Ma, H., Tang, W. and Woo, J. (2011) Predictors of in-hospital mortality of older patients admitted for com-
munity-acquired pneumonia.Age Ageing40: 736741.
Mandell, L., Wunderink, R., Anzueto, A., Bartlett, J.,
Campbell, G., Dean, N. et al. (2007) InfectiousDiseases Society of America/American Thoracic
Society consensus guidelines on the management ofcommunity-acquired pneumonia in adults. Clin Infect
Dis 44(Suppl. 2): S27S72.
Marik, P. (2001) Aspiration pneumonitis and aspir-ation pneumonia. N Engl J Med344: 665671.
Marik, P. and Kaplan, D. (2003) Aspiration pneumo-nia and dysphagia in the elderly. Chest124: 328336.
Maruyama, T., Taguchi, O., Niederman, M., Morser,
J., Kobayashi, H., Kobayashi, T. et al. (2010) Efficacyof 23-valent pneumococcal vaccine in preventing
Therapeutic Advances in Infectious Disease2 (1)
14 http://tai.sagepub.com
by guest on March 6, 2014tai.sagepub.comDownloaded from
http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/8/12/2019 Therapeutic Advances in Infectious Disease 2014 Simonetti 3 16
14/15
pneumonia and improving survival in nursing home
residents: double blind, randomised and placebo con-
trolled trial. BMJ 340: c1004.
May, D., Kelly, J., Mendlein, J. and Garbe, P. (1991)
Surveillance of major causes of hospitalization among
the elderly, 1988. MMWR Morb Mortal Wkly Rep
40: 7
21.
Metlay, J., Schulz, R., Li, Y., Singer, D., Marrie, T.,
Coley, C.et al.(1997) Influence of age on symptoms at
presentation in patients with community-acquired
pneumonia. Arch Intern Med157: 14531459.
Meyer, K. (2001) The role of immunity in suscepti-
bility to respiratory infection in the aging lung. Respir
Physiol128: 2331.
Moberley, S., Holden, J., Tatham, D. and Andrews, R.
(2013) Vaccines for preventing pneumococcal infec-
tion in adults. Cochrane Database Syst Rev
1: CD000422.
Myint, P., Kamath, A., Vowler, S., Maisey, D. and
Harrison, B. (2006) Severity assessment criteria rec-
ommended by the British Thoracic Society (BTS) for
community-acquired pneumonia (CAP) and older
patients. Should SOAR (systolic blood pressure, oxy-
genation, age and respiratory rate) criteria be used in
older people? A compilation study of two prospective
cohorts. Age Ageing35: 286291.
Naito, T., Suda, T., Yasuda, K., Yamada, T., Todate,
A., Tsuchiya, T. et al. (2006) A validation and poten-
tial modification of the pneumonia severity index in
elderly patients with community-acquired pneumonia.
J Am Geriatr Soc 54: 12121219.
Neupane, B., Walter, S., Krueger, P., Marrie, T. and
Loeb, M. (2010) Predictors of inhospital mortality and
re-hospitalization in older adults with community-
acquired pneumonia: a prospective cohort study.BMC
Geriatr10: 22.
Nichol, K., Nordin, J., Mullooly, J., Lask, R.,
Fillbrandt, K. and Iwane, M. (2003) Influenza vac-
cination and reduction in hospitalizations for cardiac
disease and stroke among the elderly. N Engl J Med
348: 13221332.
Niederman, M. (1994) Empirical therapy of commu-
nity-acquired pneumonia. Semin Respir Infect
9: 192198.
Niederman, M., McCombs, J., Unger, A., Kumar, A.
and Popovian, R. (1998) The cost of treating
community-acquired pneumonia. Clin Ther20: 820837.
Ochoa-Gondar, O., Vila-Corcoles, A., de Diego, C.,
Arija, V., Maxenchs, M., Grive, M. et al. (2008) The
burden of community-acquired pneumonia in the
elderly: the Spanish EVAN-65 study. BMC Public
Health 8: 222.
Ochoa Gondar, O., Vila Corcoles, A., Rodriguez
Blanco, T., de Diego Cabanes, C., Salsench Serrano,
E. and Hospital Guardiola, I. (2013) Ability of the
modified CRB75 severity scale in assessing elderly
patients with community acquired pneumonia.
Aten Primaria 45: 208215.
Oshitani, Y., Nagai, H. and Matsui, H. (2013)
Rationale for physicians to propose do-not-resuscitate
orders in elderly community-acquired pneumo-
nia cases. Geriatr Gerontol Int. DOI: 10.1111/
ggi.12054.
Polverino, E., Dambrava, P., Cilloniz, C., Balasso, V.,
Marcos, M., Esquinas, C. et al.(2010) Nursing home-
acquired pneumonia: a 10 year single-centre experi-
ence. Thorax 65: 354359.
Rello, J., Rodriguez, R., Jubert, P. and Alvarez, B.
(1996) Severe community-acquired pneumonia in the
elderly: epidemiology and prognosis. Study Group for
Severe Community-Acquired Pneumonia. Clin Infect
Dis 23: 723728.
Renshaw, M., Rockwell, J., Engleman, C., Gewirtz, A.,
Katz, J. and Sambhara, S. (2002) Cutting edge:
impaired Toll-like receptor expression and function in
aging. J Immunol169: 4697
4701.
Riquelme, R., Torres, A., El-Ebiary, M., de la
Bellacasa, J., Estruch, R., Mensa, J. et al. (1996)
Community-acquired pneumonia in the elderly: a
multivariate analysis of risk and prognostic factors. Am
J Respir Crit Care Med154: 14501455.
Riquelme, R., Torres, A., el-Ebiary, M., Mensa, J.,
Estruch, R., Ruiz, M. et al. (1997) Community-
acquired pneumonia in the elderly. Clinical and
nutritional aspects. Am J Respir Crit Care Med
156: 19081914.
Skull, S., Andrews, R., Byrnes, G., Campbell, D.,
Kelly, H., Brown, G. et al. (2009) Hospitalized com-
munity-acquired pneumonia in the elderly: an
Australian case-cohort study. Epidemiol Infect
137: 194202.
Teramoto, S., Fukuchi, Y., Sasaki, H., Sato, K.,
Sekizawa, K. and Matsuse, T. (2008) High incidence
of aspiration pneumonia in community- and hospital-
acquired pneumonia in hospitalized patients: a multi-
center, prospective study in Japan.J Am Geriatr Soc
56: 577579.
Thiem, U., Heppner, H. and Pientka, L. (2011)
Elderly patients with community-acquired pneumonia:
optimal treatment strategies. Drugs Aging
28: 519537.
Thiem, U., Niklaus, D., Sehlhoff, B., Stuckle, C.,
Heppner, H., Endres, H. et al. (2009) C-reactiveprotein, severity of pneumonia and mortality in elderly,
hospitalised patients with community-acquired pneu-
monia. Age Ageing38: 693697.
Tracy, J., Logemann, J., Kahrilas, P., Jacob, P.,
Kobara, M. and Krugler, C. (1989) Preliminary
observations on the effects of age on oropharyngeal
deglutition.Dysphagia 4: 9094.
Trifiro, G., Gambassi, G., Sen, E., Caputi, A.,
Bagnardi, V., Brea, J. et al. (2010) Association of
community-acquired pneumonia with antipsychotic
AF Simonetti, D Viasus et al.
http://tai.sagepub.com 15
by guest on March 6, 2014tai.sagepub.comDownloaded from
http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/http://tai.sagepub.com/8/12/2019 Therapeutic Advances in Infectious Disease 2014 Simonetti 3 16
15/15
Visit SAGE journals onlinehttp://tai.sagepub.com
drug use in elderly patients: a nested case-controlstudy. Ann Intern Med152: 418425, W139-W140.
Vecchiarino, P., Bohannon, R., Ferullo, J. andMaljanian, R. (2004) Short-term outcomes and their
predictors for patients hospitalized with community-acquired pneumonia. Heart Lung33: 301307.
Viasus, D., Cordero, E., Rodrguez-Bano, J., Oteo, J.,Fernandez-Navarro, A., Ortega, L. et al. (2012)Changes in epidemiology, clinical features and severity
of influenza A (H1N1) 2009 pneumonia in the firstpost-pandemic influenza season. Clin Microbiol Infect
18: E55E62.
Viasus, D., Pano-Pardo, J., Pachon, J., Campins, A.,Lopez-Medrano, F., Villoslada, A.et al.(2011) Factorsassociated with severe disease in hospitalized adults
with pandemic (H1N1) 2009 in Spain. Clin MicrobiolInfect17: 738746.
Vila Corcoles, A., Ochoa Gondar, O. and RodrguezBlanco, T. (2010) Usefulness of the CRB-65 scale forprognosis assessment of patients 65 years or older with
community-acquired pneumonia. Med Clin (Barc)
135: 97102.
Vila-Corcoles, A., Ochoa-Gondar, O., Rodriguez-Blanco, T., Raga-Luria, X. and Gomez-Bertomeu, F.
(2009) Epidemiology of community-acquired pneu-monia in older adults: a population-based study. Respir
Med103: 309
316.
Woo, J., Ho, S., Mak, Y., Law, L. and Cheung, A.(1994) Nutritional status of elderly patients during
recovery from chest infection and the role of nutri-tional supplementation assessed by a prospective ran-domized single-blind trial. Age Ageing23: 4048.
Woodhead, M., Blasi, F., Ewig, S., Garau, J., Huchon,G., Ieven, M. et al. (2011) Guidelines for the man-agement of adult lower respiratory tract infections - full
version. Clin Microbiol Infect17(Suppl. 6): E1E59.
Zalacain, R., Torres, A., Celis, R., Blanquer, J., Aspa,J., Esteban, L. et al. (2003) Community-acquiredpneumonia in the elderly: Spanish multicentre study.Eur Respir J21: 294302.
Therapeutic Advances in Infectious Disease2 (1)
16 http://tai.sagepub.com
http://tai.sagepub.com/