REVIEW

CURRENT
OPINION New guidelines for severe community-
acquired pneumonia
Ignacio Martin-Loeches a,b and Antoni Torres b

Purpose of review
We highlight the recent advances in the guidelines for treating patients with severe community-acquired
pneumonia (sCAP).
Downloaded from http://journals.lww.com/co-pulmonarymedicine by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 05/06/2021

Recent findings
sCAP is a significant cause of hospital admissions. We performed an extensive review of the literature,
covering studies from the last several years, to summarise the most important points in the diagnosis and
treatment of patients hospitalised with sCAP.
Summary
sCAP is associated with a high clinical burden. Therefore, deep knowledge is necessary for its
management. In general, diagnosis, treatment and management are based on many published guidelines.
However, the mortality rate is still unacceptably high, indicating the need for clear recommendations in the
management of patients with sCAP. The choice of empirical antibiotic therapy for sCAP depends on
multiple factors, such as national and local antimicrobial susceptibility data and the characteristics of the
patients, including their risk factors for acquiring infections caused by multidrug-resistant pathogens.
Currently, there are several published international guidelines. The aim of this review is to explore the
areas that require further knowledge and new recommendations for current clinical practice.
Keywords
macrolides, pneumonia, sepsis, severe community-acquired pneumonia

INTRODUCTION mortality, and healthcare costs due to the ongoing

&

Lower respiratory tract infections (LRTI) are a lead-
ing cause of death worldwide from infectious dis-
eases. Severe Community-acquired pneumonia
(sCAP) is one of the most common serious causes
of sepsis in hospitalised patients [1].
sCAP is associated with a high clinical burden;
therefore, deep knowledge is necessary for its man-
agement. In general, diagnosis, treatment and man-
agement are based on many published guidelines.
However, the mortality rate is still unacceptably
high, indicating the need for clear recommenda-
&
tions in the management of patients with CAP [2 ].
The microbial aetiology of sCAP is often unclear
in clinical practice, with different studies reporting
varying results. Streptococcus pneumoniae is the most
common pathogen associated with CAP [3]. Viruses
have also been increasingly identified as aetiolog-
ical agents in recent years through the greater
implementation of molecular testing. Furthermore,
there has been an increase in the prevalence of
multidrug-resistant Gram-negative bacteria (MDR-
GNB), which can substantially increase morbidity,
spread of antimicrobial resistance [4 ].
The choice of empirical antibiotic treatment for
sCAP depends on multiple factors, such as national
and local antimicrobial susceptibility data and the
characteristics of patients, including their risk fac-
tors for acquiring infections caused by MDR patho-
gens. Currently, there are several published
international guidelines. The aim of this review is
to explore the areas that require further knowledge
and new recommendations for current clinical prac-
tice (Table 1).
a
Multidisciplinary Intensive Care Research Organization (MICRO),
Department of Intensive Care Medicine, St. James’s University Hospital,
Trinity Centre for Health Sciences, Dublin, Ireland and bHospital Clinic,
IDIBAPS, Universidad de Barcelona, CIBERes, Barcelona, Spain
Correspondence to Ignacio Martin-Loeches, St James’s Hospital, Dublin
8, Ireland. E-mail: drmartinloeches@gmail.com
Curr Opin Pulm Med 2021, 27:210–215
DOI:10.1097/MCP.0000000000000760

www.co-pulmonarymedicine.com Volume 27  Number 3  May 2021

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.


KEY POINTS
 Lower respiratory tract infections (LRTI) are a leading
cause of death worldwide from infectious diseases, with
severe community-acquired pneumonia (sCAP) one of
the most common serious causes of sepsis in patients
admitted to a hospital.
 The microbial aetiology of sCAP is often unclear in
clinical practice, with different studies reporting varying
results. A systematic aetiological investigation should
be performed in hospitalised patients. The main goal of
a systematic aetiological investigation is to tailor
empirical antibiotic treatment in order to reduce
treatment failure and decrease the overuse
of antimicrobials.
 The choice of empirical antibiotics for sCAP depends
on multiple factors, such as the national and local
antimicrobial susceptibility data and patient
characteristics, including their risk factors for acquiring
infections caused by MDR pathogens. Biomarkers can
be used to determine whether to reduce
treatment duration.
 The optimal treatment duration in patients with sCAP is
not well defined. Different guidelines have published
different recommendations. Generally, the longer the
treatment, the higher the potential to develop antibiotic-
resistant strains and the greater the likelihood of
complications such as a Clostridium difficile infection
(CDI).
 Corticosteroids are useful in treating sCAP and can
help decrease treatment failure and likely mortality.
AETIOLOGY BEYOND COMMON
PATHOGENS
Aetiology is one of the most controversial points in
CAP. A systematic aetiological investigation should be
performed in hospitalised patients. The goal of such a
recommendation is to ensure a proper diagnosis so
that adequate antibiotic treatment can be adminis-
tered. In nonsevere cases, determining the aetiology
might not be very important since the antibiotic
treatment might not be changed. However, in sCAP,
determining the aetiology is a cornerstone in tailoring
antibiotic treatment as the likelihood of MDR patho-
gens being present is high [5].
The main goal of a systematic aetiological inves-
tigation is to adjust the empirical antibiotic treat-
ment in order to reduce treatment failure and
decrease the overuse of antimicrobials. Blood cultures
have a low rate of detection (5–15%) but have high
clinical value as they provide very valuable informa-
tion about antimicrobial resistance. A shorter time to
positivity of blood cultures (<10 h) has been found to
be independently associated with a high risk of inva-
sive mechanical ventilation, longer hospital stays,
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Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
New guidelines for sCAP Martin-Loeches and Torres
higher in-hospital mortality and higher 30-day mor-
tality [6]. Amaro et al. [7] found that high levels of C-
reactive protein (CRP) ( 20 mg dL –1), pleural effu-
sion and multilobar involvement were indepen-
dently associated with bacteraemic CAP, whereas
nursing home residence was found to be a protective
factor. Despite clinical differences, the authors of the
study reported that patients with bacteraemic pneu-
mococcal CAP showed similar outcomes as those
with blood culture-negative pneumococcal pneumo-
nia. In the current guidelines of the Infectious Dis-
eases Society of America/American Thoracic Society
&&
(IDSA/ATS) [8 ], aetiological determination is only
recommended for individuals with sCAP, patients
being treated for methicillin-resistant Staphylococcus
aureus (MRSA) or Pseudomonas aeruginosa CAP,
patients previously infected with MRSA or P. aerugi-
nosa, or individuals hospitalised in the previous
90 days.
Molecular diagnostic techniques, with a sensitiv-
ity of 70–80% and high specificity (99–100%), have
revealed a higher incidence of respiratory viruses in
CAP and can easily diagnose atypical bacteria [9].
These techniques are better at diagnosing either bac-
terial or viral pneumonia, identifying multiple iso-
lates from one sample, and providing information
about drug resistance mechanisms [10]. Currently,
20–40% of the isolates causing pneumococcal CAP
show high resistance to macrolides, whereas 3–8%
&
present high resistance to fluoroquinolones [11 ].
The b-lactam-resistant S. pneumoniae PMEN3 clone
is present in 10% of the isolates causing invasive
pneumococcal infections and has been associated
with CAP in old subjects with significant comorbid-
ities [12]. Baudel et al. [13] evaluated the performance
of multiplex polymerase chain reaction in bron-
choalveolar lavage (BAL) samples from critically ill
patients suspected of having CAP. The authors found
that this approach was associated with a higher
degree of aetiological diagnosis (66%) compared to
nonmolecular techniques, especially in patients who
had previously received antibiotics.
In summary, rapid diagnostic tests present ben-
efits in the treatment of patients with CAP, espe-
cially in critically ill subjects where the initial and
appropriate antibiotic treatment is very important
for their survival. However, it is still uncertain how
the rapid molecular diagnostic tests will provide the
valuable information required to de-escalate empir-
ical antibiotic treatment in daily clinical practice.
USE OF PROGNOSTIC TOOLS FOR
ADMISSION AND SEPSIS PREDICTION
The place where a patient with CAP is managed has
important implications in prognosis and healthcare
www.co-pulmonarymedicine.com 211
Infectious diseases

Table 1. Summary of recommendations

Aetiology Perform a complete aetiological study in cases of hospitalised CAP, sCAP and CAP that does not respond to
treatment.
Select microbiological tests based on associated risk factors, such as age and comorbidities, and the risk
factors for antibiotic-resistant pathogens. They should be performed preferably before the start of
antimicrobial therapy.
Scales PSI and CURB-65 are useful in the initial decision to hospitalise cases, as a support for clinical judgement.
The use of qSOFA may be justified if the diagnosis of CAP is uncertain.
Antibiotic choices Antimicrobial treatment: combination of a beta-lactam and a macrolide or a quinolone in monotherapy.
Combination with a macrolide (clarithromycin or azithromycin) is preferable in sCAP.
Assess the risk of antimicrobial resistance: apply the PES scale. If the PES score is 5, collect respiratory
samples for culture and molecular diagnostic techniques, and initiate empirical antibiotic treatment.
In patients with severe COPD or bronchiectasis who had received antibiotic treatment in the last 90 days or
had previous respiratory colonisation by Pseudomonas aeruginosa, initial treatment with an
antipseudomonal antibiotic is recommended that also covers S. pneumoniae and H. influenzae.
Antibiotic treatment duration Duration of antimicrobial treatment must be individualised and based on the criteria for clinical stability,
lasting a minimum of 5 days that can be suspended after 48 h of no fever and without more than one sign
of clinical instability.
Consider prolonging antibiotic treatment for: necrotising pneumonia, lung abscesses, complicated pleural
effusion, extrapulmonary infections and/or suspicion of the presence of atypical pathogens.
Corticosteroids Recommended their use (prednisolone or methylprednisolone over hydrocortisone) only in patients with sCAP.

CURB-65, confusion, urea, respiratory rate, blood pressure and age 65; PES, pseudomonas; PSI, Pneumonia Severity Index; sCAP, severe community-acquired
pneumonia; COPD, chronic obstructive pulmonary disease; qSOFA, quick Sequential Organ Failure Assessment.

costs. There are numerous tools such as the Pneu-
monia Severity Index (PSI) and the CURB-65 (con-
fusion, urea, respiratory rate, blood pressure and age
65) score to identify and evaluate patients with
CAP [14,15]. In parallel to these specific scales for
CAP, there are other more generic ones for patients
with sepsis, such as the National Early Warning
Score (NEWS) and the quick Sequential Organ Fail-
ure Assessment (qSOFA) [16,17]. Five systematic
reviews and four meta-analyses have been published
to date to determine the predictive value of these
scales, assessing predictions for mortality and inten-
sive care unit (ICU) admission. They have reported
that the PSI, CURB-65 and CRB-65 are the most
used scales for hospital admission. The PSI helps
to identify patients with low clinical risk. Current
IDSA/ATS guidelines recommend the use of the PSI
&&
alongside clinical judgement [8 ]. For ICU admis-
sion, the IDSA/ATS major and minor criteria, the
sCAP (Spanish version) score and the SMART-COP
(systolic blood pressure, multilobar infiltrates, albu-
min, respiratory rate, tachycardia, confusion, oxy-
gen and pH) score show higher predictive values
than the PSI and CURB-65 score [18,19]. The major-
ity of studies have found that the predictive value of
the qSOFA is similar or inferior to the PSI, CURB-65,
CRB and CRB-65 scores [20]. However, the qSOFA
performs better than the CURB-65 score in predict-
ing ICU admission [21]. Recently, lymphopenia
(<724 lymphocytes/mm3) has been associated with
an increase in the risk of mortality at 30 days in
patients with CAP [22].
In summary, current IDSA/ATS guidelines rec-
ommend the PSI over the CURB-65 score for hospital
&&
admission [8 ]. Generic scales such as the qSOFA
show moderate predictive value and their use might
be very beneficial when the diagnosis of CAP is
uncertain. However, they do not show improved
predictive values when compared to pneumonia-
specific scales such as the CRB or CRB-65 score.
For ICU admission, current IDSA/ATS guidelines still
recommend the implementation of their minor and
major criteria, but they do not recommend the
&&
qSOFA [8 ].
DIFFERENCES IN EFFICACY OF THE
RECOMMENDED ANTIBIOTIC
TREATMENTS OF CAP IN HOSPITALISED
PATIENTS
Current guidelines recommend the administration of
fluoroquinolones alone or a combination of a beta-
lactam and a macrolide to treat CAP, except in patients
admitted to an ICU, individuals with concomitant
diseases or those with risk factors associated with
greater resistance to the pathogens causing pneumo-
coccal CAP. In patients admitted to an ICU, a beta-
lactam in combination with either a macrolide or a
fluoroquinolone is recommended [23].
A randomised controlled trial (RCT) found no
differences between combination therapy and a
monotherapy with a beta-lactam, although the
more severe patients (PSI IV) showed slower clinical
progression when treated with the beta-lactam

212 www.co-pulmonarymedicine.com Volume 27  Number 3  May 2021

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monotherapy [24]. A meta-analysis, including over
9,000 patients from 28 observational studies, found
a 3% reduction (relative risk [RR] 0.82, P ¼ 0.02) in
mortality when a macrolide was included in the
antibiotic regimen compared to a regimen without
a macrolide [25]. A recent study by Ceccato et al.
&&
[26 ] found that the combination of a beta-lactam
and a macrolide was associated with a reduced mor-
tality in patients admitted with pneumococcal CAP
and a high inflammatory response. Apart of the
classical beta-lactams, a new generation cephalospo-
rin, ceftaroline, has been included in recent guide-
&&
lines [8 ].
The appearance of drug-resistant strains is of
great concern. Several scores have been published
in the past to predict the appearance of MDR [27,28].
The ’PES’ (Pseudomonas, Enterobacteriaceae ESBL,
MRSA) score might be a useful tool [29], with a high
score indicating the need for respiratory samples for
molecular diagnosis if possible and treatment with
broad-spectrum antibiotics. The recently published
IDSA/ATS guidelines recommend treating MRSA
and/or P. aeruginosa in patients with locally vali-
dated risk factors for either pathogen and only with
agents with antianaerobic coverage if there is a
suspicion of an abscess or empyema.
TREATMENT DURATION IN PATIENTS
WITH CAP AND sCAP
The optimal duration of treatment in patients with
CAP is not well defined. Different guidelines have
published different recommendations [30]. Gener-
ally, the longer the treatment is, the higher the
potential to develop resistant strains and the greater
the likelihood of complications such as a Clostridium
difficile infection (CDI). A retrospective cohort study
in patients admitted with CAP found that the
median antibiotic treatment duration was longer
than the recommended time in 74% and 71% of
patients aged 18–64 years and 65 years, respec-
tively [31].
In a meta-analysis published more than a decade
ago that included a total of 2,796 patients with mild
to moderate CAP from 15 studies, no differences
were found in efficacy between treatment lasting <
7 days and that lasting > 7 days [32]. Another meta-
analysis, which included data from 5 clinical trials of
adult patients with mild to moderate CAP and with
similar antibiotic regimens, found no differences in
terms of clinical cure, mortality and adverse events
when comparing antibiotic courses lasting 3–7 days
vs that lasting 7–10 days [33]. A recent meta-analysis
that compared treatment duration of < 6 days to
&&
that of > 7 days found very interesting results [34 ].
The rates of clinical cure and relapses were similar,
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Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
New guidelines for sCAP Martin-Loeches and Torres
but the group treated with the ’short-course’ antibi-
otic regimen had both fewer adverse events and
lower mortality when compared to the group on
the ’long-course’ regimen (RR 0.52, 95% confidence
interval [CI] 0.33–0.82). In addition, when the anal-
ysis was performed in a subgroup of patients with
sCAP, the mortality rate remained lower in those on
the short-course regimen (2.2% vs 4.7%). A non-
inferiority trial was conducted in Spain in hospital-
ised patients with CAP that aimed to validate the
IDSA/ATS recommendation that antibiotic treat-
ment should be for at least 5 days and stopped after
48 h of clinical stability. Despite a significant reduc-
tion in treatment duration between the interven-
tion and control groups (median 5 and 10 days,
respectively, P < 0.001), the clinical cure rates at
days 10 and 30 were not different [35].
Biomarkers can be used to decide whether to
reduce treatment duration. There are different bio-
markers, with procalcitonin (PCT) one of the most
&
studied ones. Walsh et al. [36 ] conducted a retro-
spective preintervention/postintervention study to
compare the management of patients admitted with
pneumonia before and after the implementation of
PCT guidance in the USA. In the postintervention
period, the mean duration of therapy decreased (9.9
vs 6.0 days; P < 0.001) and the mean duration of
therapy was shorter in patients with PCT lev-
els < 0.25 mg/L than in those with levels > 0.25 mg/
L (4.6 vs 8.0 days; P < 0.001). Schuetz et al. [37]
conducted a meta-analysis of 32 eligible RCTs,
including 18 new trials, for the 2017 Cochrane
review update. This meta-analysis included individ-
ual participant data from 6,708 individuals from 12
countries. According to the Grading of Recommen-
dations Assessment, Development and Evaluation
(GRADE), the quality of the evidence was high for
the outcomes mortality and antibiotic exposure,
and moderate for the outcomes treatment failure
and antibiotic-related side effects. The meta-analysis
found a lower mortality associated with PCT-guided
therapy (adjusted OR 0.83, 95% CI 0.70–0.99,
P ¼ 0.037) as well as a 2.4-day reduction in antibiotic
exposure (5.7 vs 8.1 days, 95% CI -2.71 to -2.15,
P < 0.001) and a lower risk of antibiotic-related side
effects (16.3% vs 22.1%; adjusted OR 0.68, 95% CI
0.57–0.82, P < 0.001) in the group receiving PCT-
guided therapy. Therefore, an international experts
consensus on PCT-guided antibiotic stewardship
was recently published for guidance on how to
interpret PCT results to initiate, withhold or discon-
tinue antibiotic treatment [38]. This consensus rec-
ommends combining clinical patient assessment
and data on PCT levels to improve the therapeutic
management of patients with CAP and increase the
effectiveness of the antibiotic stewardship.
www.co-pulmonarymedicine.com 213
Infectious diseases
IDSA/ATS guidelines recommend that antibiotic
treatment duration should be individualised and
last at least 5 days, stopping treatment after 48 h
&&
of clinical stability and no fever [8 ]. In the case of
complications such as necrotising pneumonia, lung
abscesses, complicated parapneumonic pleural effu-
sion, extrapulmonary infections or infections due to
atypical pathogens (e.g., P. aeruginosa, MRSA or
anaerobes), antibiotic treatment should be pro-
longed. The use of biomarkers, especially PCT, could
be valuable for implementing antibiotic steward-
ship programmes [39]. Further studies are needed
in sCAP and in cases involving atypical pathogens.
CORTICOSTEROID USE
After the publication of the ATS/IDSA guidelines for
CAP, a group of experts gave a perspective on the
recommendations related to the management of
CAP and one of the points of agreement was the
&&
use of corticosteroids [40 ].
The use of corticosteroids has been continuously
criticised over the last 20 years for the management
of severe infections. Not surprisingly sCAP has been
one of those diseases were the controversy was high-
est. In patients with sCAP the mortality remains still
high despite the developments in antimicrobial
therapy and life-support measures and this is the
rationale behind for using adjunct therapeutic inter-
ventions along with antibiotics to improve outcome
of patients with sCAP. Different guidelines have
different recommendations. Although South Afri-
can guidelines [41] support their use in patients with
sCAP requiring ICU admission, the American guide-
lines suggest not to use routinely corticosteroids in
&&
adults with sCAP [8 ].
There have been several systematic reviews and
metanalysis published that explored the efficacy of
corticosteroid in treatment of patients with sCAP.
The Cochrane published in 2017 a metanalysis that
included 17 RCTs comprising a total of 2,264 par-
ticipants and found a lower mortality and morbidity
in adults with sCAP who were treated with cortico-
steroids [42]. More recently, another metanalysis
that focussed on sCAP found differences depending
on the type of corticosteroids. Whilst prednisolone
or methylprednisolone therapy reduced total mor-
tality, hydrocortisone use did not. They also found
that the length of ICU stay was significantly shorter
in the steroid group compared to control and there
was a reduction trend in the need for mechanical
&&
ventilation in corticosteroid group [43 ]. Two
important remarks for their use should be acknowl-
edged: the benefit when a high systemic inflamma-
tory response is present [44] and the lack of benefit
&&
in influenza pneumonia [45 ].
214 www.co-pulmonarymedicine.com
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
CONCLUSIONS
sCAP is a systemic infectious disease with a mortality
rate that is still unacceptably high. Current interna-
tional guidelines stress the importance of determin-
ing the aetiology of the infection through molecular
testing. Duration of antibiotic treatment is a popular
area of research and should balance clinical success
with the need to avoid the development of antibi-
otic resistance. Biomarkers are a cornerstone in the
management of patients with CAP, most impor-
tantly in those with severe forms, to decrease treat-
ment failure. Guidelines for the management of
sCAP of the European Respiratory Society, European
Society of Intensive Care Medicine, European Soci-
ety of Clinical Microbiology and Infectious Diseases
and Asociación Latinoamericana del Tórax are
under development.
Acknowledgements
Not applicable.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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