Armitage. curr opin infect dis 2007. new guidelines for the management of adult community acquired pneumonia

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

New guidelines for the management of adultcommunity-acquired pneumoniaKathryn Armitage and Mark Woodhead

Purpose of reviewCommunity-acquired pneumonia is a major cause ofmorbidity and mortality, and is the leading cause of deathfrom an infectious disease. International societies havepublished and revised guidelines aiming to improve themanagement of adult community-acquired pneumonia,based on the best available evidence. The aim of this reviewis to compare the current guideline recommendations.Recent findingsAspects of guidelines differ based on local factors includingresources and antimicrobial factors, as well as thedifferences in interpretation of existing evidence.SummaryThe lack of robust evidence behind aspects of guidelinerecommendations as well as the lack of adherence topublished guidelines both need to be addressed if themanagement of community-acquired pneumonia is to beimproved.

Keywordsadherence, antibiotics, community-acquired pneumonia,guidelines

Curr Opin Infect Dis 20:170–176. ! 2007 Lippincott Williams & Wilkins.

Department of Respiratory Medicine, University of Manchester, Manchester RoyalInfirmary, Manchester, UK

Correspondence to Dr Mark Woodhead, Consultant in General and RespiratoryMedicine and Honorary Lecturer, Department of Respiratory Medicine, Universityof Manchester, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL,UKTel: +44 (0)161 276 4381; fax: +44 (0)161 276 4989;e-mail: [email protected]

Current Opinion in Infectious Diseases 2007, 20:170–176

Abbreviations

ATS American Thoracic SocietyBTS British Thoracic SocietyCAP community-acquired pneumoniaERS European Respiratory SocietyICU intensive care unitIDSA Infectious Diseases Society of AmericaJRS Japanese Respiratory Society

! 2007 Lippincott Williams & Wilkins0951-7375

IntroductionCommunity-acquired pneumonia (CAP) is a major causeof morbidity and mortality, and internationally is theleading cause of death from an infectious disease andthe sixth leading cause of death overall. Over the pastdecade international societies have published and revisedguidelines for the management of patients with CAP.The aim of this article is to review recent updates andhighlight areas both of consensus and difference, as wellas to evaluate the use of guidelines as a whole. A com-bined American Thoracic Society (ATS) and InfectiousDiseases Society of America (IDSA) guideline is due tobe published early in 2007, but at the time of writing themain national and international guidelines include theATS (2001), IDSA (2003), British Thoracic Society(BTS) (2004; www.brit-thoracic.org.uk/guidelines) andEuropean Respiratory Society (ERS) (2005). Their aimis to standardise care by providing management strategiesbased on best available evidence. The evidence may bethe same; however, differences exist between guidelinesnot only in the scope of recommendations, but also due toregional differences in patient populations, causativeagents, bacterial antibiotic resistance rates, drug licen-sing, healthcare structure and available resources.Recommendations made by one national organisationmay therefore not be applicable to other countries.

MethodologyWhilst most societies have restricted their guidelines toCAP, the IDSA includes acute bronchitis and empyemawithin its guidelines [1], while the ERS addresses allaspects of care for respiratory tract infections both in thecommunity and hospital settings [2!!].

DiagnosisThe diagnosis of CAP is usually defined as the presenceof signs or symptoms compatible with a respiratory tractinfection in the presence of new consolidation on a chestradiograph. The chest radiograph is the gold standard;however, in primary care, given the frequency of attend-ances for respiratory tract infection it may not be cost-effective or practical for all patients with such symptomsto undergo chest radiography. The frequency of pneu-monia is quoted as 5–10% among patients with symp-toms of lower respiratory tract infection. The ATSrecommend chest radiography if ‘symptoms and physicalexamination suggest the possibility of pneumonia’ [3].The ERS similarly recommend that patients suspected of

170

mailto:[email protected]

http://www.brit-thoracic.org.uk/guidelines


having pneumonia (i.e. acute cough plus new focal chestsigns, dyspnoea, tachypnoea or fever for more than4 days) should undergo radiography [1]. The BTS includea definition of pneumonia in the community as thepresence of focal clinical signs without any other expla-nation, without emphasis on radiology [4].

There is consensus that a chest radiograph should beperformed on all patients admitted to hospital withsuspected pneumonia [1,2!!,3–9].

Microbial investigationThere is little evidence to suggest that microbial inves-tigation affects mortality, but it can provide informationto assist with antibiotic selection as well as epidemiolo-gical data. Controversy still exists over sputum examin-ation. The ATS, BTS and ERS are all in agreement thatdue to the wide variability in sensitivity and specificity ofsputum Gram staining, based not only on a patient’sability to expectorate, but also technical differencesin slide preparation and interobserver variability,routine Gram staining should not be performed. It issuggested that sputum be sent for Gram stain only wheregood quality sputum is expectorated, as observed byqualified medical staff, and transported to the laboratoryin a timely fashion. Thereafter, strict criteria should beused for both the quality assessment of the sputumsample and an agreed level of sensitivity adopted.Gram staining results should be considered when inter-preting the significance of sputum cultures. Concordancesuggests a definitive pathogen.

Between 5 and 38% cases of CAP are due to mixedorganisms. The ERS and ATS recommend thatGram stain results are useful to expand the breadth ofantimicrobial coverage based on the discovery of anunexpected organism, unlike the IDSA which not onlyrecommends that Gram staining is conducted on allpatients, but that positive results be used to narrowthe therapeutic antimicrobial spectrum.

Except for the Japanese Respiratory Society (JRS), allsocieties recommend that two sets of blood cultures betaken from all patients admitted to hospital with pneu-monia, preferably before the administration of antibiotics[1,2!!,3,4,6]. The JRS only recommend this in cases ofsevere pneumonia. Routine serological investigationand urinary antigen testing for Legionella pneumophilaserogroup I and Streptococcus pneumoniae are only recom-mended for those with severe pneumonia by the BTS,ATS, IDS and ERS. The JRS advocates the use of urinaryantigen testing for S. pneumoniae in all patients, andwhere appropriate Legionella and influenza A virus.Serological testing may be informative during outbreaksfor epidemiological purposes, but due to the need for aconvalescent sample it rarely impacts on clinical care.

Risk stratificationEvidence shows that clinicians may both overestimate theseverity of pneumonia and yet still fail to recognise thoseat higher risk [10,11]. All guidelines recommend thatclinical judgement be supplemented by objective sever-ity scoring. Two main tools exist to risk stratify patientswith pneumonia. The Pneumonia Severity Index classi-fies patients in terms of their mortality based on thepresence of comorbidity, vital signs and laboratoryabnormalities [10] (Table 1). These data have beenextrapolated to provide data to determine who can safelybe treated as outpatients. Classes I and II should notrequire hospital admission, class III may be suitable foroutpatient care, and classes IV and V require admission.Classes IV and V are considered to have a high mortalityand to be at greater risk of requiring admission to theintensive care unit (ICU). The Pneumonia Severity Indexhas been shown to reduce the admission of low-riskpatients to hospital, although not by as much as wouldbe thought, as over one-third of low-risk patients areadmitted for other reasons including lack of social supportor comorbidities [12]. This risk stratification is adopted bythe IDSA and discussed in the ATS guidelines.

The CURB-65 score recommended by the BTS providesa complementary guide for identification of the moreseverely ill [4,5,13] (Fig. 1). It is simple and easilycalculated based on only five variables. It too has been

New guidelines for adult CAP Armitage and Woodhead 171

Table 1 Pneumonia Severity Index [10]

Criteria

AgeMale age (years)–0Female age (years)–10

Nursing home resident 10Comorbidity

Neoplastic 30Liver 20Congestive heart failure 10Cerebrovascular disease 10Renal disease 10

Vital signs abnormalityMental confusion 20Respiratory rate >30/min 20Systolic blood pressure <90mmHg 20Temperature <35 or >408C 15Tachycardia >125b.p.m 10

Laboratory abnormalitiesBlood urea nitrogen >11mmol/l 20Sodium <130mmol/l 20Glucose >250mg/dl 10Haematocrit <30% 10

Radiographic abnormalitiesPleural effusion 10

Oxygenation parametersArterial pH<7.35 30PaO2<60mmHg 10SaO2<90% 10

Risk class 1: age <50 year no comorbidity, no vital signs abnormality;risk class II: <70 points; risk class III: 71–90 points; risk class IV: 91–130 points; risk class V: >130 points. Copyright 1997 MassachusettsMedical Society.


validated, although with fewer patients than the Pneu-monia Severity Index. The CURB-65 scoring system isalso recommended by the Japanese and Swedish Guide-lines [7,9]. The ERS guidelines offer both severity scoresas options. All societies acknowledge that severityindicators should be used only as an adjunct to clinicaljudgement when deciding which patients require hospi-tal admission.

The ATS has modified the criteria used to define severeCAP requiring admission to the ICU. Previous strategieswere over sensitive and lacked specificity as they defined65–68% of all patients admitted to hospital as havingsevere pneumonia [6]. Revised guidelines define severeCAP as the presence of either one major criteria (need formechanical ventilation or septic shock) or two of the threeminor criteria (systolic blood pressure below 90mmHg,multilobular disease, PaO2/FiO2 ratio below 250) [3].The BTS defines severe CAP as a CURB-65 score of 3 ormore and a score of 4 or 5 requires assessment for ICUadmission, although it has not been formally tested todefine the need for ICU [5]. A difficulty with the end-point of ICU admission is that admission criteria varyfrom hospital to hospital.

Microbiology and antibioticsEarly administration of antibiotics after diagnosis ofpneumonia has been shown to be associated with adecrease in mortality. The evidence for the exact timingof administration is somewhat inconclusive, however, as a

subsequent trial found patients who received antibioticswithin 2 h actually had worse outcomes [14,15]. The ATSand BTS advocate administration within 8 h of admissionto hospital. The IDSA advocate timely administrationrather than recommending specific time periods [16].

Recommended antibiotic therapy differs between thevarious guidelines and this is probably due to differentperceptions of the importance of infections caused byatypical organisms, differences in antibiotic resistance,differences in the interpretation of the clinical relevanceof antibiotic resistance as well as antibiotic licensing.Penicillin resistance among S. pneumoniae varies withlevels as high as 9.2% in Spain and 15.9% in the US[17]. Resistance in the UK and Holland is much lower(quoted at 1.5 and 0.5%, respectively [18]), and theseguidelines support the use of more traditional b-lactamantibiotics as first-line therapy. In Japan, the rate of S.pneumoniae resistance to macrolides is over 50% andalthough penicillin resistance is increasing, their use isstill recommended for treatment of outpatient presumedbacterial pneumonia. The clinical significance of in-vitroresistance remains controversial.

All guidelines aim to rationalise antibiotic selectionbased on the prevalence of different causative organismsas well as disease severity. The ATS makes furthersubclassification based on modifying factors such as thelikelihood of drug-resistant S. pneumoniae, Gram-negativeorganisms and Pseudomonas aeruginosa amongst select

172 Respiratory infections

Figure 1 CURB-65 index [13]

The CURB-65 score recommended by the BritishThoracic Society provides a complementaryguide for identification of the more severely ill.ICU, intensive care unit.

Any of• Confusion• Urea > 7 mmol/l• Respiratory rate > 30/min• Blood pressure (systolic < 90 mmHg,

diastolic < 60 mmHg)• Age > 65 years

0 or 1 2 3 or more

Likely to be suitablefor home treatment

Consider hospitalsupervised treatment

Manage in hospital assevere pneumoniaAssess need for ICU ifCURB-65 score 4–5


groups (Table 2). The IDSA follows similar recommen-dations and categorises patients in terms of comorbiditiesand the use of antibiotics in the preceding 3 months toidentify those at greater risk of drug-resistantS. pneumoniaeand Gram-negative organisms. The ERS gives criteriawhen P. aeruginosa might be suspected. Both the ATSand IDSA now class nursing home-acquired pneumoniaas a form of hospital-acquired pneumonia.

Nonsevere community-acquired pneumoniaThe ATS, IDSA and Canadian Thoracic Society rely onthe use of advanced generation macrolides and respirat-ory quinolones. The ERS and BTS advocate the con-tinued use of b-lactams as first-line therapy with theaddition if required of simple macrolides (Table 3). Thisis in part related to resistance levels, but may also berelated to the more limited experience with the newerantibiotics due to their period of licence. Resistance tothe respiratory quinolones is increasingly reported whichmay well increase as their use becomes more widespread[19]. The JRS only advocates the use of respiratoryfluoroquinolones in select groups (older, comorbidity,recent antibiotics use and in severe pneumonia) as resist-ance rates in Japan, particularly in those over 65 years, areabove 15%. Other issues regarding their use relates togreater costs and the recent association with Clostridiumdifficile diarrhoea [20].

Severe community-acquired pneumoniaThe BTS and ERS guide antibiotic therapy based on theseverity of disease. The ATS, IDSA and Canadian Thor-acic Society define different management strategiesbased on the site of treatment and the presence ofcomorbidities or modifying factors and the likelihoodof Pseudomonas infection (Table 4). This aims to identifygroups with a higher prevalence of resistant pathogens.The American societies also distinguish between patientsin the community and those in nursing homes. TheATS and IDSA both consider nursing home-acquired

pneumonia as a form of hospital-acquired pneumoniaas specified in the 2005 hospital-acquired pneumoniaguidelines [21]. This is in contrast to the BTS, whoseantibiotic strategy in this group is based on evidence thatthe prevalence of pathogens follows the same distributionas patients in the community.

Guideline impactGuidelines will only be useful if they are adopted andshown to alter outcome. Several articles have focused onthe effect of adherence to guidelines on the quality ofcare delivered. Menendez et al. [22] concluded thatnonadherence to published guidelines when selectingempirical antibiotic therapy, particularly amongstpatients classified as having severe pneumonia, wasassociated with a higher mortality. Another study con-cluded that the adoption of moderate and high-intensityguideline implementation reduced the number of low-risk patients admitted to hospital. They also found thatmoderate intensity guideline use increased the numberof high-risk patients managed inappropriately in thecommunity, thus supporting the adoption of high-inten-sity strategies. Even within this group they found thatover 25% of patients were treated with inappropriateantibiotic therapy [23]. As well as varying between hos-pitals and the training status of physicians, nonadherenceto guidelines has been found to be greater amongstnonrespiratory physicians. The adherence rate amongstintensive care units is quoted as low as 67% [24].

One factor in encouraging adherence to guidelines mustbe their effectiveness at delivering the information. TheATS guideline is a long document with complicatedantibiotic strategies summarised on no less than fivetables, but clear algorithms help to transmit the message.The IDSA does incorporate tabled information, but againit is a document that requires time to digest. The BTSguidelines offer a brief summary statement and simplepresentation and management strategies, while the ERSadopts a question and answer format.

With the assumption that adherence to national guide-lines is associated with better outcomes, the CommunityAcquired Pneumonia Organisation evaluated the actualcare delivered to patients hospitalised with a diagnosis ofcommunity acquired pneumonia. Performance indicatorswere calculated for all aspects of management includingdiagnosis, hospitalisation, respiratory isolation, microbio-logical investigation, empirical antibiotic selection anddischarge. They concluded practice was frequently not inaccordance with recommended guidelines and it is therole of international organisations to help to improvecompliance [25]. These findings are supported byMaxwell et al. [26] in the CAPTION (Community-Acquired Pneumonia: Towards Improving OutcomesNationally) study. They evaluated the management of


Table 2 Modifying factors that increase the risk of infectionwithspecific pathogens (American Thoracic Society guidelines) [3]

Penicillin-resistantand drug-resistantpneumococci

age >65 yearsb-lactam therapy in past 3 monthsalcoholismimmune-suppressive illness(including steroids)

multiple medical comorbiditiesexposure to child in day care centre

Enteric Gram-negatives residence in nursing homeunderlying cardiopulmonary diseasemultiple medical comorbiditiesrecent antibiotic therapy

Pseudomonas aeruginosa structural lung diseasecorticosteroid therapy (>10mg day)broad spectrum antibiotics of >7 daysin past month

malnutrition



Table

3Antibiotictherapyin

nonse

vere

community-acq

uiredpneumonia

American

Thorac

icSoc

iety

Infectious

Disea

sesSoc

iety

ofAmerica

Can

adianTh

orac

icSoc

iety

Europ

eanRespira

tory

Soc

iety

BritishTh

orac

icSoc

iety

Outpa

tient:no

cardiopu

lmon

ary

diseaseor

mod

ifyingfactors

(Group

1)

advanc

edmac

rolide

ordo

xycycline

Mac

rolideor

doxycycline

mac

rolideor

doxycycline

amoxicillin

ortetrac

ycline

amoxicillin

orerythrom

ycin/

clarith

romycina

resp

iratory

fluoroq

uino

lone

b

advanc

edmac

rolideþam

oxycillinb

advanc

edmac

rolideþau

gmen

tin

Outpatient:ca

rdiopulmon

arydisea

se#

mod

ifyingfactors(G

roup

2)

b-lactam

þmac

rolide

ordo

xycyclineor

resp

iratory

fluoroq

uino

lone

alon

e

advanc

edmac

rolide

orresp

iratory

fluoroq

uino

lone

advanc

edmac

rolideor

resp

iratory

fluoroq

uino

lone

oram

oxicillin/clavulana

teþmac

rolide

asab

ove

asab

ove

resp

iratory

fluoroq

uino

lone

b

advanc

edmac

rolideþb-lactam

Inpatient:ca

rdiopulmon

arydisea

se#mod

ifyingfactors(G

roup

3a)

intraven

ousb-lactam

þintraven

ous/

peros

mac

rolideor

doxycycline

orresp

iratory

fluoroq

uino

lone

alon

e

resp

iratory

fluoroq

uino

lone

advanc

edmac

rolideþb-lactam

advanc

edmac

rolideþresp

iratory

fluoroq

uino

lone

b

resp

iratory

fluoroq

uino

lone

,or

seco

nd-,third

-or

fourth-

gen

eration

ceph

alos

porin

þmac

rolide

pen

icillin

Gor

aminop

enicillin

orco

amoxiclavor

seco

nd/third-gen

eration

ceph

alos

porin

#mac

rolide

orresp

iratory

fluoroq

uino

lone

(a)as

home

trea

ted

(b)am

oxicillin

þmac

rolideor

resp

iratory

fluoroq

uino

lone

Inpatient:no

cardiopulmon

arydisea

se#mod

ifyingfactors(G

roup

3b)

intraven

ousazith

romycin

alon

e(doxycyclineþb-lactam

a )or

resp

iratory

fluoroq

uino

lone

alon

e

asab

ove

asab

ove

asab

ove

asab

ove

Advanc

ed-gen

erationmac

rolide:

azith

romycinor

clarythrom

ycin.b

-Lac

tam:o

ralcefpod

oxime,

cefuroxime,

high-dos

eam

oxicillin,amoxicillin/clavulana

teor

intraven

ousce

ftriaxone

then

oralce

fpod

oxime.

Respira

tory

fluoroq

uino

lone

:levoflo

xacin,

moxifloxac

in.

aPen

icillin

allergic/in

tolerant.A

dmitted

forno

nclinical

reason

sor

previou

slyun

trea

tedin

commun

ity.

bRec

entan

tibiotic

therap

y.Cop

yright

American

Thorac

icSoc

iety.



Table

4Antibiotictherapyin

seve

reco

mmunity-acq

uiredpneumonia

American

Thorac

icSoc

iety

Infectious

Disea

sesSoc

iety

ofAmerica

Can

adianTh

orac

icSoc

iety

Europ

eanRespira

tory

Soc

iety

BritishTh

orac

icSoc

iety

ICU:riskof

Pseud

omon

asan

tipseud

omon

alb-lactam

þan

tipseud

omon

alquino

lono

neor

antip

seud

omon

alb-lactam

þam

inog

lyco

side

þmac

rolideor

nonp

seud

omon

alfluoroq

uino

lone

antip

seud

omon

alag

ent

þciprolfloxac

inor

antip

seud

omon

alag

entþ

aminog

lyco

sideþeither

resp

iratory

fluoroq

uino

lone

ormac

rolide

antip

seud

omon

alfluoroq

uino

lone

þan

tipseud

omon

alb-lactam

oram

inog

lyco

sideor

antip

seud

omon

alb-lactam

þam

inog

lyco

side

þmac

rolide

antip

seud

omon

alce

pha

losp

orin

þciproflo

xacin

carbap

enem

orac

ylureidop

enpen

icillin/

b-lactam

aseinhibito

rþciproflo

xacin

coam

oxiclav

orseco

nd/third-

gene

ratio

nce

phalos

porin

þmac

rolide#rifam

picin

orresp

iratory

fluoroq

uino

lone

þben

zylpen

icillin

ICU:no

riskof

Pseud

omon

asb-lactam

þeither

mac

rolide

orfluoroq

uino

lone

b-lactam

þeither

advanc

edmac

rolideor

resp

iratory

fluoroq

uino

lone

resp

iratory

fluoroq

uino

lone

þthird

-gen

erationce

pha

losp

orin

oram

oxicillin/clavulana

teor

mac

rolide

þthird

-gen

erationce

pha

losp

orin

oram

oxicillin/clavulana

te

third

-gen

erationce

pha

losp

orin

þmac

rolide

orthird

-gen

erationce

pha

losp

orin

þresp

iratory

fluoroq

uino

lone

resp

iratory

fluoroq

uino

lone

#clindam

ycin

(pen

icillin

allergic)

Nursing

home

asGroup

3a

resp

iratory

fluoroq

uino

lone

outpatient

asGroup

2;

inpatient

asGroup

3resp

iratory

fluoroq

uino

lone

oram

oxicillin/clavulantateþmac

rolide

orseco

nd-gen

erationce

pha

losp

orin

þmac

rolide(o/p)

sametrea

tmen

tas

per

severity

advanc

edmac

rolide

þam

oxicillin/clavulantate

ICU,intensive

care

unit.

Antipseud

omon

alb

-lactam

:ce

fepime,

imipen

em,merop

enem

,piperac

illin/tazob

actam.Sec

ond-gen

eration

cepha

losp

orin:ce

furoxime.

Thrid

-gen

eration

cepha

losp

orin:

cefotaxime,

ceftriaxone

.Respiratory

fluoroq

uino

lone

:levoflo

xacin,

moxifloxac

in(m

oxifloxac

inno

tlicen

sedin

theUKforsevere

commun

ity-acq

uiredpn

eumon

ia).


CAP in Australian emergency departments as comparedto national guidelines. They concluded that overall con-cordance was very low, with only 18% of antibioticsprescribed in accordance with recommended guidelinesand severity assessment documented in only 5% of pre-sentations. Maxwell et al. [26] also acknowledge thatdespite low compliance with guidelines in Australianemergency departments, this had no effect on patientmortality or length of stay.

Performance indicators act as standards, based on evi-dence or consensus opinion, with which quality ofmedical care can be measured. The IDSA guidelinesare the only guidelines to recommend specific perform-ance indicators. There is, however, a surprising lack ofquality evidence behind the majority of the guidelinerecommendations. As Woodhead [27] addresses in arecent Editorial, only 6.5% of ATS guidelines, 9.6% ofCanadian guidelines, 15% of BTS guidelines and 21% ofIDSAguidelines are based on ‘best-level’ evidence.Afinalword would emphasise the need for further randomisedcontrolled trials to provide more evidence in this field.

ConclusionGuidelines are here to stay and provide standards bywhich to guide and judge care. CAP is a diverse illnessand its management has been dealt with by many guide-lines. In some areas there is concurrence, in others thereis not. Where guidelines differ it is often for lack of robustevidence. The highlighting of such evidence gaps shouldact as a spur to researchers and those funding research forthe future.

References and recommended readingPapers of particular interest, published within the annual period of review, havebeen highlighted as:! of special interest!! of outstanding interestAdditional references related to this topic can also be found in the CurrentWorld Literature section in this issue (p. 221).

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Documents

Armitage. curr opin infect dis 2007. new guidelines for the management of adult community acquired pneumonia