community-acquired pneumonia: a review and recent advances

Pediatric Pulmonology 42:1095–1103 (2007)

State of the Art Series: Global Pediatric Pulmonary Issues

Community-Acquired Pneumonia:A Review and Recent Advances

Renato T. Stein, MD1* and Paulo Jose Cauduro Marostica, MD

2{

Summary. In the beginning of this 21st century, community-acquired pneumonias (CAP) are still

responsible for a significant numberof deaths amongyoung children inmanydeveloping countries.

Public health initiatives such as those proposed by the World Health Organization (WHO) for the

management of CAP by means of identifying highly predictable signs and symptoms have had

great positive impact in some communities. Still, this approach induces an overdiagnosis and

overtreatmentofCAP inchildrenbelow theageof 5yearsdue to themisclassificationof pneumonia

in childrenwith fast breathing associatedwith viral bronchiolitis. Evenamongchildren of developed

countries, CAP is an important public health problem and many aspects of current diagnostic and

management measures are discussed here. In this article, we review the epidemiology and basic

concepts of CAP and update current information on clinical evaluation and management of the

disease. Pediatr Pulmonol. 2007; 42:1095–1103. � 2007 Wiley-Liss, Inc.

Key words: pediatrics; pneumonia; community-acquired; CAP.

INTRODUCTION

Community-acquired pneumonia (CAP) is still todayone of the most important causes of mortality in children,especially among those under the age of 5 years. This ismost significant in developing countries, where incidencerates are up to 10 times greater than in developedcountries.1 Almost 2 million children died from acuterespiratory infections in the year 2000, most frompneumonia. More than half of such children were bornin Africa and in Southeast Asia.2 In North America, theannual incidence of pneumonia varies from 6 to 12 per1,000 in children older than 9 years, and from 30 to 45 per1,000 children amongst those younger than 5 years old.3

The human immunodeficiency virus (HIV) epidemicincreased the number of childhood deaths due to CAP,especially in sub-Saharan Africa. The specific mortalityrate for pneumonia in HIV-infected children is three tosix times that of non-infected children.Although the use ofeffective anti-retroviral medicine in developing countrieshas significantly decreased the mortality due to pneumo-nia associated with HIV, these drugs are not alwaysavailable in many places.4

In healthy children, the upper airways are colonized bya variety of pathogens, in contrast with the lower respi-ratory tract, which is sterile under normal conditions.Bacterial infections are usually preceded by viral infec-

tions. Impairment of defense mechanisms like the coughreflex, mucociliary clearance by cilia, and viral-inducedenhancement of bacterial adherence are believed to becontributory for a series of events that may lead to CAP.Lower airways’ infection precipitates a series of eventsthat lead to inflammation and additional lung damage.5

This article is one in a series of articles on Global Pediatric Pulmonary

Issues. This series will span upcoming issues of Pediatric Pulmonology.

1Department of Pediatrics, Pontifıcia Universidade Catolica do Rio Grande

do Sul, Porto Alegre, Brazil.

2Department of Pediatrics, Universidade Federal do Rio Grande do Sul,

Porto Alegre, Brazil.

{Assistant Professor.

*Correspondence to: Renato Tetelbom Stein, MD, Assistant Professor,

R. Barao de Uba, 708/401, Porto Alegre, RS, Brazil, CEP 90450-090.

E-mail: [email protected]

Received 18 December 2006; Revised 25 April 2007; Accepted 25 April

2007.

DOI 10.1002/ppul.20652

Published online in Wiley InterScience

(www.interscience.wiley.com).

� 2007 Wiley-Liss, Inc.

ETIOLOGY

Viruses are the most common cause of pneumoniain young children but the prevalence decreases withincreasing age.6 Studies describing the relation of specificviruses with CAP due to non-viral agents have to beinterpreted with some caution because many interveningfactors may play a significant role in this outcome.7 Limi-tations on how to interpret the results of these studies arerelated to the difficulty in confirming a causal associationbetween the findings of a specific virus in nasal aspiratesand the development of pneumonia. Other co-infectingnot-detected agents may play some role or may be moreclosely related to pneumonia. Respiratory sincitial virus(RSV) is a highly prevalent agent affecting the lowerairways and may indeed progress with pulmonaryinfiltrates, not necessarily corresponding to pneumonia.5

RSV, influenza, and rhinovirus are the most commonviruses associated with either CAP or wheeze-relatedrespiratory diseases in childhood. In a prospective seriesof CAP in children in the UK, RSVand influenza Awereresponsible for 18 and 16%of theCAP cases, respectively.The high 16% prevalence of influenza A may reflect theseason of enrollment of patients, as well as the use of themore sensitive and recently incorporated PCR diagnostictechniques. Adenovirus, parainfluenza, and enteroviruswere also identified as CAP-associated agents and thisadded to 43% of viral etiology among all CAP-diagnosedcases. Tests for rhinovirus were not performed in thisstudy.7 When reverse transcription-PCR for rhinoviruswas included in a series of CAP in children from Finland,this agent was detected in 24%of the cases.8 In yet anotherprospective study, influenza burden in respiratory infec-tions was greater amongst children younger than 3 yearsof age (19%).9

Recently, human metapneumovirus (hMPV) wasdescribed in association with infection of the lowerairways, with a very similar clinical picture to that of RSV.It causes upper and lower airway infection (bronchiolitisand pneumonia) especially in infants and immunocom-promised hosts. Most school-age children have alreadybeen infected by hMPV in the past. This virus has beendescribed in different continents and may show impor-tant yearly oscillation in incidence although it peaks inwinter months. Most studies, evaluating hospitalizedchildren due to lower airway infections suggest thatbetween 5 and 20% of such cases could be attributableto hMPV.10–14

The recently discovered bocavirus, a virus of theparvovirus family, is also associated with wheezing,bronchiolitis, and pneumonia diagnosis in a small butsignificant proportion of children.15

The impact of these and other newly discovered virusesin the epidemiology of CAP in developing countries is yetto be completely elucidated but recent data suggest it is

unlikely that the distribution is much different from thatfound in developed countries.16,17

Other viruses like influenza B, parainfluenza 1 and 2,and cytomegalovirus are often implicated in the etio-logy of CAP in children and have to be accountedfor.1,4,18

Streptococcus pneumoniae is the main bacteriumcausing pneumonia in children under the age of 5. Thedetection of resistant strains has been reported more oftenin the recent past years. The National Committee forClinical Laboratory Standards in the USA defines strainsas resistant when theMIC to penicillin is above 2.0 mg/ml;intermediate, for MIC values between 0.1 and 1.0 mg/ml;and sensitive for MIC values below 0.06 mg/ml. A reportfrom the Drug-Resistant S. pneumoniae TherapeuticWorking Group has recently proposed a change on thecutoff levels to MIC levels of 4.0, 2.0, and 1.0 mg/mlrespectively, a fact that would change how we interpretpneumococcal resistance data. Such trend derives fromthe observation that strains of S. pneumoniaewhichwouldbe classified as resistant, show excellent clinical responsesto penicillin.19

S. pneumoniae is a common pathogen throughoutinfancy and childhood with the possible exception of theneonatal period. A recent study in Belgium showed thatover 98% of pneumococcal strains from cultures obtainedthrough BAL, blood, or pleural fluids were either suscep-tible or intermediately sensitive to penicillin.20 In LatinAmerica, resistance rates ranged from 2.0 to 21.1%.Factors associated with resistance are the use of penicillinor ampicillin within 3 months of the acute event, ageless than 2 years and the isolation of S. pneumoniaeserotype 14.21

Mycoplasma pneumoniae and Chlamydia pneumoniaetend to be more prevalent in older children and adole-scents. In the case series of CAPbyKorppi and coworkers,children older than 10 years had at least one of these twoagents involved in 80% of CAP cases.22 Interestingly,in yet another series, C. pneumoniae was diagnosed inchildren with a mean age of 1.5 years.23 Recent studiessuggest that both Mycoplasma and Chlamydia may beassociated with CAP in children younger than age 5 years,more frequently than previously predicted. It is possiblethat regional and annual rates may vary or that differentdiagnostic tests may explain such discrepant figures.In a Finnish series, transthoracic needle aspiration was

used to obtain lung samples for viral and bacterialidentification tests in children hospitalized with CAP.The authors identified a causative agent in 59% out of34 cases. All samples were obtained from patients withunequivocal pulmonary consolidation on chest radio-graph. There was a low yield of virus, Mycoplasmaand Chlamydia in this study possibly because of thehigh specificity of the radiographic findings. Eighteenpatients (53%) had S. pneumoniae, one patient had

1096 Stein and Marostica

M. pneumoniae, and one patient had a positive viralculture (RSVand parainfluenza).24

Type b Haemophilus influenza (Hib) used to be animportant cause of CAP in childhood, but the widespreaduse of vaccines against this pathogen in developedcountries had a great impact on CAP due to this agent.24

Non-typable Hib seems to be an infrequent cause ofpneumonia in developed countries, in striking contrastwith data from some developing countries, wherenearly half of CAP cases seem to be accounted to thisagent.1 In any circumstances, it is important to note thatcurrently the majority of the population at risk for CAP indeveloping countries worldwide is not covered by Hibvaccination which may cause an increase of these cases inthe future.

Legionella pneumophila is a rare cause of bothcommunity and hospital-acquired pneumonia (HAP).In the review of Greenberg and coworkers, an overallmortality rate of 33% was observed amongst 76 reportedcases from Europe, USA, and Israel, being higher amongimmunosuppressed children and neonates. Frequently, anenvironmental source is found, especially contaminatedpotable water.25

There are important age-related causal agents ofCAP during childhood. In the first 20 days of life, mostcases are secondary to Group B Streptococci or gram-negative enteric bacteria. Viruses prevail in youngchildren. C. pneumoniae andM. pneumoniae occur moreoften in school-age children and during adolescence,although there are many reports of these agents causingCAP in younger children as well. Infants in the first3 months of life may present with a characteristic pictureof low-grade or no fever, cough, and respiratory distress.This may be caused by Chlamydia trachomatis, a varietyof respiratory viruses, Bordetella pertussis, or possibly,Ureaplasma urealyticum. Staphylococcus aureus used tobe a much more common pathogen in infants, but itsprevalence has substantially decreased in developedcountries, while it remains a significant causal agent ofCAP in less-affluent communities.26–28

In HIV-infected children, other pathogens, like Pneu-mocystis jiroveci andMycobacterium tuberculosis shouldbe considered, besides the usual bacteria that infectimmunocompetent patients.4

CLINICAL PICTURE

The clinical picture of children with CAP is highlyvariable, especially in the first years of life. Children canbe acutely sick or in good general status and at times theymay not present characteristic signs of respiratory distress.Fever, chills, abdominal or chest pain, and productivecough are suggestive of typical bacterial pneumonia,although a more gradual clinical onset associated withheadache, malaise, non-productive cough, and low-grade

fever, is more likely related to infection by atypicalpathogens like M. pneumoniae.29,30

Tachypnea is a sensitive and specific clinical finding inCAP. In the series by Mahabee-Gittens and coworkers,respiratory rates above 50 breaths per minute and oxygensaturation below 96% had a specificity of 97% to predictradiographic evidence of pneumonia in children older than12 months seen in an emergency department because ofcough and signs of lower respiratory illness. In this series,the presence or absence of fever did not contribute to thediagnosis of pneumonia. In infants, the presence of nasalflaring increased the specificity to 98%.31

Wheezing is most frequently associated with eitherviral, Mycoplasma or Chlamydia infections, and truewheezemakes a bacterial cause improbable in this setting.In Wubbel’s case series of pneumonias, viruses were themost frequent pathogens amongst children who werewheezing.32

Pleural effusions are a relatively common complicationof CAP in children, and in developing countries areespecially associatedwith poor social standards. In a studyfrom Brazil, with children from a poor background, Pintoand coworkers evaluated 154 subjects under the age of5 years, who had been hospitalized due to severe pneu-monia according to the WHO’s diagnostic criteria forpneumonia. Significant risk factors for pleural involve-ment were low income, birth weight below 2,500 g, livingin a rural area, and in homes with less than two rooms.33

Michelow in a series of 154 children, hospitalized becauseof CAP in Texas found that the presence of pleuraleffusion increased about six times the chance of a bacterialetiology.6

In a series of cases from Israel, Wexler and coworkerswere able to show that subjects with Sreptococcuspneumoniae CAP were more likely to present com-plications like pleural effusions or empyema if theywere below the 10th percentile for weight, had anemia andrespiratory distress.34 Complicated cases neededmore days of hospitalization and took longer to becomeafebrile. The incidence of complications was not higherin cases where S. pneumoniae showed an MIC above0.1 mg/ml to penicillin. In the retrospective series byBuckingham and coworkers in the USA, S. pneumoniaewas also the most frequent causative agent of complicatedparapneumonic effusions. The mean duration of fever atthe diagnosis of effusionwas 5 days. Interestingly, after anincrease in incidence of pneumonias between 1996 and2000, (from 2.9/1,000 to 11/1,000), it dropped again to4.8/1,000, temporally associated with the introduction ofthe 7-valent pneumococcal vaccine (PCV-7).35

In summary, although some clinical features are moreprevalent among childrenwith bacterial CAP compared toviral and atypical pathogens’ CAP, one has to be cautiouswhen deciding therapeutic measures, because there ismuch overlap of findings.

CAP in Children 1097

DIAGNOSIS

CAP should be suspected in children with fever, cough,tachypnea, respiratory distress, and crackles on chestauscultation. Signs of severe respiratory distress like chestindrawing and nasal flaring usually appear later in thecourse of the disease. There is better inter-observeragreement over signs that can be observed than for theones that require auscultation of the chest, especiallywhenexamining infants; a high index of suspicion is essential inthis age group.36

The WHO Clinical Diagnosis Approach

The World Health Organization (WHO) developed amanagement strategy that was introduced almost twodecades ago with an important impact on mortality ratesdue to CAP in developing countries. The program takes inconsideration for diagnosing CAP, a series of compre-hensive clinical signs, especially respiratory rate andchest indrawing. Tachypnea has the greatest sensitivity/specificity combination for the diagnosis of CAP.4 In astudy in western Uganda, 96 community health workerswere able to accurately classify respiratory rates accord-ing to the WHO criteria with a sensitivity of 83% andspecificity of 75%, after a 2-day training by experiencedresearchers.37

Although this and other studies point toward animpressive good record of the WHO’s CAP diagnosisand management strategy, a series of recent studies raiseconcerns of a possible overestimation of bacterialpneumonia diagnosis, with the possible undesired con-sequences in bacterial resistance pressure.38 As part of adouble-blind randomized trial that compared the effec-tiveness of either a 3 or a 5-day amoxicillin regimen totreat CAP defined according to the WHO criteria, Hazirand coworkers performed chest radiographs on 1,848 outof 2,000 children aged 2–59 months. Of all these childrenwith a clinical diagnosis of pneumonia, evaluated by apanel of three radiologists using WHO-establishedcriteria, only 263 (14%) had confirmed radiologicalevidence of pneumonia; lobar consolidation was presentin only 26 children and there were an extra 66 cases(4%) with radiographs compatible with bronchiolitis. Animpressive total of 1,519 children (82%) presented normalradiographs.39 In areas where the poor resources are alimiting factor in diagnosing CAP, there is a need forsimple and reliable methods, probably through clinicalalgorithms for easy diagnosis. New studies that aim ataccessiblemolecular diagnostic tools or newmanagementstrategies need to be evaluated through validation andefficacy measures.In a recent publication, Moreno and coworkers aimed

to develop a scoring system to predict CAP. The authorscompared children less than 5 years of age with definitebacterial CAPwith cases where a viral respiratory antigen

could be identified. They propose a model that diagnosedCAP with 100% sensitivity and 93% specificity. Periph-eral band counts equal or greater than 5%, childrenaged over 9 months, absolute neutrophil counts over8,000 cells/mm3, axillary temperature over 398C, anda chest X-ray score were included in this model. Althoughthis or similar scoring systems may have a useful clinicalapplication, one has to be cautious with an importantlimitation of the study. In this model, only bacterial-proven pneumonia would be safely diagnosed, whichtheoretically corresponds to the more severe end of thespectrum, especially since only hospitalized patients wereevaluated.40 The question of how reproducible is thisstudy to clinical situations of milder and more commonlyfound pneumonias in the community remains to beelucidated.

Chest Radiographs

British Thoracic Society (BTS) guidelines on CAP donot recommend chest radiographs in patients over the ageof 2 months, eligible for ambulatory care, because thisapproach does not seem to modify outcomes.41–43 Onthe other hand, recommendations published by Canadianexperts state that chest X-rays are necessary for the diag-nosis of pneumonia.36 Certainly the degree of respiratorycompromise, and the child’s general appearance should beincluded in the decision making process. It is the authors’opinion that especially in severely sick children, whereCAP is suspected, chest radiographs are warranted.One of the problems about interpreting chest radio-

graphs is the lack of standardization in terms of whatshould be considered pneumonia. Because of this, theWHO developed criteria where radiological findingswould be classified as consolidation/pleural effusion orinfiltrates or normal exam.44 Through the use of trainingand standardized definitions, these authors were able toachieve agreement in identifying radiological pneumonia,thus facilitating the comparison of results of epidemio-logical studies where radiological pneumonia is thechosen outcome.44

In a study by Rigsby and coworkers, three pediatricradiologists independently and retrospectively analyzedchest radiographs from 1,268 patients who had beenevaluated at the emergency department and comparedresults between lateral plus antero–posterior (A–P) viewsagainst AP-only. In situations where pneumonia wascharacterized by a streaky infiltrate, 15% of cases wouldbe missed if only the frontal view was performed. On theother hand, no pneumonias of the confluent-lobar typewould be missed, using this more conservative approach.45

Radiological findings can be considered suggestive ofcertain etiologic agents, but they lack sufficient specificityto be considered diagnostic. Alveolar densities aremore commonly found associated with typical bacteria


although interstitial pulmonary densities are associatedwith both viral infections and atypical agents.3,32,46–48

Although hylar lymphadenopathy and bilateralpatchy infiltration are commonly associated with bothM. pneumoniae and C. pneumoniae infections, otherpresentations are also usual.22 Lobar consolidation waspresent in 20 out of 38 cases ofMycoplasma in the Turkishseries by Somer and coworkers.22,23

Follow-up radiographs should be reserved for caseswhere clinical response is taking an unexpectedly slowcourse, in round pneumonias and atelectasis, or when amass lesion or bronchial abnormalities should be ruledout. Virkki and coworkers performed follow-up chestradiographs in 196 children with CAP. The additionalinformation obtained did not change the treatment in anypatient. Thirty per cent of the patients still had radio-graphic abnormalities, mostly interstitial changes andsmall atelectasis 3 to 7 weeks after the acute event. Someof the children in this series had recurrent pneumonia, butthe follow-up chest radiograph was unable to predict suchoutcome.49

WBCs, CRP

Unfortunately, in a clinical setting current laboratorytests have little value in differentiating bacterial frompneumonia caused by other agents, because of the greatoverlap of findings secondary to infection by differentagents. Esposito and coworkers demonstrated higherlevels of white blood cell (WBC) counts and C-reactiveprotein (CRP) in children with bacterial pneumonias, butthe results showed such great variability that these findingsare not of great help in a clinical situation.46

Blood Cultures

Both the BTS and the Canadian CAP consensus ofexperts recommend that a blood culture be performed incases that require hospital care. Although the test positiveyield is generally low, it may be the only chance to identifya causative pathogen in more severe cases.29,36,41 How-ever, worldwide, the majority of children with CAP areappropriately managed without this or any further labo-ratory investigation.

Sputum

Sputum examination is a possible alternative forrespiratory secretion sampling. It is practical for adoles-cent and school-age children but it should be interpretedwith caution because upper airway commensals, whichcan be pathogenic to lower airways, generally contami-nate the specimen.

Antigen Detection/Serology

Detection of antigens in urine or plasma has been usedfor diagnostic purposes, but the results are conflicting, and

the sensitivity and specificity are both low. In 1999, theFood and Drug Administration in the USA approved arapid immunochromatographic test for pneumococcusantigen detection. The sensitivity and specificity wererespectively 86 and 94% in urine for adult patients 50 Inchildren, a positive test may be associated with clinicalinfection, but may also be secondary to carriage orsubclinical infection. One possible advantage of antigendetection methods is that they do not depend on bacterialviability. Serology is useful for some agents likeM. pneumoniae, C. pneumoniae, and S. pneumoniae butpaired acute and convalescent titers are needed leading tothe situation where diagnosis becomes retrospective formost cases. In children under the age of 6 months, there isonly a weak immunologic response to capsular bacterialantigens, making this test less useful.32,47 Antibodies toseveral different pneumococcal antigens can bemeasured.In a Finnish study, S. pneumoniaewas considered to be thecause of CAP when increases in titers of these antibodieswere detected. The prevalence of these findings wassignificantly higher in children with the diagnosis of CAPthan in healthy controls. Although all patients had radio-logical or clinical findings suggestive of CAP related to S.pneumoniae, the high titers could have been secondary toinfections at other sites as well or to non-specific amnesticresponses to viral infections.26,47,51

PCR-Based Evaluation

PCR has been usedmore recently as a diagnostic tool inrespiratory infections. It may be applied to specimensfrom respiratory secretions, lung aspirate samples, orblood. Viruses, M. pneumoniae, C. pneumoniae, andbacteria can be diagnosed through thismethod. It is a rapiddiagnostic tool, but it does not differentiate carrier statefrom disease, except when lung aspirates samples arestudied.28,46

In summary, different infectious agents may presentwith similar clinical findings in CAP. Evaluation ofclinical, radiological, and laboratory findings, in manycases, may indicate a probable or possible agent. Onthe other hand, only a small proportion of CAP willhave a definite pathogen identified. This is largely becausemethods like obtaining a lung puncture specimen orperforming a bronchoalveolar lavage are considered to bethe gold standard for etiologic diagnosis. Clearly, theseapproaches are far too invasive to be used in the ordinarycase of CAP. Conversely, in cases of HAP, in a life-threatening clinical situation, or in children with immunedeficiencies, these approaches may be necessary.

CLINICAL MANAGEMENT

Because viruses are the sole cause of most cases ofpneumonia in childhood, it is appropriate not to treat every


child with antibiotics. However, therapeutic decisions canbe difficult because the majority of diagnostic tests do notadequately differentiate viral from bacterial infection inthe individual child. A further issue is the knowledge thatsome patients harbormixed viral and bacterial agents.32,50

The choice of antibiotics is usually based on clinicalfeatures and most specifically on prevalence data fordifferent organisms in different age groups. The WHOsuggests that oral penicillin drugs, i.e., amoxicillin, be thefirst option for treating pneumococci pneumonia inchildren below age 5. A large study in Pakistan where2,000 children were treated for CAP with either a 3 or a5-day course of oral amoxicillin showed that bothregimens were equally effective.52

Although not a common feature, pneumococci resist-ance rates of a specific locale is also an important factor inthe decision making process. Brazilian CAPManagementGuidelines suggest low-dose amoxicillin as the firstchoice for ambulatory treatment in children over the ageof 2 months, taking into account that highly resistantstrains are infrequent. One more factor supporting thisapproach is the fact that resistant strains behave likesusceptible, when confined to the lungs.21,53

In most instances, the etiologic agent will not beidentified, so empirical treatment is mandatory. Inchildren under the age of 5, most guidelines recommendthe use of amoxicillin either in low or high range doses,according to the local prevalence of susceptibility ofS. pneumoniae. When clinical findings suggest severedisease, intravenous penicillin or third-generation ceph-alosporin can be chosen. Vancomycin has remaineduniformly active against pneumococci, but should bepreserved for non-responding cases or in situations wherepenicillin MIC levels are �4 mg/ml. In older children,where atypical bacteria are more prevalent, the use ofmacrolides should be considered as a first-line therapeuticoption. This may not be true in cases where a typicalbacterium is probable, likewhen there is a pleural effusionor a lobar consolidation. Whenever there is no clinicalimprovement, extension of anti-microbial coverage is tobe considered, because mixed infections may occur.19

It should be emphasized though, that the degree ofpenicillin resistance does not appear to harm a goodtreatment outcome of a pneumococcus pneumonia. Intra-venous penicillin serum concentrations of up to 15–18mg/ml are commonly achieved, which are much higher thanthe usual levels of resistance for these bacteria. Thus, itwould be appropriate tomodifyMIC cut-off levels, so thatmore pneumonia isolates would be classified as suscep-tible to penicillin, giving more reason for these childrento be safely treated with simple and inexpensive anti-biotics.19

In regions of the world, where Hemophilus influenzatype-B immunization is not available, the use of amoxi-cillin/clavulanate, cefprozil, cefdinir, cefpodoxime, cefur-

oxime, or ceftriaxone should be considered. The additionof a beta-lactamase inhibitor does not confer additionalcoverage for pneumococcus, because this is not theresistance-associated mechanism.Lee and coworkers report a series of M. pneumoniae

cases in children, for which macrolides are the drugs ofchoice, and a short course of oral steroids was added tomacrolides in atypical severe circumstances associatedwith lymphopenia. This measure was associated with afavorable outcome.54

S. aureus has become a less frequent agent associatedwith CAP in later decades (especially in developedcommunities). In cases of positive cultures or suggestiveclinical picture, antibiotic against this pathogen should beadded (e.g., methicillin, oxacillin, clyndamicin, or vanco-mycin in case of MRSA strains). In most settings, MRSAis not common in the community; expert advice should besought in cases of CAP caused by suspected MRSA.24,46

Neonates with CAP should receive a combination of IVampicillin and gentamicin. For children between 3 weeksand 3 months old with an interstitial infiltrates on chestradiographs, a macrolide should be used to cover foragents such as C. trachomatis, B. pertussis, and U.urealyticum.

When to Hospitalize

According to the BTS guidelines, SaO2� 92%, cyano-sis, respiratory rate >70 bpm, difficulty in breathing,intermittent apnea, grunting, not being able to feed, and afamily incapable of providing appropriate observation orsupervision are indicators for hospital admission amonginfants.41 In the case of older children, these indicators areSaO2� 92%, cyanosis, respiratory rate �50 bpm, diffi-culty in breathing, grunting, signs of dehydration, or afamily incapable of providing either appropriate observa-tion or supervision. The Canadian board of expertsalso includes age less than 6 months as a threshold foradmission.36

In a recent systematic review discussing optional anti-biotic regimens for CAP, Rojas and Granados concludedthat oral therapy appears to be an effective and safealternative to IV antibiotics in hospitalized children withsevere pneumonia, according to theWHO criteria, regard-ed they do not present signs or symptoms of seriousdisease, like somnolence, lethargy, convulsions, or diffi-culties in oral ingestion.55

The Impact of HIV on CAP

Specific guidelines for HIV-infected children mayinclude different drugs, because specific agents shouldbe considered in such instances, especially in the moresevere or unresponsive cases. HIV-infected childrenrequiring hospitalization may present pneumonia caused


by gram-negative bacteria and they should either havean aminoglycoside added to their empirical treatmentregimen, or be coveredwith an alternative regimen againstgram-negative bacteria. If P. jiroveci pneumonia issuspected, co-trimoxazole should be added to the regimenand when hypoxia is present, corticosteroids may be ofbenefit.4,56

NEW VACCINES

After the introduction of the 7-valent pneumococcalconjugate vaccine (PCV-7), a reduction in the prevalenceof complicated parapneumonic pleural effusions andpneumonias in children was observed. Reductions inthe range of 20–88% in the rate of pneumococcalpneumonia have been estimated with this approach.1,6,21

A randomized controlled trial carried out by Espositoand coworkers showed that three doses of PCV-7,administered in the first year of life, caused a significantdecrease in radiologically diagnosed CAP cases.57

Hansen and coworkers, in the USA, were able todemonstrate an increase from 20 to 30% in the efficacyof the PCV-7 vaccine when the more specific WHOcriteria for radiological diagnosis of pneumonia wereused.58 A recent systematic review of randomized control-led trials by the Cochrane Database identified an overallreduction of 22% in the incidence of radiologicallydiagnosed pneumonia in immunized children.59 On theother hand, a study in the USA, comparing pre- and post-immunization rates from ambulatory surveys, was unableto prove a significant decrease in pneumonia cases afterthe PCV-7 introduction. The authors speculate thatdifferent pneumonia definitions (patients were oftenclinically diagnosed) and a trend for increasing pneumo-nia just before the use of the vaccinemay have caused suchdivergent results.60

De Schutter and coworkers in Belgium observed apotential increase (from45 to 72%) in efficacy of the PCV-7 vaccine if two other serotypes, especially the serotype 1would be used, as in the 9-valent conjugated vaccine(PCV-9). This benefit would be more noticeable forchildren aged 2 or more, where a greater prevalence of theserotype 1 was found.20 Likewise, a recently publishedrandomized controlled trial of the PCV-9 from theGambiawas able to demonstrate an efficacy of 37% in reducing afirst episode of radiological pneumonia.61 In the series byBuckinghamand coworkers, an increase of the proportion,although not in the absolute figures, of cases due to S.aureus, followed a proportional decrease in pneumococcalcases after the widespread use of the vaccine. Such anobservation still needs further follow-up, because differ-ent authors actually report a decrease in the incidence ofS. aureus as cause of CAP.35

The reduction of cases of H. influenzae CAP indeveloped countries was striking after the introduction

of the type b immunization (Hib),62 but such impact seemsless obvious in some developing countries, where non-capsulated strains aremore likely to be present. In a recentmeta-analysis of randomized trials using this vaccine,a protective effect of 69% against H. influenzae wasobserved.63 Also, protection rates for HIV-infectedchildren are smaller.1,4,35,32,63 Similarly, in a case-controlstudy from Colombia, a 55% efficacy after three dosesofHib for preventing radiologically confirmed pneumoniawas observed.64

FINAL CONSIDERATIONS

In conclusion, CAP is still nowadays a diseaseassociated with social and economic burden, affectingthe health of a large number of children worldwide. Themain message we would like to convey with this review isa simple one. The great majority of cases of CAP are ofviral etiology although we should all worry with thepotential deadly impact of bacterial pneumonia, espe-cially in very poor communities.The WHO criteria for diagnosing CAP in communities

with few resources has had a positive impact record onmortality in the past decades but concomitantly itintroduced a practice associated with the overuse ofantibiotics due to criteria that clearly have far greatersensitivity than specificity, especially for children underthe age of 5 years. We may be facing a time where weshould look for different strategies for communities withdistinct levels of access to diagnosis and treatment.There is also a need for new, rapid, and inexpensive tests

able to differentiate viral from bacterial CAP and tocontinue investing in the development of ever moreefficient vaccines for agents associated with CAP. Even ifthis time is yet at some distance, this review calls theattention for the still valid and highly efficacious use ofpenicillin as a first-line drug use for CAP althoughacknowledging that in some specific situations, this maynot be the case. This message should not be read only byphysicians taking care of children in developing countriesbecause the overuse of unnecessary antibiotics in viralCAPs and the use of second or third-line antibiotics fornon-complicated pneumonias seem, even nowadays, to bemore the norm than the exception rule in most clinicalsettings.

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