Encouraging rational antibiotic use in childhood pneumonia: a focus on Vietnam and the Western Pacific Region
Identifieur interne : 000403 ( Pmc/Corpus ); précédent : 000402; suivant : 000404Encouraging rational antibiotic use in childhood pneumonia: a focus on Vietnam and the Western Pacific Region
Auteurs : Nguyen T. K. Phuong ; Tran T. Hoang ; Pham H. Van ; Lolyta Tu ; Stephen M. Graham ; Ben J. MaraisSource :
- Pneumonia [ 2200-6133 ] ; 2017.
Abstract
Globally, pneumonia is considered to be the biggest killer of infants and young children (aged <5 years) outside the neonatal period, with the greatest disease burden in low- and middle-income countries. Optimal management of childhood pneumonia is challenging in settings where clinicians have limited information regarding the local pathogen and drug resistance profiles. This frequently results in unnecessary and poorly targeted antibiotic use. Restricting antibiotic use is a global priority, particularly in Asia and the Western Pacific Region where excessive use is driving high rates of antimicrobial resistance. The authors conducted a comprehensive literature review to explore the antibiotic resistance profile of bacteria associated with pneumonia in the Western Pacific Region, with a focus on Vietnam. Current management practices were also considered, along with the diagnostic dilemmas faced by doctors and other factors that increase unnecessary antibiotic use. This review offers some suggestions on how these issues may be addressed.
Url:
DOI: 10.1186/s41479-017-0031-4
PubMed: 28702309
PubMed Central: 5471677
Links to Exploration step
PMC:5471677Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Encouraging rational antibiotic use in childhood pneumonia: a focus on Vietnam and the Western Pacific Region</title><author><name sortKey="Phuong, Nguyen T K" sort="Phuong, Nguyen T K" uniqKey="Phuong N" first="Nguyen T. K." last="Phuong">Nguyen T. K. Phuong</name><affiliation><nlm:aff id="Aff1">Respiratory Department, Da Nang Hospital for Women and Children, Da Nang, Vietnam</nlm:aff></affiliation><affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="GRID">grid.1013.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 1936 834X</institution-id><institution>Infectious Disease Team, The Children’s Hospital at Westmead and Discipline of Paediatrics and Adolescent Medicine, University of Sydney,</institution></institution-wrap>Sydney, NSW Australia</nlm:aff></affiliation></author><author><name sortKey="Hoang, Tran T" sort="Hoang, Tran T" uniqKey="Hoang T" first="Tran T." last="Hoang">Tran T. Hoang</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.459448.0</institution-id><institution>Neonatal Department,</institution><institution>Da Nang Hospital for Women and Children,</institution></institution-wrap>Da Nang, Vietnam</nlm:aff></affiliation></author><author><name sortKey="Van, Pham H" sort="Van, Pham H" uniqKey="Van P" first="Pham H." last="Van">Pham H. 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K." last="Phuong">Nguyen T. K. Phuong</name><affiliation><nlm:aff id="Aff1">Respiratory Department, Da Nang Hospital for Women and Children, Da Nang, Vietnam</nlm:aff></affiliation><affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="GRID">grid.1013.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 1936 834X</institution-id><institution>Infectious Disease Team, The Children’s Hospital at Westmead and Discipline of Paediatrics and Adolescent Medicine, University of Sydney,</institution></institution-wrap>Sydney, NSW Australia</nlm:aff></affiliation></author><author><name sortKey="Hoang, Tran T" sort="Hoang, Tran T" uniqKey="Hoang T" first="Tran T." last="Hoang">Tran T. Hoang</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.459448.0</institution-id><institution>Neonatal Department,</institution><institution>Da Nang Hospital for Women and Children,</institution></institution-wrap>Da Nang, Vietnam</nlm:aff></affiliation></author><author><name sortKey="Van, Pham H" sort="Van, Pham H" uniqKey="Van P" first="Pham H." last="Van">Pham H. Van</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.413054.7</institution-id><institution-id institution-id-type="ISNI">0000 0004 0468 9247</institution-id><institution>Microbiology Department,</institution><institution>The University of Medicine and Pharmacy,</institution></institution-wrap>Ho Chi Minh, Vietnam</nlm:aff></affiliation></author><author><name sortKey="Tu, Lolyta" sort="Tu, Lolyta" uniqKey="Tu L" first="Lolyta" last="Tu">Lolyta Tu</name><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.413973.b</institution-id><institution-id institution-id-type="ISNI">0000 0000 9690 854X</institution-id><institution>Antimicrobial Stewardship Team,</institution><institution>The Children’s Hospital at Westmead,</institution></institution-wrap>Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Graham, Stephen M" sort="Graham, Stephen M" uniqKey="Graham S" first="Stephen M." last="Graham">Stephen M. Graham</name><affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.1058.c</institution-id><institution-id institution-id-type="ISNI">0000 0000 9442 535X</institution-id><institution>Centre for International Child Health, University of Melbourne and Murdoch Children’s Research Institute,</institution></institution-wrap>Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Marais, Ben J" sort="Marais, Ben J" uniqKey="Marais B" first="Ben J." last="Marais">Ben J. Marais</name><affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="GRID">grid.1013.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 1936 834X</institution-id><institution>Infectious Disease Team, The Children’s Hospital at Westmead and Discipline of Paediatrics and Adolescent Medicine, University of Sydney,</institution></institution-wrap>Sydney, NSW Australia</nlm:aff></affiliation></author></analytic><series><title level="j">Pneumonia</title><idno type="eISSN">2200-6133</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Globally, pneumonia is considered to be the biggest killer of infants and young children (aged <5 years) outside the neonatal period, with the greatest disease burden in low- and middle-income countries. Optimal management of childhood pneumonia is challenging in settings where clinicians have limited information regarding the local pathogen and drug resistance profiles. This frequently results in unnecessary and poorly targeted antibiotic use. Restricting antibiotic use is a global priority, particularly in Asia and the Western Pacific Region where excessive use is driving high rates of antimicrobial resistance. The authors conducted a comprehensive literature review to explore the antibiotic resistance profile of bacteria associated with pneumonia in the Western Pacific Region, with a focus on Vietnam. Current management practices were also considered, along with the diagnostic dilemmas faced by doctors and other factors that increase unnecessary antibiotic use. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Pneumonia (Nathan)</journal-id><journal-id journal-id-type="iso-abbrev">Pneumonia (Nathan)</journal-id><journal-title-group><journal-title>Pneumonia</journal-title></journal-title-group><issn pub-type="epub">2200-6133</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28702309</article-id><article-id pub-id-type="pmc">5471677</article-id><article-id pub-id-type="publisher-id">31</article-id><article-id pub-id-type="doi">10.1186/s41479-017-0031-4</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Encouraging rational antibiotic use in childhood pneumonia: a focus on Vietnam and the Western Pacific Region</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Phuong</surname><given-names>Nguyen T. K.</given-names></name><address><phone>+84 905 561 593</phone><phone>+61 414 36 35 38</phone><email>phuongty832000@gmail.com</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Hoang</surname><given-names>Tran T.</given-names></name><address><email>hoangtrandn@yahoo.com</email></address><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Van</surname><given-names>Pham H.</given-names></name><address><email>phhvan.nkbiotek@gmail.com</email></address><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Tu</surname><given-names>Lolyta</given-names></name><address><email>Lolita.tu@health.nsw.gov.au</email></address><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Graham</surname><given-names>Stephen M.</given-names></name><address><email>Steve.Graham@rch.org.au</email></address><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Marais</surname><given-names>Ben J.</given-names></name><address><email>ben.marais@health.nsw.gov.au</email></address><xref ref-type="aff" rid="Aff6">6</xref></contrib><aff id="Aff1"><label>1</label>Respiratory Department, Da Nang Hospital for Women and Children, Da Nang, Vietnam</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="GRID">grid.459448.0</institution-id><institution>Neonatal Department,</institution><institution>Da Nang Hospital for Women and Children,</institution></institution-wrap>Da Nang, Vietnam</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="GRID">grid.413054.7</institution-id><institution-id institution-id-type="ISNI">0000 0004 0468 9247</institution-id><institution>Microbiology Department,</institution><institution>The University of Medicine and Pharmacy,</institution></institution-wrap>Ho Chi Minh, Vietnam</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="GRID">grid.413973.b</institution-id><institution-id institution-id-type="ISNI">0000 0000 9690 854X</institution-id><institution>Antimicrobial Stewardship Team,</institution><institution>The Children’s Hospital at Westmead,</institution></institution-wrap>Sydney, Australia</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="GRID">grid.1058.c</institution-id><institution-id institution-id-type="ISNI">0000 0000 9442 535X</institution-id><institution>Centre for International Child Health, University of Melbourne and Murdoch Children’s Research Institute,</institution></institution-wrap>Melbourne, Australia</aff><aff id="Aff6"><label>6</label><institution-wrap><institution-id institution-id-type="GRID">grid.1013.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 1936 834X</institution-id><institution>Infectious Disease Team, The Children’s Hospital at Westmead and Discipline of Paediatrics and Adolescent Medicine, University of Sydney,</institution></institution-wrap>Sydney, NSW Australia</aff></contrib-group><pub-date pub-type="epub"><day>25</day><month>4</month><year>2017</year></pub-date><pub-date pub-type="pmc-release"><day>25</day><month>4</month><year>2017</year></pub-date><pub-date pub-type="collection"><year>2017</year></pub-date><volume>9</volume><elocation-id>7</elocation-id><history><date date-type="received"><day>21</day><month>11</month><year>2016</year></date><date date-type="accepted"><day>3</day><month>4</month><year>2017</year></date></history><permissions><copyright-statement>© The Author(s) 2017</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold>This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>) applies to the data made available in this article, unless otherwise stated.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">Globally, pneumonia is considered to be the biggest killer of infants and young children (aged <5 years) outside the neonatal period, with the greatest disease burden in low- and middle-income countries. Optimal management of childhood pneumonia is challenging in settings where clinicians have limited information regarding the local pathogen and drug resistance profiles. This frequently results in unnecessary and poorly targeted antibiotic use. Restricting antibiotic use is a global priority, particularly in Asia and the Western Pacific Region where excessive use is driving high rates of antimicrobial resistance. The authors conducted a comprehensive literature review to explore the antibiotic resistance profile of bacteria associated with pneumonia in the Western Pacific Region, with a focus on Vietnam. Current management practices were also considered, along with the diagnostic dilemmas faced by doctors and other factors that increase unnecessary antibiotic use. This review offers some suggestions on how these issues may be addressed.</p></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>Antibiotic Prescription</kwd><kwd>Cefaclor</kwd><kwd>Pneumococcal Conjugate Vaccine</kwd><kwd>Vaccine Uptake</kwd><kwd>Macrolide Resistance</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2017</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec id="Sec1"><title>Background</title><p id="Par21">Childhood pneumonia is a major contributor to under-5 mortality, especially in developing countries [<xref ref-type="bibr" rid="CR1">1</xref>, <xref ref-type="bibr" rid="CR2">2</xref>]. In the Western Pacific Region, the highest burden of childhood pneumonia and pneumonia-related deaths occur in six countries: Cambodia, China, Laos, Papua New Guinea, the Philippines and Vietnam [<xref ref-type="bibr" rid="CR3">3</xref>]. These countries report at least 0.2 pneumonia episodes per child year—more than 10 times the rates reported in developed countries from the same region such as Australia, New Zealand and Japan [<xref ref-type="bibr" rid="CR4">4</xref>]. The management of childhood pneumonia is problematic in settings where a microbiological diagnosis is rarely pursued and the drug resistance profiles of common bacteria which cause respiratory disease are not readily available [<xref ref-type="bibr" rid="CR5">5</xref>]. In many Asian countries this encourages excessive use of broad-spectrum antibiotics, irrespective of the child’s disease severity. In the authors’ experience, children are frequently hospitalized with pneumonia to administer intravenous antibiotics, despite relatively mild disease.</p><p id="Par22">Unnecessary hospitalization for intravenous antibiotics increases healthcare cost, as well as treatment-related complications and the likelihood of nosocomial disease transmission. In order to encourage more rational use of intravenous antibiotics in children with community-acquired pneumonia, the authors performed a comprehensive review of common bacterial pathogens and their reported drug resistance profiles in the Western Pacific Region—Vietnam in particular. Factors that increase unnecessary antibiotic use (and measures that might reduce use) were also considered. PubMed, Google Scholar and Embase databases were searched using the following terms: antibacterial agents OR antibiotics OR drug therapy AND community acquired pneumonia OR acute respiratory tract infection AND child OR children OR childhood. Manuscript titles and abstracts were reviewed to identify original research papers that included children less than 5 years of age with pneumonia, with a geographic focus on Vietnam and the Western Pacific Region. In addition, the references of selected publications were reviewed, and co-authors suggested additional relevant papers. The term ‘acute respiratory tract infection (ARTI)’ describes all acute infections that involve the lungs or airways (upper and lower). The World Health Organization (WHO) defines ‘pneumonia’ as a child with tachypnoea, with or without signs of respiratory distress. Given the huge overlap in how these terms are applied in clinical practice, the authors considered ‘pneumonia’ and acute lower respiratory tract infection (LRTI) to be synonymous for the purpose of this review.</p></sec><sec id="Sec2"><title>Common bacterial pathogens</title><p id="Par23">Bacteria classically described to cause community-acquired pneumonia in children include <italic>Streptococcus pneumoniae, Haemophilus influenzae</italic> type b (Hib) and <italic>Staphylococcus aureus</italic> [<xref ref-type="bibr" rid="CR6">6</xref>]. Table <xref rid="Tab1" ref-type="table">1</xref> presents an overview of pathogens commonly associated with acute LRTIs in children less than 5 years of age. With enhanced diagnostic tools, respiratory viruses and atypical bacteria such as <italic>Mycoplasma pneumonia</italic> are commonly detected in children with community-acquired pneumonia, particularly in studies from the Western Pacific Region [<xref ref-type="bibr" rid="CR7">7</xref>–<xref ref-type="bibr" rid="CR9">9</xref>]. This review focused on bacterial pathogens because they are the major cause of pneumonia-related mortality and the primary indication for antibiotic use. However, it is important to appreciate that accurate differentiation between viral and/or bacterial infection is a major challenge to clinicians and complicates management [<xref ref-type="bibr" rid="CR10">10</xref>]. This review provides a brief overview of the most common bacterial pathogens and their reported drug resistance profiles from surveys conducted in the Western Pacific Region.<table-wrap id="Tab1"><label>Table 1</label><caption><p>Pathogens commonly associated with pneumonia or acute lower respiratory tract infection in children less than 5 years of age<sup>e</sup></p></caption><table frame="hsides" rules="groups"><thead><tr><th>Age group</th><th>Bacteria</th><th>Viruses</th></tr></thead><tbody><tr><td><5 years</td><td><p><italic>Streptococcus pneumoniae</italic><sup>a</sup></p><p><italic>Haemophilus influenzae</italic><sup>a</sup></p><p><italic>Mycoplasma pneumoniae</italic><sup>b</sup></p><p><italic>Staphylococcus aureus</italic></p><p><italic>Klebsiella pneumoniae</italic></p><p><italic>Streptococcus pyogenes</italic></p><p><italic>Bordetella pertussis</italic><sup>c</sup></p><p><italic>Mycobacterium tuberculosis</italic><sup>d</sup></p></td><td rowspan="2"><p>RSV</p><p>Rhinovirus</p><p>Influenza virus (A and B)</p><p>Parainfluenza virus</p><p>Human metapneumovirus</p><p>Adenovirus</p><p>Human corona virus</p></td></tr><tr><td>Neonates</td><td><p>Group B streptococcus</p><p><italic>Listeria monocytogenes</italic></p><p>Enteric (gram negative) bacteria</p><p><italic>Chlamydia trachomatis</italic></p></td></tr></tbody></table><table-wrap-foot><p><italic>RSV</italic> Respiratory Syncytial Virus, <italic>Staphylococcus aureus</italic> includes methicillin resistant strains (MRSA); <italic>Haemophilus influenzae</italic> includes type b and other encapsulated strains</p><p><sup>a</sup>Disease greatly reduced in settings with universal access to conjugated vaccines; <sup>b</sup>Typically considered as “atypical bacteria” requiring macrolide therapy; <sup>c</sup>mainly in unvaccinated babies, in older children it can present as a chronic cough; <sup>d</sup>The risk of tuberculosis is dependent on the likelihood of <italic>Mycobacteria tuberculosis</italic> exposure/infection, which is a particular problem in areas with uncontrolled tuberculosis transmission</p><p><sup>e</sup>Adapted from [<xref ref-type="bibr" rid="CR3">3</xref>, <xref ref-type="bibr" rid="CR6">6</xref>]</p></table-wrap-foot></table-wrap></p><sec id="Sec3"><title>Streptococcus pneumoniae</title><p id="Par24">The development of resistance mutations against multiple antibiotics is well documented in <italic>S. pneumoniae</italic>, as well as the expansion of resistant clones under antibiotic pressure. Resistance has been recorded against penicillin, tetracycline, cotrimoxazole, chloramphenicol, fluoroquinolones and macrolides [<xref ref-type="bibr" rid="CR5">5</xref>, <xref ref-type="bibr" rid="CR11">11</xref>, <xref ref-type="bibr" rid="CR12">12</xref>]. Although the correlation between <italic>in vitro</italic> and <italic>in vivo</italic> resistance remains contentious, it is generally assumed that penicillin (at adequate dosages) should still be effective against pneumococcal pneumonia (not meningitis) caused by strains with low or intermediate levels of resistance <italic>in vitro</italic> [<xref ref-type="bibr" rid="CR13">13</xref>]. This is difficult to verify, as many factors that influence the outcome of pneumonia treatment—such as underlying comorbid conditions, disease severity and supportive treatment—are poorly described in historical datasets and adequately powered head-to-head comparisons are rare [<xref ref-type="bibr" rid="CR14">14</xref>–<xref ref-type="bibr" rid="CR16">16</xref>]. Another important factor to take into consideration is the roll-out of pneumococcal conjugate vaccines. Routine administration of pneumococcal conjugate vaccine (PCV) in infancy has led to major reductions in pneumonia hospitalization and invasive pneumococcal disease in young children [<xref ref-type="bibr" rid="CR17">17</xref>]. Given that the most common drug resistant strains were included in 7- and 13-valent pneumococcal conjugate vaccines, drug resistant pneumococcal disease has been greatly reduced in areas with high vaccine uptake [<xref ref-type="bibr" rid="CR18">18</xref>], while reductions in strain carriage also reduced secondary pneumonia cases among older adults [<xref ref-type="bibr" rid="CR17">17</xref>]. However, recent studies from Canada and the United Kingdom demonstrated substantial increases in multi-drug resistant non-vaccine serotypes in both colonizing and invasive strains since introducing PCV13, with similar findings for colonizing strains after introducing PCV7 in Korean children [<xref ref-type="bibr" rid="CR19">19</xref>–<xref ref-type="bibr" rid="CR21">21</xref>].</p><p id="Par25">High penicillin and macrolide resistance rates have been reported in published surveys, but many of these surveys included select patient populations and used minimal inhibitory concentration (MIC) breakpoints with variable stringency, and were also done prior to routine PCV delivery [<xref ref-type="bibr" rid="CR5">5</xref>, <xref ref-type="bibr" rid="CR22">22</xref>, <xref ref-type="bibr" rid="CR23">23</xref>]. The use of variable MIC breakpoints in different studies is a major source of confusion and complicates study comparison. MIC breakpoints defined by the Clinical and Laboratory Standards Institute (CLSI) are widely used in the United States, while Europe has adopted the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards. They use broadly similar <italic>in vitro</italic> methods and specify MIC breakpoints by considering the pharmacokinetic–pharmacodynamic (PK-PD) properties of the drug, the clinical site of disease and the specific mechanism of drug resistance [<xref ref-type="bibr" rid="CR24">24</xref>]. Studies have shown reasonable comparability between antibiotic susceptibility profiles using revised CLSI and EUCAST breakpoints [<xref ref-type="bibr" rid="CR25">25</xref>, <xref ref-type="bibr" rid="CR26">26</xref>], but some significant differences remain. Against <italic>S. pneumoniae</italic> and <italic>H. influenzae</italic>, cefuroxime and cefaclor breakpoints still produce divergent results [<xref ref-type="bibr" rid="CR26">26</xref>]. Global surveillance efforts would be greatly enhanced if uniform surveillance criteria can be agreed upon and MIC breakpoint definitions harmonized.</p><p id="Par26">A study conducted in 11 Asian countries reported a low (0.7%; 365/2184) prevalence of penicillin resistance in <italic>S. pneumoniae</italic> from non-meningeal isolates, [<xref ref-type="bibr" rid="CR12">12</xref>] but it used an MIC breakpoint of ≥8 μg/ml as recommended by CLSI, which is much higher than the >0.06 μg/ml breakpoint proposed by EUCAST. A small case series of children with S. <italic>pneumoniae</italic> septicemia in China reported high drug resistance rates (96%; 24/25) [<xref ref-type="bibr" rid="CR23">23</xref>], but MIC breakpoints were not specified. In Malaysia, 18% (5/28) of <italic>S. pneumoniae</italic> isolated from blood in children with community-acquired pneumonia was resistant to penicillin (using revised CLSI breakpoints) [<xref ref-type="bibr" rid="CR27">27</xref>]. Since nasopharyngeal carriage may create a reservoir of resistant <italic>S. pneumoniae</italic> clones, it is important to monitor resistance in carriage specimens as well [<xref ref-type="bibr" rid="CR28">28</xref>]. Nasopharyngeal <italic>S. pneumoniae</italic> carriage has been reported in 17% (102/614) of healthy Chinese children; 51% were resistant to macrolides by the E-test method [<xref ref-type="bibr" rid="CR29">29</xref>]. In rural Vietnam, <italic>S. pneumoniae</italic> carriage has been detected in 50% of children, with higher rates in those less than 2 years of age (6–23 months). The resistance rate to amoxicillin and benzylpenicillin was low (4%; 17/421), based on revised CLSI breakpoints, but 95% were resistant to at least one antibiotic (cotrimoxazole 78%, erythromycin 70%, ciprofloxacin 28%) [<xref ref-type="bibr" rid="CR30">30</xref>]. A more recent Vietnamese survey confirmed excellent penicillin susceptibility in <italic>S. pneumoniae</italic> isolates from respiratory specimens (penicillin 87% using revised CLSI breakpoints), although cephalosporin and macrolide susceptibility was poor (cefuroxime 19%, cefaclor 8%; azithromycin 4%) [<xref ref-type="bibr" rid="CR31">31</xref>]. This supports the Vietnam national guidance to use high dose (90 mg/kg/day) amoxicillin as first-line treatment of community-acquired pneumonia in children [<xref ref-type="bibr" rid="CR13">13</xref>].</p></sec><sec id="Sec4"><title>Haemophilus influenzae</title><p id="Par27">Although the prevalence of <italic>H. influenzae</italic> type b (Hib) has declined dramatically with widespread roll-out of conjugated Hib vaccine [<xref ref-type="bibr" rid="CR32">32</xref>, <xref ref-type="bibr" rid="CR33">33</xref>], it remains prevalent in settings with poor vaccine uptake. B-lactamase production is commonly associated with Hib infection. In Vietnam, 41% of respiratory Hib isolates produced β-lactamase and 14% were β-lactamase non-producing ampicillin-resistant [<xref ref-type="bibr" rid="CR31">31</xref>]. However, it is impossible to differentiate clinical infection from asymptomatic colonization using respiratory specimens from non-sterile sites. In China, Hib carriage decreased from 36% in 2000 to 19% in 2012, but β-lactamase-producing isolates increased from 4 to 31% over the same time period. Amoxicillin/clavulanic acid and 2nd or 3rd generation cephalosporins remained universally effective [<xref ref-type="bibr" rid="CR34">34</xref>]. Despite the national Hib vaccine roll-out in Vietnam, Hib remains a common invasive pathogen [<xref ref-type="bibr" rid="CR31">31</xref>], but this is expected to decrease as vaccine uptake improves. With increased vaccination uptake, the role of other encapsulated <italic>H. influenzae</italic> strains have increased [<xref ref-type="bibr" rid="CR35">35</xref>]. A study in China found that 100% of <italic>H. influenzae</italic> strains identified in the sputum of children with pneumonia were non-typable; 1% (2/279) were β-lactamase-positive and 5% were β-lactamase non-producing ampicillin-resistant or intermediately resistant [<xref ref-type="bibr" rid="CR36">36</xref>].</p></sec><sec id="Sec5"><title>Staphylococcus aureus</title><p id="Par28"><italic>S. aureus</italic> remains a common cause of community-acquired pneumonia. Pioneering lung puncture studies performed in Chile and Papua New Guinea identified <italic>S. aureus</italic> as a common pathogen in children with community-acquired pneumonia [<xref ref-type="bibr" rid="CR37">37</xref>]. More recent studies found the pathogen predominantly in children at the severe end of the pneumonia disease spectrum, with increased frequency in severely malnourished children [<xref ref-type="bibr" rid="CR38">38</xref>, <xref ref-type="bibr" rid="CR39">39</xref>]. <italic>S. aureus</italic> also poses particular problems following influenza or measles infection, and as a secondary infection in hospitalized children [<xref ref-type="bibr" rid="CR38">38</xref>, <xref ref-type="bibr" rid="CR40">40</xref>, <xref ref-type="bibr" rid="CR41">41</xref>]. A major challenge has been the emergence of methicillin-resistant <italic>S. aureus</italic> (MRSA) and more recently, a decrease in vancomycin susceptibility [<xref ref-type="bibr" rid="CR42">42</xref>, <xref ref-type="bibr" rid="CR43">43</xref>]. Among positive <italic>S. aureus</italic> blood cultures in Australian and New Zealand children, MRSA has been reported in 13% (142/1,073) with three times the average rate (incidence rate ratio, 3 [95%, CI: 2–4]), found among Aboriginal and Pacific Islander populations [<xref ref-type="bibr" rid="CR44">44</xref>, <xref ref-type="bibr" rid="CR45">45</xref>]. A recent Malaysian survey reported MRSA in 8% (3/38) of children with community-acquired S. <italic>aureus</italic> bacteremia; 32% had skin or soft tissues infections and 32% had community-acquired pneumonia [<xref ref-type="bibr" rid="CR27">27</xref>]. A study assessing the prevalence of heterogeneous vancomycin-intermediately-resistant <italic>S. aureus</italic> (hVISA<italic>)</italic> in Asian countries (including South Korea, Taiwan, Hong Kong, Thailand, the Philippines, Vietnam, India and Sri Lanka) reported that among 462 MRSA isolates, 3.5% were hVISA, with the highest prevalence in South Korea and Vietnam (7.0%) [<xref ref-type="bibr" rid="CR46">46</xref>]. A more extensive report on antibiotic resistance in 15 hospitals throughout Vietnam found MRSA in 20% of children and adults with <italic>S. aureus</italic> bacteremia; vancomycin resistance rates were very low [<xref ref-type="bibr" rid="CR47">47</xref>].</p></sec><sec id="Sec6"><title>Atypical bacteria</title><p id="Par29"><italic>Mycoplasma pneumoniae</italic> is highly prevalent in children diagnosed with pneumonia in the Western Pacific Region [<xref ref-type="bibr" rid="CR4">4</xref>]. <italic>M. pneumoniae</italic> is inherently resistant to all β-lactams antibiotics and vancomycin, because it does not have a cell wall. With excessive macrolide use in recent years, reported macrolide resistance is near universal (90–100%) in parts of Asia [<xref ref-type="bibr" rid="CR48">48</xref>]. Most countries report high rates of macrolide resistance (Japan 89% [<xref ref-type="bibr" rid="CR49">49</xref>, <xref ref-type="bibr" rid="CR50">50</xref>], China 83–98% [<xref ref-type="bibr" rid="CR5">5</xref>, <xref ref-type="bibr" rid="CR51">51</xref>, <xref ref-type="bibr" rid="CR52">52</xref>], South Korea 63% [<xref ref-type="bibr" rid="CR53">53</xref>], Hong Kong 47% [<xref ref-type="bibr" rid="CR54">54</xref>], Taiwan 23% [<xref ref-type="bibr" rid="CR55">55</xref>]), although the methods for <italic>M. pneumoniae</italic> susceptibility testing are poorly standardized. <italic>M. pneumoniae</italic> remains susceptible to macrolides in Australia where it is less frequently used [<xref ref-type="bibr" rid="CR56">56</xref>]. Resistance to tetracyclines and fluoroquinolones have not been reported in clinical isolates and may provide a treatment alternative in some children, although reduced <italic>in vitro</italic> susceptibility has been reported [<xref ref-type="bibr" rid="CR48">48</xref>]. However, most <italic>M. pneumoniae</italic> cases recover either without antibiotic treatment or despite documented drug resistance, thus the clinical value of antibiotic treatment remains uncertain [<xref ref-type="bibr" rid="CR57">57</xref>].</p><p id="Par30">Treatment of ARTIs is a major driver of antibiotic use in children. It is important for clinicians to be familiar with the most common bacterial causes, their local drug resistance profiles and the likely impact of antibiotic therapy (both positive and negative) in order to develop a rational treatment approach. Because a timely and definitive bacteriological diagnosis is currently impossible, empiric antibiotic treatment is justified in any acutely ill child. However, there is a need to critically consider factors that promote unnecessary and irrational antibiotic use, especially in children who are not acutely ill.</p></sec></sec><sec id="Sec7"><title>Factors promoting irrational antibiotic use</title><p id="Par31">Antibiotic use generates selective pressure that increases the prevalence of drug resistant strains; hence, strategies to improve rational antibiotic use are important to protect antibiotics as a precious resource. A study of antibiotic use in Vietnamese hospitals showed that a large proportion of in-patients received inappropriate antibiotic therapy [<xref ref-type="bibr" rid="CR58">58</xref>]. The main factors that promote unnecessary antibiotic use in the Western Pacific Region, using Vietnam as an exemplar, are listed below.</p><sec id="Sec8"><title>Unrestricted antibiotic access</title><p id="Par32">Given unrestricted access to over-the-counter antibiotics, treatment of any respiratory infection with antibiotics is a common practice in Vietnam, Malaysia, and South Korea [<xref ref-type="bibr" rid="CR59">59</xref>]. In Vietnam, the <italic>Pharmaceutical Law</italic> passed in 2005 requires an antibiotic prescription, but 38% of caregivers still access antibiotics without any formal medical assessment [<xref ref-type="bibr" rid="CR60">60</xref>]; even injectable antibiotics can be acquired at local shops without prescription [<xref ref-type="bibr" rid="CR61">61</xref>]. In the Western Pacific Region, antibiotic use before presentation to a doctor is common; more than 40% in Mongolia [<xref ref-type="bibr" rid="CR62">62</xref>] and more than 50% of children admitted with ARTIs in the Philippines [<xref ref-type="bibr" rid="CR63">63</xref>]. A study in nine international sites—Colombia, Ghana, India, Mexico, Pakistan, South Africa (2 sites), Vietnam and Zambia—found that the use of antibiotics in the 48 h prior to hospital admission was associated with treatment failure (OR: 1.8; 95% CI: 1.27–2.66) [<xref ref-type="bibr" rid="CR64">64</xref>]. In addition, agricultural use of antibiotics remains essentially unregulated in most Asian countries, with high rates of colistin and cephalosporin use in the pig and poultry industries, resulting in increased rates of drug-resistant infections in human populations [<xref ref-type="bibr" rid="CR65">65</xref>, <xref ref-type="bibr" rid="CR66">66</xref>].</p></sec><sec id="Sec9"><title>Unrealistic expectations and limited awareness</title><p id="Par33">Limited awareness among the general public (including politicians) is a challenge in all settings; the WHO recently launched a program to increase awareness about antimicrobial resistance and the need for more prudent antibiotic use [<xref ref-type="bibr" rid="CR59">59</xref>]. In response, country-specific strategies to limit antimicrobial resistance have been launched in the United Kingdom, the United States and Australia [<xref ref-type="bibr" rid="CR67">67</xref>–<xref ref-type="bibr" rid="CR69">69</xref>], but few Asian countries have followed suit. Unrealistic public expectation is a major factor driving excessive antibiotic use [<xref ref-type="bibr" rid="CR59">59</xref>, <xref ref-type="bibr" rid="CR70">70</xref>]. A study in rural Vietnam showed that just 13% of caregivers had correct knowledge about acute respiratory infections and 38% of caregivers self-managed common colds by buying antibiotics without prescription at the local pharmacy [<xref ref-type="bibr" rid="CR60">60</xref>]. In Malaysia, 67% of people believed antibiotics to be effective against viral infections, with 47% using antibiotics during a common cold [<xref ref-type="bibr" rid="CR61">61</xref>]. Moreover, antibiotic use is strongly influenced by cultural preferences and beliefs. Patients in Vietnam and China believe injectable antibiotics are more potent than oral options, and readily access injectable antibiotics without prescription [<xref ref-type="bibr" rid="CR71">71</xref>]. A lack of adequate knowledge is also a problem among healthcare providers. A study in Vietnam demonstrated poor awareness about the risks and consequences of drug resistance among rural health-care providers when treating ARTIs; only 19% complied with recommended guidelines and 79% used antibiotics for common colds [<xref ref-type="bibr" rid="CR72">72</xref>].</p></sec><sec id="Sec10"><title>Physician-related factors</title><p id="Par34">Table <xref rid="Tab2" ref-type="table">2</xref> provides an overview of physician-related factors that explains some of the excessive antibiotic use seen in Vietnam and parts of the Western Pacific Region. The difficulty in accurately differentiating viral from bacterial pneumonia is a major challenge in all settings. A study in Finland showed that of the routine blood tests, only the C-reactive protein (CRP) level differed significantly between bacterial and viral pneumonia patients [<xref ref-type="bibr" rid="CR10">10</xref>]. Most children with dense lobar infiltrates on chest radiograph had laboratory evidence of a bacterial infection, but interstitial infiltrates were seen in both viral and bacterial pneumonia [<xref ref-type="bibr" rid="CR10">10</xref>]. A recent randomized-controlled trial in Vietnam showed that point-of-care CRP testing reduced inappropriate antibiotic use for non-severe ARTIs [<xref ref-type="bibr" rid="CR73">73</xref>]. A previous randomized-controlled trial in China investigated whether serum pro-calcitonin (PCT) could reduce unnecessary antibiotic use [<xref ref-type="bibr" rid="CR74">74</xref>], but although the mean duration of antibiotic treatment was shorter in the PCT group, the antibiotic prescription rate was higher. It is hoped that rapid point-of-care testing for common respiratory viruses and biomarkers of severe bacterial infection will offer better bedside guidance in the near future, assisting more appropriate antibiotic use.<table-wrap id="Tab2"><label>Table 2</label><caption><p>Physician related factors that contribute to excessive antibiotic use in the Western Pacific Region</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Factor identified</th><th>Examples from the Western Pacific Region</th></tr></thead><tbody><tr><td>Professional hierarchy</td><td><p>• Junior physicians adopt the prescription habits of senior physicians without rigorous discussion or review of the evidence [<xref ref-type="bibr" rid="CR86">86</xref>].</p><p>• In Vietnam, inappropriate antibiotic use is a particular problem in obstetrics, gynecology and surgery wards where professional hierarchy is most pronounced [<xref ref-type="bibr" rid="CR58">58</xref>]</p></td></tr><tr><td>No consideration of “societal risk”</td><td><p>• Doctors and patients often prefer newer and more expensive antibiotics, which are considered more “powerful” [<xref ref-type="bibr" rid="CR62">62</xref>]</p><p>• Physicians provide antibiotics to help individual patients; potential societal risks are not considered [<xref ref-type="bibr" rid="CR86">86</xref>];</p><p>• In the absence of functional microbiology services, physicians have limited information on local drug-resistance profiles and the impact of excessive antibiotic use;</p></td></tr><tr><td>Perceived patient/parent expectation</td><td><p>• Doctors strive for patient satisfaction and if patients request antibiotics it is usually prescribed [<xref ref-type="bibr" rid="CR70">70</xref>, <xref ref-type="bibr" rid="CR87">87</xref>]; In Korea, 73% of doctors prescribe antibiotics for a common cold if requested by parents [<xref ref-type="bibr" rid="CR88">88</xref>]; In Malaysia, 67% of patients believe that antibiotics help for viral infections [<xref ref-type="bibr" rid="CR61">61</xref>]</p><p>• Doctors have no time or motivation to explain the rationale for not using antibiotics</p></td></tr><tr><td>Fear of poor patient outcome or litigation</td><td><p>• Fear of poor patient outcomes is often listed as a key motivation for the use of broad-spectrum antibiotics by doctors [<xref ref-type="bibr" rid="CR58">58</xref>, <xref ref-type="bibr" rid="CR59">59</xref>, <xref ref-type="bibr" rid="CR89">89</xref>]</p><p>• Fear of litigation is not yet a major driver in the Western Pacific, but is likely to become a more prominent factor with increased development [<xref ref-type="bibr" rid="CR90">90</xref>]</p></td></tr><tr><td>Inadequate microbiology services</td><td><p>• Near universal use of empiric broad spectrum antibiotics is common in places with poor microbiology services [<xref ref-type="bibr" rid="CR70">70</xref>, <xref ref-type="bibr" rid="CR87">87</xref>].</p><p>• In Vietnam, antibiotic use was reduced in hospitals with functional microbiology laboratories [<xref ref-type="bibr" rid="CR58">58</xref>]</p></td></tr><tr><td>Financial incentives to use antibiotics</td><td><p>• Doctors’ prescribing habits is influenced by personal income generated and incentives provided by pharmaceutical companies [<xref ref-type="bibr" rid="CR70">70</xref>, <xref ref-type="bibr" rid="CR86">86</xref>, <xref ref-type="bibr" rid="CR87">87</xref>]. In China, as in many other Western Pacific countries, drug prescriptions supplement a doctor’s income [<xref ref-type="bibr" rid="CR62">62</xref>].</p><p>• In South-Korea drug dispensing by health care workers was banned in 2000, resulting in major reductions in antibiotic use [<xref ref-type="bibr" rid="CR62">62</xref>]</p></td></tr></tbody></table></table-wrap></p><p id="Par35">Because most child pneumonia deaths are caused by bacterial pathogens, current WHO guidelines recommend antibiotic use in all pneumonia cases, as defined by the presence of fast breathing. This approach may encourage the overuse of antibiotics, especially in children without danger signs who present with wheezing as a sign of reactive airway disease, which usually indicates a viral infection. Audible wheezing has been noted in 49% of Vietnamese children admitted with ‘pneumonia’ [<xref ref-type="bibr" rid="CR75">75</xref>], which may identify a subgroup that does not require antibiotics [<xref ref-type="bibr" rid="CR76">76</xref>]. WHO guidelines previously advised intravenous antibiotics in all children diagnosed with severe pneumonia (signs of respiratory distress), but oral amoxicillin was found to be effective in 92% (948/1,025) of children with a clinical diagnosis of severe pneumonia in Pakistan [<xref ref-type="bibr" rid="CR77">77</xref>]. Subsequent trials demonstrated that home-based treatment can be applied to a wide variety of settings [<xref ref-type="bibr" rid="CR74">74</xref>]. A multi-center study conducted in Bangladesh, Egypt, Ghana and Vietnam reported 9% (95% CI: 7–11%) treatment failure with 5 days of high dose oral amoxicillin (80–90 mg/kg/day), varying from 6% (95% CI: 3–10%) in Ghana to 13% (95% CI: 8–18%) in Vietnam [<xref ref-type="bibr" rid="CR75">75</xref>]. A sizeable (but unknown) proportion of cases enrolled in these “clinical pneumonia” studies would have had viral infections. Therefore, it is not clear how much “treatment failure” actually resulted from inadequate antibiotic treatment for bacterial pneumonia; most children found to be “unresponsive to antibiotics” probably had viral pneumonia [<xref ref-type="bibr" rid="CR78">78</xref>, <xref ref-type="bibr" rid="CR79">79</xref>]. Despite the available evidence, most doctors in Vietnam routinely hospitalize children with “clinical pneumonia” to administer intravenous antibiotics; unnecessary hospitalization increases both healthcare cost and the risk of nosocomial infection.</p></sec></sec><sec id="Sec11"><title>Proposed recommendations</title><p id="Par36">Actions and recommendations to improve rational antibiotic use in both the community and hospital environment are summarized in Table <xref rid="Tab3" ref-type="table">3</xref>. Unrestricted antibiotic access and self-medication are firmly entrenched in Vietnam and most other Asian countries [<xref ref-type="bibr" rid="CR80">80</xref>]. Given the multiple vested interests that protect the status quo, strong regulation and effective law enforcement will be required to limit excessive antibiotic use. In addition to public education programs, better training of healthcare providers to critically review the need for antibiotic use is essential [<xref ref-type="bibr" rid="CR59">59</xref>]. Only 31% of countries in the Western Pacific Region report high awareness of antimicrobial resistance among their healthcare providers [<xref ref-type="bibr" rid="CR59">59</xref>]. An educational program in Indonesia, including face-to-face clinician visits and group discussions, significantly reduced the use of injectable drugs [<xref ref-type="bibr" rid="CR81">81</xref>], but has not been replicated elsewhere.<table-wrap id="Tab3"><label>Table 3</label><caption><p>Actions and recommendations to improve rational antibiotic use</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Actions</th><th>Suggested high-level recommendations<sup>a</sup></th></tr></thead><tbody><tr><td colspan="2">In general</td></tr><tr><td>Enhanced regulation</td><td><p>• Limit over-the-counter availability of antibiotics; establish strong national policies for appropriate antibiotic regulation; implement measures to ensure compliance</p><p>• Improved national surveillance of antimicrobial resistance and adherence to treatment guidelines</p><p>• Regulate agricultural use of antibiotics</p></td></tr><tr><td>Patient/public education</td><td><p>• Increase general awareness of adverse effects associated with excessive antibiotic use</p><p>• Educate parents, caretakers, politicians and the general community about the benefits of restricted antibiotic use</p></td></tr><tr><td>Universal Hib and PCV</td><td><p>• Make Hib and PCV universally available free of charge</p><p>• Maintain high uptake of other vaccines (e.g. pertussis and measles)</p></td></tr><tr><td colspan="2">Within hospitals</td></tr><tr><td>Provide information on local drug resistance patterns</td><td>• Maintain a network of functional microbiology laboratories, with adequate quality assurance and sharing of information</td></tr><tr><td>Establish functional antimicrobial stewardship programs</td><td><p>• Each hospital should have an antimicrobial stewardship program and a Drug and Therapeutics Committee with access to reliable and up-to-date data on antibiotic usage and drug resistance profiles</p><p>• Each hospital should have regular/annual antibiotic use audits led by pharmacists or infectious disease control personnel</p></td></tr><tr><td>Provide clear guidance</td><td>• Develop national/regional consensus treatment guidelines that consider the international evidence base, as well as local disease etiology and drug resistance data</td></tr><tr><td>Eliminate perverse incentives</td><td><p>• Delink remuneration from antibiotic prescription</p><p>• Ban incentives to doctors to provide antibiotics or use specific medical products</p></td></tr><tr><td>Educate medical students and trainees</td><td><p>• Include antimicrobial stewardship in the undergraduate medical, nursing and pharmacy curriculum</p><p>• Highlight the growing drug resistance problem and need for prudent use</p></td></tr></tbody></table><table-wrap-foot><p><italic>PCV</italic> pneumococcal conjugate vaccine, <italic>Hib Haemophilus influenzae</italic> type b</p><p><sup>a</sup>In addition, a detailed assessment of pneumonia case management should be conducted to understand clinical decision-making and provide more pragmatic guidance to clinicians in the field. Exemplars of comprehensive national strategies to address antimicrobial resistance and limit excessive antibiotic use include the United Kingdom, the United States and Australia [<xref ref-type="bibr" rid="CR67">67</xref>–<xref ref-type="bibr" rid="CR69">69</xref>]</p></table-wrap-foot></table-wrap></p><p id="Par37">In 2013, the WHO facilitated a meeting of Western Pacific Region countries in Manila to identify feasible antimicrobial resistance (AMR) strategies [<xref ref-type="bibr" rid="CR59">59</xref>], but this has not yet translated into revised childhood pneumonia guidance or management practices. In Vietnam, the Vietnam Resistance (VINARES) project aims to strengthen laboratory surveillance and reduce irrational antibiotic use. The project covers 16 participating hospitals [<xref ref-type="bibr" rid="CR82">82</xref>], but outside of the participating hospitals AMR surveillance remains weak. Laboratory capacity to assist microbiological diagnosis and guide clinical management is insufficient throughout the region [<xref ref-type="bibr" rid="CR83">83</xref>]. Functional antibiotic stewardship programs have been established in some countries, but this should become standard practice and be adapted to the local context [<xref ref-type="bibr" rid="CR44">44</xref>]. An antibiotic stewardship program in Chinese hospitals set targets for antibiotic prescriptions and penalized doctors who prescribed antibiotics inappropriately [<xref ref-type="bibr" rid="CR84">84</xref>]. After 2 years, antibiotic prescriptions decreased by 58–68% in inpatients and 15–25% in outpatients [<xref ref-type="bibr" rid="CR85">85</xref>]. An antimicrobial stewardship program is currently being implemented in Vietnam (through VINARES), but the scope of the program is limited and there is a need for similar programs, including regular audits of antibiotic use, in every hospital [<xref ref-type="bibr" rid="CR82">82</xref>].</p></sec><sec id="Sec12"><title>Conclusion</title><p id="Par38">Optimal child pneumonia management presents an opportunity to reduce excessive antibiotic use in the Western Pacific Region. However, encouraging the rational use of antibiotics requires education of healthcare professionals, facilitation of cultural change, improved clinical guidance and the establishment of functional microbiology laboratories to monitor disease etiology and drug resistance patterns, together with the removal of inappropriate incentives and effective enforcement of national regulations to restrict antibiotic use in healthcare and agriculture.</p></sec></body><back><glossary><title>Abbreviations</title><def-list><def-item><term>ARTI</term><def><p id="Par2">Acute respiratory tract infection</p></def></def-item><def-item><term>AMR</term><def><p id="Par3">Antimicrobial resistance</p></def></def-item><def-item><term>CRP</term><def><p id="Par4">C-reactive protein</p></def></def-item><def-item><term>CLSI</term><def><p id="Par5">Clinical and Laboratory Standards Institute</p></def></def-item><def-item><term>CI</term><def><p id="Par6">Confidence interval</p></def></def-item><def-item><term>EUCAST</term><def><p id="Par7">European Committee on Antimicrobial Susceptibility Testing</p></def></def-item><def-item><term><italic>H. influenzae</italic></term><def><p id="Par8"><italic>Haemophilus influenzae</italic></p></def></def-item><def-item><term>Hib</term><def><p id="Par9"><italic>Haemophilus influenzae</italic> type b</p></def></def-item><def-item><term>hVISA</term><def><p id="Par10">Heterogeneous vancomycin-intermediate S.<italic>aureus</italic></p></def></def-item><def-item><term>MRSA</term><def><p id="Par11">Methicillin resistant <italic>staphylococcus aureus</italic></p></def></def-item><def-item><term>MIC</term><def><p id="Par12">Minimal inhibitory concentration</p></def></def-item><def-item><term>M. <italic>pneumoniae</italic></term><def><p id="Par13"><italic>Mycoplasma pneumonia</italic></p></def></def-item><def-item><term>PK-PD</term><def><p id="Par14">Pharmacokinetic-pharmacodynamic</p></def></def-item><def-item><term>PCV</term><def><p id="Par15">Pneumococcal conjugate vaccine</p></def></def-item><def-item><term>PCT</term><def><p id="Par16">Procalcitonin</p></def></def-item><def-item><term>S. <italic>aureus</italic></term><def><p id="Par17"><italic>Staphylococcus aureus</italic></p></def></def-item><def-item><term>S. <italic>pneumoniae</italic></term><def><p id="Par18"><italic>Streptococcus pneumoniae</italic></p></def></def-item><def-item><term>VINARES</term><def><p id="Par19">Vietnam resistance project</p></def></def-item><def-item><term>WHO</term><def><p id="Par20">World Health Organization</p></def></def-item></def-list></glossary><ack><title>Acknowledgements</title><p>Not applicable</p><sec id="FPar1"><title>Funding</title><p id="Par39">Not applicable</p></sec><sec id="FPar2" sec-type="data-availability"><title>Availability of data and material</title><p id="Par40">Not applicable</p></sec><sec id="FPar3"><title>Authors’ contributions</title><p id="Par41">NTKP and BJM conceptualized the manuscript and wrote the first draft. 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