<?xml version="1.0" encoding="utf-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.0 20120330//EN" "JATS-journalpublishing1.dtd">
<article article-type="editorial" dtd-version="1.0" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">CEP</journal-id>
<journal-title-group>
<journal-title>Clinical and Experimental Pediatrics</journal-title><abbrev-journal-title>Clin Exp Pediatr</abbrev-journal-title></journal-title-group>
<issn pub-type="epub">2713-4148</issn>
<publisher>
<publisher-name>Korean Pediatric Society</publisher-name></publisher></journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3345/cep.2020.01830</article-id>
<article-id pub-id-type="publisher-id">cep-2020-01830</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Editorial</subject>
<subj-group subj-group-type="heading">
<subject>Infection</subject>
</subj-group></subj-group></article-categories>
<title-group>
<article-title>Should we prescribe carbapenem for treating febrile urinary tract infection caused by extended-spectrum &#x003b2;-lactamase-producing <italic>Enterobacteriaceae</italic> in children with vesicoureteral reflux?</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-6777-0494</contrib-id>
<name><surname>Park</surname><given-names>Ji Young</given-names></name>
<degrees>MD</degrees>
<degrees>PhD</degrees>
<xref ref-type="corresp" rid="c1-cep-2020-01830"/>
<xref ref-type="aff" rid="af1-cep-2020-01830"></xref>
</contrib>
<aff id="af1-cep-2020-01830">
Department of Pediatrics, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, <country>Korea</country></aff>
</contrib-group>
<author-notes>
<corresp id="c1-cep-2020-01830">Corresponding author: Ji Young Park, MD, PhD, Division of Pediatric Infectious Diseases, Department of Pediatrics, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea  Email: <email>jypark@caumc.or.kr</email></corresp>
</author-notes>
<pub-date pub-type="collection">
<month>6</month>
<year>2021</year></pub-date>
<pub-date pub-type="epub">
<day>5</day>
<month>1</month>
<year>2021</year></pub-date>
<volume>64</volume>
<issue>6</issue>
<fpage>284</fpage>
<lpage>285</lpage>
<history>
<date date-type="received">
<day>3</day>
<month>11</month>
<year>2020</year></date>
<date date-type="rev-recd">
<day>16</day>
<month>12</month>
<year>2020</year></date>
<date date-type="accepted">
<day>28</day>
<month>12</month>
<year>2020</year></date>
</history>
<permissions>
<copyright-statement>Copyright &#x000a9; 2021 by The Korean Pediatric Society</copyright-statement>
<copyright-year>2021</copyright-year>
<license>
<license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions>
<related-article related-article-type="commentary-article" id="cep-2020-01830" elocation-id="cep.2020.00773"/>
</article-meta>
<notes>
<title>Key message</title>
<boxed-text>
<p>Recent studies are focused on the noninferiority of noncarbapenem therapy for the treatment of extended-spectrum β-lactamases producing <italic>Enterobacteriaceae</italic> infections to reduce the utilization of carbapenem.</p>
</boxed-text>
</notes>
</front>
<body>
<p>Urinary tract infections (UTIs) are the most common serious bacterial infections in children &#x0005b;<xref ref-type="bibr" rid="b1-cep-2020-01830">1</xref>&#x0005d;. The most common pathogens causing UTIs are <italic>Enterobacteriaceae</italic>, such as <italic>Escherichia coli</italic> and <italic>Klebsiella</italic> species &#x0005b;<xref ref-type="bibr" rid="b2-cep-2020-01830">2</xref>&#x0005d;. Antimicrobial drug resistance to fluoroquinolone, cephalosporin, and carbapenem among <italic>Enterobacteriaceae</italic> has spread globally over the past few decades and become a pressing problem &#x0005b;<xref ref-type="bibr" rid="b3-cep-2020-01830">3</xref>&#x0005d;. The dissemination of drug-resistant organisms is troublesome for clinicians when selecting empirical antibiotics. Patients with UTIs were historically administered broad-spectrum cephalosporin as the empirical therapy. Carbapenem is the definitive therapy for infections caused by extended-spectrum &#x003b2;-lactamases (ESBL)&#x02013;producing bacteria. However, carbapenemsparing options are on the rise for mild infections with ESBL producers because its overuse is leading to the emergence of carbapenem-resistant organisms.</p>
<p>Recent studies have focused on the noninferiority of noncarbapenem therapy for the treatment of ESBL-producing <italic>Enterobacteriaceae</italic> infections to reduce carbapenem utilization &#x0005b;<xref ref-type="bibr" rid="b4-cep-2020-01830">4</xref>-<xref ref-type="bibr" rid="b7-cep-2020-01830">7</xref>&#x0005d;. A review article examined noncarbapenem &#x003b2;-lactam (cephamycin, cefepime, piperacillin/tazobactam, and newer &#x003b2;-lactam/&#x003b2;-lactamase inhibitors) therapy for ESBL-producing bacterial infections. The authors suggested that noncarbapenem could be considered in patients with mild to moderate low-inoculum infections &#x0005b;<xref ref-type="bibr" rid="b6-cep-2020-01830">6</xref>&#x0005d;. A recent literature review summarized published articles regarding the treatment of ESBL-producing <italic>Enterobacteriaceae</italic> infections. Patients were divided into 3 groups: group 1, severe or nonsevere infections from high-risk sources and/or severely immunocompromised patients; group 2, nonsevere infections and intermediate-risk sources; and group 3, nonsevere infections and low-risk sources (<xref rid="f1-cep-2020-01830" ref-type="fig">Fig. 1</xref>). They concluded that carbapenem should be the choice of drug for the treatment of ESBL-producing <italic>Enterobacteriaceae</italic> in severe infections, whereas other antimicrobial agents could be considered for mild infections such as UTIs &#x0005b;<xref ref-type="bibr" rid="b7-cep-2020-01830">7</xref>&#x0005d;. Thus, using noncarbapenem therapy for treating UTIs caused by ESBL-producing bacteria could be an effective way to prevent carbapenem overuse.</p>
<p>Furthermore, children with vesicoureteral reflux (VUR) are at high risk for acute and recurrent pyelonephritis &#x0005b;<xref ref-type="bibr" rid="b8-cep-2020-01830">8</xref>&#x0005d;. In patients with VUR, it is unknown whether carbapenem therapy can reduce the short-term recurrence. Therefore, a prospective study is needed to compare the treatment outcomes of carbapenemtreated and non&#x02013;carbapenem-treated patients diagnosed with UTIs due to ESBL producers underlying VUR. To enable a careful conclusion, large samples and multivariate analysis are required.</p>
<p>If UTIs caused by ESBL-producing bacteria are alleviated through empirical noncarbapenem therapy, switching to carbapenem therapy is a difficult decision for clinicians. To solve this challenge and develop management guidelines, additional large-scale randomized controlled trials are required.</p>
</body>
<back>
<fn-group>
<fn fn-type="conflict"><p>No potential conflicts of interest for this article are reported.</p></fn>
</fn-group>
<ref-list>
<title>References</title>
<ref id="b1-cep-2020-01830">
<label>1</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Lindsey</surname><given-names>K</given-names></name>
<name><surname>Marianella</surname><given-names>H</given-names></name>
<name><surname>John</surname><given-names>DS</given-names></name>
</person-group>
<article-title>The clinical diagnosis and management of urinary tract infections in children and adolescents</article-title>
<source>Paediatr Int Child Health</source>
<year>2017</year>
<volume>37</volume>
<fpage>273</fpage>
<lpage>9</lpage>
</element-citation></ref>
<ref id="b2-cep-2020-01830">
<label>2</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Zorc</surname><given-names>JJ</given-names></name>
<name><surname>Kiddoo</surname><given-names>DA</given-names></name>
<name><surname>Shaw</surname><given-names>KN</given-names></name>
</person-group>
<article-title>Diagnosis and management of pediatric urinary tract infections</article-title>
<source>Clin Microbiol Rev</source>
<year>2005</year>
<volume>18</volume>
<fpage>417</fpage>
<lpage>22</lpage>
</element-citation></ref>
<ref id="b3-cep-2020-01830">
<label>3</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Amy</surname><given-names>JM</given-names></name>
<name><surname>Giswlw</surname><given-names>P</given-names></name>
<name><surname>Johann</surname><given-names>DDP</given-names></name>
</person-group>
<article-title>The role of epidemic resistance plasmids and international high risk clones in the spread of multidrug-resistant Enterobacteriaceae</article-title>
<source>Clin Microbiol Rev</source>
<year>2015</year>
<volume>28</volume>
<fpage>565</fpage>
<lpage>91</lpage>
</element-citation></ref>
<ref id="b4-cep-2020-01830">
<label>4</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Lee</surname><given-names>B</given-names></name>
<name><surname>Kang</surname><given-names>SY</given-names></name>
<name><surname>Kang</surname><given-names>HM</given-names></name>
<name><surname>Yang</surname><given-names>NR</given-names></name>
<name><surname>Kang</surname><given-names>HG</given-names></name>
<name><surname>Ha</surname><given-names>IS</given-names></name>
<etal/>
</person-group>
<article-title>Outcome of antimicrobial therapy of pediatric urinary tract infections caused by extended-spectrum &#x003b2;-lactamase-producing Enterobacteriaceae</article-title>
<source>Infect Chemother</source>
<year>2013</year>
<volume>45</volume>
<fpage>415</fpage>
<lpage>21</lpage>
</element-citation></ref>
<ref id="b5-cep-2020-01830">
<label>5</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Yoshifusa</surname><given-names>A</given-names></name>
<name><surname>Isil</surname><given-names>IE</given-names></name>
<name><surname>Kunihiko</surname><given-names>F</given-names></name>
<name><surname>Hitomi</surname><given-names>W</given-names></name>
<name><surname>Yasuha</surname><given-names>O</given-names></name>
<name><surname>Satoshi</surname><given-names>H</given-names></name>
<etal/>
</person-group>
<article-title>Efficacy of non-carbapenem antibiotics for pediatric patients with first febrile urinary tract infection due to extended-spectrum beta-lactamaseproducing Escherichia coli</article-title>
<source>J Infect Chemother</source>
<year>2017</year>
<volume>23</volume>
<fpage>517</fpage>
<lpage>22</lpage>
</element-citation></ref>
<ref id="b6-cep-2020-01830">
<label>6</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Pranita</surname><given-names>DT</given-names></name>
<name><surname>Jesus</surname><given-names>RB</given-names></name>
</person-group>
<article-title>The use of noncarbapenem &#x003b2;-lactams for the treatment of extended-spectrum &#x003b2;-lactamase infections</article-title>
<source>Clin Infect Dis</source>
<year>2017</year>
<volume>64</volume>
<fpage>972</fpage>
<lpage>80</lpage>
</element-citation></ref>
<ref id="b7-cep-2020-01830">
<label>7</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Guti&#x000e9;rez-Guti&#x000e9;rrez</surname><given-names>B</given-names></name>
<name><surname>Rodr&#x000ed;guez-Bano</surname><given-names>J</given-names></name>
</person-group>
<article-title>Current options for the treatment of infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae in different groups of patients</article-title>
<source>Clin Microbiol Infect</source>
<year>2019</year>
<volume>25</volume>
<fpage>932</fpage>
<lpage>42</lpage>
</element-citation></ref>
<ref id="b8-cep-2020-01830">
<label>8</label>
<element-citation publication-type="book">
<person-group person-group-type="author">
<name><surname>Elder</surname><given-names>JS</given-names></name>
</person-group>
<chapter-title>Vesicoureteral reflux</chapter-title>
<person-group person-group-type="editor">
<name><surname>Kliegman</surname><given-names>RM</given-names></name>
<name><surname>Stanton</surname><given-names>BF</given-names></name>
<name><surname>St. Geme JW</surname><given-names>III</given-names></name>
<name><surname>Schor</surname><given-names>NF</given-names></name>
<name><surname>Behrman</surname><given-names>RE</given-names></name>
</person-group>
<source>Nelson textbook of pediatrics</source>
<edition>21st ed</edition>
<publisher-loc>Philadelphia (PA)</publisher-loc>
<publisher-name>Elsevier</publisher-name>
<year>2019</year>
<fpage>2796</fpage>
<lpage>800</lpage>
</element-citation></ref></ref-list>
<sec sec-type="display-objects">
<title>Figure</title>
<fig id="f1-cep-2020-01830" position="float">
<label>Fig. 1.</label><caption><p>Classification of patients according to immune status, severity at presentation, source of infection, and treatment options for infections caused by extended-spectrum β-lactamase–producing <italic>Enterobacteriaceae</italic> by group.&#x0005b;<xref ref-type="bibr" rid="b7-cep-2020-01830">7</xref>&#x0005d; <sup>a)</sup>Severely immunocompromised: neutropenia (&#x0003c;500/µL), leukemia, lymphoma, HIV infection with &#x0003c;200 CD4/µL, solid organ or hematopoietic stem cell transplantation, cytotoxic chemotherapy, steroids (15 mg of prednisone daily for >2 weeks); <sup>b)</sup>Severe: Pitt score ≥4, Acute Physiology and Chronic Health Evaluation II score > 10, intensive care unit admission, and presentation with severe sepsis or septic shock; <sup>c)</sup> High risk: high-inoculum infections, drainage impossible or inadequate (e.g., pneumonia, endocarditis, inadequately drained deepseated infections); <sup>d)</sup>Intermediate risk: not high or low risk; <sup>e)</sup>Low risk: urinary tract infection with no or a released obstruction.</p></caption>
<graphic xlink:href="cep-2020-01830f1.tif"/></fig>
</sec>
</back></article>