<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1d1 20130915//EN" "http://jats.nlm.nih.gov/publishing/1.1d1/JATS-journalpublishing1.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" article-type="research-article" xml:lang="en">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">SAJID</journal-id>
<journal-title-group>
<journal-title>Southern African Journal of Infectious Diseases</journal-title>
</journal-title-group>
<issn pub-type="ppub">2312-0053</issn>
<issn pub-type="epub">2313-1810</issn>
<publisher>
<publisher-name>AOSIS</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">SAJID-40-689</article-id>
<article-id pub-id-type="doi">10.4102/sajid.v40i1.689</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Research</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Type and antibiotic susceptibility of bacteria cultured in paediatric acute appendicitis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6422-9272</contrib-id>
<name>
<surname>Brits</surname>
<given-names>Elizabeth</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0009-0000-8154-4621</contrib-id>
<name>
<surname>Kruger</surname>
<given-names>Estie</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0009-0004-1398-1271</contrib-id>
<name>
<surname>Fivaz</surname>
<given-names>Karlize</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0009-0004-3221-3227</contrib-id>
<name>
<surname>Oosthuizen</surname>
<given-names>Koot</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0009-0008-6295-2062</contrib-id>
<name>
<surname>Joubert</surname>
<given-names>Mariska</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0009-0007-1891-6067</contrib-id>
<name>
<surname>van Pletzen</surname>
<given-names>Petro-Mari</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0009-0006-0338-913X</contrib-id>
<name>
<surname>Roux</surname>
<given-names>Ronelle</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0009-0002-9304-8259</contrib-id>
<name>
<surname>Fourie</surname>
<given-names>Tahlita</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0009-0002-8292-7987</contrib-id>
<name>
<surname>van Aswegen</surname>
<given-names>Trewhella</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1062-0417</contrib-id>
<name>
<surname>Sempa</surname>
<given-names>Joseph B.</given-names>
</name>
<xref ref-type="aff" rid="AF0002">2</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5868-181X</contrib-id>
<name>
<surname>le Grange</surname>
<given-names>Susanna</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<aff id="AF0001"><label>1</label>Department of Surgery, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa</aff>
<aff id="AF0002"><label>2</label>Department of Biostatistics, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa</aff>
</contrib-group>
<author-notes>
<corresp id="cor1"><bold>Corresponding author:</bold> Elizabeth Brits, <email xlink:href="britse@ufs.ac.za">britse@ufs.ac.za</email></corresp>
</author-notes>
<pub-date pub-type="epub"><day>28</day><month>02</month><year>2025</year></pub-date>
<pub-date pub-type="collection"><year>2025</year></pub-date>
<volume>40</volume>
<issue>1</issue>
<elocation-id>689</elocation-id>
<history>
<date date-type="received"><day>13</day><month>09</month><year>2024</year></date>
<date date-type="accepted"><day>23</day><month>12</month><year>2024</year></date>
</history>
<permissions>
<copyright-statement>&#x00A9; 2025. The Authors</copyright-statement>
<copyright-year>2025</copyright-year>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
<license-p>Licensee: AOSIS. This work is licensed under the Creative Commons Attribution License.</license-p>
</license>
</permissions>
<abstract>
<sec id="st1">
<title>Background</title>
<p>Studying the microbial profile and their antibiotic resistance in paediatric appendicitis is essential for tracking susceptibility, guiding treatment choices and ensuring effectiveness. Understanding variations in therapies can improve outcomes and reduce complications. Despite its importance, limited research has been conducted in South Africa on microbial profiles and antibiotic resistance in paediatric appendicitis.</p>
</sec>
<sec id="st2">
<title>Objectives</title>
<p>To identify bacteria cultured from pus specimens obtained from paediatric patients with acute appendicitis and determine their antibiotic susceptibility.</p>
</sec>
<sec id="st3">
<title>Method</title>
<p>This was a prospective case series of children aged 13 years and younger, who had appendectomies for acute appendicitis. Data were collected via REDCap and analysed using R software. Pus swabs were obtained for microscopy, culture and sensitivity of organisms isolated.</p>
</sec>
<sec id="st4">
<title>Results</title>
<p>The study comprised 20 patients, of whom 12 (60&#x0025;) were male. Most cases (<italic>n</italic> = 17; 85&#x0025;) were complicated appendicitis. <italic>Escherichia coli</italic> was the most prevalent bacterial species isolated, accounting for 60&#x0025; of cases, while no bacterial growth was observed in 30&#x0025; of cases. All the isolates (100&#x0025;) were susceptible to cefepime, gentamicin, amikacin, ertapenem, imipenem and meropenem, while high sensitivity rates of 92.9&#x0025; were found for ciprofloxacin, ceftazidime and piperacillin-tazobactam. Short-term complications (predominantly surgical site infections) were present in 6 patients (30&#x0025;).</p>
</sec>
<sec id="st5">
<title>Conclusion</title>
<p><italic>Escherichia coli</italic> was the most common bacterium in paediatric acute appendicitis, with all isolates sensitive to ciprofloxacin.</p>
</sec>
<sec id="st6">
<title>Contribution</title>
<p>Regional monitoring and research are useful to adapt protocols and combat increasing antibiotic resistance.</p>
</sec>
</abstract>
<kwd-group>
<kwd>acute appendicitis</kwd>
<kwd>microbe</kwd>
<kwd>antibiotic sensitivity</kwd>
<kwd>paediatric</kwd>
<kwd>resistance</kwd>
</kwd-group>
<funding-group>
<funding-statement><bold>Funding information</bold> The authors received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.</funding-statement>
</funding-group>
</article-meta>
</front>
<body>
<sec id="s0001">
<title>Introduction</title>
<p>Acute appendicitis, the leading cause of emergency surgery worldwide, is a common and severe paediatric condition that requires urgent diagnosis and treatment to prevent severe complications such as perforation and peritonitis.<sup><xref ref-type="bibr" rid="CIT0001">1</xref>,<xref ref-type="bibr" rid="CIT0002">2</xref>,<xref ref-type="bibr" rid="CIT0003">3</xref>,<xref ref-type="bibr" rid="CIT0004">4</xref></sup> Symptomatology includes abdominal pain, fever and vomiting,<sup><xref ref-type="bibr" rid="CIT0005">5</xref></sup> and the diagnosis is confirmed with imaging, mainly ultrasound and/or computed tomography.<sup><xref ref-type="bibr" rid="CIT0005">5</xref>,<xref ref-type="bibr" rid="CIT0006">6</xref></sup> Treatment usually involves an appendectomy, either laparoscopic or open. Postoperative care focuses on pain management and minimising complications.<sup><xref ref-type="bibr" rid="CIT0005">5</xref>,<xref ref-type="bibr" rid="CIT0006">6</xref></sup></p>
<p>The appendiceal microbiome plays a crucial role in the pathogenesis of acute appendicitis.<sup><xref ref-type="bibr" rid="CIT0007">7</xref>,<xref ref-type="bibr" rid="CIT0008">8</xref></sup> Age, environment, diet and antibiotic use can disrupt this microbiome, increasing the risk of appendicitis.<sup><xref ref-type="bibr" rid="CIT0009">9</xref>,<xref ref-type="bibr" rid="CIT0010">10</xref></sup> Recent studies suggested that microbial dysbiosis in the appendix may trigger inflammation, leading to acute appendicitis.<sup><xref ref-type="bibr" rid="CIT0011">11</xref>,<xref ref-type="bibr" rid="CIT0012">12</xref>,<xref ref-type="bibr" rid="CIT0013">13</xref>,<xref ref-type="bibr" rid="CIT0014">14</xref></sup> Microbial shifts may lead to new therapies to restore a healthy microbiome and prevent appendicitis.<sup><xref ref-type="bibr" rid="CIT0013">13</xref>,<xref ref-type="bibr" rid="CIT0015">15</xref></sup> Probiotics and dietary changes show promise to reduce the risk in vulnerable groups. Genetic research could improve tailored treatments. Understanding how these factors interact with microbes is key to developing prevention strategies targeting genetics and lifestyle. Integrating this research into public health efforts on gut health and its link to appendicitis is crucial.<sup><xref ref-type="bibr" rid="CIT0013">13</xref>,<xref ref-type="bibr" rid="CIT0015">15</xref></sup></p>
<p>Identifying microorganisms cultured in association with acute appendicitis and their antibiotic sensitivity is an important component of effective treatment. Targeted antimicrobial therapy reduces complications and limits broad-spectrum antibiotic use.<sup><xref ref-type="bibr" rid="CIT0016">16</xref></sup> With increasing antibiotic resistance, region-specific data are essential, as empiric treatment can lead to ineffective therapies and higher costs.<sup><xref ref-type="bibr" rid="CIT0017">17</xref>,<xref ref-type="bibr" rid="CIT0018">18</xref></sup> As non-operative antibiotic management gains popularity, understanding local resistance patterns becomes even more important.<sup><xref ref-type="bibr" rid="CIT0003">3</xref>,<xref ref-type="bibr" rid="CIT0019">19</xref>,<xref ref-type="bibr" rid="CIT0020">20</xref></sup> This approach enhances antibiotic stewardship and improves treatment outcomes.<sup><xref ref-type="bibr" rid="CIT0001">1</xref>,<xref ref-type="bibr" rid="CIT0018">18</xref>,<xref ref-type="bibr" rid="CIT0021">21</xref></sup></p>
<p>Limited information is available on the microorganisms cultured in acute appendicitis and their antibiotic susceptibility in the South African paediatric population, with no data available from our own unit.<sup><xref ref-type="bibr" rid="CIT0022">22</xref></sup> Given the increasing challenge of antibiotic resistance, region-specific research is vital. This study addresses this need by identifying the microorganisms isolated in acute appendicitis in children under 13 years of age in central South Africa, and evaluating the antibiotic susceptibility patterns of these organisms. The study was conducted from July 2023 to November 2023 aiming to provide data to inform more effective treatment strategies based on the most recent antibiotic susceptibility profiles, enhance patient care, and contribute to the global effort against antibiotic resistance.</p>
</sec>
<sec id="s0002">
<title>Methods</title>
<sec id="s20003">
<title>Study sample and measurement</title>
<p>This prospective descriptive study involved 20 patients under 13 years of age who underwent an appendectomy for acute appendicitis at the Paediatric Surgical Department in Pelonomi Tertiary Hospital, Bloemfontein, from July 2023 to November 2023. The standard empiric treatment for acute appendicitis during the study period was amoxicillin-clavulanic acid adjusted to intraoperative pus swab microscopy, culture and sensitivity (MCS) results. Patients treated non-operatively and those with missing microbiology test results were excluded. All patients were referred from peripheral hospitals or clinics, and no data pertaining to initial antibiotics or stat treatment provided by the referral institutions were documented. A pus swab was taken during the appendectomy for MCS to determine the identified organisms and antimicrobial drug sensitivities. Agar plates were also incubated under anaerobic conditions for the isolation of potential anaerobes. No blood cultures were sent for analysis. All methods were performed according to the standard operating procedures (SOPs) of the local medical microbiology laboratory. Basic demographic information, appendicitis classification,<sup><xref ref-type="bibr" rid="CIT0023">23</xref></sup> and MCS results were captured using REDCap (REDCap Consortium; Nashville, TN, US), an electronic data capturing tool hosted by the University of the Free State. Appendicitis is uncomplicated when confined to the appendix without perforation, abscess formation, or phlegmon, managed with appendectomy or occasionally antibiotics. Complicated cases involve perforation, abscess formation, or phlegmon, requiring surgery and prolonged antibiotics.<sup><xref ref-type="bibr" rid="CIT0023">23</xref>,<xref ref-type="bibr" rid="CIT0024">24</xref></sup></p>
</sec>
<sec id="s20004">
<title>Data analysis</title>
<p>The Department of Biostatistics, Faculty of Health Sciences, UFS analysed the data using the statistical analysis software R (The R Foundation; Vienna, Austria).<sup><xref ref-type="bibr" rid="CIT0025">25</xref></sup> The results were summarised as frequencies and percentages.</p>
</sec>
<sec id="s20005">
<title>Ethical considerations</title>
<p>Ethical approval was obtained from the Health Sciences Research Ethics Committee (HSREC) of the University of the Free State (reference no. UFS-HSD2023/0465/2908) and the Free State Province Department of Health. Informed consent was obtained from the parents and/or legal guardians and assent from patients old enough to understand. Patient information was anonymised, and no identifying details were documented. Data were stored on REDCap, which was password-protected.</p>
</sec>
</sec>
<sec id="s0006">
<title>Results</title>
<sec id="s20007">
<title>Study population</title>
<p>The study comprised 20 patients, of whom 12 (60&#x0025;) were male. The ages ranged from 4 years to 12 years, with a mean of 8 years. All the surgical procedures were open appendectomies performed via a Lanz incision. Most patients had complicated appendicitis (<italic>n</italic> = 17; 85&#x0025;). Short-term complications occurred in 6 patients (30&#x0025;), including surgical site infection (<italic>n</italic> = 4), intra-abdominal pus collection (<italic>n</italic> = 1) and adhesive bowel obstruction (<italic>n</italic> = 1). There were no mortalities, and all patients were discharged from the hospital.</p>
</sec>
<sec id="s20008">
<title>Isolated bacterial species</title>
<p><xref ref-type="table" rid="T0001">Table 1</xref> shows the number of isolated bacteria in males and females. <italic>Escherichia coli</italic> was the most prevalent (<italic>n</italic> = 12; 60&#x0025;). No bacterial growth was observed in 30&#x0025; (<italic>n</italic> = 6) of cases. An extended-spectrum &#x03B2;-lactamase (ESBL) producing isolate (<italic>Enterobacter cloacae</italic> complex) was cultured from the pus specimen of one patient (<italic>n</italic> = 1/20; 5&#x0025;). Bacteria isolated in the complicated appendicitis cases were <italic>E.coli</italic> (<italic>n</italic> = 4), <italic>Enterobacter cloacae</italic> complex (<italic>n</italic> = 1), and <italic>Pseudomonas aeruginosa</italic> (<italic>n</italic> = 1); no growth was observed in four cases.</p>
<table-wrap id="T0001">
<label>TABLE 1</label>
<caption><p>Bacterial species isolated from paediatric patients with acute appendicitis (<italic>N</italic> = 20).</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th valign="top" align="left" rowspan="2">Species</th>
<th valign="top" align="center" rowspan="2">Total (<italic>N</italic>)</th>
<th valign="top" align="center" colspan="2">Male (<italic>N</italic> = 12)<hr/></th>
<th valign="top" align="center" colspan="2">Female (<italic>N</italic> = 8)<hr/></th>
<th valign="top" align="center" rowspan="2">Total (%)</th>
</tr>
<tr>
<th valign="top" align="center"><italic>n</italic></th>
<th valign="top" align="center">&#x0025;</th>
<th valign="top" align="center"><italic>n</italic></th>
<th valign="top" align="center">&#x0025;</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left"><italic>Escherichia coli</italic></td>
<td align="center">12</td>
<td align="center">6</td>
<td align="center">50.0</td>
<td align="center">6</td>
<td align="center">75.0</td>
<td align="center">60.0</td>
</tr>
<tr>
<td align="left"><italic>Pseudomonas aeruginosa</italic></td>
<td align="center">1</td>
<td align="center">1</td>
<td align="center">8.3</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">5.0</td>
</tr>
<tr>
<td align="left"><italic>Enterobacter cloacae</italic> complex</td>
<td align="center">1</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">1</td>
<td align="center">12.5</td>
<td align="center">5.0</td>
</tr>
<tr>
<td align="left">No growth</td>
<td align="center">6</td>
<td align="center">5</td>
<td align="center">41.7</td>
<td align="center">1</td>
<td align="center">12.5</td>
<td align="center">30.0</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s20009">
<title>Antibiotic susceptibility</title>
<p><xref ref-type="table" rid="T0002">Table 2</xref> shows the antibiotic sensitivity and resistance of the isolated bacteria (<italic>n</italic> = 14). All isolates (<italic>n</italic> = 14; 100&#x0025;) were susceptible to cefepime, amikacin, imipenem and meropenem, followed by a 92.9&#x0025; (<italic>n</italic> = 13) sensitivity rate to ciprofloxacin, ceftazidime, gentamicin, piperacillin-tazobactam, ertapenem, colistin and tigecycline.</p>
<table-wrap id="T0002">
<label>TABLE 2</label>
<caption><p>Antibiotic susceptibility and resistance of all bacteria isolated from acute appendicitis pus swabs against the drugs listed (<italic>N</italic> = 14).</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th valign="top" align="left" rowspan="3">Antimicrobial agent</th>
<th valign="top" align="center" colspan="7">Profile of isolates cultured<hr/></th>
</tr>
<tr>
<th valign="top" align="center" colspan="2">Susceptible<hr/></th>
<th valign="top" align="center" colspan="2">Resistant<hr/></th>
<th valign="top" align="center" colspan="2">Intermediate<hr/></th>
<th valign="top" align="center" rowspan="2">Not tested (<italic>n</italic>)</th>
</tr>
<tr>
<th valign="top" align="center"><italic>n</italic></th>
<th valign="top" align="center">&#x0025;</th>
<th valign="top" align="center"><italic>n</italic></th>
<th valign="top" align="center">&#x0025;</th>
<th valign="top" align="center"><italic>n</italic></th>
<th valign="top" align="center">&#x0025;</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left">Trimethoprim-sulfamethoxazole</td>
<td align="center">9</td>
<td align="center">64.3</td>
<td align="center">5</td>
<td align="center">35.7</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Ampicillin and/or amoxicillin</td>
<td align="center">7</td>
<td align="center">53.8</td>
<td align="center">6</td>
<td align="center">46.2</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">1</td>
</tr>
<tr>
<td align="left">Amoxicillin-clavulanic acid</td>
<td align="center">10</td>
<td align="center">76.9</td>
<td align="center">3</td>
<td align="center">23.1</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">1</td>
</tr>
<tr>
<td align="left">Nitrofurantoin</td>
<td align="center">12</td>
<td align="center">85.7</td>
<td align="center">1</td>
<td align="center">7.1</td>
<td align="center">1</td>
<td align="center">7.1</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Ciprofloxacin</td>
<td align="center">13</td>
<td align="center">92.9</td>
<td align="center">1</td>
<td align="center">7.1</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Cefuroxime (parenteral)</td>
<td align="center">12</td>
<td align="center">85.7</td>
<td align="center">2</td>
<td align="center">14.3</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Cefuroxime (oral)</td>
<td align="center">11</td>
<td align="center">78.6</td>
<td align="center">2</td>
<td align="center">14.3</td>
<td align="center">1</td>
<td align="center">7.1</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Cefoxitin</td>
<td align="center">12</td>
<td align="center">85.7</td>
<td align="center">2</td>
<td align="center">14.3</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Cefotaxime and/or ceftriaxone</td>
<td align="center">12</td>
<td align="center">85.7</td>
<td align="center">2</td>
<td align="center">14.3</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Ceftazidime</td>
<td align="center">13</td>
<td align="center">92.9</td>
<td align="center">1</td>
<td align="center">7.1</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Cefepime</td>
<td align="center">14</td>
<td align="center">100.0</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Gentamicin</td>
<td align="center">13</td>
<td align="center">100.0</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">1</td>
</tr>
<tr>
<td align="left">Amikacin</td>
<td align="center">14</td>
<td align="center">100.0</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Piperacillin-tazobactam</td>
<td align="center">13</td>
<td align="center">92.9</td>
<td align="center">1</td>
<td align="center">7.1</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Ertapenem</td>
<td align="center">13</td>
<td align="center">100.0</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">1</td>
</tr>
<tr>
<td align="left">Imipenem</td>
<td align="center">14</td>
<td align="center">100.0</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Meropenem</td>
<td align="center">14</td>
<td align="center">100.0</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Tigecycline</td>
<td align="center">13</td>
<td align="center">92.9</td>
<td align="center">1</td>
<td align="center">7.1</td>
<td align="center">0</td>
<td align="center">0.0</td>
<td align="center">-</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p>Note: The susceptibility profile for specific bacterial isolates is shown in <xref ref-type="table" rid="T0003">Table 3</xref>. Of the 12 <italic>Escherichia coli</italic> isolates, 5 (41.7&#x0025;) were resistant to ampicillin and/or amoxicillin, followed by trimethoprim-sulfamethoxazole (<italic>n</italic> = 4; 33.3&#x0025;), amoxicillin-clavulanic acid (<italic>n</italic> = 2; 16.7&#x0025;) and ciprofloxacin (<italic>n</italic> = 1; 8.3&#x0025;). <italic>Pseudomonas aeruginosa</italic> and the <italic>Enterobacter cloacae</italic> complex both showed resistance to the cephalosporins.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="T0003">
<label>TABLE 3</label>
<caption><p>Susceptibility profiles for specific bacterial isolates cultured from pus swabs of children with acute appendicitis.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th valign="top" align="left" rowspan="2">Organism</th>
<th valign="top" align="center" rowspan="2">Total (<italic>N</italic>)</th>
<th valign="top" align="center" colspan="3">Susceptible<hr/></th>
<th valign="top" align="center" colspan="3">Resistant<hr/></th>
<th valign="top" align="center" colspan="3">Intermediate<hr/></th>
</tr>
<tr>
<th valign="top" align="center">Agent</th>
<th valign="top" align="center"><italic>n</italic></th>
<th valign="top" align="center">&#x0025;</th>
<th valign="top" align="center">Agent</th>
<th valign="top" align="center"><italic>n</italic></th>
<th valign="top" align="center">&#x0025;</th>
<th valign="top" align="center">Agent</th>
<th valign="top" align="center"><italic>n</italic></th>
<th valign="top" align="center">&#x0025;</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="17"><italic>Escherichia coli</italic></td>
<td align="left" rowspan="17">12</td>
<td align="left">Trimethoprim-sulfamethoxazole</td>
<td align="center">8</td>
<td align="center">-</td>
<td align="left">Trimethoprim-sulfamethoxazole</td>
<td align="center">4</td>
<td align="center">33.3</td>
<td align="left">Cefuroxime (oral)</td>
<td align="center">1</td>
<td align="center">8.3</td>
</tr>
<tr>
<td align="left">Ampicillin and/or amoxicillin</td>
<td align="center">7</td>
<td align="center">58.3</td>
<td align="left">Ampicillin and/or amoxicillin</td>
<td align="center">5</td>
<td align="center">41.7</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Nitrofurantoin</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="left">Amoxicillin-clavulanic acid</td>
<td align="center">2</td>
<td align="center">16.7</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Ciprofloxacin</td>
<td align="center">11</td>
<td align="center">92.7</td>
<td align="left">Ciprofloxacin</td>
<td align="center">1</td>
<td align="center">8.3</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Cefuroxime (parenteral)</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Cefuroxime (oral)</td>
<td align="center">11</td>
<td align="center">92.7</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Cefoxitin</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Cefotaxime and/or ceftriaxone</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Ceftazidime</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Cefepime</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Gentamicin</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Amikacin</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Piperacillin-tazobactam</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Ertapenem</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Imipenem</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Meropenem</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Tigecycline</td>
<td align="center">12</td>
<td align="center">100.0</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left" rowspan="8"><italic>Pseudomonas aeruginosa</italic></td>
<td align="center" rowspan="8">1</td>
<td align="left">Ciprofloxacin</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Trimethoprim-sulfamethoxazole</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Ceftazidime</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Ampicillin and/or amoxicillin</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Cefepime</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Nitrofurantoin</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Amikacin</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Cefuroxime (parenteral)</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Piperacillin-tazobactam</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Cefuroxime (oral)</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Imipenem</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Cefoxitin</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Meropenem</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Cefotaxime and/or ceftriaxone</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Tigecycline</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left" rowspan="9"><italic>Enterobacter cloacae</italic> complex</td>
<td align="center" rowspan="9">1</td>
<td align="left">Trimethoprim-sulfamethoxazole</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Amoxicillin-clavulanic acid</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Nitrofurantoin</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Ciprofloxacin</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Cefuroxime (parenteral)</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Cefepime</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Cefuroxime (oral)</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Gentamicin</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Cefoxitin</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Amikacin</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Cefotaxime and/or ceftriaxone</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Ertapenem</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Ceftazidime</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Imipenem</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="left">Piperacillin-tazobactam</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Meropenem</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
<tr>
<td align="left">Tigecycline</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
<td align="center">-</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>In six of the cases (42.9&#x0025;), the bacteria showed resistance to ampicillin and/or amoxicillin, in five cases (35.7&#x0025;) to trimethoprim-sulfamethoxazole and in three cases (21.4&#x0025;) to amoxicillin-clavulanic acid. As shown in <xref ref-type="table" rid="T0002">Table 2</xref>, no resistance was observed against cefepime, gentamicin, amikacin, ertapenem, imipenem, meropenem and colistin.</p>
</sec>
</sec>
<sec id="s0010">
<title>Discussion</title>
<sec id="s20011">
<title>Demographic characteristics</title>
<p>Our research showed that more cases of appendicitis occurred in males, with a male-to-female ratio of 1.5:1. This finding was consistent with several other South African studies on paediatric appendicitis, which consistently reported a male predominance.<sup><xref ref-type="bibr" rid="CIT0022">22</xref>,<xref ref-type="bibr" rid="CIT0026">26</xref>,<xref ref-type="bibr" rid="CIT0027">27</xref>,<xref ref-type="bibr" rid="CIT0028">28</xref></sup> The male majority supports underlying biological and environmental determinants. The mean age in our study was 8 years, matching previous findings.<sup><xref ref-type="bibr" rid="CIT0022">22</xref>,<xref ref-type="bibr" rid="CIT0026">26</xref>,<xref ref-type="bibr" rid="CIT0027">27</xref>,<xref ref-type="bibr" rid="CIT0028">28</xref></sup> This could indicate a constant age for paediatric appendicitis in South Africa.</p>
</sec>
<sec id="s20012">
<title>Microbial profile</title>
<p>Our research showed that there was no difference in species isolation between male and female patients. <italic>Escherichia coli</italic> was the most common organism, representing 85.7&#x0025; of isolates. This was consistent with some studies (67&#x0025; &#x2013; 80&#x0025;),<sup><xref ref-type="bibr" rid="CIT0016">16</xref>,<xref ref-type="bibr" rid="CIT0021">21</xref>,<xref ref-type="bibr" rid="CIT0029">29</xref>,<xref ref-type="bibr" rid="CIT0030">30</xref></sup> but showed a higher occurrence than others (28&#x0025; &#x2013; 50&#x0025;).<sup><xref ref-type="bibr" rid="CIT0018">18</xref>,<xref ref-type="bibr" rid="CIT0031">31</xref>,<xref ref-type="bibr" rid="CIT0032">32</xref>,<xref ref-type="bibr" rid="CIT0033">33</xref></sup> <italic>Escherichia coli</italic> has been described as a notable cultured organism in appendicitis, indicating a diverse microbial profile in different groups.<sup><xref ref-type="bibr" rid="CIT0034">34</xref></sup> This variation could imply that while <italic>E. coli</italic> is frequently isolated in paediatric acute appendicitis, its prevalence can differ based on location and population characteristics. Therefore, it is essential to consider this organism when prescribing antibiotics.<sup><xref ref-type="bibr" rid="CIT0035">35</xref></sup> Understanding variations in antibiotic therapies can enhance treatment effectiveness, improve patient outcomes, and minimise complications from inappropriate treatment.</p>
<p>In our study, 30&#x0025; <italic>(n</italic> = 6) of cases yielded no positive cultures, including four patients with complicated appendicitis (<italic>n</italic> = 4/6; 66.7&#x0025;). These findings were consistent with recent literature, which reported a 39.2&#x0025; rate of culture negativity in uncomplicated appendicitis cases.<sup><xref ref-type="bibr" rid="CIT0036">36</xref></sup> The absence of growth in some cases might be because of the nature of the infection (less severe cases) or the effectiveness of prior empiric antibiotic therapy, although not documented in this study.<sup><xref ref-type="bibr" rid="CIT0021">21</xref></sup> This highlights the complexity of appendicitis and the limitations of microbiological testing in predicting infectious outcomes.<sup><xref ref-type="bibr" rid="CIT0036">36</xref></sup> The findings underscore the importance of comprehensive clinical evaluation and using the most susceptible empiric antibiotic therapy for individual units to manage paediatric appendicitis effectively.</p>
</sec>
<sec id="s20013">
<title>Antibiotic sensitivity</title>
<p>All 14 organisms isolated from these patients were susceptible to cefepime, amikacin, imipenem, meropenem, ertapenem and gentamicin, including <italic>E. coli</italic>, the most common isolate.<sup><xref ref-type="bibr" rid="CIT0016">16</xref>,<xref ref-type="bibr" rid="CIT0018">18</xref>,<xref ref-type="bibr" rid="CIT0029">29</xref>,<xref ref-type="bibr" rid="CIT0030">30</xref>,<xref ref-type="bibr" rid="CIT0032">32</xref>,<xref ref-type="bibr" rid="CIT0033">33</xref>,<xref ref-type="bibr" rid="CIT0037">37</xref>,<xref ref-type="bibr" rid="CIT0038">38</xref></sup> Other paediatric studies identified cefuroxime-metronidazole and ampicillin-sulbactam combinations<sup><xref ref-type="bibr" rid="CIT0039">39</xref></sup> as their most effective antibiotics.</p>
<p>Our study found an 85.7&#x0025; sensitivity rate for cefotaxime-ceftriaxone, showing strong effectiveness, consistent with other studies.<sup><xref ref-type="bibr" rid="CIT0018">18</xref>,<xref ref-type="bibr" rid="CIT0032">32</xref></sup> Combining ceftriaxone with metronidazole can be more effective than cefoxitin alone in treating uncomplicated appendicitis and reducing postoperative complications.<sup><xref ref-type="bibr" rid="CIT0040">40</xref>,<xref ref-type="bibr" rid="CIT0041">41</xref></sup> Gentamicin had a 100&#x0025; sensitivity rate, higher than the 68&#x0025; &#x2013; 82&#x0025; range reported for aminoglycosides.<sup><xref ref-type="bibr" rid="CIT0018">18</xref>,<xref ref-type="bibr" rid="CIT0030">30</xref>,<xref ref-type="bibr" rid="CIT0032">32</xref>,<xref ref-type="bibr" rid="CIT0038">38</xref></sup> However, recent paediatric studies do not mention gentamicin.<sup><xref ref-type="bibr" rid="CIT0039">39</xref>,<xref ref-type="bibr" rid="CIT0040">40</xref></sup> The adverse effects associated with gentamicin, such as nephrotoxicity and ototoxicity, may limit its use.<sup><xref ref-type="bibr" rid="CIT0042">42</xref></sup> Clinicians should regularly monitor peak and trough levels when prescribing aminoglycosides to reduce the risk of adverse effects.<sup><xref ref-type="bibr" rid="CIT0043">43</xref></sup> Aminoglycosides are also ineffective against anaerobes.<sup><xref ref-type="bibr" rid="CIT0044">44</xref>,<xref ref-type="bibr" rid="CIT0045">45</xref></sup> Therefore, adding metronidazole to the regimen in acute appendicitis cases is advisable,<sup><xref ref-type="bibr" rid="CIT0040">40</xref>,<xref ref-type="bibr" rid="CIT0041">41</xref></sup> even though no anaerobes were isolated in this study with a small sample size.</p>
<p>In our study, susceptibility to cefuroxime was observed in 78.6&#x0025; of the bacterial isolates for oral products, and 85.7&#x0025; for parenteral preparations, aligning with broader trends in susceptibility to this cephalosporin observed in recent studies.<sup><xref ref-type="bibr" rid="CIT0018">18</xref>,<xref ref-type="bibr" rid="CIT0021">21</xref></sup> Some Enterobacteriaceae produce ESBLs, conferring resistance to most &#x03B2;-lactam antibiotics, including new-generation cephalosporins. This may contribute to the cefuroxime sensitivity profile reported in the literature.<sup><xref ref-type="bibr" rid="CIT0021">21</xref></sup> It underscores the need for ongoing surveillance and adaptation of antibiotic regimens in clinical practice.</p>
<p>Our findings emphasise the necessity of customising antibiotic protocols based on local resistance patterns and clinical situations to improve outcomes. Continuous surveillance and region-specific research are essential for adjusting treatment protocols, especially given the global increase in antibiotic resistance.<sup><xref ref-type="bibr" rid="CIT0017">17</xref></sup> This approach enhances patient care and contributes to the global effort to promote antibiotic stewardship.</p>
</sec>
<sec id="s20014">
<title>Antibiotic resistance</title>
<p>We found 42.9&#x0025; resistance rates for ampicillin-amoxicillin, 35.7&#x0025; for trimethoprim-sulfamethoxazole and 21.4&#x0025; for amoxicillin-clavulanic acid, making them fairly unreliable as first-line treatment for appendicitis in our unit. The rates for ampicillin-amoxicillin and trimethoprim-sulfamethoxazole resistance are higher than those reported in recent studies (15&#x0025; &#x2013; 32&#x0025;),<sup><xref ref-type="bibr" rid="CIT0016">16</xref>,<xref ref-type="bibr" rid="CIT0039">39</xref>,<xref ref-type="bibr" rid="CIT0040">40</xref></sup> and reflect global concerns about increasing antibiotic resistance and the need for region-specific research to guide treatment.<sup><xref ref-type="bibr" rid="CIT0017">17</xref>,<xref ref-type="bibr" rid="CIT0030">30</xref>,<xref ref-type="bibr" rid="CIT0033">33</xref></sup> The findings highlight the urgent need to determine alternative therapies and improved stewardship programmes to address resistance trends.</p>
<p>Cefoxitin showed a 14.3&#x0025; resistance rate, which was not mentioned in recent paediatric appendicitis studies.<sup><xref ref-type="bibr" rid="CIT0018">18</xref>,<xref ref-type="bibr" rid="CIT0039">39</xref>,<xref ref-type="bibr" rid="CIT0040">40</xref></sup> The resistance rate of 14.3&#x0025; for cefotaxime and/or ceftriaxone was consistent with observed ranges for other antibiotics in paediatric appendicitis.<sup><xref ref-type="bibr" rid="CIT0039">39</xref>,<xref ref-type="bibr" rid="CIT0040">40</xref></sup> Because of this resistance rate, we will not consider these two antibiotics as empiric treatment in our setting. This suggests the need to evaluate the effectiveness of different antibiotic agents in paediatric populations and use combination therapies to help overcome resistance and improve patient outcomes.</p>
<p>It is generally advised to avoid using antibiotics with resistance rates between 10&#x0025; and 20&#x0025;.<sup><xref ref-type="bibr" rid="CIT0030">30</xref></sup> Continuous monitoring of resistance patterns, adherence to guidelines and regular culture testing are crucial for tracking susceptibility, guiding antibiotic choices and ensuring effective treatments.</p>
</sec>
<sec id="s20015">
<title>Study limitations</title>
<p>The study has several limitations. Data were collected from a single tertiary public sector hospital, with a small sample size and short time period of the study, limiting its generalisability of the findings. The use of empiric antibiotic treatment was not documented from either referring institutions or our own pre-operative regimens potentially biasing our culture results. This study can serve as a pilot study to more extensive research in our unit. Despite these limitations, the results align with previous studies, and antibiotic treatment regimens can be adjusted for the unit.</p>
</sec>
<sec id="s20016">
<title>Recommendations</title>
<p>To optimise treatment outcomes, we recommend that empiric antibiotic treatment for acute appendicitis in our unit be changed to the local susceptibility patterns detected in this study. Intravenous ciprofloxacin and metronidazole can be used and then tailored to the susceptibility of the bacterial isolates based on the MCS results of the swabs taken intraoperatively. Given the high rate of susceptibility to ciprofloxacin, it can be used in empiric antibiotic therapy in acute appendicitis. Ciprofloxacin may cause adverse effects in 5&#x0025; &#x2013; 15&#x0025; of paediatric patients,<sup><xref ref-type="bibr" rid="CIT0046">46</xref></sup> although these events (musculoskeletal effects, abnormal liver functions, nausea and vomiting, and changes in white cell counts) are usually reversible<sup><xref ref-type="bibr" rid="CIT0047">47</xref></sup> with no long-term sequelae. Cefepime also had a 100&#x0025; susceptibility but will not be recommended for empiric treatment to preserve its effectiveness against <italic>P. aeruginosa, Serratia</italic> or <italic>Enterobacter</italic> infections in general. Future and ongoing regular culture testing should be conducted in all units to track susceptibility and guide antibiotic selection to ensure effective treatment of acute appendicitis in children.</p>
</sec>
<sec id="s20017">
<title>Rationale for the recommendations</title>
<p>Despite the 100&#x0025; susceptibility in this study, using broad-spectrum antibiotics such as amikacin, imipenem, ertapenem and meropenem is discouraged for uncomplicated acute appendicitis because of stewardship concerns and potential drug resistance.<sup><xref ref-type="bibr" rid="CIT0048">48</xref></sup> The Surgical Infection Society (SIS) guidelines recommend reserving these drugs for high-risk or severe cases and providing education to improved appropriate antibiotic use without adverse outcomes.<sup><xref ref-type="bibr" rid="CIT0048">48</xref></sup> Simpler antibiotic regimens succeed in approximately 60&#x0025; of uncomplicated cases, with outcomes comparable to surgery.<sup><xref ref-type="bibr" rid="CIT0049">49</xref>,<xref ref-type="bibr" rid="CIT0050">50</xref></sup> Overusing potent antibiotics increases risks such as <italic>Clostridium difficile</italic> colitis, resistance, and major complications, reinforcing the importance of careful antibiotic selection.<sup><xref ref-type="bibr" rid="CIT0049">49</xref>,<xref ref-type="bibr" rid="CIT0051">51</xref></sup></p>
<p>Metronidazole targets anaerobic bacteria such as <italic>Bacteroides fragilis</italic>, although not isolated in this study, possibly because of pre-operative antibiotic administration and the small sample size.<sup><xref ref-type="bibr" rid="CIT0052">52</xref>,<xref ref-type="bibr" rid="CIT0053">53</xref>,<xref ref-type="bibr" rid="CIT0054">54</xref></sup> It is cost-effective, can be given orally and reduces hospital costs by about 30&#x0025; in complicated cases.<sup><xref ref-type="bibr" rid="CIT0054">54</xref></sup> It shortens hospital stays by about 1 day<sup><xref ref-type="bibr" rid="CIT0053">53</xref>,<xref ref-type="bibr" rid="CIT0054">54</xref></sup> and helps prevent postoperative infections in severe cases.<sup><xref ref-type="bibr" rid="CIT0055">55</xref></sup> Its pharmacokinetics allow once-daily dosing.<sup><xref ref-type="bibr" rid="CIT0056">56</xref></sup></p>
</sec>
</sec>
<sec id="s0018">
<title>Conclusion</title>
<p><italic>Escherichia coli</italic> was the main bacterium cultured in acute appendicitis, followed by <italic>P. aeruginosa</italic> and the <italic>E. cloacae</italic> complex. Ciprofloxacin was 92.7&#x0025; effective against <italic>E. coli</italic>. High resistance rates to ampicillin-amoxicillin, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole are unreliable as first-line treatments in our unit. Thus, ciprofloxacin and metronidazole are recommended for empiric management in our paediatric population. Metronidazole is recommended to cover potential mixed infections involving anaerobic bacteria, although no anaerobes were cultured in this study. Local resistance patterns should guide tailored antibiotic protocols to reduce broad-spectrum use and complications. Ongoing monitoring and region-specific research are essential for adapting treatment protocols and managing resistance. Further studies are needed to refine protocols, reduce costs and address evolving resistance patterns.</p>
</sec>
</body>
<back>
<ack>
<title>Acknowledgements</title>
<p>The authors would like to thank Dr Daleen Struwig, medical writer and editor, Faculty of Health Sciences, University of the Free State, for technical and editorial preparation of the article.</p>
<sec id="s20019" sec-type="COI-statement">
<title>Competing interests</title>
<p>The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.</p>
</sec>
<sec id="s20020">
<title>Authors&#x2019; contributions</title>
<p>E.K., K.F., K.O., M.J., P.-M.v.P., R.R., T.F., and T.v.A. developed the study protocol, collected the data, and prepared the initial manuscript draft. J.B.S. performed the statistical analysis of data. S.l.G. was the study supervisor. S.l.G. and E.B. suggested the concept, assisted with protocol development, data interpretation, and manuscript preparation, and wrote the article&#x2019;s final draft. E.B., E.K., K.F., K.O., M.J., P.-M.v.P., R.R., T.F., T.v.A., J.B.S., and S.l.G. approved the final version of the article.</p>
</sec>
<sec id="s20021" sec-type="data-availability">
<title>Data availability</title>
<p>The data that support the findings of this study are available from the corresponding author, E.B., upon reasonable request.</p>
</sec>
<sec id="s20022">
<title>Disclaimer</title>
<p>The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of any affiliated agency of the authors.</p>
</sec>
</ack>
<ref-list id="references">
<title>References</title>
<ref id="CIT0001"><label>1</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Da Silva Filho</surname> <given-names>DG</given-names></string-name>, <string-name><surname>De Melo Alexandrino</surname> <given-names>DB</given-names></string-name>, <string-name><surname>Ferreira Junqueira</surname> <given-names>J</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Assessment and surgical management of appendicitis in pediatrics</article-title>. <source>Braz J Implantol Health Sci</source>. <year>2024</year>;<volume>6</volume>(<issue>2</issue>):<fpage>2167</fpage>&#x2013;<lpage>2179</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.36557/2674-8169.2024v6n2p2167-2179">https://doi.org/10.36557/2674-8169.2024v6n2p2167-2179</ext-link></comment></mixed-citation></ref>
<ref id="CIT0002"><label>2</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Ibarra-Guerrero</surname> <given-names>MF</given-names></string-name>, <string-name><surname>Noguera-Echeverr&#x00ED;a</surname> <given-names>AE</given-names></string-name>, <string-name><surname>Mart&#x00ED;nez-Morales</surname> <given-names>MG</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Appendicitis on pediatric patients: Current evidence in diagnosis and treatment</article-title>. <source>Int J Med Sci Clin Res Stud</source>. <year>2023</year>;<volume>3</volume>(<issue>11</issue>):<fpage>2597</fpage>&#x2013;<lpage>2602</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.47191/ijmscrs/v3-i11-10">https://doi.org/10.47191/ijmscrs/v3-i11-10</ext-link></comment></mixed-citation></ref>
<ref id="CIT0003"><label>3</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Demir</surname> <given-names>&#x015E;</given-names></string-name>, <string-name><surname>Mert</surname> <given-names>M</given-names></string-name>, <string-name><surname>K&#x00F6;ksal Yasin</surname> <given-names>Y</given-names></string-name>, <string-name><surname>Kahya</surname> <given-names>MO</given-names></string-name>, <string-name><surname>Demirta&#x015F;</surname> <given-names>O</given-names></string-name></person-group>. <article-title>Importance of pediatric appendicitis scoring system and ultrasonography in the diagnosis of acute appendicitis in children</article-title>. <source>Forbes J Med</source>. <year>2023</year>;<volume>4</volume>(<issue>3</issue>):<fpage>259</fpage>&#x2013;<lpage>264</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.4274/forbes.galenos.2023.48378">https://doi.org/10.4274/forbes.galenos.2023.48378</ext-link></comment></mixed-citation></ref>
<ref id="CIT0004"><label>4</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Vargas-Rodr&#x00ED;guez</surname> <given-names>LJ</given-names></string-name>, <string-name><surname>Barrera-Jerez</surname> <given-names>JF</given-names></string-name>, <string-name><surname>Avila-Avila</surname> <given-names>KA</given-names></string-name>, <string-name><surname>Rodriguez-Mongui</surname> <given-names>DA</given-names></string-name>, <string-name><surname>Munoz-Espinosa</surname> <given-names>BR</given-names></string-name></person-group>. <article-title>Biomarkers of acute appendicitis severity: Diagnostic test study</article-title>. <source>Oncol Treat Discov</source>. <year>2023</year>;<volume>1</volume>(<issue>1</issue>):<fpage>13</fpage>&#x2013;<lpage>22</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.26689/otd.v1i1.4030">https://doi.org/10.26689/otd.v1i1.4030</ext-link></comment></mixed-citation></ref>
<ref id="CIT0005"><label>5</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Dixon</surname> <given-names>F</given-names></string-name>, <string-name><surname>Singh</surname> <given-names>A</given-names></string-name></person-group>. <article-title>Acute appendicitis</article-title>. <source>Surg (Oxf)</source>. <year>2023</year>;<volume>41</volume>(<issue>7</issue>):<fpage>418</fpage>&#x2013;<lpage>425</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.mpsur.2020.03.015">https://doi.org/10.1016/j.mpsur.2020.03.015</ext-link></comment></mixed-citation></ref>
<ref id="CIT0006"><label>6</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Krzyzak</surname> <given-names>M</given-names></string-name>, <string-name><surname>Mulrooney</surname> <given-names>SM</given-names></string-name></person-group>. <article-title>Acute appendicitis review: Background, epidemiology, diagnosis, and treatment</article-title>. <source>Cureus</source>. <year>2020</year>;<volume>12</volume>(<issue>6</issue>):<fpage>e8562</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.7759/cureus.8562">https://doi.org/10.7759/cureus.8562</ext-link></comment></mixed-citation></ref>
<ref id="CIT0007"><label>7</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Fonnes</surname> <given-names>S</given-names></string-name>, <string-name><surname>Mollerup</surname> <given-names>S</given-names></string-name>, <string-name><surname>Paulsen</surname> <given-names>SJ</given-names></string-name>, <string-name><surname>Holzknecht</surname> <given-names>BJ</given-names></string-name>, <string-name><surname>Westh</surname> <given-names>H</given-names></string-name>, <string-name><surname>Rosenberg</surname> <given-names>J</given-names></string-name></person-group>. <article-title>The microbiome of the appendix differs in patients with and without appendicitis: A prospective cohort study</article-title>. <source>Surgery</source>. <year>2024</year>;<volume>175</volume>(<issue>6</issue>):<fpage>1482</fpage>&#x2013;<lpage>1488</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.surg.2024.02.020">https://doi.org/10.1016/j.surg.2024.02.020</ext-link></comment></mixed-citation></ref>
<ref id="CIT0008"><label>8</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Sal&#x00F6;</surname> <given-names>M</given-names></string-name>, <string-name><surname>Marungruang</surname> <given-names>N</given-names></string-name>, <string-name><surname>Roth</surname> <given-names>B</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Evaluation of the microbiome in children&#x2019;s appendicitis</article-title>. <source>Int J Colorectal Dis</source>. <year>2017</year>;<volume>32</volume>(<issue>1</issue>):<fpage>19</fpage>&#x2013;<lpage>28</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1007/s00384-016-2639-x">https://doi.org/10.1007/s00384-016-2639-x</ext-link></comment></mixed-citation></ref>
<ref id="CIT0009"><label>9</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Antonsen</surname> <given-names>J</given-names></string-name>, <string-name><surname>Hansen</surname> <given-names>S</given-names></string-name>, <string-name><surname>Morgen</surname> <given-names>CS</given-names></string-name>, <string-name><surname>Jess</surname> <given-names>T</given-names></string-name>, <string-name><surname>Jorgensen</surname> <given-names>LN</given-names></string-name>, <string-name><surname>Allin</surname> <given-names>KH</given-names></string-name></person-group>. <article-title>Antibiotics during childhood and development of appendicitis &#x2013; A nationwide cohort study</article-title>. <source>Aliment Pharmacol Ther</source>. <year>2021</year>;<volume>53</volume>(<issue>1</issue>):<fpage>87</fpage>&#x2013;<lpage>93</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1111/apt.16084">https://doi.org/10.1111/apt.16084</ext-link></comment></mixed-citation></ref>
<ref id="CIT0010"><label>10</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Hasan</surname> <given-names>N</given-names></string-name>, <string-name><surname>Yang</surname> <given-names>H</given-names></string-name></person-group>. <article-title>Factors affecting the composition of the gut microbiota, and its modulation</article-title>. <source>PeerJ</source>. <year>2019</year>;<volume>7</volume>:<fpage>e7502</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.7717/peerj.7502">https://doi.org/10.7717/peerj.7502</ext-link></comment></mixed-citation></ref>
<ref id="CIT0011"><label>11</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Du</surname> <given-names>ZC</given-names></string-name>, <string-name><surname>Li</surname> <given-names>GQ</given-names></string-name>, <string-name><surname>Luo</surname> <given-names>Y</given-names></string-name>, <string-name><surname>Bai</surname> <given-names>XW</given-names></string-name>, <string-name><surname>Sun</surname> <given-names>B</given-names></string-name></person-group>. <article-title>The role of gut microbiota in acute pancreatitis: New perspectives in pathogenesis and therapeutic approaches</article-title>. <source>J Pancreatol</source>. <year>2024</year>;<volume>7</volume>(<issue>1</issue>):<fpage>61</fpage>&#x2013;<lpage>71</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1097/JP9.0000000000000131">https://doi.org/10.1097/JP9.0000000000000131</ext-link></comment></mixed-citation></ref>
<ref id="CIT0012"><label>12</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Lee</surname> <given-names>MS</given-names></string-name>, <string-name><surname>Sulit</surname> <given-names>A</given-names></string-name>, <string-name><surname>Frizelle</surname> <given-names>F</given-names></string-name>, <string-name><surname>Purcell</surname> <given-names>R</given-names></string-name></person-group>. <article-title>The microbiome in adult acute appendicitis</article-title>. <source>Gut Microbiome</source>. <year>2022</year>;<volume>3</volume>:<fpage>e8</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1017/gmb.2022.7">https://doi.org/10.1017/gmb.2022.7</ext-link></comment></mixed-citation></ref>
<ref id="CIT0013"><label>13</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Vanhatalo</surname> <given-names>S</given-names></string-name>, <string-name><surname>Munukka</surname> <given-names>E</given-names></string-name>, <string-name><surname>Kallonen</surname> <given-names>T</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Appendiceal microbiome in uncomplicated and complicated acute appendicitis: a prospective cohort study</article-title>. <source>PLoS One</source>. <year>2022</year>;<volume>17</volume>(<issue>10</issue>):<fpage>e0276007</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1371/journal.pone.0276007">https://doi.org/10.1371/journal.pone.0276007</ext-link></comment></mixed-citation></ref>
<ref id="CIT0014"><label>14</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Zhang</surname> <given-names>C</given-names></string-name>, <string-name><surname>Li</surname> <given-names>G</given-names></string-name>, <string-name><surname>Lu</surname> <given-names>T</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>The interaction of microbiome and pancreas in acute pancreatitis</article-title>. <source>Biomolecules</source>. <year>2023</year>;<volume>14</volume>(<issue>1</issue>):<fpage>59</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3390/biom14010059">https://doi.org/10.3390/biom14010059</ext-link></comment></mixed-citation></ref>
<ref id="CIT0015"><label>15</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Aiyoshi</surname> <given-names>T</given-names></string-name>, <string-name><surname>Kakihara</surname> <given-names>T</given-names></string-name>, <string-name><surname>Watanabe</surname> <given-names>E</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>A comprehensive microbial analysis of pediatric patients with acute appendicitis</article-title>. <source>J Microbiol Immunol Infect</source>. <year>2023</year>;<volume>56</volume>(<issue>4</issue>):<fpage>695</fpage>&#x2013;<lpage>704</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.jmii.2023.03.006">https://doi.org/10.1016/j.jmii.2023.03.006</ext-link></comment></mixed-citation></ref>
<ref id="CIT0016"><label>16</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Kitahara</surname> <given-names>H</given-names></string-name>, <string-name><surname>Park</surname> <given-names>Y</given-names></string-name>, <string-name><surname>Seharada</surname> <given-names>K</given-names></string-name>, <string-name><surname>Yoshimura</surname> <given-names>M</given-names></string-name>, <string-name><surname>Horiuchi</surname> <given-names>A</given-names></string-name>, <string-name><surname>Karasawa</surname> <given-names>Y</given-names></string-name></person-group>. <article-title>Culture-based bacterial evaluation of the appendix lumen and antibiotic susceptibility of acute appendicitis in Japan: A single-center retrospective analysis</article-title>. <source>Medicine (Baltimore)</source>. <year>2024</year>;<volume>103</volume>(<issue>29</issue>):<fpage>e39037</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1097/MD.0000000000039037">https://doi.org/10.1097/MD.0000000000039037</ext-link></comment></mixed-citation></ref>
<ref id="CIT0017"><label>17</label><mixed-citation publication-type="web"><person-group person-group-type="author"><string-name><surname>Hu</surname> <given-names>YJ</given-names></string-name>, <string-name><surname>Qiu</surname> <given-names>H</given-names></string-name>, <string-name><surname>Harwell</surname> <given-names>JI</given-names></string-name>, <string-name><surname>Bryant</surname> <given-names>P</given-names></string-name></person-group>. <source>Global geographic patterns and trends of WHO priority pathogens and AWaRe antibiotic resistance among children: An epidemiological surveillance study [homepage on the Internet]</source>. <year>2023</year> <comment>[cited 2024 Sept 10]. Available from: <ext-link ext-link-type="uri" xlink:href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4580795">https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4580795</ext-link></comment></mixed-citation></ref>
<ref id="CIT0018"><label>18</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Zahrychuk</surname> <given-names>OM</given-names></string-name>, <string-name><surname>Mykhailyshyn</surname> <given-names>HI</given-names></string-name>, <string-name><surname>Volch</surname> <given-names>IR</given-names></string-name>, <string-name><surname>Klumnyuk</surname> <given-names>SI</given-names></string-name>, <string-name><surname>Romanyuk</surname> <given-names>LB</given-names></string-name></person-group>. <article-title>Species characteristics of causative agents of acute appendicitis in children and determination of their susceptibility to antibiotics</article-title>. <source>Microbiol J</source>. <year>2023</year>;<volume>85</volume>(<issue>3</issue>):<fpage>22</fpage>&#x2013;<lpage>31</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.15407/microbiolj85.03.022">https://doi.org/10.15407/microbiolj85.03.022</ext-link></comment></mixed-citation></ref>
<ref id="CIT0019"><label>19</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Adams</surname> <given-names>SE</given-names></string-name>, <string-name><surname>Perera</surname> <given-names>MRS</given-names></string-name>, <string-name><surname>Fung</surname> <given-names>S</given-names></string-name>, <string-name><surname>Maxton</surname> <given-names>J</given-names></string-name>, <string-name><surname>Karpelowsky</surname> <given-names>J</given-names></string-name></person-group>. <article-title>Non-operative management of uncomplicated appendicitis in children: A randomized, controlled, non-inferiority study evaluating safety and efficacy</article-title>. <source>ANZ J Surg</source>. <year>2024</year>;<volume>94</volume>(<issue>9</issue>):<fpage>1569</fpage>&#x2013;<lpage>1577</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1111/ans.19119">https://doi.org/10.1111/ans.19119</ext-link></comment></mixed-citation></ref>
<ref id="CIT0020"><label>20</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Tang</surname> <given-names>HW</given-names></string-name>, <string-name><surname>Wang</surname> <given-names>ZG</given-names></string-name>, <string-name><surname>Huang</surname> <given-names>JH</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>The development and application of pediatric complicated appendicitis prediction model</article-title>. <source>Technol Health Care</source>. <year>2023</year>;<volume>31</volume>(<issue>6</issue>):<fpage>2319</fpage>&#x2013;<lpage>2329</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3233/THC-230285">https://doi.org/10.3233/THC-230285</ext-link></comment></mixed-citation></ref>
<ref id="CIT0021"><label>21</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Garzon-Gonz&#x00E1;lez</surname> <given-names>LN</given-names></string-name>, <string-name><surname>Padilla</surname> <given-names>LT</given-names></string-name>, <string-name><surname>Pati&#x00F1;o</surname> <given-names>F</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Association between bacterial resistance profile and the development of intra-abdominal abscesses in pediatric patients with perforated appendicitis: Cohort study</article-title>. <source>Pediatr Surg Int</source>. <year>2024</year>;<volume>40</volume>(<issue>1</issue>):<fpage>18</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1007/s00383-023-05570-3">https://doi.org/10.1007/s00383-023-05570-3</ext-link></comment></mixed-citation></ref>
<ref id="CIT0022"><label>22</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Withers</surname> <given-names>A</given-names></string-name>, <string-name><surname>Loveland</surname> <given-names>J</given-names></string-name></person-group>. <article-title>Demographics of paediatric patients presenting with acute appendicitis: A 5-year retrospective review of hospitals served by the Department of Paediatric Surgery at the University of the Witwatersrand</article-title>. <source>S Afr J Child Health</source>. <year>2019</year>;<volume>13</volume>(<issue>2</issue>):<fpage>69</fpage>&#x2013;<lpage>72</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.7196/sajch.2019.v13i2.1557">https://doi.org/10.7196/sajch.2019.v13i2.1557</ext-link></comment></mixed-citation></ref>
<ref id="CIT0023"><label>23</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Di Saverio</surname> <given-names>S</given-names></string-name>, <string-name><surname>Podda</surname> <given-names>M</given-names></string-name>, <string-name><surname>De Simone</surname> <given-names>B</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Diagnosis and treatment of acute appendicitis: 2020 Update of the WSES Jerusalem guidelines</article-title>. <source>World J Emerg Surg</source>. <year>2020</year>;<volume>15</volume>(<issue>1</issue>):<fpage>27</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1186/s13017-020-00306-3">https://doi.org/10.1186/s13017-020-00306-3</ext-link></comment></mixed-citation></ref>
<ref id="CIT0024"><label>24</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Di Saverio</surname> <given-names>S</given-names></string-name>, <string-name><surname>Birindelli</surname> <given-names>A</given-names></string-name>, <string-name><surname>Kelly</surname> <given-names>MD</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>WSES Jerusalem guidelines for diagnosis and treatment of acute appendicitis</article-title>. <source>World J Emerg Surg</source>. <year>2016</year>;<volume>11</volume>:<fpage>34</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1186/s13017-016-0090-5">https://doi.org/10.1186/s13017-016-0090-5</ext-link></comment></mixed-citation></ref>
<ref id="CIT0025"><label>25</label><mixed-citation publication-type="book"><person-group person-group-type="author"><string-name><surname>Team</surname> <given-names>RC</given-names></string-name></person-group>. <chapter-title>R A language and environment for statistical computing [homepage on the Internet]</chapter-title>. <source>R Foundation for Statistical</source>. <publisher-name>Computing</publisher-name>; <year>2020</year> <comment>[cited 2024 Sept 10]. Available from: <ext-link ext-link-type="uri" xlink:href="https://cir.nii.ac.jp/crid/1370298755636824325">https://cir.nii.ac.jp/crid/1370298755636824325</ext-link></comment></mixed-citation></ref>
<ref id="CIT0026"><label>26</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Clarke</surname> <given-names>DL</given-names></string-name>, <string-name><surname>Naidoo</surname> <given-names>M</given-names></string-name>, <string-name><surname>Kong</surname> <given-names>V</given-names></string-name></person-group>. <article-title>Acute appendicitis in rural KwaZulu-Natal, South Africa</article-title>. <source>Impact Surg</source>. <year>2024</year>;<volume>1</volume>(<issue>2</issue>):<fpage>41</fpage>&#x2013;<lpage>45</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.62463/surgery.39">https://doi.org/10.62463/surgery.39</ext-link></comment></mixed-citation></ref>
<ref id="CIT0027"><label>27</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>La&#x00E4;s</surname> <given-names>R</given-names></string-name>, <string-name><surname>Clarke</surname> <given-names>DL</given-names></string-name>, <string-name><surname>Dufourq</surname> <given-names>N</given-names></string-name>, <string-name><surname>Smith</surname> <given-names>MTD</given-names></string-name>, <string-name><surname>Bruce</surname> <given-names>JL</given-names></string-name>, <string-name><surname>Naidoo</surname> <given-names>M</given-names></string-name></person-group>. <article-title>The influence of HIV status on acute appendicitis: A retrospective study from South Africa</article-title>. <source>World J Surg</source>. <year>2023</year>;<volume>47</volume>(<issue>11</issue>):<fpage>2608</fpage>&#x2013;<lpage>2616</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1007/s00268-023-07103-4">https://doi.org/10.1007/s00268-023-07103-4</ext-link></comment></mixed-citation></ref>
<ref id="CIT0028"><label>28</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Simelane</surname> <given-names>PB</given-names></string-name>, <string-name><surname>Kader</surname> <given-names>SS</given-names></string-name>, <string-name><surname>Madiba</surname> <given-names>TE</given-names></string-name></person-group>. <article-title>Clinicopathological spectrum and outcome of appendicectomy at a South African tertiary hospital: Continuing impact of delayed presentation</article-title>. <source>Afr Health Sci</source>. <year>2024</year>;<volume>24</volume>(<issue>2</issue>):<fpage>365</fpage>&#x2013;<lpage>374</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.4314/ahs.v24i2.37">https://doi.org/10.4314/ahs.v24i2.37</ext-link></comment></mixed-citation></ref>
<ref id="CIT0029"><label>29</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Felber</surname> <given-names>J</given-names></string-name>, <string-name><surname>Gross</surname> <given-names>B</given-names></string-name>, <string-name><surname>Rahrisch</surname> <given-names>A</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Bacterial pathogens in pediatric appendicitis: A comprehensive retrospective study</article-title>. <source>Front Cell Infect Microbiol</source>. <year>2023</year>;<volume>13</volume>:<fpage>1027769</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fcimb.2023.1027769">https://doi.org/10.3389/fcimb.2023.1027769</ext-link></comment></mixed-citation></ref>
<ref id="CIT0030"><label>30</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Jeon</surname> <given-names>HG</given-names></string-name>, <string-name><surname>Ju</surname> <given-names>HU</given-names></string-name>, <string-name><surname>Kim</surname> <given-names>GY</given-names></string-name>, <string-name><surname>Jeong</surname> <given-names>J</given-names></string-name>, <string-name><surname>Kim</surname> <given-names>MH</given-names></string-name>, <string-name><surname>Jun</surname> <given-names>JB</given-names></string-name></person-group>. <article-title>Bacteriology and changes in antibiotic susceptibility in adults with community-acquired perforated appendicitis</article-title>. <source>PLoS One</source>. <year>2014</year>;<volume>9</volume>(<issue>10</issue>):<fpage>e111144</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1371/journal.pone.0111144">https://doi.org/10.1371/journal.pone.0111144</ext-link></comment></mixed-citation></ref>
<ref id="CIT0031"><label>31</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Bhaskar</surname> <given-names>K</given-names></string-name>, <string-name><surname>Clarke</surname> <given-names>S</given-names></string-name>, <string-name><surname>Moore</surname> <given-names>LSP</given-names></string-name>, <string-name><surname>Hughes</surname> <given-names>S</given-names></string-name></person-group>. <article-title>Bacterial peritonitis in paediatric appendicitis; microbial epidemiology and antimicrobial management</article-title>. <source>Ann Clin Microbiol Antimicrob</source>. <year>2023</year>;<volume>22</volume>(<issue>1</issue>):<fpage>45</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1186/s12941-023-00591-1">https://doi.org/10.1186/s12941-023-00591-1</ext-link></comment></mixed-citation></ref>
<ref id="CIT0032"><label>32</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Yu</surname> <given-names>CH</given-names></string-name>, <string-name><surname>Chang</surname> <given-names>CN</given-names></string-name>, <string-name><surname>Wang</surname> <given-names>CC</given-names></string-name></person-group>. <article-title>Causative microbes and antibiotic susceptibility of acute appendicitis in adults and children</article-title>. <source>Pediatr Neonatol</source>. <year>2024</year>;<volume>65</volume>(<issue>2</issue>):<fpage>159</fpage>&#x2013;<lpage>164</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.pedneo.2023.08.003">https://doi.org/10.1016/j.pedneo.2023.08.003</ext-link></comment></mixed-citation></ref>
<ref id="CIT0033"><label>33</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Abdurrazzaaq</surname> <given-names>A</given-names></string-name>, <string-name><surname>Afuwape</surname> <given-names>O</given-names></string-name>, <string-name><surname>Ademola</surname> <given-names>A</given-names></string-name>, <string-name><surname>Fasina</surname> <given-names>O</given-names></string-name></person-group>. <article-title>Bacterial pattern in acute appendicitis</article-title>. <source>Ann Afr Surg</source>. <year>2018</year>;<volume>15</volume>(<issue>1</issue>).<fpage>8</fpage>&#x2013;<lpage>13</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.4314/aas.v15i1.3">https://doi.org/10.4314/aas.v15i1.3</ext-link></comment></mixed-citation></ref>
<ref id="CIT0034"><label>34</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Zachos</surname> <given-names>K</given-names></string-name>, <string-name><surname>Kolonitsiou</surname> <given-names>F</given-names></string-name>, <string-name><surname>Panagidis</surname> <given-names>A</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Association of the bacteria of the vermiform appendix and the peritoneal cavity with complicated acute appendicitis in children</article-title>. <source>Diagnostics (Basel)</source>. <year>2023</year>;<volume>13</volume>(<issue>11</issue>):<fpage>1839</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3390/diagnostics13111839">https://doi.org/10.3390/diagnostics13111839</ext-link></comment></mixed-citation></ref>
<ref id="CIT0035"><label>35</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Hang</surname> <given-names>T</given-names></string-name>, <string-name><surname>Chen</surname> <given-names>Q</given-names></string-name>, <string-name><surname>Guo</surname> <given-names>L</given-names></string-name>, <string-name><surname>Lin</surname> <given-names>HL</given-names></string-name></person-group>. <article-title>Comparison of the efficacy of carbapenems and cephalosporins for postoperative treatment of perforated appendicitis in children</article-title>. <source>Res Square</source>. <year>2023</year>;<volume>1</volume>:<fpage>1</fpage>&#x2013;<lpage>13</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.21203/rs.3.rs-3216176/v1">https://doi.org/10.21203/rs.3.rs-3216176/v1</ext-link></comment></mixed-citation></ref>
<ref id="CIT0036"><label>36</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Stroh&#x00E4;ker</surname> <given-names>JKH</given-names></string-name>, <string-name><surname>Br&#x00FC;schke</surname> <given-names>MJ</given-names></string-name>, <string-name><surname>Bachmann</surname> <given-names>R</given-names></string-name>, <string-name><surname>Mihaljevic</surname> <given-names>AL</given-names></string-name>, <string-name><surname>Ladurner</surname> <given-names>R</given-names></string-name>, <string-name><surname>Beltzer</surname> <given-names>CR</given-names></string-name></person-group>. <article-title>Intraoperative bacterial cultures fail to reliably predict the bacterial spectrum encountered during infectious complications after appendicitis</article-title>. <source>Updates Surg</source>. <year>2024</year>;<volume>76</volume>(<issue>1</issue>):<fpage>147</fpage>&#x2013;<lpage>154</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1007/s13304-023-01698-y">https://doi.org/10.1007/s13304-023-01698-y</ext-link></comment></mixed-citation></ref>
<ref id="CIT0037"><label>37</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Beltr&#x00E1;n</surname> <given-names>SJ</given-names></string-name>, <string-name><surname>Cruz</surname> <given-names>M</given-names></string-name>, <string-name><surname>Pedraza</surname> <given-names>EC</given-names></string-name>, <string-name><surname>Mendivelso</surname> <given-names>FO</given-names></string-name></person-group>. <article-title>Sensibilidad antimicrobiana en aislamientos de l&#x00ED;quido peritoneal de ni&#x00F1;os intervenidos por abdomen agudo e infecci&#x00F3;n intraabdominal</article-title>. <source>Rev Colomb Cir</source>. <year>2019</year>;<volume>34</volume>(<issue>4</issue>):<fpage>354</fpage>&#x2013;<lpage>363</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.30944/20117582.523">https://doi.org/10.30944/20117582.523</ext-link></comment></mixed-citation></ref>
<ref id="CIT0038"><label>38</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Markosyan</surname> <given-names>SA</given-names></string-name>, <string-name><surname>Charyshkin</surname> <given-names>SA</given-names></string-name></person-group>. <article-title>Efficacy of amikacin and ceftriaxone in the empiric antibacterial therapy of friable appendicular infiltrate and periappendicular abscess at different age groups</article-title>. <source>Russ J Pediatr Surg</source>. <year>2023</year>;<volume>27</volume>(<issue>3</issue>):<fpage>156</fpage>&#x2013;<lpage>162</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.55308/1560-9510-2023-27-3-156-162">https://doi.org/10.55308/1560-9510-2023-27-3-156-162</ext-link></comment></mixed-citation></ref>
<ref id="CIT0039"><label>39</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Elrod</surname> <given-names>J</given-names></string-name>, <string-name><surname>Yarmal</surname> <given-names>F</given-names></string-name>, <string-name><surname>Mohr</surname> <given-names>C</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Are we hitting the target? The effectiveness of distinct antibiotic regimens in pediatric appendectomies</article-title>. <source>Pediatr Infect Dis J</source>. <year>2022</year>;<volume>41</volume>(<issue>6</issue>):<fpage>460</fpage>&#x2013;<lpage>465</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1097/INF.0000000000003508">https://doi.org/10.1097/INF.0000000000003508</ext-link></comment></mixed-citation></ref>
<ref id="CIT0040"><label>40</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Gerber</surname> <given-names>F</given-names></string-name>, <string-name><surname>Joseph</surname> <given-names>JM</given-names></string-name>, <string-name><surname>Crisinel</surname> <given-names>PA</given-names></string-name>, <string-name><surname>Andrey</surname> <given-names>V</given-names></string-name></person-group>. <article-title>Evidence-based optimisation of empirical antibiotic regimens in paediatric complicated appendicitis: A retrospective study of 94 patients</article-title>. <source>Swiss Med Wkly</source>. <year>2022</year>;<volume>152</volume>(<issue>3536</issue>):<fpage>w30222</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.4414/smw.2022.w30222">https://doi.org/10.4414/smw.2022.w30222</ext-link></comment></mixed-citation></ref>
<ref id="CIT0041"><label>41</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Kashtan</surname> <given-names>MA</given-names></string-name>, <string-name><surname>Graham</surname> <given-names>DA</given-names></string-name>, <string-name><surname>Melvin</surname> <given-names>P</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Ceftriaxone combined with metronidazole is superior to cefoxitin alone in the management of uncomplicated appendicitis in children: Results from a multicenter collaborative comparative effectiveness study</article-title>. <source>Ann Surg</source>. <year>2021</year>;<volume>274</volume>(<issue>6</issue>):<fpage>e995</fpage>&#x2013;<lpage>e1000</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1097/SLA.0000000000003704">https://doi.org/10.1097/SLA.0000000000003704</ext-link></comment></mixed-citation></ref>
<ref id="CIT0042"><label>42</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Andrey</surname> <given-names>V</given-names></string-name>, <string-name><surname>Crisinel</surname> <given-names>PA</given-names></string-name>, <string-name><surname>Prod&#x2019;hom</surname> <given-names>G</given-names></string-name>, <string-name><surname>Croxatto</surname> <given-names>A</given-names></string-name>, <string-name><surname>Joseph</surname> <given-names>JM</given-names></string-name></person-group>. <article-title>Impact of co-amoxicillin-resistant <italic>Escherichia coli</italic> and <italic>Pseudomonas aeruginosa</italic> on the rate of infectious complications in paediatric complicated appendicitis</article-title>. <source>Swiss Med Wkly</source>. <year>2019</year>;<volume>149</volume>(<issue>1718</issue>):<fpage>w20055</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.4414/smw.2019.20055">https://doi.org/10.4414/smw.2019.20055</ext-link></comment></mixed-citation></ref>
<ref id="CIT0043"><label>43</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Kalmanson</surname> <given-names>OA</given-names></string-name>, <string-name><surname>McLoughlin</surname> <given-names>KC</given-names></string-name>, <string-name><surname>Kiser</surname> <given-names>TH</given-names></string-name>, <string-name><surname>Gubbels</surname> <given-names>SP</given-names></string-name></person-group>. <article-title>Debilitating gentamicin ototoxicity: Case report and recommendations against routine use in surgical prophylaxis</article-title>. <source>Ann Otol Rhinol Laryngol</source>. <year>2023</year>;<volume>132</volume>(<issue>12</issue>):<fpage>1686</fpage>&#x2013;<lpage>1689</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1177/00034894231176333">https://doi.org/10.1177/00034894231176333</ext-link></comment></mixed-citation></ref>
<ref id="CIT0044"><label>44</label><mixed-citation publication-type="web"><person-group person-group-type="author"><string-name><surname>Werth</surname> <given-names>BJ</given-names></string-name></person-group>. <source>Aminoglycosides [homepage on the Internet]</source>. <year>2024</year> <comment>[cited 2024 Sept 10]. Available from: <ext-link ext-link-type="uri" xlink:href="https://www.msdmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-medications/aminoglycosides">https://www.msdmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-medications/aminoglycosides</ext-link></comment></mixed-citation></ref>
<ref id="CIT0045"><label>45</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Pintar</surname> <given-names>T</given-names></string-name>, <string-name><surname>Beovi&#x0107;</surname> <given-names>B</given-names></string-name></person-group>. <article-title>Safety in surgery: Evaluation of safety and efficiency in use of aminoglycosides in acute appendicitis</article-title>. <source>Surg Sci</source>. <year>2020</year>;<volume>11</volume>:<fpage>99</fpage>&#x2013;<lpage>110</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.4236/ss.2020.115013">https://doi.org/10.4236/ss.2020.115013</ext-link>.</comment></mixed-citation></ref>
<ref id="CIT0046"><label>46</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Kubin</surname> <given-names>R</given-names></string-name></person-group>. <article-title>Safety and efficacy of ciprofloxacin in paediatric patients &#x2013; Review</article-title>. <source>Infection</source>. <year>1993</year>;<volume>21</volume>(<issue>6</issue>):<fpage>413</fpage>&#x2013;<lpage>421</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1007/bf01728929">https://doi.org/10.1007/bf01728929</ext-link></comment></mixed-citation></ref>
<ref id="CIT0047"><label>47</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Adefurin</surname> <given-names>A</given-names></string-name>, <string-name><surname>Sammons</surname> <given-names>H</given-names></string-name>, <string-name><surname>Jacqz-Aigrain</surname> <given-names>E</given-names></string-name>, <string-name><surname>Choonara</surname> <given-names>I</given-names></string-name></person-group>. <article-title>Ciprofloxacin safety in paediatrics: A systematic review</article-title>. <source>Arch Dis Child</source>. <year>2011</year>;<volume>96</volume>(<issue>9</issue>):<fpage>874</fpage>&#x2013;<lpage>880</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1136/adc.2010.208843">https://doi.org/10.1136/adc.2010.208843</ext-link></comment></mixed-citation></ref>
<ref id="CIT0048"><label>48</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Bauerle</surname> <given-names>W</given-names></string-name>, <string-name><surname>O&#x2019;Laughlin</surname> <given-names>M</given-names></string-name>, <string-name><surname>Evans</surname> <given-names>H</given-names></string-name></person-group>. <article-title>Improving antibiotic stewardship in acute appendicitis through risk-based empiric treatment selection</article-title>. <source>Surg Infect</source>. <year>2022</year>;<volume>23</volume>(<issue>1</issue>):<fpage>61</fpage>&#x2013;<lpage>65</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1089/sur.2021.144">https://doi.org/10.1089/sur.2021.144</ext-link></comment></mixed-citation></ref>
<ref id="CIT0049"><label>49</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Yadao</surname> <given-names>S</given-names></string-name>, <string-name><surname>Lamture</surname> <given-names>Y</given-names></string-name>, <string-name><surname>Huse</surname> <given-names>S</given-names></string-name></person-group>. <article-title>Uses of antibiotics alone in case of uncomplicated appendicitis</article-title>. <source>Cureus</source>. <year>2022</year>;<volume>14</volume>(<issue>8</issue>):<fpage>e28488</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.7759/cureus.28488">https://doi.org/10.7759/cureus.28488</ext-link></comment></mixed-citation></ref>
<ref id="CIT0050"><label>50</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Putra</surname> <given-names>RFY</given-names></string-name>, <string-name><surname>Hrp</surname> <given-names>SMH</given-names></string-name></person-group>. <article-title>The efficacy of antibiotics in acute appendicitis treatment: A comprehensive systematic review</article-title>. <source>J Adv Res Med Health Sci</source>. <year>2024</year>;<volume>10</volume>(<issue>4</issue>):<fpage>133</fpage>&#x2013;<lpage>140</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.61841/3qw8z628">https://doi.org/10.61841/3qw8z628</ext-link></comment></mixed-citation></ref>
<ref id="CIT0051"><label>51</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Allende</surname> <given-names>R</given-names></string-name>, <string-name><surname>Mu&#x00F1;oz</surname> <given-names>R</given-names></string-name></person-group>. <article-title>[Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis? &#x2013; First update.] [Article in Spanish]</article-title>. <source>Medwave</source>. <year>2018</year>;<volume>18</volume>(<issue>4</issue>):<fpage>e7228</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5867/medwave.2018.04.7229">https://doi.org/10.5867/medwave.2018.04.7229</ext-link></comment></mixed-citation></ref>
<ref id="CIT0052"><label>52</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Samee</surname> <given-names>MU</given-names></string-name>, <string-name><surname>Afzal</surname> <given-names>M</given-names></string-name>, <string-name><surname>Khan</surname> <given-names>A</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Role of metronidazole after appendicectomy in simple cases of acute appendicitis</article-title>. <source>Pak J Med Health Sci</source>. <year>2023</year>;<volume>17</volume>(<issue>1</issue>):<fpage>154</fpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.53350/pjmhs2023171154">https://doi.org/10.53350/pjmhs2023171154</ext-link></comment></mixed-citation></ref>
<ref id="CIT0053"><label>53</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Banani</surname> <given-names>SA</given-names></string-name>, <string-name><surname>Amirghofran</surname> <given-names>AA</given-names></string-name></person-group>. <article-title>The role and value of oral metronidazole in acute appendicitis</article-title>. <source>Pediatr Surg Int</source>. <year>1995</year>;<volume>10</volume>:<fpage>101</fpage>&#x2013;<lpage>104</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1007/BF00171165">https://doi.org/10.1007/BF00171165</ext-link></comment></mixed-citation></ref>
<ref id="CIT0054"><label>54</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Banani</surname> <given-names>SA</given-names></string-name>, <string-name><surname>Talei</surname> <given-names>A</given-names></string-name></person-group>. <article-title>Can oral metronidazole substitute parenteral drug therapy in acute appendicitis? A new policy in the management of simple or complicated appendicitis with localized peritonitis: A randomized controlled clinical trial</article-title>. <source>Am Surg</source>. <year>1999</year>;<volume>65</volume>(<issue>5</issue>):<fpage>411</fpage>&#x2013;<lpage>416</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1177/000313489906500505">https://doi.org/10.1177/000313489906500505</ext-link></comment></mixed-citation></ref>
<ref id="CIT0055"><label>55</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Kling</surname> <given-names>PA</given-names></string-name>, <string-name><surname>Holmlund</surname> <given-names>D</given-names></string-name>, <string-name><surname>Burman</surname> <given-names>LG</given-names></string-name></person-group>. <article-title>Prevention of post-operative infection in appendicectomy by single dose intravenous metronidazole. An open prospective randomised study</article-title>. <source>Acta Chir Scand [serial online]</source>. <year>1985</year> [cited 2024 Dec 18];<volume>151</volume>(<issue>1</issue>):<fpage>73</fpage>&#x2013;<lpage>76</lpage>. <comment>Available from: <ext-link ext-link-type="uri" xlink:href="https://europepmc.org/article/med/3885664">https://europepmc.org/article/med/3885664</ext-link></comment></mixed-citation></ref>
<ref id="CIT0056"><label>56</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><string-name><surname>Child</surname> <given-names>J</given-names></string-name>, <string-name><surname>Chen</surname> <given-names>X</given-names></string-name>, <string-name><surname>Mistry</surname> <given-names>RD</given-names></string-name>, <etal>et al</etal></person-group>. <article-title>Pharmacokinetic and pharmacodynamic properties of metronidazole in pediatric patients with acute appendicitis: A prospective study</article-title>. <source>J Pediatr Infect Dis Soc</source>. <year>2019</year>;<volume>8</volume>(<issue>4</issue>):<fpage>297</fpage>&#x2013;<lpage>302</lpage>. <comment><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1093/jpids/piy040">https://doi.org/10.1093/jpids/piy040</ext-link></comment></mixed-citation></ref>
</ref-list>
<fn-group>
<fn><p><bold>How to cite this article:</bold> Brits E, Kruger E, Fivaz K, et al. Type and antibiotic susceptibility of bacteria cultured in paediatric acute appendicitis. S Afr J Infect Dis. 2025;40(1), a689. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.4102/sajid.v40i1.689">https://doi.org/10.4102/sajid.v40i1.689</ext-link></p></fn>
</fn-group>
</back>
</article>