{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:19:02Z","timestamp":1762078742261,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Unselective use of antibiotics to treat children with COVID-19 is one of the major issues during the pandemic in Serbia. Thus far, there has been no evidence about the predictors of multiple antibiotic use in the treatment of children with COVID-19. The purpose of this study was to assess the prevalence of antibiotic use, as well as to examine demographic and clinical factors associated with a greater number of antibiotics and with a longer antibiotic treatment administered to hospitalized children with COVID-19 during the lockdown in Serbia. This study included all children who were hospitalized from 6 March to 31 May 2020 at the only pediatric COVID-19 hospital, and who were confirmed to have SARS-CoV-2 infection. Demographic, clinical, and laboratory data were collected from medical records. The antibiotic treatment included the use of azithromycin, cephalosporin (ceftriaxone), ampicillin-amikacin, and hydroxychloroquine. The overall prevalence of antibiotics use in children hospitalized with COVID-19 regardless of age was 47.2% (43.3% in children aged 1\u20135 years and 44.4% in those aged 5\u201317 years). In children aged 1\u20135 years, not having a family member affected by COVID-19 (B = \u22121.38, 95% confidence interval [CI] \u22122.43, \u22120.34, p = 0.011), having pneumonia on chest X-ray (B = 0.81, 95%CI 0.34, 1.29, p = 0.002), being a boy (B = \u22120.65, 95%CI \u22121.17, \u22120.13, p = 0.018), and having higher C-reactive protein (CRP) values on admission (B = 0.12, 95%CI 0.07, 0.17, p = 0.001) were associated with the administration of a higher number of antibiotics. These factors, along with having fever (B = 3.20, 95%CI 1.03, 5.37, p = 0.006), were associated with a longer duration of antibiotic treatment in children aged 1\u20135 years. In children aged 5\u201317 years, having pharyngeal erythema (B = 1.37, 95%CI 0.61, 2.13, p = 0.001), fever (B = 0.43, 95%CI 0.07, 0.79, p = 0.018), and pneumonia on chest X-ray (B = 0.91, 95%CI 0.53, 1.29, p = 0.001), not having rhinorrhea (B = \u22121.27, 95%CI \u22122.47, \u22120.08, p = 0.037), being a girl (B = 0.52, 95%CI 0.08, 0.97, p = 0.021), and having higher CRP values on admission (B = 0.04, 95%CI 0.01, 0.06, p = 0.006) were associated with the administration of a higher number of antibiotics. These factors, not including the absence of rhinorrhea, were associated with a longer duration of antibiotics treatment in children aged 5\u201317 years. Demographic, epidemiological, clinical, and laboratory parameters were associated with the use of multiple antibiotics and a longer duration of antibiotic treatment both among children aged 1\u20135 years and those aged 5\u201317 years.<\/jats:p>","DOI":"10.3390\/ijerph192315590","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T02:25:36Z","timestamp":1669256736000},"page":"15590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Factors Associated with the Antibiotic Treatment of Children Hospitalized for COVID-19 during the Lockdown in Serbia"],"prefix":"10.3390","volume":"19","author":[{"given":"Andreja","family":"Priji\u0107","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital for Lung Diseases and Tuberculosis, University Clinical Hospital Center \u201cDr Dragi\u0161a Mi\u0161ovi\u0107\u2013Dedinje\u201d, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatjana","family":"Gazibara","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergej","family":"Priji\u0107","sequence":"additional","affiliation":[{"name":"Mother and Child Health Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4793-1756","authenticated-orcid":false,"given":"Stefan","family":"Mandi\u0107-Raj\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Social Medicine, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nata\u0161a","family":"Maksimovi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"611","DOI":"10.31083\/j.rcm.2020.04.260","article-title":"Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection","volume":"21","author":"Procter","year":"2020","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_2","first-page":"CD015025","article-title":"Antibiotics for the treatment of COVID-19","volume":"10","author":"Popp","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/S0140-6736(22)00154-4","article-title":"Another piece in the COVID-19 treatment puzzle","volume":"399","author":"Mussini","year":"2022","journal-title":"Lancet"},{"key":"ref_4","unstructured":"World Health Organization (2022, November 05). Therapeutics and COVID-19 Living Guide. Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/345356\/WHO-2019-nCoV-therapeutics-2021.3-eng.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105403","DOI":"10.1016\/j.phrs.2020.105403","article-title":"Consumption of antibiotics at an Italian university hospital during the early months of the COVID-19 pandemic: Were all antibiotic prescriptions appropriate?","volume":"164","author":"Giacomelli","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1017\/ice.2020.381","article-title":"Antibiotic prescription during the COVID-19 pandemic: A biphasic pattern","volume":"41","author":"Rombauts","year":"2020","journal-title":"Infect. Control. Hosp. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"778386","DOI":"10.3389\/fphar.2021.778386","article-title":"Increased Use of Antibiotics in the Intensive Care Unit During Coronavirus Disease (COVID-19) Pandemic in a Brazilian Hospital","volume":"12","author":"Silva","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106324","DOI":"10.1016\/j.ijantimicag.2021.106324","article-title":"Increased antimicrobial resistance during the COVID-19 pandemic","volume":"57","author":"Lai","year":"2021","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.jiph.2021.02.011","article-title":"Antimicrobial Resistance Threats in the emerging COVID-19 pandemic: Where do we stand?","volume":"14","author":"Ghosh","year":"2021","journal-title":"J. Infect Public Health"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gajd\u00e1cs, M., Urb\u00e1n, E., St\u00e1jer, A., and Bar\u00e1th, Z. (2021). Antimicrobial Resistance in the Context of the Sustainable Development Goals: A Brief Review. Eur. J. Investig. Health Psychol. Educ., 11.","DOI":"10.3390\/ejihpe11010006"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Capalbo, C., Aceti, A., Simmaco, M., Bonfini, R., Rocco, M., Ricci, A., Napoli, C., Rocco, M., Alfonsi, V., and Teggi, A. (2020). The Exponential Phase of the COVID-19 Pandemic in Central Italy: An Integrated Care Pathway. Int. J. Environ. Res. Public Health., 17.","DOI":"10.3390\/ijerph17113792"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ijid.2020.12.087","article-title":"Antibiotics and antimicrobial resistance in the COVID-19 era: Perspective from resource-limited settings","volume":"104","author":"Lucien","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chitungo, I., Dzinamarira, T., Nyazika, T.K., Herrera, H., Musuka, G., and Murewanhema, G. (2022). Inappropriate Antibiotic Use in Zimbabwe in the COVID-19 Era: A Perfect Recipe for Antimicrobial Resistance. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020244"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1080\/23744235.2021.1995628","article-title":"Pneumonia, gastrointestinal symptoms, comorbidities, and coinfections as factors related to a lengthier hospital stay in children with COVID-19-analysis of a paediatric part of Polish register SARSTer","volume":"54","author":"Mania","year":"2022","journal-title":"Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1111\/apa.15847","article-title":"High rates of antibiotic prescriptions in children with COVID-19 or multisystem inflammatory syndrome: A multinational experience in 990 cases from Latin America","volume":"110","author":"Lenzi","year":"2021","journal-title":"Acta Paediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/jpids\/piac003","article-title":"Antibiotic Prescribing in Children Hospitalized With COVID-19 and Multisystem Inflammatory Syndrome in Spain: Prevalence, Trends, and Associated Factors","volume":"11","author":"Epalza","year":"2022","journal-title":"J. Pediatr. Infect. Dis. Soc."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Despotovi\u0107, A., Bara\u0107, A., Cucani\u0107, T., Cucani\u0107, K., and Stevanovi\u0107, G. (2022). Antibiotic (Mis) Use in COVID-19 Patients before and after Admission to a Tertiary Hospital in Serbia. Antibiotics, 11.","DOI":"10.3390\/antibiotics11070847"},{"key":"ref_18","unstructured":"Statistical Office of the Republic of Serbia (2020, May 29). Estimates of Population by Age and Gender, Available online: https:\/\/data.stat.gov.rs\/Home\/Result\/18010403?languageCode=sr-Latn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1097\/INF.0000000000002660","article-title":"Coronavirus infections in children including COVID-19: An overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children","volume":"39","author":"Zimmermann","year":"2020","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_20","first-page":"484","article-title":"COVID-19 pneumonia: Relationship between initial chest X-rays and laboratory findings","volume":"63","author":"Cabeza","year":"2021","journal-title":"Radiol. (Engl. Ed.)"},{"key":"ref_21","unstructured":"D-Maps (2022, May 20). Terms and Conditions of Use. Available online: https:\/\/d-maps.com\/conditions.php?lang=en."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"619","DOI":"10.21037\/atm-20-3300","article-title":"Efficacy and safety of antibiotic agents in children with COVID-19: A rapid review","volume":"8","author":"Wang","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_23","first-page":"100252","article-title":"Household transmission of COVID-19 cases associated with SARS-CoV-2 delta variant (B.1.617.2): National case-control study","volume":"12","author":"Allen","year":"2022","journal-title":"Lancet Reg. Health-Eur."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s12098-020-03322-y","article-title":"Pathophysiology of COVID-19: Why Children Fare Better than Adults?","volume":"87","author":"Dhochak","year":"2020","journal-title":"Indian J. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1080\/20469047.2020.1781356","article-title":"Human and novel coronavirus infections in children: A review","volume":"41","author":"Rajapakse","year":"2021","journal-title":"Paediatr. Int. Child Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.cca.2020.03.009","article-title":"Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020","volume":"505","author":"Liu","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e2021052273","DOI":"10.1542\/peds.2021-052273","article-title":"Deaths in Children and Adolescents Associated With COVID-19 and MIS-C in the United States","volume":"148","author":"McCormick","year":"2021","journal-title":"Pediatrics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s13052-021-01045-0","article-title":"Clinical characteristics of children infected with SARS-CoV-2 in Italy","volume":"47","author":"Vona","year":"2021","journal-title":"Ital. J. Pediatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e051506","DOI":"10.1136\/bmjopen-2021-051506","article-title":"Sex and gender differences in COVID-19: An Italian local register-based study","volume":"11","author":"Fortunato","year":"2021","journal-title":"BMJ Open"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.ijid.2020.07.076","article-title":"Does gender influence clinical expression and disease outcomes in COVID-19? A systematic review and meta-analysis","volume":"99","author":"Ortolan","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.clinthera.2021.01.015","article-title":"Sex- or Gender-specific Differences in the Clinical Presentation, Outcome, and Treatment of SARS-CoV-2","volume":"43","author":"Wolfe","year":"2021","journal-title":"Clin. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e13785","DOI":"10.1111\/dth.13785","article-title":"Azithromycin and COVID-19: Prompt early use at first signs of this infection in adults and children, an approach worthy of consideration","volume":"33","author":"Schwartz","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s13052-020-00900-w","article-title":"Treatment of children with COVID-19: Position paper of the Italian Society of Pediatric Infectious Disease","volume":"46","author":"Venturini","year":"2020","journal-title":"Ital. J. Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.1002\/ppul.25087","article-title":"Coronavirus global pandemic: An overview of current findings among pediatric patients","volume":"55","author":"Perikleous","year":"2020","journal-title":"Pediatr. Pulmonol."},{"key":"ref_35","unstructured":"National Institutes of Health (2022, November 01). Therapeutic Management of Hospitalized Children with COVID-19, Available online: https:\/\/www.covid19treatmentguidelines.nih.gov\/management\/clinical-management-of-children\/hospitalized-children-therapeutic-management\/."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ijid.2021.10.001","article-title":"COVID-19 and antimicrobial stewardship: Lessons learned, best practices, and future implications","volume":"113","author":"Pierce","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.cmi.2020.12.018","article-title":"Antibiotic prescribing in patients with COVID-19: Rapid review and meta-analysis","volume":"27","author":"Langford","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kalam, A., Shano, S., Khan, M.A., Islam, A., Warren, N., Hassan, M.M., and Davis, M. (2021). Understanding the social drivers of antibiotic use during COVID-19 in Bangladesh: Implications for reduction of antimicrobial resistance. PLoS ONE., 16.","DOI":"10.1371\/journal.pone.0261368"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Papst, L., Luzzati, R., Carevi\u0107, B., Tascini, C., Miksi\u0107, N.G., Pal\u010devski, V.V., Djordjevic, Z.M., Simonetti, O., Sozio, E., and Luki\u0107, M. (2022). Antimicrobial Use in Hospitalised Patients with COVID-19: An International Multicentre Point-Prevalence Study. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020176"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.cca.2020.08.019","article-title":"Laboratory findings in COVID-19 diagnosis and prognosis","volume":"510","author":"Bashash","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/S2352-4642(21)00198-X","article-title":"Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2","volume":"5","author":"Molteni","year":"2021","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Molteni, E., Sudre, C.H., Canas, L.D.S., Bhopal, S.S., Hughes, R.C., Chen, L., Deng, J., Murray, B., Kerfoot, E., and Antonelli, M. (2022). Illness Characteristics of COVID-19 in Children Infected with the SARS-CoV-2 Delta Variant. Children, 9.","DOI":"10.3390\/children9050652"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lazova, S., Alexandrova, T., Gorelyova-Stefanova, N., Atanasov, K., Tzotcheva, I., and Velikova, T. (2021). Liver Involvement in Children with COVID-19 and Multisystem Inflammatory Syndrome: A Single-Center Bulgarian Observational Study. Microorganisms, 9.","DOI":"10.3390\/microorganisms9091958"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100337","DOI":"10.1016\/j.ejro.2021.100337","article-title":"Chest radiograph in hospitalized children with COVID-19. A review of findings and indications","volume":"8","author":"Veintemilla","year":"2021","journal-title":"Eur. J. Radiol. Open"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00247-020-04830-x","article-title":"Imaging of children with COVID-19: Experience from a tertiary children\u2019s hospital in the United States","volume":"51","author":"Biko","year":"2021","journal-title":"Pediatr. Radiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"fmaa045","DOI":"10.1093\/tropej\/fmaa045","article-title":"Radiological Findings of COVID-19 in Children: A Systematic Review and Meta-Analysis","volume":"67","author":"Kumar","year":"2021","journal-title":"J. Trop. Pediatr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3855\/jidc.15353","article-title":"COVID-19 disease characteristics in different pediatric age groups","volume":"16","author":"Kepenekli","year":"2022","journal-title":"J. Infect. Dev. Ctries."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/23\/15590\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:25:41Z","timestamp":1760145941000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/23\/15590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":47,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijerph192315590"],"URL":"https:\/\/doi.org\/10.3390\/ijerph192315590","relation":{},"ISSN":["1660-4601"],"issn-type":[{"type":"electronic","value":"1660-4601"}],"subject":[],"published":{"date-parts":[[2022,11,24]]}}}