Changes in Antimicrobial Resistance in Pediatric Urinary Pathogens Before, During, and After the COVID-19 Pandemic
Abstract
1. Introduction
2. Results
2.1. Baseline Characteristics
2.2. Antibiotic Susceptibility by Age Group
2.3. Antibiotic Susceptibility by COVID-19 Period
2.4. Interrupted Time-Series Analysis (ITS)
2.5. Multivariable Analysis
3. Discussion
4. Materials and Methods
4.1. Study Design and Population
4.2. Definition and Data Collection
4.3. Microbiological Methods
4.4. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
| AMR | Antimicrobial resistance |
| ALT | Alanine aminotransferase |
| AST | Aspartate Transaminase |
| BUN | Blood Urea Nitrogen |
| CFU/mL | Colony-forming units per milliliter |
| CI | Confidence interval |
| CLSI | Clinical and Laboratory Standards Institute |
| COVID-19 | Coronavirus disease 2019 |
| CRP | C-reactive protein |
| DMSA | Dimercaptosuccinic Acid |
| E. coli | Escherichia coli |
| ESBL | Extended-spectrum β-lactamase |
| ESR | Erythrocyte Sedimentation Rate |
| HPF | High power field |
| ITS | Interrupted time-series |
| OR | Odds ratio |
| PIP/TAZ | Piperacillin and tazobactam |
| SD | Standard deviation |
| TMP/SMX | Trimethoprim/sulfamethoxazole |
| USG | Ultrasonography |
| UTI | Urinary tract infection |
| WBC | White blood cell |
References
- Shaikh, N.; Morone, N.E.; Bost, J.E.; Farrell, M.H. Prevalence of urinary tract infection in childhood: A meta-analysis. Pediatr. Infect. Dis. J. 2008, 27, 302–308. [Google Scholar] [CrossRef]
- Bryce, A.; Hay, A.D.; Lane, I.F.; Thornton, H.V.; Wootton, M.; Costelloe, C. Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of antibiotics in primary care: Systematic review and meta-analysis. BMJ 2016, 352, i939. [Google Scholar] [CrossRef]
- Tamma, P.D.; Rodriguez-Bano, J. The Use of Noncarbapenem β-Lactams for the Treatment of Extended-Spectrum β-Lactamase Infections. Clin. Infect. Dis. 2017, 64, 972–980. [Google Scholar] [CrossRef]
- Langford, B.J.; So, M.; Raybardhan, S.; Leung, V.; Soucy, J.R.; Westwood, D.; Daneman, N.; MacFadden, D.R. Antibiotic prescribing in patients with COVID-19: Rapid review and meta-analysis. Clin. Microbiol. Infect. 2021, 27, 520–531. [Google Scholar] [CrossRef]
- World Health Organization. WHO Reports Widespread Overuse of Antibiotics in Patients Hospitalized with COVID-19. 2024. Available online: https://www.who.int/news/item/26-04-2024-who-reports-widespread-overuse-of-antibiotics-in-patients--hospitalized-with-covid-19 (accessed on 2 December 2025).
- Ryu, S.; Hwang, Y.; Ali, S.T.; Kim, D.S.; Klein, E.Y.; Lau, E.H.Y.; Cowling, B.J. Decrease in broad-spectrum antibiotic prescriptions in children during the COVID-19 pandemic in Korea. J. Infect. Dis. 2021, 224, 949–957. [Google Scholar] [CrossRef]
- Jeong, Y.-I.; Lee, H.-Y.; Lee, S.; Jeong, G.Y.; Kim, S.H.; Kim, S.; Seo, S.-H.; Shin, N.-R. Korea’s National Action Plan on Antimicrobial Resistance: Focusing on the Appropriate Use of Antibiotics. Infect. Chemother. 2025, 57, 203–214. [Google Scholar] [CrossRef] [PubMed]
- Park, J.; Kang, H.M. National level cross-sectional study on antibiotic use in children during the pre- and early COVID-19 eras. Antibiotics 2024, 13, 249. [Google Scholar] [CrossRef]
- Hong, J.H.; Paek, S.H.; Kim, T.; Kim, S.; Ko, E.; Ro, Y.S.; Kim, J.; Kwon, J.H. Characteristics of pediatric emergency department visits before and during the COVID-19 pandemic: A report from the National Emergency Department Information System (NEDIS) of Korea, 2018–2022. Clin. Exp. Emerg. Med. 2023, 10, S13–S25. [Google Scholar] [CrossRef] [PubMed]
- Woo, B.; Jung, Y.; Kim, H.S. Antibiotic Sensitivity Patterns in Children with Urinary Tract Infection: Retrospective Study over 8 Years in a Single Center. Child. Kidney Dis. 2019, 23, 22–28. [Google Scholar] [CrossRef]
- Yong, H.T.; Park, S.C.; Lee, J.W. Changes in Causative Organisms and Antimicrobial Susceptibility of the Urinary Tract Infection. J. Korea Acad.-Ind. Coop. Soc. 2017, 18, 85–93. [Google Scholar]
- Logan, L.K.; Weinstein, R.A. The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace. J. Infect. Dis. 2017, 215 (Suppl. S1), S28–S36. [Google Scholar] [CrossRef] [PubMed]
- Banerjee, R.; Robicsek, A.; Kuskowski, M.A.; Porter, S.; Johnston, B.D.; Sokurenko, E.; Tchesnokova, V.; Price, L.B.; Johnson, J.R. Molecular epidemiology of Escherichia coli sequence type 131 and Its H30 and H30-Rx subclones among extended-spectrum-β-lactamase-positive and -negative E. coli clinical isolates from the Chicago Region, 2007 to 2010. Antimicrob. Agents Chemother. 2013, 57, 6385–6388. [Google Scholar] [CrossRef]
- Romandini, A.; Pani, A.; Schenardi, P.A.; Pattarino, G.A.C.; De Giacomo, C.; Scaglione, F. Antibiotic Resistance in Pediatric Infections: Global Emerging Threats, Predicting the Near Future. Antibiotics 2021, 10, 393. [Google Scholar] [CrossRef]
- Park, P.G.; Lim, S.H.; Song, J.Y.; Ahn, Y.H.; Kim, S.H.; Kang, H.G. Trends in antibiotic resistance of urinary tract infections in young children, 2010–2023. Pediatr. Neonatol. 2025, 30, S1875. [Google Scholar] [CrossRef]
- Kim, J.-A.; Song, S.A.; Kim, S.; Park, S.; Woo, K.; Kim, Y.K. A multicenter study on antimicrobial resistance in bloodstream pathogens isolated in Korea: A survey study. Ann. Clin. Microbiol. Antimicrob. 2025, 28, 10. [Google Scholar] [CrossRef]
- Begum, R.S. Global Perspectives on Pediatric Antimicrobial Resistance: A Systematic Literature Review. Medtigo J. Med. 2024, 2, e3062221. [Google Scholar]
- Jo, S.B.; Ahn, S.T.; Joo, H.J.; Kim, J.W.; Oh, M.M. Carbapenem Resistance and ESBL-Producing Enterobacteriaceae in Patients with Urological Infections from 2012 to 2021 in Three Korean Hospitals. Diagnostics 2025, 15, 2004. [Google Scholar] [CrossRef] [PubMed]
- Bandac, C.A.; Ristescu, C.; Onofrei, P.; Miftode, I.L.; Radu, R.; Boiculese, V.L.; Pauna, A.R.; Pantilimonescu, T.F.; Luduşanu, A.; Radu, V.D. Assessment of Factors Contributing to Multidrug Resistance in Urinary Tract Infections: Focus on Carbapenem Resistance. Antibiotics 2025, 14, 918. [Google Scholar] [CrossRef]
- El Zein, Z.; Boutros, C.F.; El Masri, M.; El Tawil, E.; Sraj, M.; Salameh, Y.; Ghadban, S.; Salameh, R.; El Baasiri, S.; Haddara, A.; et al. The challenge of multidrug resistance in hospitalized pediatric patients with urinary tract infections. Front. Cell Infect. Microbiol. 2025, 15, 1570405. [Google Scholar] [CrossRef]
- Otake, S.; Shoji, T.; Yamada, K.; Kimura, M.; Myojin, S.; Kamiyoshi, N.; Ochi, F.; Nezu, M.; Ishida, A.; Miyairi, I.; et al. Trend in antibiotic prescription at pediatric primary emergency medical centers in Japan: A multi-center, cross-sectional study. J. Infect. Chemother. 2024, 30, 616–620. [Google Scholar] [CrossRef]
- Muramatsu, D.; Yanai, T.; Yoshida, S.; Kawakami, K. Prescribing Pattern and Efficacy of Oral Antibiotics for Pediatric Urinary Tract Infections in Japan: A Descriptive Study Using a Nationwide Claims Database. Pediatr. Infect. Dis. J. 2024, 43, 21–25. [Google Scholar] [CrossRef] [PubMed]
- Ono, A.; Koizumi, R.; Tsuzuki, S.; Asai, Y.; Ishikane, M.; Kusama, Y.; Ohmagari, N. Antimicrobial Use Fell Substantially in Japan in 2020-The COVID-19 Pandemic May Have Played a Role. Int. J. Infect. Dis. 2022, 119, 13–17. [Google Scholar] [CrossRef] [PubMed]
- Jeon, K.; Jeong, S.; Lee, N.; Park, M.-J.; Song, W.; Kim, H.-S.; Kim, H.S.; Kim, J.-S. Impact of COVID-19 on Antimicrobial Consumption and Spread of Multidrug-Resistance in Bacterial Infections. Antibiotics 2022, 11, 535. [Google Scholar] [CrossRef]
- Choi, Y.; Kang, M.; Shin, D.H.; Jung, J.; Choi, S.J.; Kim, N.-H.; Moon, S.M.; Song, K.-H.; Kim, E.S.; Jung, J.; et al. Antibiotic Prescription in Patients With Coronavirus Disease 2019: Analysis of National Health Insurance System Data in the Republic of Korea. J. Korean Med. Sci. 2023, 38, e189. [Google Scholar] [CrossRef]
- Chan, G.J.; Lee, A.C.; Baqui, A.H.; Tan, J.; Black, R.E. Risk of early-onset neonatal infection with maternal infection or colonization: A global systematic review and meta-analysis. PLoS Med. 2013, 10, e1001502. [Google Scholar] [CrossRef]
- Denkel, L.A.; Schwab, F.; Kola, A.; Leistner, R.; Garten, L.; von Weizsäcker, K.; Geffers, C.; Gastmeier, P.; Piening, B. The mother as most important risk factor for colonization of very low birth weight (VLBW) infants with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E). J. Antimicrob. Chemother. 2014, 69, 2230–2237. [Google Scholar] [CrossRef]
- Rettedal, S.; Löhr, I.; Bernhoff, E.; Natås, O.; Sundsfjord, A.; Øymar, K. Extended-spectrum β-lactamase-producing Enterobacteriaceae among pregnant women in Norway: Prevalence and maternal–neonatal transmission. J. Perinatol. 2015, 35, 907–912. [Google Scholar] [CrossRef]
- Johnson, J.R.; Johnston, B.; Clabots, C.; Kuskowski, M.A.; Castanheira, M. Escherichia coli sequence type ST131 as the major cause of serious multidrug-resistant E. coli infections in the United States. Clin. Infect. Dis. 2010, 51, 286–294. [Google Scholar] [CrossRef]
- Nicolas-Chanoine, M.H.; Bertrand, X.; Madec, J.Y. Escherichia coli ST131, an intriguing clonal group. Clin. Microbiol. Rev. 2014, 27, 543–574. [Google Scholar] [CrossRef] [PubMed]
- Tchesnokova, V.; Radey, M.; Chattopadhyay, S.; Larson, L.; Weaver, J.L.; Kisiela, D.; Sokurenko, E.V. Pandemic fluoroquinolone resistant Escherichia coli clone ST1193 emerged via simultaneous homologous recombinations in 11 gene loci. Proc. Natl. Acad. Sci. USA 2019, 116, 14740–14748. [Google Scholar] [CrossRef] [PubMed]
- Yun, K.W.; Lee, M.K.; Kim, W.; Lim, I.S. Uropathogenic Escherichia coli ST131 in urinary tract infections in children. Korean J. Pediatr. 2017, 60, 221–226. [Google Scholar] [CrossRef] [PubMed]
- Kim, B.; Seo, M.-R.; Kim, J.; Kim, Y.; Wie, S.-H.; Ki, M.; Cho, Y.K.; Lim, S.; Lee, J.S.; Kwon, K.T.; et al. Molecular Epidemiology of Ciprofloxacin-Resistant Escherichia coli Isolated from Community-Acquired Urinary Tract Infections in Korea. Infect. Chemother. 2020, 52, 194–203. [Google Scholar] [CrossRef] [PubMed]
- Robicsek, A.; Jacoby, G.A.; Hooper, D.C. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect. Dis. 2006, 6, 629–640. [Google Scholar] [CrossRef] [PubMed]
- Rodríguez-Martínez, J.M.; Cano, M.E.; Velasco, C.; Martínez-Martínez, L.; Pascual, A. Plasmid-mediated quinolone resistance: An update. J. Infect. Chemother. 2011, 17, 149–182. [Google Scholar] [CrossRef]



| Early-Onset (n = 605) | Delayed-Onset (n = 544) | |
|---|---|---|
| Male sex | 514 (85.0) | 335 (61.6) |
| Fever duration (days) | 1.8 ± 1.0 | 2.9 ± 1.6 |
| Initial Laboratory findings | ||
| WBC (×103/μL) | 14.6 ± 5.5 | 16.9 ± 6.1 |
| Hemoglobin (g/dL) | 10.3 ± 1.2 | 11.2 ± 0.8 |
| Platelet (×103/μL) | 437.0 ± 120.5 | 396.0 ± 109.6 |
| ESR (mm/h) | 19.3 ± 17.8 | 27.5 ± 24.0 |
| CRP (mg/dL) | 4.1 ± 3.7 | 5.3 ± 4.7 |
| Urinary structural anomalies in USG | 292/433 (67.4) | 218/364 (59.9) |
| Cortical defect in DMSA scan | 117/378 (31.0) | 183/417 (43.9) |
| Early-Onset (n = 605) | Delayed-Onset (n = 544) | p Value * | |
|---|---|---|---|
| Amoxicillin/Clavulanate | 430/573 (75.0) | 366/512 (71.5) | 0.186 |
| Ampicillin | 207/573 (36.1) | 166/506 (32.8) | 0.253 |
| Amikacin | 572/573 (99.8) | 514/516 (99.6) | 0.503 |
| Aztreonam | 470/573 (82.0) | 414/516 (80.2) | 0.450 |
| Ceftazidime | 465/573 (81.2) | 411/515 (79.8) | 0.576 |
| Cefazolin | 367/520 (70.6) | 325/468 (69.4) | 0.698 |
| Ciprofloxacin | 415/542 (76.6) | 388/474 (81.9) | 0.039 |
| Cefotaxime | 457/575 (79.5) | 407/517 (78.7) | 0.759 |
| Ertapenem (n = 969) | 508/508 (100) | 461/461 (100) | - |
| Cefepime (n = 1087) | 469/571 (82.1) | 418/516 (81.0) | 0.631 |
| Gentamycin (n = 1086) | 445/571 (77.9) | 415/515 (80.6) | 0.283 |
| Imipenem (n = 1083) | 569/569 (100) | 514/514 (100) | - |
| TMP/SMX (n = 1091) | 383/576 (66.5) | 343/515 (66.6) | 0.970 |
| Tigecycline (n = 989) | 521/521 (100) | 464/468 (99.1) | 0.134 |
| PIP/TAZ (n = 1027) | 519/540 (96.1) | 457/487 (93.8) | 0.094 |
| ESBL (n = 1036) | 448/551 (81.3) | 388/485 (80) | 0.595 |
| Pre-COVID-19 (n = 274) | During-COVID-19 (n = 171) | Post-COVID-19 (n = 158) | p Value * | |
|---|---|---|---|---|
| Amoxicillin/clavulanate | 189/269 (70.3) | 112/166 (67.5) | 85/145 (58.6) | 0.021 |
| ampicillin | 79/267 (29.6) | 53/162 (32.7) | 48/144 (33.3) | 0.402 |
| Amikacin | 269/269 (100) | 165/166 (99.4) | 146/146 (100) | 0.796 |
| Aztreonam | 214/269 (79.6) | 123/166 (74.1) | 91/146 (62.3) | <0.001 |
| Ceftazidime | 212/269 (78.8) | 121/166 (72.9) | 117/146 (80.1) | 0.974 |
| Cefazolin | 188/269 (69.9) | 107/166 (64.5) | 100/146 (68.5) | 0.635 |
| Ciprofloxacin | 223/274 (81.4) | 116/170 (68.2) | 110/158 (69.6) | 0.003 |
| Cefotaxime | 206/269 (76.6) | 120/167 (71.9) | 116/146 (79.5) | 0.686 |
| Ertapenem | 269/269 (100) | 166/166 (100) | 146/146 (100) | - |
| Cefepime | 216/269 (80.3) | 123/166 (74.1) | 118/146 (80.8) | 0.877 |
| Gentamicin | 198/269 (73.6) | 130/166 (78.3) | 116/147 (78.9) | 0.188 |
| Imipenem | 269/269 (100) | 165/165 (100) | 141/141 (100) | - |
| TMP/SMX | 165/269 (61.3) | 104/167 (62.3) | 99/147 (67.3) | 0.249 |
| Tigecycline | 273/273 (100) | 171/171 (100) | 156/157 (99.4) | 0.147 |
| PIP/TAZ | 254/269 (94.4) | 160/166 (96.4) | 140/145 (96.6) | 0.276 |
| ESBL negative | 208/261 (79.7) | 114/157 (72.6) | 104/132 (78.8) |
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Lim, S.H.; Jo, K.J.; Byun, S.Y.; Lee, Y.-J.; Park, S.E.; Song, J.Y. Changes in Antimicrobial Resistance in Pediatric Urinary Pathogens Before, During, and After the COVID-19 Pandemic. Antibiotics 2025, 14, 1243. https://doi.org/10.3390/antibiotics14121243
Lim SH, Jo KJ, Byun SY, Lee Y-J, Park SE, Song JY. Changes in Antimicrobial Resistance in Pediatric Urinary Pathogens Before, During, and After the COVID-19 Pandemic. Antibiotics. 2025; 14(12):1243. https://doi.org/10.3390/antibiotics14121243
Chicago/Turabian StyleLim, Seon Hee, Kyo Jin Jo, Shin Yun Byun, Yun-Jin Lee, Su Eun Park, and Ji Yeon Song. 2025. "Changes in Antimicrobial Resistance in Pediatric Urinary Pathogens Before, During, and After the COVID-19 Pandemic" Antibiotics 14, no. 12: 1243. https://doi.org/10.3390/antibiotics14121243
APA StyleLim, S. H., Jo, K. J., Byun, S. Y., Lee, Y.-J., Park, S. E., & Song, J. Y. (2025). Changes in Antimicrobial Resistance in Pediatric Urinary Pathogens Before, During, and After the COVID-19 Pandemic. Antibiotics, 14(12), 1243. https://doi.org/10.3390/antibiotics14121243

