Retrospective 8-Year Study on the Antibiotic Resistance of Uropathogens in Children Hospitalised for Urinary Tract Infection in the Emilia-Romagna Region, Italy
Abstract
:1. Introduction
2. Methods
2.1. Study Design and Population
2.2. Data Evaluation
2.3. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Stephens, G.M.; Akers, S.; Nguyen, H.; Woxland, H. Evaluation and management of urinary tract infections in the school-aged child. Prim. Care 2015, 42, 33–41. [Google Scholar] [CrossRef] [PubMed]
- Korbel, L.; Howell, M.; Spencer, J.D. The clinical diagnosis and management of urinary tract infections in children and adolescents. Paediatr. Int. Child Health 2017, 37, 273–279. [Google Scholar] [CrossRef]
- Balighian, E.; Burke, M. Urinary Tract Infections in Children. Pediatr. Rev. 2018, 39, 3–12. [Google Scholar] [CrossRef]
- Edlin, R.S.; Shapiro, D.J.; Hersh, A.L.; Copp, H.L. Antibiotic resistance patterns of outpatient pediatric urinary tract infections. J. Urol. 2013, 190, 222–227. [Google Scholar] [CrossRef] [Green Version]
- Khoshnood, S.; Heidary, M.; Mirnejad, R.; Bahramian, A.; Sedighi, M.; Mirzaei, H. Drug-resistant gram-negative uropathogens: A review. Biomed Pharmacother. 2017, 94, 982–994. [Google Scholar] [CrossRef]
- Raman, G.; McMullan, B.; Taylor, P.; Mallitt, K.A.; Kennedy SEMultiresistant, E. coli urine infections in children: A case-control study. Arch. Dis. Child 2018, 103, 336–340. [Google Scholar] [CrossRef] [PubMed]
- Logan, L.K.; Braykov, N.P.; Weinstein, R.A.; Laxminarayan, R.; CDC Epicenters Prevention Program. Extended-Spectrum β-Lactamase-Producing and Third-Generation Cephalosporin-Resistant Enterobacteriaceae in Children: Trends in the United States, 1999–2011. J. Pediatric. Infect. Dis. Soc. 2014, 3, 320–328. [Google Scholar] [CrossRef]
- Erol, B.; Culpan, M.; Caskurlu, H.; Sari, U.; Cag, Y.; Vahaboglu, H.; Özumut, S.H.; Karaman, M.I.; Caskurlu, T. Changes in antimicrobial resistance and demographics of UTIs in pediatric patients in a single institution over a 6-year period. J. Pediatr. Urol. 2018, 14, 176.e1–176.e5. [Google Scholar] [CrossRef] [PubMed]
- Mahony, M.; McMullan, B.; Brown, J.; Kennedy, S.E. Multidrug-resistant organisms in urinary tract infections in children. Pediatr. Nephrol. 2019, 35, 1563–1573. [Google Scholar] [CrossRef] [PubMed]
- Perez Heras, I.; Sanchez-Gomez, J.C.; Beneyto-Martin, P.; Ruano-de-Pablo, L.; Losada-Pinedo, B. Community-onset extendedspectrum beta-lactamase producing Escherichia coli in urinary tract infections in children from 2015 to 2016: Prevalence, risk factors, and resistances. Medicine 2017, 96, e8571. [Google Scholar] [CrossRef]
- Ammenti, A.; Alberici, I.; Brugnara, M.; Chimenz, R.; Guarino, S.; La Manna, A.; La Scola, C.; Maringhini, S.; Maringhini, S.; Materassi, M.; et al. Italian Society of Pediatric Nephrology. Updated Italian recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children. Acta Paediatr. 2020, 109, 236–247. [Google Scholar] [CrossRef] [PubMed]
- Magiorakos, A.P.; Srinivasan, A.; Carey, R.B.; Carmeli, Y.; Falagas, M.E.; Giske, C.G.; Harbarth, S.; Hindler, J.F.; Kahlmeter, G.; Olsson-Liljequist, B.; et al. Multidrug-Resistant, Extensively Drug-Resistant and Pandrug-Resistant Bacteria: An International Expert Proposal for Interim Standard Definitions for Acquired Resistance. Clin. Microbiol. Infect. 2012, 18, 268–281. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Koçak, M.; Büyükkaragöz, B.; Çelebi Tayfur, A.; Çaltik, A.; Köksoy, A.Y.; Çizmeci, Z.; Günbey, S. Causative pathogens and antibiotic resistance in children hospitalized for urinary tract infection. Pediatr. Int. 2016, 58, 467–471. [Google Scholar] [CrossRef] [PubMed]
- Belete, Y.; Asrat, D.; Woldeamanuel, Y.; Yihenew, G.; Gize, A. Bacterial Profile And Antibiotic Susceptibility Pattern Of Urinary Tract Infection Among Children Attending Felege Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia. Infect. Drug Resist. 2019, 12, 3575–3583. [Google Scholar] [CrossRef] [Green Version]
- Vazouras, K.; Velali, K.; Tassiou, I.; Anastasiou-Katsiardani, A.; Athanasopoulou, K.; Barbouni, A.; Jackson, C.; Folgori, L.; Zaoutis, T.; Basmaci, R.; et al. Antibiotic treatment and antimicrobial resistance in children with urinary tract infections. J. Glob. Antimicrob. Resist. 2020, 20, 4–10. [Google Scholar] [CrossRef]
- Montagnani, C.; Tersigni, C.; D’Arienzo, S.; Miftode, A.; Venturini, E.; Bortone, B.; Bianchi, L.; Chiappini, E.; Forni, S.; Gemmi, F.; et al. Resistance Patterns from Urine Cultures in Children Aged 0 to 6 Years: Implications for Empirical Antibiotic Choice. Infect. Drug Resist. 2021, 14, 2341–2348. [Google Scholar] [CrossRef]
- Wragg, R.; Harris, A.; Patel, M.; Robb, A.; Chandran, H.; McCarthy, L. Extended spectrum beta lactamase (ESBL) producing bacteria urinary tract infections and complex pediatric urology. J. Pediatr. Surg. 2017, 52, 286–288. [Google Scholar] [CrossRef] [PubMed]
- Pierantoni, L.; Andreozzi, L.; Ambretti, S.; Dondi, A.; Biagi, C.; Baccelli, F.; Lanari, M. Three-Year Trend in Escherichia coli Antimicrobial Resistance among Children’s Urine Cultures in an Italian Metropolitan Area. Children 2021, 8, 597. [Google Scholar]
- Degnan, L.A.; Milstone, A.M.; Diener-West, M.; Lee, C.K. Extended-Spectrum Beta-Lactamase Bacteria from Urine Isolates in Children. J. Pediatr. Pharmacol. Ther. 2015, 20, 373–377. [Google Scholar] [CrossRef]
- Zerr, D.M.; Miles-Jay, A.; Kronman, M.P.; Zhou, C.; Adler, A.L.; Haaland, W.; Weissman, S.J.; Elward, A.; Newland, J.G.; Zaoutis, T.; et al. Previous Antibiotic Exposure Increases Risk of Infection with Extended-Spectrum-β-Lactamase- and AmpC-Producing Escherichia coli and Klebsiella pneumoniae in Pediatric Patients. Antimicrob. Agents Chemother. 2016, 60, 4237–4243. [Google Scholar] [CrossRef] [Green Version]
- Shettigar, S.C.G.; Roche, R.; Nayak, N.; Anitha, K.B.; Soans, S. Bacteriological profile, antibiotic sensitivity pattern, and detection of extended-spectrum β-lactamase in the isolates of urinary tract infection from children. J. Child Health 2016, 3, 5. [Google Scholar] [CrossRef]
- Moore, C.E.; Sona, S.; Poda, S.; Putchhat, H.; Kumar, V.; Sopheary, S.; Stoesser, N.; Bousfield, R.; Day, N.; Parry, C.M. Antimicrobial susceptibility of uropathogens isolated from Cambodian children. Paediatr. Int. Child Health 2016, 36, 113–117. [Google Scholar] [CrossRef]
- Topaloglu, R.; Er, I.; Dogan, B.G.; Bilginer, Y.; Ozaltin, F.; Besbas, N.; Ozen, S.; Bakkaloglu, A.; Gur, D. Risk factors in community-acquired urinary tract infections caused by ESBL-producing bacteria in children. Pediatr. Nephrol. 2010, 25, 919–925. [Google Scholar] [CrossRef] [PubMed]
- American Academy of Pediatrics. Reaffirmation of AAP Clinical Practice Guideline: The Diagnosis and Management of the Initial Urinary Tract Infection in Febrile Infants and Young Children 2–24 Months of Age. Pediatrics 2016, 138, e20163026. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- American Academy of Pediatrics. Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months. Pediatrics 2011, 128, 595–610. [Google Scholar] [CrossRef] [Green Version]
- National Institute for Health and Care Excellence. Urinary Tract Infection in under 16s: Diagnosis and Management. Available online: https://www.nice.org.uk/guidance/cg54 (accessed on 2 January 2021).
- Poirel, L.; Kieffer, N.; Nordmann, P. In vitro evaluation of dual carbapenem combinations against carbapenemase-producing Enterobacteriaceae. J. Antimicrob. Chemother. 2016, 71, 156–161. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gerber, J.S.; Newland, J.G.; Coffin, S.E.; Hall, M.; Thurm, C.; Prasad, P.A.; Feudtner, C.; Zaoutis, T.E. Variability in antibiotic use at children’s hospitals. Pediatrics 2010, 126, 1067–1073. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fanelli, U.; Chiné, V.; Pappalardo, M.; Gismondi, P.; Esposito, S. Improving the Quality of Hospital Antibiotic Use: Impact on Multidrug-Resistant Bacterial Infections in Children. Front. Pharmacol. 2020, 11, 745. [Google Scholar] [CrossRef]
- Principi, N.; Esposito, S. Unsolved problems and new medical approaches to otitis media. Expert Opin. Biol. Ther. 2020, 20, 741–749. [Google Scholar] [CrossRef]
- Principi, N.; Esposito, S. Antimicrobial stewardship in paediatrics. BMC Infect Dis. 2016, 16, 424. [Google Scholar] [CrossRef] [Green Version]
- Moro, M.L.; Marchi, M.; Gagliotti, C.; Di Mario, S.; Resi, D. “Progetto Bambini a Antibiotici [ProBA]” Regional Group. Why do paediatricians prescribe antibiotics? Results of an Italian regional project. BMC Pediatr. 2009, 9, 69. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fanelli, U.; Pappalardo, M.; Chinè, V.; Gismondi, P.; Neglia, C.; Argentiero, A.; Calderaro, A.; Prati, A.; Esposito, S. Role of Artificial Intelligence in Fighting Antimicrobial Resistance in Pediatrics. Antibiotics 2020, 9, 767. [Google Scholar] [CrossRef] [PubMed]
- Di Mario, S.; Gagliotti, C.; Buttazzi, R.; Cisbani, L.; Di Girolamo, C.; Brambilla, A.; Moro, M.L.; Regional Working Group. Progetto ProBA-Progetto Bambini e Antibiotici-2014. Observational pre-post study showed that a quality improvement project reduced paediatric antibiotic prescribing rates in primary care. Acta Paediatr. 2018, 107, 1805–1809. [Google Scholar] [CrossRef]
- Montini, G.; Hewitt, I. Urinary tract infections: To prophylaxis or not to prophylaxis? Pediatr. Nephrol. 2009, 24, 1605–1609. [Google Scholar] [CrossRef]
- Meena, J.; Thomas, C.C.; Kumar, J.; Raut, S.; Hari, P. Non-antibiotic interventions for prevention of urinary tract infections in children: A systematic review and meta-analysis of randomized controlled trials. Eur. J. Pediatr. 2021. [Google Scholar] [CrossRef] [PubMed]
- Alsubaie, S.S.; Barry, M.A. Current status of long-term antibiotic prophylaxis for urinary tract infections in children: An antibiotic stewardship challenge. Kidney Res. Clin. Pract. 2019, 38, 441–454. [Google Scholar] [CrossRef] [Green Version]
- Kim, Y.H.; Yang, E.M.; Kim, C.J. Urinary tract infection caused by community-acquired extended-spectrum beta-lactamase producing bacteria in infants. J. Pediatr. 2017, 93, 260–266. [Google Scholar] [CrossRef] [Green Version]
- Shaikh, N.; Ewing, A.L.; Bhatnagar, S.; Hoberman, A. Risk of renal scarring in children with a first urinary tract infection: A systematicreview. Pediatrics 2010, 126, 1084–1091. [Google Scholar] [CrossRef] [Green Version]
- Wang, M.E.; Lee, V.; Greenhow, T.L.; Beck, J.; Bendel-Stenzel, M.; Hames, N.; McDaniel, C.E.; King, E.E.; Sherry, W.; Parmar, D.; et al. Clinical Response to Discordant Therapy in Third-Generation Cephalosporin-Resistant UTIs. Pediatrics 2020, 145, e20191608. [Google Scholar] [CrossRef]
- Newman, T.B.; Bernzweig, J.A.; Takayama, J.I.; Finch, S.A.; Wasserman, R.C.; Pantell, R.H. Urine Testing and Urinary Tract Infections in Febrile Infants Seen in Office Settings: The Pediatric Research in Office Settings’ Febrile Infant Study. Arch. Pediatr. Adolesc. Med. 2002, 156, 44–54. [Google Scholar] [CrossRef] [Green Version]
- Esposito, S.; Marchisio, P.; Tenconi, R.; Principi, N. Antibiotic treatment of acute otitis media in pediatrics. Future Microbiol. 2011, 6, 485–488. [Google Scholar] [CrossRef] [PubMed]
- Frimodt-Møller, N. Correlation between pharmacokinetic/pharmacodynamic parameters and efficacy for antibiotics in the treatment of urinary tract infection. Int. J. Antimicrob. Agents 2002, 19, 546–553. [Google Scholar] [CrossRef]
- Edson, R.S.; Terrell, C.L. The aminoglycosides. Mayo Clin. Proc. 1999, 74, 519–528. [Google Scholar] [CrossRef]
Characteristic | Hospitalisation Period 2012–2015 n = 627 | Hospitalisation Period 2016–2020 n = 1174 | p Value |
---|---|---|---|
Mean age (SD), years | 1.7 (3.3) | 2.1 (3.8) | 0.04 |
Sex, n. | 0.3 | ||
F | 296 (47%) | 585 (50%) | |
M | 331 (53%) | 589 (50%) | |
Ethnicity, n. | <0.001 | ||
Caucasian | 395 (78%) | 902 (83%) | |
Other | 11 (2.2%) | 19 (1.7%) | |
Prenatal pyelectasis, n. | 83 (14%) | 141 (12%) | 0.3 |
Prematurity at birth, n. | 54 (9.0%) | 111 (9.7%) | 0.6 |
Neonatal complications, n. | 64 (11%) | 122 (11%) | >0.9 |
Vescico-ureteral reflux, n. | 58 (9.3%) | 86 (7.3%) | 0.2 |
Other urological malformations, n. | 58 (9.8%) | 95 (8.4%) | 0.3 |
Urological surgery, n. | 17 (2.8%) | 49 (4.2%) | 0.13 |
History of recurrent UTI 1, n. | 69 (12%) | 98 (8.6%) | 0.029 |
Antibiotic therapy in the 30 days before enrolment, n. | 72 (12%) | 131 (11%) | 0.7 |
Pathogen | Hospitalisation Period 2012–2015 n = 627 | Hospitalisation Period 2016–2020 n = 1174 | p Value |
---|---|---|---|
Escherichia coli, n. | 453 (72.0%) | 908 (77.0%) | 0.017 |
Proteus mirabilis, n. | 9 (1.4%) | 18 (1.5%) | 0.9 |
Klebsiella pneumoniae, n. | 49 (7.8%) | 75 (6.4%) | 0.3 |
Pseudomonas aeruginosa, n. | 22 (3.5%) | 23 (2.0%) | 0.045 |
Enterococcus faecalis, n. | 14 (2.2%) | 21 (1.8%) | 0.5 |
Enterobacter spp., n. | 7 (1.1%) | 16 (1.4%) | 0.7 |
Citrobacter koseri,n. | 5 (0.8%) | 8 (0.7%) | 0.8 |
Staphylococcus aureus,n. | 1 (0.2%) | 4 (0.3%) | 0.7 |
Group B Streptococcus, n. | 2 (0.3%) | 1 (<0.1%) | 0.3 |
Other, n. | 10 (1.7%) | 13 (1.2%) | 0.4 |
Missing, n. | 55 (8.8%) | 87 (7.4%) | 0.6 |
Characteristic | Hospitalisation Period 2012–2015 n = 627 | Hospitalisation Period 2016–2020 n = 1174 | p Value |
---|---|---|---|
Antimicrobial susceptibility | 364 (58.1%) | 597 (50.9%) | <0.001 |
Antimicrobial resistance other than ESBL, MDR, XDR | 180 (28.7%) | 454 (38.7%) | <0.001 |
ESBL | 26 (4.1%) | 57 (4.9%) | 0.7 |
MDR | 56 (8.9%) | 63 (5.4%) | 0.001 |
XDR | 1 (0.2%) | 3 (0.3%) | >0.9 |
Antimicrobial Resistance other than ESBL, MDR, XDR n = 634 | ESBL n = 83 | MDR/XDR n = 123 | |||||||
---|---|---|---|---|---|---|---|---|---|
Characteristic | OR | 95% CI | p Value | OR | 95% CI | p Value | OR | 95% CI | p Value |
Age | 1.03 | 0.98, 1.08 | 0.18 | 1.02 | 0.96, 1.08 | 0.45 | 1.03 | 0.98, 1.08 | 0.18 |
Sex | |||||||||
F | - | - | - | - | |||||
M | 1.16 | 0.80, 1.69 | 0.42 | 1.1 | 0.70, 1.71 | 0.68 | 1.16 | 0.80, 1.69 | 0.42 |
Recurrent UTI | 4.31 | 2.70, 6.75 | <0.001 | 2.57 | 1.40, 4.47 | 0.001 | 4.31 | 2.70, 6.75 | <0.001 |
Antibiotic prophylaxis | 5.34 | 2.74, 10.2 | <0.001 | 2.65 | 1.18, 5.55 | 0.013 | 5.34 | 2.74, 10.2 | <0.001 |
Antibiotic therapy in the preceding 30 days | 2.83 | 1.76, 4.44 | <0.001 | 2.08 | 1.13, 3.60 | 0.013 | 2.83 | 1.76, 4.44 | <0.001 |
Vescico-ureteral reflux, n. | 1.10 | 0.76, 1.63 | 0.63 | ||||||
Other urological malformations | 2.67 | 1.71, 4.09 | <0.001 | 1.18 | 0.61, 2.10 | 0.6 | 2.67 | 1.71, 4.09 | <0.001 |
Nephromegaly | 1.14 | 0.39, 2.66 | 0.78 | 0.95 | 0.23, 2.64 | 0.93 | 1.14 | 0.39, 2.66 | 0.78 |
Pyelectasis | 1.19 | 0.79, 1.77 | 0.41 | 0.93 | 0.57, 1.50 | 0.76 | 1.19 | 0.79, 1.77 | 0.41 |
Therapy | Hospitalisation Period 2012–2015 n = 627 | Hospitalisation Period 2016–2020 n = 1174 | p Value |
---|---|---|---|
Amoxicillin | 14 (2.2%) | 20 (1.7%) | 0.4 |
Amoxicillin/clavulanate | 130 (21%) | 363 (31%) | <0.001 |
Ampicillin +.aminoglycosides | 112 (18%) | 185 (16%) | 0.3 |
third-generation cephalosporins | 284 (45%) | 479 (41%) | 0.066 |
third-generation cephalosporins + aminoglycosides | 29 (4.6%) | 60 (5.1%) | 0.7 |
Aminoglycosides | 12 (1.9%) | 15 (1.3%) | 0.3 |
Quinolones | 1 (0.2%) | 2 (0.2%) | >0.9 |
TMX-SMZ | 2 (0.3%) | 0 (0%) | 0.12 |
Other therapies | 17 (2.7%) | 30 (2.6%) | 0.8 |
Characteristic | OR | 95% CI | p Value |
---|---|---|---|
Antimicrobial resistance other than ESBL, MDR/XDR | 1.39 | 1.00, 1.93 | 0.051 |
ESBL pathogens | 3.69 | 2.12–6.21 | <0.001 |
MDR/XDR pathogens | 4.07 | 2.57, 6.36 | <0.001 |
Age | 1.03 | 0.98, 1.07 | 0.21 |
Male sex | 1.08 | 0.78, 1.48 | 0.65 |
Recurrent UTI | 2.04 | 1.28, 3.16 | 0.002 |
Antibiotic prophylaxis | 1.87 | 0.93, 3.56 | 0.064 |
Antibiotic therapy in the previous 30 days | 1.75 | 1.12, 2.66 | 0.011 |
Vescico-ureteral reflux | 1.17 | 0.79, 1.80 | 0.45 |
Other urological malformations | 1.49 | 0.98, 2.22 | 0.055 |
Pielectasis | 1.41 | 1.01, 1.96 | 0.045 |
Nephromegaly | 2.85 | 1.01, 1.96 | <0.001 |
Treatment with amoxicillin | 5.06 | 2.38, 10.2 | <0.001 |
Treatment with amoxicillin/clavulanate | 1.67 | 1.20, 2.32 | 0.002 |
Treatment with ampicillin + aminoglycosides | 0.99 | 0.64, 1.49 | 0.96 |
Treatment with third-generation cephalosporins | 0.46 | 0.32, 0.65 | <0.001 |
Treatment with third-generation cephalosporins + aminoglycosides | 0.77 | 0.32, 1.57 | 0.51 |
Treatment with aminoglycosides | 1.20 | 0.28, 3.50 | 0.77 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Esposito, S.; Maglietta, G.; Di Costanzo, M.; Ceccoli, M.; Vergine, G.; La Scola, C.; Malaventura, C.; Falcioni, A.; Iacono, A.; Crisafi, A.; et al. Retrospective 8-Year Study on the Antibiotic Resistance of Uropathogens in Children Hospitalised for Urinary Tract Infection in the Emilia-Romagna Region, Italy. Antibiotics 2021, 10, 1207. https://doi.org/10.3390/antibiotics10101207
Esposito S, Maglietta G, Di Costanzo M, Ceccoli M, Vergine G, La Scola C, Malaventura C, Falcioni A, Iacono A, Crisafi A, et al. Retrospective 8-Year Study on the Antibiotic Resistance of Uropathogens in Children Hospitalised for Urinary Tract Infection in the Emilia-Romagna Region, Italy. Antibiotics. 2021; 10(10):1207. https://doi.org/10.3390/antibiotics10101207
Chicago/Turabian StyleEsposito, Susanna, Giuseppe Maglietta, Margherita Di Costanzo, Martina Ceccoli, Gianluca Vergine, Claudio La Scola, Cristina Malaventura, Alice Falcioni, Alessandra Iacono, Antonella Crisafi, and et al. 2021. "Retrospective 8-Year Study on the Antibiotic Resistance of Uropathogens in Children Hospitalised for Urinary Tract Infection in the Emilia-Romagna Region, Italy" Antibiotics 10, no. 10: 1207. https://doi.org/10.3390/antibiotics10101207