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Resistance to oral antibiotics in 4569 Gram-negative rods isolated from urinary tract infection in children


To investigate antibiotic resistance among pathogens isolated from urines in a tertiary care children’s hospital in Italy. Retrospective analysis of prospectively collected data on antibiotic susceptibility of Gram-negatives isolated from urines at the Istituto Giannina Gaslini, Genoa - Italy from 2007 to 2014. Antibiotic susceptibility was evaluated. By means of CLSI criteria from 2007 to 2010, while from 2011 EUCAST criteria were adopted. Data on susceptibility to amoxicillin-clavulanate, co-trimoxazole, cefuroxime, nitrofurantoin, fosfomycin and ciprofloxacin were evaluated for Escherichia coli, while for other Enterobacteriaceae data were collected for amoxicillin-clavulanate, co-trimoxazole and ciprofloxacin and for ciprofloxacin against Pseudomonas aeruginosa. Univariate and multivariable analyses were performed for risk factors associated with resistance. A total of 4596 Gram-negative strains were observed in 3364 patients. A significant increase in the proportion of resistant strains was observed for E.coli against amoxicillin-clavulanate, cefuroxime and ciprofloxacin and for others Enterobacteriaceae against co-trimoxazole and ciprofloxacin. Resistance to nitrofurantoin and fosfomycin was very infrequent in E.coli. Logistic regression analysis showed that repeated episode of urinary tract infections was a risk factor for E.coli resistance to amoxicillin-clavulanate, co-trimoxazole and cefuroxime, while admission in one of the Units usually managing children with urinary tract malformations was significantly associated to resistance to amoxicillin-clavulanate and cefuroxime.

Conclusion: In conclusion the present study shows an increase in antibiotic resistance in pediatric bacteria isolated from urines in children, especially in presence of repeated episodes and/or urinary tract malformations. This resistance is worrisome for beta-lactams and cotrimoxazole, and start to increase also for fluoroquinolones while nitrofurantoin and fosfomycin still could represent useful drugs for oral treatment of these infections.

What is Known:
Infections are frequent in patients with urinary tract malformations
Antibiotic prophylaxis can select for resistant pathogens
What is New:
• The increase in the resistance to β-lactams, co-trimoxazole or fluoroquinolones in pathogens causing urinary tract infections cause a reduction of drugs with oral formulations available for therapy
Old drugs like nitrofurantoin and fosfomycin can represent attractive compounds for oral treatment of urinary tract infections in children presence of resistance to other drug classes

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colony forming units




confidence intervals


Clinical and Laboratory Standard Institute




European Centre for Disease Prevention and Control


European Committee on Antimicrobial Susceptibility Testing






Istituto Giannina Gaslini, Genoa – Italy


odds ratios


standard deviation




urinary tract infections


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Authors’ contributions

AC and SG were responsible for data analysis, results interpretation and for writing manuscript.

IC was responsible for data collection.

MGC was responsible for statistical analysis.

GL was responsible for data collection and analysis.

GP was responsible for data collection and analysis.

RB was responsible for study design, data collection and analysis.

EC was responsible for study design, results interpretation and supervising work and approved the final manuscript as submitted.

Author information

Correspondence to Elio Castagnola.

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This article does not contain any studies with human participants or animals performed by any of the authors.


This project was done with no specific support or funds.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Anna Calzi and Sara Grignolo are shared first authors.

Revisions received: 16 June 2016; 28 July 2016

Communicated by David Nadal

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Calzi, A., Grignolo, S., Caviglia, I. et al. Resistance to oral antibiotics in 4569 Gram-negative rods isolated from urinary tract infection in children. Eur J Pediatr 175, 1219–1225 (2016). https://doi.org/10.1007/s00431-016-2763-1

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  • Oral antibiotics
  • Gram-negative rods
  • Urinary tract infection
  • Children