To investigate the clinical features, bacterial species, and treatment of urinary tract infection (UTI) in children with neurogenic bladder (NB) with or without vesicoureteral reflux (VUR).

Collect clinical data of 37 NB children with UTI admitted to our department from 2013 to 2023, with a total of 73 hospitalizations. According to the results of voiding cystourethrogram, they were divided into a non-VUR and VUR group. Compare the differences in symptoms and bacterial spectrum, drug sensitivity test and antibiotic use between the two groups.

A total of 37 children with 73 hospitalizations were enrolled, including 17 males and 20 females. There were 13 children with 25 hospitalizations in the non-VUR group and 24 children with 48 hospitalizations in VUR group. In VUR group, there were 8 cases of left reflux, 4 cases of right reflux, and 12 cases of bilateral reflux. All of them were high-grade reflux, including 5 cases of grade 3, 11 cases of grade 4, and 8 cases of grade 5. Fever was the most common clinical manifestation of UTI, accounting for 84% (42/60) of all symptomatic UTI. Compared with non-VUR group, VUR group had a higher frequency of symptomatic UTI (P=0.049). A total of 18 strains of bacteria were cultured in 13 cases in non-VUR group and 48 strains were cultured in 31 cases in VUR group. The culture probability was not statistically significant (P>0.05). Among them, 48 (72.7%) were gram-negative bacteria, 14 (21.2%) were Gram-positive bacteria, and 4 (6.1%) were fungi. The most common gram-negative bacteria was Escherichia coli (16/48, 33.3%), followed by Klebsiella pneumoniae (11/48, 22.9%). 2 strains of Escherichia coli were cultured with  1 strain (50.0%) produced extended-spectrum beta-lactamase (ESBL) in non-VUR group, while 15 strains with 12 strains (80.0%) in VUR group. 3 strains of Klebsiella pneumoniae without drug resistance in non-VUR group with 8 strains of with 1 strain (12.5%) produced ESBL, 1 strain (12.5%) was carbapenem-resistant Enterobacteriaceae (CRE) and 1 strain (12.5%) was CRE combined with ESBL in VUR group. Compared with non-VUR group, VUR cultured more drug-resistant bacteria (P=0.047). The most common gram-positive bacteria was Enterococcus faecalis (7/14, 50.0%), including 5 strains (71.4%) in non-VUR group and 2 strains (28.6%) in VUR group, followed by Enterococcus faecium (4/14, 8.3%), all from VUR group. The number of Enterococcus faecalis infection was more in non-VUR group (P=0.020). The results of drug sensitivity analysis showed that Escherichia coli and Klebsiella pneumoniae had high resistance rates to second-generation cephalosporin and ceftriaxone. The former was sensitive to ceftazidime, nitrofurantoin, carbapenems and β-lactam antibiotics combined with β-lactamase inhibitors (e.g. piperacillin/tazobactam, cefoperazone/sulbactam and amoxicillin clavulanate potassium), while the latter was sensitive to ceftazidime, piperacillin-tazobactam and carbapenems. Enterococcus faecalis and Enterococcus faecium were resistant to erythromycin and clindamycin, and sensitive to ampicillin, linezolid and vancomycin. The resistance rate of Enterococcus faecium was higher than that of Enterococcus faecalis (P=0.000). Compared with non-VUR group, VUR group used ceftazidime more frequently (P=0.003) and cefuroxime less frequently (P=0.004), while there was no statistically significant difference in the number of cured cases using piperacillin tazobactam between the two groups (P>0.05).

VUR is a common complication of NB, and high-grade VUR can lead to recurrent UTI[1]. All the NB children with UTI and VUR collected in this study were high-grade VUR. Fever is the most common clinical manifestation of UTI, and VUR group has a higher proportion of symptomatic UTI, which may be due to the reflux of pathogens into the upper urinary tract, making it more likely to develop clinical symptoms. Gram-negative bacteria are the most common bacteria of UTI, among which Escherichia coli and Klebsiella pneumoniae are the most common bacteria, which is consistent with the results of many other studies. Enterococcus faecalis and Enterococcus faecium are common Gram-positive enterococci of UTI. In this study, the drug resistance rate of Enterococcus faecium was higher, and they all existed in the reflux group and was still sensitive to ampicillin, linezolid and vancomycin. Enterococcus faecalis is also sensitive to some oral antibiotics such as amoxicillin, clavulanate potassium and nitrofurantoin. The increased proportion of Enterococcus infection is a characteristic of complicated UTI[2]. Cefuroxime was more frequently used in non-VUR group, while ceftazidime was more frequently used in VUR group, which may be related to the high proportion of drug-resistant bacteria in VUR group, suggesting that the combination of VUR is more prone to complex UTI and has a higher proportion of antibiotic resistance. There was no significant difference in the proportion of use of piperacillin-tazobactam between the two groups, because it is sensitive to most Gram-negative bacilli and it can reduce the prevalence of ESBL-producing strains[3].

NB children should be actively treated the primary disease, and paid attention to the presence of VUR and UTI. NB children with VUR are more likely to have symptomatic UTI, of which fever is the most common. Children with VUR are more likely to develop drug-resistant bacterial infections. Therefore, for UTI children with NB and VUR, ceftazidime or piperacillin tazobactam can be chosen. For those without VUR, cefuroxime can be used first. If ineffective, it can be upgraded to piperacillin tazobactam, and urine culture and drug sensitivity results should be monitored during treatment. If the culture result is enterococcus, it is necessary to pay special attention to the etiological basis and use antibiotics rationally.

Chiba H, Kitta T, Higuchi M, et al. Ureteral reimplantation during augmentation cystoplasty is not needed for vesicoureteral reflux in patients with neurogenic bladder: a long-term retrospective study. BMC urology. 2022;22(1):48.
Qiao LD, Chen S, Yang Y, et al. Characteristics of urinary tract infection pathogens and their in vitro susceptibility to antimicrobial agents in China: data from a multicenter study. BMJ open. 2013;3(12):e004152.
Lee SJ, Lee DS, Choe HS, et al. Antimicrobial resistance in community-acquired urinary tract infections: results from the Korean Antimicrobial Resistance Monitoring System. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2011;17(3):440-446.