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Prophylactic cephalosporin for urinary reflux increases risk of extended-spectrum beta-lactamase-producing bacteria for breakthrough UTIs

Tuesday, December 16 2008 | Comments

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What's This? Children with vesicoureteral reflux (VUR) receiving cephalosporin prophylaxis are at an increased risk of having extended-spectrum beta-lactamase (ESBL)-producing bacteria or multidrug-resistant uropathogens for breakthrough urinary tract infections (UTIs), a new retrospective study concludes.

Researchers in Taiwan sought to examine bacterial antimicrobial resistance of recurrent UTIs in children receiving antibiotic prophylaxis because of primary VUR. To do so, they analyzed data retrospectively for pediatric patients at 2 tertiary medical centers, the Chang Gung Children's Hospital (CGCH) and the National Taiwan University Hospital (NTUH), selecting as participants patients with a confirmed diagnosis of primary VUR and who had developed breakthrough UTIs during the prophylaxis period.

At CGCH, the researchers enrolled 324 patients who had received prophylactic antibiotic therapy for >=3 months before surgery or >=6 months without surgery during the period of January 2001 through December 2002. Of these patients, 109 received trimethoprim/sulfamethoxazole, 100 received cephalexin, 44 received cefaclor, and 71 received 2 to 3 kinds of prophylactic antibiotics sequentially (alternative monotherapy). During the same period, the team enrolled 96 children at NTUH using the same criteria. These patients all received trimethoprim/sulfamethoxazole prophylaxis. Follow-up lasted 5 years.

Children at both hospitals experienced breakthrough UTIs (20.4% at CGCH and 25.0% at NTUH). Escherichia coli infection was significantly less common for breakthrough UTIs compared with initial episodes of UTI, a finding supported by earlier studies, according to the authors. This was true at both hospitals (CGCH relative risk [RR] for a pathogen other than E. coli for breakthrough UTIs, 3.0; 95% CI, 2.1-4.3; P<.0001; NTUH RR, 2.3; 95% CI, 1.4-3.8; P=.003).

Children receiving cephalexin or cefaclor prophylaxis were more likely to have ESBL-producing bacteria compared with children receiving trimethoprim/sulfamethoxazole prophylaxis (RR, 9.8; 95% CI, 1.3-73.3; P=.005). This cephalosporin effect on ESBL-producing bacteria and pathogens other than E. coli was still present and dominant in children with alternative monotherapy who received a sequence of different antibiotics including trimethoprim/sulfamethoxazole, cephalexin, and cefaclor (P=.06 for ESBL-producing organisms and P=.01 for pathogens other than E. coli, compared with trimethoprim/sulfamethoxazole). Furthermore, antimicrobial susceptibilities to almost all antibiotics decreased with cephalosporin prophylaxis when recurrent UTIs developed. Antimicrobial susceptibilities decreased minimally in the trimethoprim/sulfamethoxazole prophylaxis groups.

"The present study provides evidence to support the current recommendations that [trimethoprim/sulfamethoxazole] is appropriate for prophylaxis and that cephalosporins will not suffice," the authors concluded. (Cheng C-H, et al. Pediatrics 2008;122:1212-1217.)

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