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For children with a history of recurrent urinary tract infection (RUTI), the antibiotic nitrofurantoin and cranberry products appeared to decrease the incidence of symptomatic episodes, a meta-analysis suggested.

Across 23 randomized controlled trials involving 3,335 participants, nitrofurantoin took top place in significantly lowering odds of symptomatic UTI episodes during prophylaxis, whether compared with controls (OR 0.21, 95% CI 0.07-0.65, P=0.007) or compared with either trimethoprim or sulfamethoxazole antibiotics (OR 0.29, 95% CI 0.10-0.82, P=0.02) or trimethoprim alone (OR 0.23, 95% CI 0.08-0.66, P<0.01).

However, prophylaxis with cranberry juice or tablets also yielded 59% lower odds of symptomatic UTI episodes compared with controls (OR 0.41, 95% CI 0.23-0.74, P=0.003), reported Nikolaos Gkiourtzis, MD, MSc, of Aristotle University of Thessaloniki in Greece, and colleagues writing in .

In a accompanying the study, Joshua Watson, MD, and Jason Newland, MD, MEd, both of Nationwide Children's Hospital in Columbus, Ohio, wrote that "negative consequences related to antibiotic prophylaxis makes the non-antibiotic options for preventing RUTI an exciting area of research," and thus the finding of benefit from cranberry products was "encouraging."

The literature has supported "some benefit" of low-dose antibiotics in preventing repeated episodes of UTI in vulnerable children by inhibiting bacterial growth that causes acute pyelonephritis and kidney scarring, Gkiourtzis's group wrote. "Nevertheless, according to a recent Cochrane Systematic Review, long-term antibiotic prophylaxis may have a small impact on UTI prevention with a concurrent increase in the risk for antibiotic resistance, concluding that they should be reserved only for children at risk for RUTI."

Although nitrofurantoin and cranberry products "may decrease the incidence of symptomatic UTI episodes in pediatric patients with a history of RUTI," Gkiourtzis and colleagues noted, "[n]o prophylaxis option can lead to a reduction of the risk of kidney scarring after RUTI."

"Febrile UTI and acute pyelonephritis in children may contribute to kidney scar formation with the subsequent risk of future complications," Gkiourtzis and colleagues wrote, adding that a recent post hoc analysis of data from two multicenter studies showed kidney scarring incidence of 2.8% after one febrile UTI, 25.7% after two febrile UTIs, and 28.6% after three or more febrile UTIs.

The study by Gkiourtzis and colleagues compared nine interventions, including placebo, cephadroxil (Duricef), lactobacillus, vitamin D, and cefprozil (Cefzil), for a total of 18 theoretical comparisons.

"Although other interventions had clinical significance, with respect to reducing UTI incidence, they did not reach statistical significance in this analysis," Gkiourtzis and colleagues noted. Additionally, "nitrofurantoin was ranked as the best intervention for reducing UTI incidence as compared with all available interventions."

Among the studies, the mean age of participants ranged from 3.8 to 14.7 years. More than half of the included studies were conducted in Europe. Others were from Asia, the U.S., Argentina, and Australia.

The studies were conducted between 1975 and 2023, and treatment and follow-up ranged from 2 months to 3 years. Fourteen of the studies were deemed to be of "high risk of bias."

The researchers called for studies to elucidate the optimal formulation, dose, and patient population where these products achieve their maximal benefit.

Meanwhile, decisions about treatment "should be individualized based on the patients' profile," they added. "Future studies with optimal methodology, studying non-antibiotic prophylaxis options, focusing on children with RUTI, and the risk for kidney scarring are needed to draw further conclusions."

Other options might hold potential as well, Watson and Newland noted: "Several other antibiotic alternatives have not yet been adequately studied in children, including probiotics, methenamine, and D-mannose. ... Additionally, vaccine development is underway and, if successful, may be a powerful tool for RUTI prevention."

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