Reviewed: Bonetta A, Roviello G, Generali D, et al. Enteric-coated and highly standardized cranberry extract reduces antibiotic and nonsteroidal anti-inflammatory drug use for urinary tract infections during radiotherapy for prostate carcinoma. Res Rep Urol. 2017;9:65-69.
Bacterial resistance to antibiotics is a growing concern, and new approaches are needed to prevent and treat bacterial infections. Consumption of cranberry (Vaccinium macrocarpon, Ericaceae) products that contain A-type double interflavan-bond proanthocyanidins (PAC-A) from cranberry fruit may reduce urinary tract infections by limiting the ability of bacteria to adhere to the lining of the bladder. Patients with prostate cancer who are treated with pelvic external beam radiotherapy (EBRT) have an increased risk of urinary tract infections. Previous research by the authors showed that an enteric-coated, standardized cranberry extract was effective in reducing EBRT-induced lower urinary tract infections (LUTIs) and symptoms.1 The purpose of this randomized, open-label, controlled study was to confirm those findings in a larger population and show that prophylactic use of the cranberry extract can decrease antibiotic use.
Patients (N = 924; mean age of approximately 70 years) diagnosed with prostatic adenocarcinoma and treated with radiotherapy were recruited between 2006 and 2016 at the Radiation Oncology Unit of Cremona Hospital in Cremona, Italy. Patients received radiotherapy to the prostate region and also to the pelvic area if the risk of lymph node spread was estimated to be more than 15%. Included patients were treated with radical (2.3 grays [Gy; a measure of radiation dose] per fraction per day), postsurgical (2.23/2.3 Gy per fraction per day), or personalized (3 Gy per fraction per day) radiotherapy five times per week. Patients were excluded if they refused daily treatment with cranberry extract, or if they had a history of pelvic EBRT, previous pelvic malignancies, a Karnofsky score (an assessment of the patients’ general wellbeing) of less than 80, or renal failure.
Patients received 200 mg per day of cranberry extract (MonoSelect Macrocarpon; PharmExtracta Srl; Pontenure, Piacenza, Italy [also called Ressuro; Helsinn Healthcare SA; Lugano, Switzerland]; standardized to 30% PACs according to the “European Pharmacopoeia method (version 6.0)”*) for six to seven weeks. There were 489 patients in the cranberry group and 435 in the untreated control group. The primary endpoint was the number of patients who had LUTIs in each group. Secondary endpoints included the recurrence of LUTIs, days of antibiotic use, number of patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs), and incidence of dysuria (painful urination). Urinary symptoms, NSAID use, and antibiotic use were assessed weekly. Urine cultures were performed at week three and week six.
The baseline characteristics of both groups were comparable except that the cranberry group had a higher percentage of patients who received both prostate and pelvic lymph node irradiation (50% of the cranberry group vs. 32% of the control group). Treatment compliance was excellent, and no patients discontinued treatment. Four patients with chronic gastritis complained of gastric pain with cranberry use, and “a protecting agent” (no further information provided) was used. There were no other adverse events.
After the completion of EBRT, a total of 10.8% of the cranberry group and 24.6% of the control group had LUTIs (P = .0001). Recurrent infection occurred in 0.8% of the cranberry group and 2.3% of the control group (P = .004). Escherichia coli was the most common pathogen implicated in LUTIs, with 72% of E. coli infections occurring in the control group and 28% in the cranberry group. Enterococcus faecalis was the second most frequent cause of LUTIs in the entire study population.
The decreased incidence of LUTIs in the cranberry group correlated with decreased antibiotic use. Accordingly, the cranberry group had significantly fewer days of antibiotic use than the control group (285 days vs. 585 days, respectively; P = .001). The cranberry group also had significantly more patients with no dysuria compared with the control group (62.8% vs. 36.6%, respectively; P = .001). Moreover, the cranberry group had significantly fewer patients than the control group who used NSAIDs to treat urinary symptoms (23.1% vs. 46.2%, respectively; P = .001). Various urinary symptoms due to radiotherapy were observed in a smaller percentage of the cranberry group compared with the control group, including nocturia (waking to urinate; 29% vs. 52%), urgency (30% vs. 55%), and average daily urination frequency change (1.8 vs. 3.35) (P values not given).
The authors conclude that the use of this cranberry preparation correlated with a lower risk of developing a LUTI in the study population. This study used objective and subjective measures to demonstrate that the enteric-coated cranberry extract was associated with fewer LUTI episodes and reduced urinary discomfort. The authors state that this is the first study to demonstrate “that the prophylactic use of cranberry can reduce antibiotic treatment by ~50%.” A limitation of this study is that it was not double-blinded or placebo-controlled. According to the authors, they are currently conducting a double-blind, placebo-controlled study to confirm the data.
— Heather S. Oliff, PhD
- Bonetta A, Di Pierro F. Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary symptoms during radiotherapy for prostate carcinoma. Cancer Manag Res. 2012;4:281-286.