Chronic bacterial prostatitis (CBP) type II, although its prevalence is low, is a frustrating condition for patients because it is characterized by a high impact on quality of life (QoL) and also by a frequent recurrence rate [
16,
17]. This condition represents a challenge for urologists and, to date, the optimal management remains controversial and the only recommended treatment is antibiotic therapy and surgery in those limited cases with severe complications [
18,
19]. Other treatments, commonly adopted, are anti-inflammatory drugs, α-blockers, phytotherapy and alternative therapies such as biofeedback, psychotherapy and acupuncture [
20]. Long-lasting therapy with fluoriquinolones antibiotics is one of the best treatments in patients with CBP because of a pharmacokinetic favourable profile and in particular ciprofloxacin and levofloxacin are recommended. The latter also has a favourable action against Gram + pathogens. Prulifloxacin, a third generation fluoroquinolone, has been approved for the treatment of lower urinary tract infection. Furthermore, it has demonstrated its ability to better penetrate into prostatic tissue compared to other quinolones, thus confirming a potential therapeutic role in the treatment of bacterial prostatic infections [
21]. Giannarini et al., comparing a 4-weeks course of prulifoxacin in comparison with levofloxacin in the treatment of chronic bacterial prostatitis, report, at 6 months, a microbiological eradication of 72.73% and 71.11%, repectively, and a reduction in the NIH-CPSI of 10.75 and 10.73. The authors conclude that prulifloxacin is at last as effective and safe as levofloxacin [
15]. Serenoa repens, saw palmetto extract, the most widely used supplement for lower urinary tracts (LUTS), and in particular for prostatic infection and inflammation, has a multimodal effect that is explained with a set of different mechanisms of action: selective antagonism of the link between dihydrotestosterone and androgen receptor; inhibition of 5-alpha-reductase, involved in the transformation of testosterone to its biologically active metabolite, that stimulates cell proliferation and hypertrophy of the prostate tissue; anti-inflammatory and anti-oedema effect, demonstrated by reduced capillary permeability induced by histamine; anti-estrogenic effect given by decline in estrogen receptors, which seems to potentiate the action of hormones in the development of BHP [
22,
23]. Unlike 5-α-reductase inhibitors (5-ARI), a selective competitive inhibitors of α-reductase type II that is more specific for prostate, serenoa repens isn’t selective and acts against both types (type I and II). Cai et al., comparing the usage of prulifloxacin alone with plurifloxacin in association with serenoa repens, urtica dioica, quercitin and curcumin in the treatment of chronic bacterial prostatitis type II, report a statistically significant difference in QoL and symptoms (absence of symptoms: 27% vs 89.6%) [
17]. Probiotics are important to reduce gastrointestinal side-effects caused by the prolonged use of broad-band antibiotics. Considering that pathogens found in the prostate often derive from intestinal bacterial overgrowth, it is important to remark the role of probiotics in maintaining a regular intestinal bacterial flora [
24]. Some authors have postulated that urethral dysbacteriosis is one of the primary causes of CP, further contributing to its recidivity and refractoriness [
12]. In particular, when this condition occurs, the urethral microflora infects the prostate through prostatic reflux of urine into prostatic ducts causing bacterial prostatitis and inflammation [
25]. Overused and overprescribed antibiotics are usually the cause of urethral dysbacteriosis while probiotics are considered a viable potential alternative for treating and preventing prostatitis and all urinary tract infections. Probiotics, with different mechanisms of action, have the ability to attach to uroepithelial cells and obtain direct antimicrobial activity [
26]. The reason we suggest using probiotics in association with a long-course antibiotic is to rebalance intestinal bacterial flora and to avoid any urinary tract dysbacteriosis and to prevent UTI recurrences [
12]. One of the limits of many studies on chronic prostatitis is that they focus only on infection eradication instead of symptoms improvement. Inflammation, together with neuromuscular spasm, is often the most important cause of chronic prostatitis symptoms [
27]. Arbutin, a glycoside extracted from bearberry plant, is a traditional supplement for treating UTI mainly because of its anti-inflammatory effect due to antioxidant capability dispatched on lypopolisaccharide, induced production of NO and expression of iNOS and COX-2 [
11].
Our study has been drawn to evaluate the efficacy of a short-course, broad band antibiotic therapy (21 days of prulifloxacin 600 mg) to eradicate pathogens in patients with CBP and to evaluate if an association with a supplement (30 days of serenoa repens 320 mg, lactobacillus sporogens 200 mg and arbutin 100 mg) is able to prevent recurrences and improve symptoms in those patients with this particularly frustrating condition. To evaluate the outcomes, patients, divided in two different groups (A and B), have been submitted to different therapies: antibiotic or antibiotic plus supplement. Looking at the results we can notice, with a statistically significant difference, that patients treated with the association of compounds obtain better effects as demonstrated with the NIH-CPSI questionnaire. Analysing first, second and third follow-up, patients in Group A obtain an improvement at 2 and 4 months while there is a decrease in results at the 6th month. Patients in Group B obtain better results in comparison with Group A, and furthermore the NIH-CPSI score continues to also decrease at the 6th month follow-up. Symptoms, probably the most invalidating condition for the patients, have been reported by patients in Group A to improve only at 2nd month follow-up while at 4th and 6th month there is a turnaround. Patients in Group B continued to report benefits till the end of follow-up time. Reported symptoms together with the NIH-CPSI questionnaire score are better in all patients treated with antibiotic plus supplement, confirming more stable and long-standing results in QoL that is always the main target of CBP patients. Prostatic specific antigen (PSA) decreases in both groups with a lower value in Group B probably because of the effect of serenoa repens that acts on type I-II 5-α-reductase, inhibiting testosterone conversion to its active metabolite. With regards to this, it is important to remark that the prostate specific antigen does not always increase during a prostatitis and does not seem to be systematically correlated to prostate inflammation [
28]; this is the most important reason why it isn’t a good parameter to show a therapy’s response. Finally we found a difference between Group A and B in uropathogens eradication; in particular we have a recurrence rate at 2 months of 27.6% and 7.8%, respectively. Pathogens found during follow-up are often different from pathogens found at baseline. We think that the main reason is because repeated cycles of antibiotic therapy are never able to prevent bacteria relapsing [
29] and this is why we can improve results by adding compounds to antibiotic therapy alone. In particular, results, show that association therapy obtains better results in avoiding the majority of recurrences and prolonging the recurrence-free time.
Limitations of the study are: small number of patients, not randomized double-blind placebo controlled trial, impossibility to attribute to single components of the compound the action, antibiotic therapy duration scientifically debated, and difficulty to evaluate if the results in the patients with recurrence have been altered by different antibiotic administered in accordance with antibiogram.