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Introduction: Chronic bacterial prostatitis (CBP) is a difficult-to-eradicate infection. Antibacterial therapy with currently licensed agents is hindered due to the increasing emergence of pathogen resistance worldwide and to frequent infection relapse. With limited treatment options, physicians are investigating new agents, which, however, may raise safety concerns., Areas Covered: Antibacterial agents currently licensed for CBP were not considered. Available reports about the safety and efficacy of antibacterial agents that have been clinically tested or tentatively used to treat CBP in single cases were evaluated. This review also focused on agents targeting Gram-positive pathogens, whose prevalence as causative agents of CBP is increasing., Expert Opinion: (i) Most antibacterial agents considered in this review have been administered off-label in the interest of patients, and their use requires particular caution. (ii) Reports describing the usage of many of the drugs reviewed here are still scant, and readers should be warned of the limited published evidence supporting therapy for CBP with these agents. (iii) As treatment must extend over several weeks, medium-term adverse events may occur and therapy should be individualized, taking into account the dosage and the potential toxicity of each specific antibiotic. Regarding dangerous drug-drug interactions, particular attention should be paid to the risk of ECG-QT-interval elongation.

Purpose: To evaluate the efficacy of Lactobacillus paracasei CNCM I-1572 (L. casei DG®) in both prevention of symptomatic recurrences and improvement of quality of life in patients with chronic bacterial prostatitis (CBP)., Methods: Patients with CBP attending a single Urological Institution were enrolled in this phase IV study. At enrollment, all patients were treated with antibiotics in agreement with EAU guidelines and then were treated with L. casei DG® (2 capsules/day for 3 months). Clinical and microbiological analyses were carried out before (enrollment, T0) and 6 months (T2) after the treatment. Both safety and adherence to the treatment were evaluated 3 months (T1) after the enrollment. NIH Chronic Prostatitis Symptom Index (CPSI), International Prostate Symptom Score (IPSS) and Quality of Well-Being (QoL) questionnaires were used. The outcome measures were the rate of symptomatic recurrence, changes in questionnaire symptom scores and the reduction of antibiotic use., Results: Eighty-four patients were included. At T2, 61 patients (72.6%) reported a clinical improvement of symptoms with a return to their clinical status before symptoms. A time dependent improvement in clinical symptoms with significant changes in NIH-CPSI, IPSS and QoL (mean difference T2 vs T0: 16.5 ± 3.58; - 11.0 ± 4.32; + 0.3 ± 0.09; p < 0.001), was reported. We recorded that L. casei DG® treatment induced a statistically significant decrease in both (p < 0.001) symptomatic recurrence [1.9/3 months vs 0.5/3 months] and antibiotic use [- 7938 UDD]. No clinically relevant adverse effects were reported., Conclusions: L. casei DG® prevents symptomatic recurrences and improves the quality of life in patients with CBP, reducing the antibiotic use., (© 2021. The Author(s).)

Background: The pathogenesis of infectious complications after retrograde intrarenal surgery (RIRS) is not fully understood., Objective: To evaluate spreading of bacteria into irrigation fluid and blood during RIRS for stone management and to correlate such spreading with infectious complications., Design, Setting, and Participants: From January to December 2017, 38 patients who underwent RIRS for stones in two urological units were enrolled in this prospective, longitudinal cohort study., Intervention: A urine culture was taken before surgery and antimicrobial prophylaxis was given in line with the European Association of Urology guidelines. Blood and irrigation fluid samples were collected at the start of the endoscopic procedure and every 30min during the procedure. All samples were microbiologically examined and findings were compared with clinical data., Outcome Measurements and Statistical Analyses: Symptomatic and asymptomatic urinary tract infectious complications were correlated with microbiological and clinical data, using Student t test or Mann-Whitney U test., Results and Limitations: Ten patients showed significant bacterial growth in irrigation fluid samples (seven Escherichia coli, two Klebsiella pneumoniae, and one Pseudomonas aeruginosa). Eight patients (21%) got febrile urinary tract infections during hospital stay: two had bacterial growth in the irrigation fluid (25%) and one also had bacteremia (12.5%). No correlation was found either between the bacterial growth in the irrigation fluid samples and the urine cultures that were taken before the procedure, or between the bacterial growth in the irrigation fluid samples and the development of postoperative infectious complications. Previous use of fluoroquinolones and a history of urinary tract infections were associated with infectious complications after RIRS., Conclusions: We demonstrated spreading of bacteria into the irrigation fluid during RIRS procedures, but this spreading was not associated with the development of infectious complications. Particular attention should be given to previous antibiotic treatment before administration of antimicrobial prophylaxis., Patient Summary: Bacterial spreading into irrigation fluid is a common finding during retrograde intrarenal surgery, but it is not associated with infectious complications after the procedure. Particular attention should be given to previous antibiotic treatment before administration of antimicrobial prophylaxis., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Mounting worldwide resistance trends make the use of fluoroquinolone (FQ) antibacterial agents increasingly difficult. This is felt more acutely in the case of urogenital infections, which are mainly caused by Gram-negative pathogens. For years, levofloxacin and other FQs have been the first-line drugs for treating National Institutes of Health (NIH) category II chronic bacteria prostatitis (CBP). Eradication rates achieved by levofloxacin in the frame of randomized trials vary greatly, ranging between 71 and 86%., Objectives: This was a retrospective observational study to investigate the efficacy of levofloxacin against CBP in a real-life setting (urological outpatient wards)., Methods: A database including the clinical records of >2,500 CBP patients was reviewed. Patients were selected based on strict inclusion criteria. They were treated for 4 weeks with 500 mg levofloxacin per day, alone or combined with other antibacterials. Besides standard urological procedures including the 4-glass test for pathogen isolation, international symptom questionnaires (the NIH Chronic Prostatitis Symptom Index [NIH-CPSI] and International Prostate Symptom Score [IPSS]) were administered., Results: Pathogen eradication was achieved in 79% of the cases treated with levofloxacin as a single agent and 87.8% of patients who received a combination of levofloxacin and azithromycin. The 11% increase in the eradication rate in the latter group is statistically significant. In addition, the levofloxacin-azithromycin combination caused a significant decrease in prostate volume and significantly increased the bladder-voided volume. IPSS and NIH-CPSI values and the urinary peak flow rate decreased to a similar extent in both treatment groups. No adverse effects were reported by patients belonging to either treatment group., Conclusion: Levofloxacin retained its therapeutic efficacy in patients assessed in a real-life setting, and high eradication rates were attained when it was administered as a single agent. A combination of an FQ with azithromycin induced a significant improvement of eradication rates. This strategy may be an interesting option in both first-referral and relapsing cases, although caution should be exercised when patients are at risk of developing arrhythmias, tendinitis, or other adverse effects., (© 2019 S. Karger AG, Basel.)

Azithromycin is a macrolide antibiotic which inhibits bacterial protein synthesis, quorum-sensing and reduces the formation of biofilm. Accumulating effectively in cells, particularly phagocytes, it is delivered in high concentrations to sites of infection, as reflected in rapid plasma clearance and extensive tissue distribution. Azithromycin is indicated for respiratory, urogenital, dermal and other bacterial infections, and exerts immunomodulatory effects in chronic inflammatory disorders, including diffuse panbronchiolitis, post-transplant bronchiolitis and rosacea. Modulation of host responses facilitates its long-term therapeutic benefit in cystic fibrosis, non-cystic fibrosis bronchiectasis, exacerbations of chronic obstructive pulmonary disease (COPD) and non-eosinophilic asthma. Initial, stimulatory effects of azithromycin on immune and epithelial cells, involving interactions with phospholipids and Erk1/2, are followed by later modulation of transcription factors AP-1, NFκB, inflammatory cytokine and mucin release. Delayed inhibitory effects on cell function and high lysosomal accumulation accompany disruption of protein and intracellular lipid transport, regulation of surface receptor expression, of macrophage phenotype and autophagy. These later changes underlie many immunomodulatory effects of azithromycin, contributing to resolution of acute infections and reduction of exacerbations in chronic airway diseases. A sub-group of post-transplant bronchiolitis patients appears to be sensitive to azithromycin, as may be patients with severe sepsis. Other promising indications include chronic prostatitis and periodontitis, but weak activity in malaria is unlikely to prove crucial. Long-term administration of azithromycin must be balanced against the potential for increased bacterial resistance. Azithromycin has a very good record of safety, but recent reports indicate rare cases of cardiac torsades des pointes in patients at risk., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Chronic bacterial prostatitis (CBP) is frequently diagnosed in men of fertile age, and is characterized by a disabling array of symptoms, including pain in the pelvic area (for example, perineum, testicles), voiding symptoms (increased frequency and urgency, also at night; pain or discomfort at micturition), and sexual dysfunction. Cure of CBP can be attempted by long-term therapy with antibacterial agents, but relapses are frequent. Few antibacterial agents are able to distribute to the prostatic tissue and achieve sufficient concentrations at the site of infection. These agents include fluoroquinolones, macrolides, tetracyclines and trimethoprim. After the introduction of fluoroquinolones into clinical practice, a number of studies have been performed to optimize the antimicrobial treatment of CBP, and to improve eradication rates and symptom relief., Objectives: To assess and compare the efficacy and harm of antimicrobial treatments for chronic bacterial prostatitis., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE, other national or international databases and abstracts from conference proceedings on 8 August 2012., Selection Criteria: We included all randomized controlled comparisons of one antimicrobial agent versus placebo or one or more comparator antimicrobial agents, combined or not with non-antimicrobial drugs. We also included trials comparing different doses, treatment durations, dosing frequencies, or routes of administration of antimicrobial agents. We excluded studies in which patients were not diagnosed according to internationally recommended criteria, or were not subjected to lower urinary tract segmented tests., Data Collection and Analysis: Study data were extracted independently by two review authors. Study outcomes were microbiological efficacy (pathogen eradication), clinical efficacy (symptom cure or improvement, or symptom scores) at test-of-cure visits or at follow-up, or both, and adverse effects of therapy. Secondary outcomes included microbiological recurrence rates.Statistical analysis was performed using a fixed-effect model for microbiological outcomes and a random-effects model for clinical outcomes and adverse effects. The results were expressed as risk ratios for dichotomous outcomes (with 95% confidence intervals) or as standardized mean differences for continuous or non-dichotomous variables., Main Results: We identified 18 studies, enrolling a total of 2196 randomized patients. The oral fluoroquinolones ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin and prulifloxacin were compared. There were no significant differences in clinical or microbiological efficacy or in the rate of adverse effects between these fluoroquinolones. In chlamydial prostatitis, (i) azithromycin showed improved eradication rates and clinical cure rates compared to ciprofloxacin, with no significant differences regarding adverse effects; (ii) azithromycin was equivalent to clarithromycin, both microbiologically and clinically; (iii) prulifloxacin appeared to improve clinical symptoms, but not eradication rates, compared to doxycycline. In ureaplasmal prostatitis, the comparisons ofloxacin versus minocycline and azithromycin versus doxycycline showed similar microbiological, clinical and toxicity profiles., Authors' Conclusions: The microbiological and clinical efficacy, as well as the adverse effect profile, of different oral fluoroquinolones are comparable. No conclusions can be drawn regarding the optimal treatment duration of fluoroquinolones in the treatment of CBP caused by traditional pathogens.Alternative antimicrobial agents tested for the treatment of CBP caused by traditional pathogens are co-trimoxazole, beta-lactams and tetracyclines, but no conclusive evidence can be drawn regarding the role of non-fluoroquinolone antibiotics in the treatment of CBP caused by traditional pathogens.In patients with CBP caused by obligate intracellular pathogens, macrolides showed higher microbiological and clinical cure rates compared to fluoroquinolones.

Chronic bacterial prostatitis (CBP) is characterized by intense clinical symptoms, frequent relapse episodes and poor quality of life. Aggressive antibacterial therapy is warranted to eradicate the causative pathogens and to achieve a permanent cure. We administered a "switch-therapy" protocol to 30 patients showing severe CBP symptoms and two or more relapse episodes in the previous 12 months. Patients received intravenous azithromycin (500 mg/day) and ciprofloxacin (800 mg/day) for 3 days, followed by oral ciprofloxacin (1 g/day) for 25 days.Twenty-seven (90%) patients showed pathogen eradication at test-of-cure (TOC) visit. Five cases of infection relapse were detected at follow-up. At the TOC visit, 25 patients (83%) showed mild/absent symptoms, measured with the NIH-chronic prostatitis symptom index.These results indicate the efficacy of a "switch-therapy" protocol, based on combined azithromycin and ciprofloxacin. Comparative studies on larger CBP patient populations are warranted to confirm these encouraging results.

Chronic bacterial prostatitis (CBP) is a persistent infection of the prostate characterized by poor quality of life mainly due to frequent relapse episodes caused by incomplete eradication of causative pathogens. Aggressive antibacterial therapy is required to attenuate the severe symptoms of CBP and to achieve a permanent cure. Although fluoroquinolones are currently recommended as first-choice agents, macrolide antibiotics are emerging as a noteworthy option for the treatment of CBP. Macrolide antibiotics are characterized by an impressive array of distinct pharmacokinetic (PK) and pharmacodynamic (PD) properties. These properties include high intracellular accumulation in phagocytes and at sites of infection, including the prostate; broad antibiotic but also biofilm-inhibiting properties; immunomodulating and inflammation-resolving activities. These features offer particular advantages for the treatment of chronic infections of the prostate gland, which are not easily amenable to drug therapy. Macrolides may be exploited to counteract the unsatisfactory rates of clinical symptom improvement and pathogen eradication. The results of a number of clinical trials support this proposal.

We previously demonstrated the safety and efficacy of fluoroquinolone-macrolide combination therapy in category II chronic bacterial prostatitis (CBP). The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin (500 mg, thrice-weekly) with a once-daily 500- or 750-mg dose of ciprofloxacin (Cipro-500 or Cipro-750 cohort, respectively). Combined administration of azithromycin (1500 mg week(-1)) with ciprofloxacin at the rate of 750 mg day(-1) for 4 weeks rather than at 500 mg day(-1) for 6 weeks increased the eradication rates from 62.35% to 77.32% and the total bacteriological success from 71.76% to 85.57%. A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen (PSA) were sustained throughout an 18-month follow-up period in both groups. Ejaculatory pain, haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups, but the latter subsided more promptly in the Cipro-750 cohort. In total, 59 Cipro-750 patients showed mild-to-severe erectile dysfunction (ED) at baseline, while 22 patients had no ED on microbiological eradication and throughout the follow-up period. In conclusion fluoroquinolone-macrolide therapy resulted in pathogen eradication and CBP symptom attenuation, including pain, voiding disturbances and sexual dysfunction. A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks. Our results are open to further prospective validation.

To investigate the association between eradication of Chlamydia trachomatis (CT) and symptom regression in chronic prostatitis, 55 symptomatic patients were subjected to segmented tests to localise CT in first voided urine (VB1), prostatic secretions (EPS), post-massage voided (VB3) or semen specimens. Patients were divided in three treatment groups: the 'urethral involvement' group ('U': VB1 positive, EPS/VB3/Semen negative) was treated with 500 mg day(-1) azithromycin for 3 days. The 'prostatitis' group ('P': VB1 negative, EPS/VB3/semen positive) with 4-week levofloxacin-azithromycin combination. A third group, 'U+P' (VB1, EPS/VB3/semen positive) received both treatments in sequence. In P patients, eradication of CT was paralleled by marked, sustained symptom improvement and by significant decrease of serum prostate-specific antigen (PSA) levels. Compared with U patients, undergoing rapid regression of symptoms related to painful micturition after short-term azithromycin, U+P patients showed symptom and pathogen persistence in VB3/EPS/semen and required additional treatment with 4-week levofloxacin-azithromycin to achieve pathogen eradication, symptom regression, and decrease of PSA. Our results support a causative role of CT in chronic bacterial prostatitis. In the presence of a positive urethral localisation of the pathogen, thorough microbiological investigation together with focused symptom analysis may reveal an underlying chlamydial prostatitis and direct effective therapy with appropriate antibacterial agents., (© 2010 Blackwell Verlag GmbH.)

Importance of the Field: Bacterial urinary tract infections (UTIs) are amongst the most common infectious diseases. Therefore, any improvement in UTI management will have a high impact on the quality of life of the individual patient and the entire healthcare system. A dramatic, clinically significant increase in the antimicrobial resistance of uropathogens over the past 5 - 10 years calls for new concepts in the treatment of UTIs., Areas Covered in This Review: This article focuses on uncomplicated and complicated UTIs, and discusses antimicrobial resistance trends and antibacterial strategies. A literature search was undertaken concerning treatment studies in UTI from 1998 on. Emerging drugs for the treatment of UTI were mainly selected using the Investigational Drugs Database., What the Reader Will Gain: The aim of this review is to highlight new and emerging drugs in the antibacterial treatment of uncomplicated and complicated UTIs. This article discusses current and future aspects for recommending antibacterials for the treatment of UTIs., Take Home Message: Resistance rates of uropathogens are also significantly increasing. Emerging antimicrobial substances are not always investigated for their suitability in the treatment of UTIs. Especially, substances active against multiresistant Gram-negative pathogens will rarely be developed in the coming years.

It has been demonstrated that patients showing symptoms of chronic bacterial prostatitis but culture-negative prostate-specific specimens can benefit from administration of antibacterial agents. This suggests that organisms that are not isolated in the routine practice may be responsible for prostate infection in an undefined fraction of subjects. Anaerobic bacteria have been proposed to play a pathogenic role in CBP, on the basis of studies describing clinical remission after eradication of pathogens like Peptostreptococcus spp or Bacterioides spp from prostatic secretions of symptomatic patients, or the significant association between prostatic infection by anaerobes and the presence of inflammation markers in prostatic secretions. In this paper, we report in detail a case of severely symptomatic chronic prostatitis in a patient with evidence of infection by Peptostreptococcus. We also report for the first time that treatment with the 3rd generation fluoroquinolone moxifloxacin was successful in eradicating the pathogen and in causing dramatic resolution of signs and symptoms of chronic bacterial prostatitis. The strict association between eradication of Peptostreptococcus and the rapid disappearance of clinical signs/symptoms points to a causative role of this anaerobe in the chronic bacterial prostatitis case described in this report., (2009 Elsevier Ltd. All rights reserved.)

The significance and diagnostic value of semen analysis in chronic bacterial prostatitis has been extensively debated and remains controversial. To investigate the diagnostic relevance of semen culture in the bacteriological workup of prostatitis patients, we retrospectively analyzed a clinical database of 696 symptomatic patients. All patients were routinely subjected to a four-glass test, followed by semen culture and analysis. This allowed to dissect from the database three different diagnostic scenarios, and to compare the 'two-glass' pre-/post- massage test and the standard 'four-glass' test with a 'five-glass' test (four-glass plus post-VB3 semen culture). The 'five-glass' test showed 3.6- or 6.5-fold increases in relative sensitivity and lesser reductions (-13.2% or -14.7%) in relative specificity for traditional uropathogens (TUs) compared with the four-glass or two-glass test, respectively. The area under the ROC curve and Jouden's index were increased, whereas positive and negative likelihood ratios were lower than comparators, indicating that the 'five-glass' assay may be superior in confirming the negative outcome of both standard tests. The five-, four-, and two-glass tests detected TUs (Enterobacteriaceae, Enterococci, etc.) in 120, 33, and 20 patients and unusual pathogens (Streptococci, other Gram-positive species, Mycoplasmata, and others) in 130, 56, and 45 patients, respectively. When patients were subjected to pharmacological treatment, including a combination of a fluoroquinolone and a macrolide, no differences in eradication rates were observed between groups diagnosed with different tests, irrespective of pathogen category. Eradication was associated with long-term sign/symptom remission; no significant intergroup differences in sign/symptom scores were observed throughout a 24-month off-therapy follow-up period. In conclusion, our data support the usefulness of semen analysis in the diagnostic workup of prostatitis patients when this test is used to complement the four-glass Meares and Stamey test. Improvement of microbiological assays conveys important diagnostic and therapeutic implications.

A recently published pharmacokinetic trial showed that the fluoroquinolone moxifloxacin administered to healthy volunteers at the single oral dose of 400mg accumulates in prostatic secretions (PS) up to a median concentration of 3.99 mg/L and reaches a PS/plasma concentration ratio of 1.57, far higher than values shown by other fluoroquinolones such as norfloxacin (ratio 0.1) or ciprofloxacin (ratio 0.2). Ion trapping mechanisms were hypothesised to be among the determinants of this effect. However, whether ion trapping would solely account for the observed differences in fluoroquinolone pharmacokinetics was left to further research and discussion. In this hypothesis paper, we review various published evidence on the tissue distribution of moxifloxacin and other quinolones, suggesting that increased lipophilicity, binding to cellular matrices and fast cellular uptake/release kinetics may be mechanisms compatible with enhanced prostatic accumulation and secretion of fourth-generation fluoroquinolones.

Bacterial urinary tract infections (UTI) are frequently found in the outpatient as well as in the nosocomial setting. The bacterial UTI can be stratified into uncomplicated and complicated UTI. Antibiotic resistance is continuously increasing in uncomplicated as well as complicated UTI. In uncomplicated UTI efforts are made to use antibiotic substances exclusively for this indication. In complicated UTI as broad spectrum antibiotics are increasingly used, the higher the antimicrobial resistance rates are reported. There are two predominant aims in the antimicrobial treatment of both uncomplicated and complicated UTI: 1.) rapid and effective response to therapy, prevention of complications and prevention of recurrence in the individual patient treated, and 2.) prevention of emergence of resistance to anti-infective agents in the microbial environment. The use of antibiotics has to keep up with the continuous change in antimicrobial resistance and the tailored needs in the individual patient. Antibiotic substances therefore need to become evaluated for each indication and continuously followed for clinical usage. The knowledge of structure-activity relationships of antimicrobial substances and bacterial resistance mechanisms to antibiotics help to use antibiotics better in daily routine and design new derivatives and substances. The aim of this review is to describe the chemistry and structure-activity relationships of current antibiotics and promising substances in development for the treatment of UTI.

A total of 137 patients with a diagnosis of chronic bacterial prostatitis (CBP) were subjected to combination pharmacological therapy with antibacterial agents (ciprofloxacin/azithromycin), alpha-blockers (alfuzosin) and Serenoa repens extracts. Of those, 88 patients (64.2%) showed microbiological eradication at the completion of a 6-week cycle of therapy. Of the remaining 49 patients showing persistence of the causative organism(s) or reinfection at the end of treatment, 36 completed a second cycle of combination therapy for 6 weeks: 27 patients (75%) showed eradication of the causative organism, whereas in nine cases persistence or reinfection was observed. The cumulative eradication rate of the present study - calculated on a total of 137 enrolled patients - is 83.9%. Clinical examination showed a marked improvement of signs and symptoms linked to prostatitis. Remarkably, combination therapy could attenuate CBP symptoms prior to microbiological eradication, thus rapidly decreasing the impact of the disease on the quality of life of patients. Clinical remission was extended throughout a follow-up period of 30 months for 94% of patients, whereas seven patients showed relapse of the disease. In summary, our results indicate that about 20% of patients enrolled in this study, who were refractory to a protocol of 6-week combination therapy, could be 'rescued' by a second cycle of treatment. Clinical follow-up data show that combination therapy could ensure extended relief from CBP symptoms, and a general improvement in quality of life.