fosfomycin and Prostatitis

There has been growing interest in fosfomycin for the treatment of bacterial prostatitis due to evidence suggesting that it achieves adequate prostatic concentrations for antimicrobial effect, has activity against resistant micro-organisms, and has a low-toxicity profile. This review evaluated the current clinical evidence for fosfomycin in acute and chronic bacterial prostatitis to elucidate the clinical implications of fosfomycin in an era of increasing antimicrobial resistance. PubMed, Scopus, EMBASE, Web of Science, Google Scholar and ClinicalTrials.gov were searched for studies published in the English language from January 1984 to November 2019. The inclusion criteria were met if the study reported the use of fosfomycin (more than one dose) to treat bacterial prostatitis. Ten observational studies were identified that met the inclusion criteria. The evidence for the use of fosfomycin in acute bacterial prostatitis is sparse. The majority of the available evidence is for chronic bacterial prostatitis caused by Escherichia coli. Despite the implementation of variable dosing regimens, extended courses of fosfomycin appear to be safe and effective in achieving clinical and microbiological cure. In these studies, the use of fosfomycin was restricted to cases of treatment failure, intolerance to first-line therapy, or multi-resistant organisms. However, given the development of resistant organisms and the undesirable adverse effects of many first-line therapeutic options, fosfomycin has the potential to be considered as an effective first-line alternative for acute and chronic bacterial prostatitis in the future. Further studies, including randomized controlled trials, would be helpful to firmly establish its optimal dosing regimen, efficacy and place in therapy.

Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Bacterial Infections; Enterobacteriaceae; Enterococcus faecium; Escherichia coli; Fosfomycin; Humans; Male; Prostate; Prostatitis; Pseudomonas aeruginosa; Treatment Outcome

Fosfomycin (FOM) is an antibiotic with a small relative molecular weight (138.1) and a long half-life, and has a unique chemical structure and antibacterial mechanisms. It exerts a bactericidal activity by inhibiting the early synthesis of bacterial cell walls. It is also a broad-spectrum antibiotic with a good drug tolerance and compliance and a low pressure to bacterial resistance, but no cross-resistance with other antibiotics. Recent studies show the effectiveness of FOM in the treatment of acute uncomplicated urinary tract infections and urogenital tract infections as well, such as prostatitis and epididymitis. This review focuses on the clinical application of FOM in the treatment of infectious diseases of the urogenital tract.

Topics: Anti-Bacterial Agents; Epididymitis; Fosfomycin; Humans; Male; Male Urogenital Diseases; Prostatitis; Urinary Tract Infections

Bacterial prostatitis can be difficult to treat as more and more bacteria are resistant to fluoroquinolone and/or Sulfamethoxazole-Trimethoprim which are the antibiotics of choice. Fosfomycin-Trometamol which is registered for uncomplicated urinary tract infections can be an option when other treatments can't be used.. To describe a case of prostatitis cured using a prolonged course of Fosfomycin-Trometamol. Patient: A 67 years-old man with a chronic bacterial prostatitis, with recurrences for more than 3 years, due to. Fosfomycin-Trometamol can be a good option for the treatment of bacterial prostatitis when other antibiotics can't be used either for resistance or allergy.

Topics: Aged; Anti-Bacterial Agents; Escherichia coli; Fosfomycin; Humans; Male; Prostatitis; Tromethamine; Urinary Tract Infections

This paper presents the results of a pilot study of difficult-to-treat patients (exhibiting several previous treatment failures or detection of extended-spectrum beta-lactamase [ESBL] strains) with chronic bacterial prostatitis (CBP) who underwent treatment with fosfomycin trometamol (FT) and N-acetyl-L-cysteine (NAC). Twenty-eight patients with clinically- and microbiologically-confirmed CBP who attended a single urological institution between January 2018 and March 2019 were treated with oral administration of 3 g FT once a day for 2 days, followed by a dose of 3 g every 48 h for 2 weeks, in combination with oral administration of NAC 600 mg once a day for 2 weeks. Clinical and microbiological analyses were carried out at the time of admission (T0) and during follow-up at 1 month (T1) and 6 months (T2) after the end of treatment. Symptoms were assessed by the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and International Prostatic Symptom Score (IPSS), and quality of life was assessed by Quality of Well-Being (QoL) questionnaires. Isolated strains were Escherichia coli (23 patients), Enterococcus spp. (3 patients), and Klebsiella oxytoca (2 patients). ESBL strain was found in 19 (67.8%) patients. Microbiological eradication was documented in 21 (75%) patients at the second follow-up visit and clinical cure was achieved in 20 (71.4%) patients. Significant changes on questionnaires were recorded between baseline and follow-up visits. Fifteen of 19 patients (78.9%) with ESBL strains were cured. No significant side effects were reported. FT in combination with NAC is a promising alternative therapy in difficult-to-treat CBP patients.

Topics: Acetylcysteine; Adult; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Escherichia coli; Fosfomycin; Humans; Klebsiella oxytoca; Male; Middle Aged; Pilot Projects; Prostatitis; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Young Adult

Chronic bacterial prostatitis (CBP) is a difficult-to-treat infection as only a few antibiotics achieve therapeutic concentrations in the prostate. Data on the efficacy and safety of oral fosfomycin for the treatment of CBP are limited.. To analyse the efficacy and safety of fosfomycin in CBP due to MDR pathogens.. In a prospective observational study, an oral regimen of 3 g of fosfomycin q24h for 1 week followed by 3 g q48h for a treatment duration of 6-12 weeks was administered. The outcome was clinical and microbiological cure rate at the end of treatment (EOT) and rate of relapse at 3 and 6 months.. The study included 44 patients. The most common pathogen was Escherichia coli (66%), followed by Klebsiella spp. (14%) and Enterococcus faecalis (14%). Most strains were MDR (59%) and 23% had an ESBL phenotype; 33 of 44 strains were resistant to fluoroquinolones, but all were susceptible to fosfomycin (median MIC for Gram-negative pathogens 1.5 mg/L). In 25 patients, treatment was administered for 6 weeks, whereas in the remaining 19 patients it was prolonged to 12 weeks based on the presence of calcifications in the prostate. Cure rate was 82% at EOT and 80% and 73% at 3 and 6 months accordingly. Microbiological eradication was achieved in 86% and 77% at EOT and at 6 months, respectively. Failure was observed in 12 patients. The most common adverse event was diarrhoea (18%).. Oral fosfomycin, particularly in the era of MDR prevalence, represents an attractive, safe and effective alternative to fluoroquinolones for the treatment of CBP.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Chronic Disease; Drug Resistance, Multiple, Bacterial; Enterococcus faecalis; Escherichia coli; Fosfomycin; Humans; Klebsiella; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Prostatitis

The emergence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) infections requires re-assessment of therapeutic choices. Here we report the efficacy of cefoxitin-based antibiotic therapy for ESBL-E prostatitis. A prospective study including patients with ESBL-E prostatitis resistant to trimethoprim/sulfamethoxazole and fluoroquinolones from January 2014 to March 2016 was conducted. Cefoxitin was administered by continuous infusion for 3 weeks in the case of acute bacterial prostatitis or 6 weeks in the case of chronic bacterial prostatitis (CBP), with intravenous fosfomycin for the first 5 days. Urological investigations were performed to diagnose underlying urinary tract pathology. Clinical and microbiological efficacy were evaluated 3 months (M3) and 6 months (M6) after the end of therapy. A total of 23 patients were included in the study. The median patient age was 74 years (range 48-88 years). Of the 23 infections, 14 (61%) were CBP and 12 (52%) were healthcare-associated infections. The bacteria involved were Escherichia coli in 11 cases, Klebsiella pneumoniae in 10 cases and Klebsiella oxytoca in 2 cases. Clinical cure was observed in 19/23 patients (83%) at M3 and in 17/22 patients (77%) at M6. Urocultures were sterile in 13/23 patients (57%) at M3 and in 9/19 patients (47%) and M6. Urinary colonisation was observed in 6/19 patients (32%) with clinical cure at M3 and 5/14 patients (36%) with clinical cure at M6. No resistance to cefoxitin was detected. Surgical treatment was required for 7/23 patients (30%). In conclusion, cefoxitin-based antibiotic therapy is suitable for difficult-to-treat ESBL-E infections such as prostatitis.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cefoxitin; Cross Infection; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Fosfomycin; Humans; Klebsiella Infections; Klebsiella oxytoca; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Pilot Projects; Prospective Studies; Prostatitis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

In this study, we assessed the therapeutic effects of fosfomycin tromethamine (FT) in a bacterial prostatitis (BP) rat model. The BP model was induced by Escherichia coli and was demonstrated after 7 days microbiologically and histologically. Then, 25 BP rats selected were randomly divided into five treatment groups: model group, positive group, FT-3 day group, FT-7 day group and FT-14 day group. Ventral lobes of prostate from all animals were removed, and the serum samples were collected at the end of the experiments. Microbiological cultures and histological findings of the prostate samples demonstrated reduced bacterial growth and improved inflammatory responses in FT-treatment groups compared with the model group, indicating that FT against prostatic infection induced by E. coli showed good antibacterial effects. Moreover, plasma pharmacokinetics and prostatic distribution of fosfomycin were studied and compared in BP and normal rats. The concentrations of fosfomycin in samples were analysed by liquid chromatography-tandem mass spectrometry. There were no differences in plasma pharmacokinetic parameters between two groups. But significantly higher penetration of fosfomycin into prostatic tissues was found in BP rats. We therefore suggested that FT had a good therapeutic effect on BP and it might be used in curing masculine reproductive system diseases.

Topics: Animals; Anti-Bacterial Agents; Escherichia coli Infections; Fosfomycin; Male; Models, Animal; Prostatitis; Rats; Rats, Sprague-Dawley; Tissue Distribution

To investigate the effects of fosfomycin tromethamine (FT) on the expressions of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6) in the prostate tissue of the rats with chronic bacterial prostatitis (CBP).. We randomly divided 70 male SD rats into 7 groups of equal number: blank control, CBP model control, positive control, 14 d low-dose FT, 7 d low-dose FT, 14 d high-dose FT, and 7 d high-dose FT. The CBP model rats in the latter five groups were treated intragastrically with levofloxacin at 100 mg/kg/d for 30 days and FT at 200 mg/kg/d for 14 and 7 days and at 300 mg/kg/d for 14 and 7 days, respectively. Then we collected the prostate tissue from the animals for determination of the levels of TNF-α, IL-8 and IL-6 by ELISA.. Compared with the blank controls, the CBP model rats showed significantly increased levels of TNF-α (［19.83 ± 6.1］ vs ［32.93 ± 6.21］ ng/g prot, P <0.01), IL-8 (［8.26 ± 0.52］ vs ［16.2 ± 2.84］ ng/g prot, P <0.01) and IL-6 (［1.55 ± 0.11］ vs ［2.51 ± 1.06］ ng/g prot, P <0.05) in the prostate tissue. In comparison with the CBP model controls, the levels of TNF-α and IL-8 were remarkably decreased in the groups of positive control (［20.54 ± 5.78］ ng/g prot, P <0.01; ［12.43 ± 4.02］ ng/g prot, P <0.05), 14 d low-dose FT (［21.95 ± 6.48］ ng/g prot, P <0.01; ［11.11 ± 2.86］ ng/g prot, P <0.01), 7 d low-dose FT (［23.8 ± 6.93］ ng/g prot, P <0.05; ［12.43 ± 4.02］ ng/g prot, P <0.05), 14 d high-dose FT (［19.97 ± 2.58］ ng/g prot, P <0.01; ［8.83 ± 1.32］ ng/g prot, P <0.01), and 7 d high-dose FT (［21.97 ± 3.38］ ng/g prot, P <0.01; ［12.68±1.97］ ng/g prot, P <0.05). No statistically significant differences were observed between the positive control and FT groups in the contents of TNF-α, IL-8 or IL-6 (P >0.05). The expression of IL-6 was markedly reduced in the 14 d high-dose FT group as compared with the model controls (［1.76 ± 0.46］ vs ［2.51 ± 1.06］ ng/g prot, P<0.05) but exhibited no significant difference between the CBP model control and the other groups (P >0.05).. Fosfomycin tromethamine inhibits the expressions of TNF-α, IL-8 and IL-6 in the prostate tissue, suppresses its inflammatory reaction, promotes the repair of damaged prostatic structure, and thus contributes to the treatment of chronic bacterial prostatitis in rats.. 目的： 探讨磷霉素氨丁三醇散（FT）对慢性细菌性前列腺炎模型大鼠肿瘤坏死因子-α（TNF-α）、白介素8（IL-8）、白介素6（IL-6）表达水平的影响。 方法： 70只雄性SD大鼠随机分为7组，每组10只。A组：假手术组；B组：模型对照组；C组：阳性对照组［左氧氟沙星：100 mg/(kg·d)，30 d］；D组：FT低剂量、14 d疗程组［200 mg/(kg·d)，14 d］；E组：FT低剂量、7 d疗程组［200 mg/(kg·d)，7 d］； F组：FT高剂量、14 d疗程组［300 mg/(kg·d)，14 d］；G组：FT高剂量、7 d疗程组［300 mg/(kg·d)，7 d］,各组均采用灌胃给药。实验结束后留取各组大鼠前列腺组织，制作病理切片并使用酶联免疫吸附实验（ELISA）检测各组大鼠前列腺组织匀浆中TNF-α、IL-8、IL-6的含量。 结果： 与空白对照组比较，模型组大鼠前列腺组织匀浆中的TNF-α、IL-8、IL-6含量均明显升高，差异均有统计学意义［（19.83±6.1）ng/g prot vs（32.93±6.21）ng/gprot，（8.26±0.52）ng/g prot vs（16.2±2.84）ng/g prot，（1.55±0.11）ng/g prot vs（2.51±1.06）ng/g prot，P<0.05或0.01］；与模型组［（32.93±6.21）ng/g prot、（16.2±2.84）ng/g prot］相比，各治疗组大鼠前列腺组织匀浆中的TNF-α、IL-8含量［（20.54±5.78）ng/g prot、（21.95±6.48）ng/g prot、（23.8±6.93）ng/g prot、（19.97±2.58）ng/g prot、（21.97±3.38）ng/g prot；（12.43±3.64）ng/g prot、（11.11±2.86）ng/g prot、（12.43±4.02）ng/g prot、（8.83±1.32）ng/g prot、（12.68±1.97）ng/g prot］明显降低，差异具有统计学意义（P<0.05或0.01）；各治疗组大鼠前列腺组织匀浆的TNF-α、IL-8、IL-6含量与阳性对照组比较差异均无统计学意义（P>0.05）；F组大鼠前列腺组织匀浆中的IL-6的表达量较模型组显著减少［（2.51±1.06）ng/g prot vs（1.76±0.46）ng/g prot，P<0.05］，其余治疗组及阳性对照组前列腺组织匀浆中的IL-6的表达与模型组比较均无显著性差异（P>0.05），但较模型组均有下降趋势。 结论： FT通过抑制TNF-α、IL-8、IL-6的表达，减轻前列腺组织的炎症反应，达到治疗大鼠CBP的目的，为临床研究提供了实验依据。.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Fosfomycin; Interleukin-6; Interleukin-8; Levofloxacin; Male; Prostate; Prostatitis; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Topics: Anti-Bacterial Agents; Fosfomycin; Humans; Male; Prostatitis; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Fosfomycin; Humans; Male; Prostatitis; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Calculi; Enterobacteriaceae; Enterobacteriaceae Infections; Fosfomycin; Humans; Male; Middle Aged; Prostatitis; Treatment Outcome

For chronic bacterial prostatitis, there are few oral antibiotics available that are active against common uropathogens and are able to penetrate the non-inflamed prostate at therapeutic concentrations. Oral options to treat chronic prostatitis due to Gram-negative bacillary multidrug-resistant organisms are even more limited. We report a case of persistent extended-spectrum β-lactamase (ESBL)-positive Escherichia coli chronic prostatitis refractory to antibiotic therapy. Prolonged courses of fosfomycin failed to eradicate the infection. Re-treatment with high-dose fosfomycin again failed to clear the infection. After repeated courses of fosfomycin, the ESBL-positive E. coli remained susceptible to fosfomycin. Transrectal ultrasound revealed prostatic calcifications that were thought to be the reason for antibiotic failure. Following transurethral resection of the prostate (TURP) to remove the prostatic calcifications, the prostatic calcifications remained and the infection persisted. Although the patient's ESBL-positive E. coli was resistant to doxycycline, he was treated with a combination of fosfomycin plus doxycycline. Treatment with fosfomycin and doxycycline rapidly cured his chronic prostatitis.

Topics: Anti-Bacterial Agents; beta-Lactamases; Doxycycline; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Male; Middle Aged; Prostatitis; Treatment Outcome

Topics: Anti-Bacterial Agents; Fosfomycin; Humans; Male; Prostatitis; Urinary Tract Infections

Treatment options for prostatitis caused by multidrug-resistant gram-negative bacilli are limited. We report two cases cured with oral fosfomycin and provide a pharmacokinetic analysis of fosfomycin predose concentrations during treatment.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Fosfomycin; Humans; Male; Prostatitis; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Fosfomycin; Gram-Negative Bacterial Infections; Humans; Male; Prostate; Prostatitis

This is a retrospective study of 15 difficult-to-treat (i.e., exhibiting previous failure, patient side effects, or resistance to ciprofloxacin and co-trimoxazole) chronic bacterial prostatitis infections (5 patients with multidrug-resistant Enterobacteriaceae [MDRE]) receiving fosfomycin-tromethamine at a dose of 3 g per 48 to 72 h for 6 weeks. After a median follow-up of 20 months, 7 patients (47%) had a clinical response, and 8 patients (53%) had persistent microbiological eradication; 4/5 patients with MDRE isolates achieved eradication. There were no side effects. Fosfomycin-tromethamine is a possible alternative therapy for chronic bacterial prostatitis.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Fosfomycin; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prostatitis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Tromethamine; Young Adult

Multidrug-resistant gram-negative bacterial (MDR-GNB) infections of the prostate are an increasing problem worldwide, particularly complicating transrectal ultrasound (TRUS)-guided prostate biopsy. Fluoroquinolone-based regimens, once the mainstay of many protocols, are increasingly ineffective. Fosfomycin has reasonable in vitro and urinary activity (minimum inhibitory concentration breakpoint ≤64 µg/mL) against MDR-GNB, but its prostatic penetration has been uncertain, so it has not been widely recommended for the prophylaxis or treatment of MDR-GNB prostatitis.. In a prospective study of healthy men undergoing a transurethral resection of the prostate for benign prostatic hyperplasia, we assessed serum, urine, and prostatic tissue (transition zone [TZ] and peripheral zone [PZ]) fosfomycin concentrations using liquid chromatography-tandem mass spectrometry, following a single 3-g oral fosfomycin dose within 17 hours of surgery.. Among the 26 participants, mean plasma and urinary fosfomycin levels were 11.4 ± 7.6 µg/mL and 571 ± 418 µg/mL, 565 ± 149 minutes and 581 ± 150 minutes postdose, respectively. Mean overall prostate fosfomycin levels were 6.5 ± 4.9 µg/g (range, 0.7-22.1 µg/g), with therapeutic concentrations detectable up to 17 hours following the dose. The mean prostate to plasma ratio was 0.67 ± 0.57. Mean concentrations within the TZ vs PZ prostate regions varied significantly (TZ, 8.3 ± 6.6 vs PZ, 4.4 ± 4.1 µg/g; P = .001). Only 1 patient had a mean prostatic fosfomycin concentration of <1 µg/g, whereas the majority (70%) had concentrations ≥4 µg/g.. Fosfomycin appears to achieve reasonable intraprostatic concentrations in uninflamed prostate following a single 3-g oral dose, such that it may be a potential option for prophylaxis pre-TRUS prostate biopsy and possibly for the treatment of MDR-GNB prostatitis. Formal clinical studies are now required.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anti-Bacterial Agents; Chromatography, Liquid; Fosfomycin; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Prospective Studies; Prostate; Prostatitis; Serum; Tandem Mass Spectrometry; Urine

An Escherichia coli isolate with New Delhi metallo-beta-lactamase was isolated from a patient with pyelonephritis and prostatitis who returned to Canada after recent hospitalization in India. The patient was successfully treated with ertapenem and fosfomycin. This patient highlights the role of international travel in the spread of antimicrobial drug resistance and blaNDM-1.

Topics: Adult; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Canada; Carbapenems; Drug Resistance, Multiple, Bacterial; Ertapenem; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; India; Male; Microbial Sensitivity Tests; Prostatitis; Pyelonephritis; Travel; Urine

Topics: Anti-Bacterial Agents; Aztreonam; beta-Lactam Resistance; beta-Lactamases; Cryptococcosis; Cryptococcus neoformans; Fosfomycin; HIV Seropositivity; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prostatitis; Pseudomonas aeruginosa; Pseudomonas Infections; Saudi Arabia

Twenty-four patients with urinary tract infections were treated with fosfomycin (FOM) to evaluate its effectiveness and safety. They all had shown allergic reactions, mainly to beta-lactams. Lymphocyte stimulation test (LST), leukocyte migration inhibition test (LMT), passive cutaneous anaphylaxis (PCA) and the precipitin reaction were performed to test whether FOM would also cause an allergic reaction. FOM was judged by the physician-in-charge to be effective in all 6 patients (100%) with acute simple cystitis and 8 (72.7%) of 11 patients with chronic complicated urinary tract infections. The drug was also effective in 15 (83.3%) of 18 patients with epididymitis, etc. Regarding the usefulness of FOM, it was judged to be useful in 21 (91.3%) of 23 patients. FOM was very useful in 8 (34.8%) of these 23. In patients tested for LST, the value was lower in cases given FOM than in cases given ampicillin (ABPC), cefazolin (CEZ) or latamoxef (LMOX); there was an especially significant (p less than 0.01) difference with ABPC. All the drugs tested were negative for the LMT, PCA and precipitin reaction tests. No subjective or objective abnormalities were attributed to the FOM treatment, and there were also no abnormal laboratory test values. FOM was evaluated to be an effective and safe antibacterial agent without in vitro or clinical allergic reactions.

Topics: Adolescent; Adult; Aged; Drug Hypersensitivity; Epididymitis; Female; Fosfomycin; Humans; Male; Middle Aged; Prostatitis; Urethritis; Urinary Tract Infections