[Taxonomic characteristics and antibiotic susceptibility of microorganisms verified in the expressed prostate secretion in post-COVID-19 patients with recurrent chronic bacterial prostatitis].

INTRODUCTION: Recurrent chronic bacterial prostatitis (rCBP) is a hard-to diagnosis-and-treat disease which there is no consensus. A particularly difficult cohort is represented by patients who had COVID-19. The study aimed to evaluate the taxonomic structure and sensitivity to antibacterial drugs of microorganisms verified in expressed prostate secretion (EPS) in rCBP-patients who had COVID-19. MATERIALS AND METHODS: A multicenter, prospective, randomized study was conducted with the inclusion of 52 rCBP patients who had COVID 19, in which the taxonomic structure and susceptibility were studied to antibacterial drugs of microorganisms that were verified and dominated in the EPS. Bacteriological study was carried out using an extended set of selective nutrient media and special cultivation conditions. Antibiotic susceptibility was determined in the taxa of microbiota dominating in the EPS. RESULTS: The mean age of the patients was 34.8+/-5.2 years, the duration of rCBP was 5.7+/-2.3 years. In all patients, various variants of aerobic-anaerobic compositions of microorganisms were recorded in the life cycle. A total of 27 microbiota taxa were isolated. The aerobic cluster was represented by 16 genera and/or species, the anaerobic cluster by 11. When studying antibiotic susceptibility to antibacterial drugs, an increase in antibiotic resistance of the most microorganisms isolated was revealed. CONCLUSIONS: The taxonomic structure of microorganisms in rCBP-patients who had COVID-19 in all cases was characterized by complex and new variants of aerobic-anaerobic associations of microorganisms. When studying the antibiotic susceptibility, multi-resistant and pan-resistant bacteria were identified that is a real threat to this category of patients.

[Extended culture study as a keypoint to rethinking antibiotic therapy for chronic bacterial prostatitis].

OBJECTIVE: To juxtapose the microbiological efficacy of standard and targeted antibiotic therapy (ABT) based on the comparison of the results of extended bacteriology of biomaterial in patients suffering chronic bacterial prostatitis (CBP) before and after treatment. STUDY DESIGN: single-centre observational comparative study. Sixty patients with CBP aged 20 to 45 years were included in the study. All patients underwent an initial examination: questioning, Meares-Stamey 4-glass test, extended bacteriology of biomaterial samples, and determination of antibacterial susceptibility (ABS). After the initial examination, the patients were randomly assigned to two groups (30/30 patients). In group (G) 1, antibacterial drugs were prescribed following the EAU guidelines on Urological Infections (monotherapy), in G2, focusing on the results of ABS (mono or combination therapy). Evaluation of the treatment effectiveness and control bacteriology were carried out three months after therapy. RESULTS: In G1 vs G2, nine vs ten aerobes and eight vs nine anaerobes were identified in the expressed prostate secretion, respectively. The microbial load of the samples in more or equal 103 CFU / ml was established in G1 vs G2 for five vs ten aerobes and seven vs eight anaerobes, respectively. The highest ABS of bacteria was determined to moxifloxacin, ofloxacin, and levofloxacin. Cefixime was the most active against anaerobes. After treatment, no significant changes in the bacterial spectrum were observed in both groups. A more reliable decrease in the frequency of microorganism identification and the microbial load of the samples was observed in patients with G2 after the targeted ABT. CONCLUSION: Targeted ABT based on extended bacteriology can be considered an effective alternative to standard guideline-approved ABT for the treatment of CBP.

[Long-term inflammatory and neoplastic reaction of prostate tissues during its transurethral infection with uropathogens: evaluation of the results of animal model study].

INTRODUCTION: There is no convincing evidence of the persistence of acute or the development of chronic bacterial-induced prostatic inflammation in the long term when infected with various titers of the uropathogen. Along with this, controversial data are presented on the relationship between post-infectious chronic inflammation and neoplastic changes in prostate tissues. OBJECTIVE: To carry out, based on the experimental data: 1) assessment of the degree of bacterial contamination and the severity of histological changes in prostate tissues on the 60th follow-up day in case of transurethral infection with various uropathogens in titers of 102,3,5 CFU/ml; 2) fundamental comparative analysis between the indicators of the inoculated test-titer and microbial load with the severity of histological changes in prostate tissues; 3) verification of neoplastic transformations in the prostate tissues during a long-term persistent bacterial-induced inflammatory process. MATERIALS AND METHODS: Animal studies were conducted using FELASA protocols. Laboratory animals: 14 New Zealand rabbits. Tested uropathogens: aerobes - E. coli, S. haemolyticus, anaerobes - P. niger. Titers: 102,3,5 CFU/ml. Uropathogen inoculation technique: topical transurethral. RANDOMIZATION: all laboratory animals were divided into 5 groups according to the uropathogen (4 experimental, 1 control). Follow-up period: 60 days. Sacrification and autopsy of the animals were performed on day 60. Biopsies were taken from various parts of the prostate, as well as from the bladder neck and the edge of the membranous urethra. Cultural, histological and immunohistochemical (expression of p53 and Ki-67) studies of prostate tissues were conducted. Statistical data processing was performed using the GraphPad Prism 9.0 program (GraphPad Software Inc., Graphpad Holdings LLC, San Diego, CA, USA) applying descriptive and non-parametric statistics. RESULTS: Two individuals infected with S. haemolyticus + P. niger had a lethal outcome. The contamination of prostate tissue was determined in all cases of infection. In 88.9% of the cases, an increase in tissue microbial load was determined compared to the initial titer. Multivariate analysis of culture study values revealed the presence of intragroup differences in prostate contamination only between infection with E. coli 103 CFU/ml and E. coli 105 CFU/ml (p=0.006), as well as intergroup differences between infection with E. coli 105 CFU/ml and P. niger 105 CFU/ml (p=0.013). The histological study revealed moderate proliferative inflammation after inoculation with 102,3,5 CFU/ml in the E. coli and S. haemolyticus groups. In the case of S. haemolyticus, it was more pronounced due to the presence of persistent alterative lesion foci; in the P. niger group, mild proliferative transformations were observed in prostate tissues in all cases. The immunohistochemical study of changes determined p53 expression (10.0%) in some areas of the glandular epithelium of prostate glands (but without a positive internal control) only in case of infection with E. coli 105 CFU/ml. Areas of glandular epithelium with Ki-67 expression ( less or equal 25.0%) were visualized in all tested groups, mainly at titers of 103 and 105 CFU/ml, but the severity of proliferative activity was not high (1+). There were no foci of prostate tissue with simultaneous nuclear activity of p53 and Ki-67. CONCLUSION: Proliferative inflammation of different intensity in prostate tissues was observed after sixty days. Its severity was mainly determined by the type of infecting agent (S. haemolyticus > E. coli > P. niger) and was not dependent on the inoculated titer and the subsequent microbial load of prostate tissues. No areas of neoplastic transformation of prostate tissues were reliably identified in the case of a bacterial-induced inflammatory process in the estimated follow-up period.

[Are bacteriological and pathomorphological signs of bacterial prostatitis related between? (An experimental study)].

INTRODUCTION: In some cases, there is a dissociation between the severity of complaints, physical examination data, and levels of contamination of the biomaterial in the differential diagnosis of various categories of prostatitis (NIH-NIDDK, 1995). Patients note the presence of pronounced symptoms when verifying the threshold indicators of microbial load (104-105 CFU / ml) of prostate secretion or post-massage urine in a few observations. However, clinical manifestations and deviations in objective indicators are not so significant in some patients with higher titers of contamination. PURPOSE OF THE STUDY: To evaluate the relationship between the microbial load indices and the degree of pathomorphological changes in the prostate tissue during infection with the "reference" uropathogen E. coli in various titers under experimental conditions MATERIALS AND METHODS: Animal model was carried out using the FELASA protocols. Experimental individuals: 16 "New Zealand" rabbits, weight: 3580 [3480; 3695] (3300-4410), age: 25 [24; 26] (23-28) weeks. Uropathogen used: E. coli. Titers: 103 CFU / ml, 105 CFU / ml, 107 CFU / ml. Infection pathway: inoculation of the uropathogen was performed through urethra according to the modified technique of J.C. Nickel. Randomization: all lab animals were evenly divided into 4 groups of 4 animals, taking into account the initial titer of the uropathogen and the observation period - experimental groups 1 (103 CFU / ml), 2 (105 CFU / ml), 3 (107 CFU / ml); group 4 was control (Sol.NaCl 0.9%). Observation terms: 1, 3, 7 and 14 days, after which the animals were euthanized and dissected. 4 biopsies (1A-1D) for bacteriological (MacConkey agar - "HiMedia", India) and 2 biopsies (P1-P2) for morphological (Hematoxylin-eosin - "BlikMediklProduction", Russia; magn. 10x, 40x, 100x, 400x) studies were formed from various parts of the prostatic complex (prostate + proprostate + paraprostate). A three-point grading system was used for morphometric assessment of destructive changes in the prostate tissue in different groups. Analytical processing of the results was carried out using the software packages Microsoft 365 ("Microsoft", USA) and Statistica 10.2 ("StatSoft Inc.", USA) by methods of descriptive and nonparametric statistics. RESULTS: The maximum total absolute / median values of the seeding of biopsy specimens of the prostatic complex were revealed ( titer, 1A-1D) in group 1 and amounted to 76 lg CFU / ml / 5.00 [4.00; 5.25] lgCFU / ml, in group 2 defined as intermediate - 57 lgCFU / ml / 3.50 [3.00; 4.00] lgCFU / ml, and in group 3 were minimal - 48 lgCFU / ml / 3.00 [3.00; 3.25] lg CFU / ml according to the indicators of bacteriological research in the period from 1 to 14 days. Nevertheless, it was found that the cumulative maximum degree of histological changes in the prostate was recorded in group 2 ( p. - 84), in group 1 it was defined as intermediate ( p. - 68), and in group 3, it was the smallest ( p. - 64) according to the data of pathomorphological studies. When comparing daily changes in the seeding values and nominal indicators of inflammatory lesions in the prostate tissue, only in group 1, the trend graphs had a synchronous trend - an increase in microbial load led to the formation of more severe pathomorphological transformations on the day 7; in group 2, destructive changes were significant, and the rates of contamination, on the contrary, were minimal on the day 7; in group 3 a pronounced pathomorphological transformations in the tissues were noted on the day 3 and 7, but the microbial load of the tissues gradually decreased from the day 1. Also, differences in the increase in the "reactivity" of changes in the affected tissues were determined: in groups 1 and 3, a torpid reaction was revealed, accompanied by the development of moderate inflammatory changes on the day 1 and an "abrupt" increase in the intensity of destruction by the day 3; in group 2, in turn, a rapid reaction was determined, that characterized by the formation of a more pronounced destructive process already from the day 1. CONCLUSION: It was found that the parameters of contamination do not fully reflect the nature and severity of pathological changes in the prostate. Low titers of the uropathogen induce the development of an inflammatory process comparable in the severity of changes with that at higher concentrations. On the contrary, inoculation of obligate pathogenic titers does not always lead to a pronounced increase in microbial load but causes significant inflammatory changes in the prostate.

[Prostatic secretion microbiota: a comparative analysis of the hronical prostatitis II and IIIA category].

BACKGROUND: Chronic bacterial prostatitis (CBP) and chronic prostatitis/chronic pelvic pain syndrome IIIa (CP/CPPS IIIa) are separate nosologies defined diagnostic verification criteria according to the NIH-NIDDK classification (1995). The identification of enterobacteria in the prostatic secretion (PS) has long been a criterion for the diagnosis of CBP, while PS in patients suffering CP/CPPS IIIa was considered as "sterile". However, the introduction of various methods of PS`s in-depth analysis and UPOINTS classification (2010) development with the allocation of site I (infection) allows us to consider the infectious factor as an etiological predictor of the initiation of inflammation in the prostate with CP/CPPS IIIa. Thus, the determination of the features of the taxonomic composition of microbiota in BP and CP/CPPS IIIa can act as a differentiating factor of these conditions. AIMS: /Objective: performing a comparative analysis of the PS microbiota in patients suffering from CBP and CP/CPPS IIIa. MATERIALS AND METHODS: Feature: full-scale, prospective, comparative, uncontrolled study. During the study, a staged PS`s bacteriological study was performed in 101 patients (aged 20-60 years) with prostatitis-like symptoms lasting more than 3 months and identified leukocytosis in PS (> 10x`). Stage I of the PS`s study: a standard nutrient medium and culturing conditions were used. Two comparison groups were formed according to the results of the initial bacteriological study: 49 patients were included in group 1 (CBP), in which E. coli, Klebsiella spp., Proteus spp. were identified in PS (causative uropathogens in CBP), in group 2 (CP/CPPS IIIa) included 52 patients, with no growth of the above microorganisms` taxa in the biomaterial and/or primary negative results of the study. Stage II of the PS`s study: an extended set of selective media and special cultivation conditions were used for accessory verification of bacteria in biomaterial. Biochemical identification of bacteria was carried out using test systems. Statistical processing of seeding rates was carried out using Statistica 10.2 package (StatSoft Inc., USA). In both groups, we used descriptive statistics methods and the Mann-Whitney U test to process the results of bacteriological studies. The significance of differences between the studied parameters was considered at the level of p<0.05 and p<0.01. RESULTS: Usage of an expanded set of selective media and special cultivation conditions (as compared with the results of the primary bacteriological culture of the exprimate) made it possible to collectively verify in PS to 28 species / genera of microorganisms in both groups (25 in group 1 and 24 in group 2). The taxonomic composition of the PS`s microbiota was almost identical in both groups and presented mainly in the form of multicomponent microbial associations. According to the results of analysis of the bacteria`s identification frequency in PS, it was found that in group 2 (CP/CPPS IIIa) significantly more often than in group 1 (CBP) discovered some representatives of the non-clostridial anaerobic flora (NAB: Peptococcus sp., Propionibacterium spp. and others), coagulase-negative staphylococci (CNS: S.haemolyticus, S.warneri) and certain taxa of gram-positive microorganisms (Corynebacterium spp. and Str. agalacticae). In turn, when analyzing the PS contamination, it was found that integrally in group 1 (CBP) in the samples of the biomaterial a higher titer of microorganisms was determined with a wide range of quantitative values, in relation to group 2 (CP/CPPS IIIa), where the titer indices were somewhat lower and had a smaller variation relative to the average. CONCLUSION: Identification in patients of both groups in PS of different mixed microbial associations, similar in the taxonomic spectral composition of microbiota, suggests that CP/CPPS IIIa in some cases is unverified CBP, which in turn necessitates a review of diagnostic and therapeutic strategies to achieve positive clinical result.

[Experimental evaluation of inflammatory process in the prostate caused by transurethral transmission of uropathogen in low counts].

BACKGROUND: According to the literature, bacterial count of uropathogens isolated from expressed prostate secretion and urine which is sufficient for a diagnosis of bacterial prostatitis I and II categories, remains contradictory. Undoubtedly, the identification of microorganisms from affected organ in high titers indicates the presence of a relevant infectious-inflammatory process. In turn, there is no consensus on the development of bacterial prostatitis at lower titers of uropathogens. Thus, the aim of our study was to identify and compare the potential features of the development and occurrence of an infectious inflammatory process in the prostate during the reproduction of bacterial prostatitis in an animal model using a low titer of causative uropathogens. MATERIALS AND METHODS: A total of 16 "New Zealand" mature male rabbits aged 24+/-2 weeks old with weight of 3.5+/-0.3 kg were examined. Inoculation was performed via transurethral route, according to the developed experimental technique. E. coli was used as bacterial agent with a count of 1 x 103 CFU/ml, 1 x 105 CFU/ml and 1 x 107 CFU/ml. All animals were randomized into 4 groups of 4 individuals depending on the titer of the inoculated microorganisms (groups 1-3, respectively), group 4 - control (with inoculation by Sol. NaCl 0.9%). Sacrification and vivisection were performed on days 1, 3, 7 and 14 of the control days. Biopsy specimens from the lower urinary tract and internal genital organs of laboratory animals (bladder, urethra, prostatic complex - 6 biopsies #1A-1D, 2A, 2B) were evaluated morphologically and bacteriologically. Analytical evaluation of the experimental data was presented using descriptive statistical methods. RESULTS: In experimental groups (Groups 1-3), bacteriological examination of prostatic complex biopsies showed growth of microflora in all samples in titers of 101-107 CFU / ml. In group 1, the maximum concentration of uropathogen was observed on day 7, compared to day 1 in both groups 2 and 3. In all observed cases, the highest degree of bacterial contamination was noted in the biopsy specimens from paraprostatic tissues and distal part of the prostate, which was 4.0+/-1.7 lg CFU/ml and 3.5+/-1.9 lg CFU/ml, respectively, and the smallest in proximal prostatic loci (1C) and bladder neck (2B) - 3.0+/-1.2 lg COE / ml and 3.0+/-1.7 lg COE / ml, respectively. According to the morphological study, a relevant progression of the suppurative and destructive inflammation (with foci of colliquation necrosis) was identified in group 1 in the biopsies from the prostate with a maximum degree of changes on day 7 with subsequent formation of loose connective tissue proliferation areas by 14 days. This indicates the conversion of the inflammatory process to the chronic stage. These changes corresponded with the results of histopathological studies in groups 2 and 3 where higher titers of bacterial agent were used. In group 4 (control) the commensal flora was bacteriologically determined in the biopsies, but there were no signs of inflammation, according to the results of the morphological study. CONCLUSION: In experimental model, we found that E. coli 103 CFU / ml induces the development of a phasic inflammatory process in the structures of the prostatic complex. These processes resulted in the formation of irreversible proliferative changes. As a consequence, it shold be recommended to consider these signs of contamination when evaluating the results of bacteriological examination of expressed prostate secretion/urine samples during planning treatment strategy.

[Correction of incontinence during radical prostates-tomy].

Postoperative stress urinary incontinence has a significant effect on reducing the quality of life of patients undergoing radical prostatectomy. This review discusses the existing methods for correcting this condition, described in the world literature and which to one degree or another improve the quality of life of patients in this category. Analysis of present data shows that currently there are 4 main basic techniques during radical prostatectomy, which allow to statistically significantly improve of functional results. In particular, usage of this methodic allows reducing the frequency and degree of postoperative incontinence: 1) preservation of neurovascular bundles, 2) anterior and/or posterior reconstruction of the fascial spaces of the pelvis, 3) preservation of the maximum length of the membranous urethra, 4) reconstruction of the bladder neck. Preservation of the neurovascular bundles, anterior and/or posterior reconstruction of the pelvic fascial spaces have already proven themselves as effective techniques currently used by many surgeons. In contrast, the clinical utility of reserve the maximum possible length of the membranous urethra and reconstructive surgery of the bladder neck are relatively new techniques. Their clinical usefulness, as well as safety, continues to be studied.

[Bacterial prostatitis: epidemiology and etiology].

Prostatitis is considered as heterogeneous group of the diseases attracting broad interest of researchers worldwide. The acute and chronic stages of the process, as particular categories of bacterial prostatitis, remain in the realities of modern practical and scientific urology with lively discussions. Despite a large number of domestic and international publications, consensus on many topical issues of bacterial prostatitis is currently not achieved. The true incidence and prevalence of bacterial prostatitis in various regions of the world has not been finally determined. The exhaustive data concerning the etiological structure, mechanisms of development and persistence of the inflammatory process in the prostate tissue are not presented. At the same time, new risk factors that can influence the development and progress of these diseases are identified and discussed. Researchers review algorithms for examining patients, obligate spectrum of diagnostic methods, as well as the desirability of using the newest investment means necessary for the successful verification of the diagnosis taking into account the development of modern medical technologies. This review describes in detail the various aspects of the epidemiology and etiology of bacterial prostatitis, based on an analysis of major literature sources in conjunction with its own scientific facts.