Adrian Pilatz

Infective Complications After Prostate Biopsy: Outcome of the Global Prevalence Study of Infections in Urology (GPIU) 2010 and 2011, A Prospective Multinational Multicentre Prostate Biopsy Study

BACKGROUND Infection is a serious adverse effect of prostate biopsy (P-Bx), and recent reports suggest an increasing incidence. OBJECTIVE The aim of this multinational multicentre study was to evaluate prospectively the incidence of infective complications after P-Bx and identify risk factors. DESIGN, SETTING, AND PARTICIPANTS The study was performed as an adjunct to the Global Prevalence Study of Infections in Urology (GPIU) during 2010 and 2011. Men undergoing P-Bx in participating centres during the 2-wk period commencing on the GPIU study census day were eligible. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Baseline data were collected and men were questioned regarding infective complications at 2 wk following their biopsy. The Fisher exact test, Student t test, Mann-Whitney U test, and multivariate regression analysis were used for data analysis. RESULTS AND LIMITATIONS A total of 702 men from 84 GPIU participating centres worldwide were included. Antibiotic prophylaxis was administered prior to biopsy in 98.2% of men predominantly using a fluoroquinolone (92.5%). Outcome data were available for 521 men (74%). Symptomatic urinary tract infection (UTI) was seen in 27 men (5.2%), which was febrile in 18 (3.5%) and required hospitalisation in 16 (3.1%). Multivariate analysis did not identify any patient subgroups at a significantly higher risk of infection after P-Bx. Causative organisms were isolated in 10 cases (37%) with 6 resistant to fluoroquinolones. The small sample size per participating site and in compared with other studies may have limited the conclusions from our study. CONCLUSIONS Infective complications after transrectal P-Bx are important because of the associated patient morbidity. Despite antibiotic prophylaxis, 5% of men will experience an infective complication, but none of the possible factors we examined appeared to increase this risk. Our study confirms a high incidence of fluoroquinolone resistance in causative bacteria.

Influence of urogenital infections and inflammation on semen quality and male fertility

BackgroundUrogenital infections and inflammation are a significant etiologic factor in male infertility.MethodsData for this review were acquired by a systematic search of the medical literature. Relevant cross-references were also taken into account.ResultsWe address infectious and inflammatory diseases of different compartments of the male genital tract and discuss their andrological sequelae. Chronic urethritis might be responsible for silent genital tract inflammation with negative impact on semen quality. In chronic pelvic pain syndrome, morphological abnormalities of spermatozoa and seminal plasma alterations are detectable. In the majority of men with epididymitis, a transient impairment of semen quality can be found during the acute infection. However, persistent detrimental effects are not uncommon, even after complete bacteriological cure. The relevance of chronic viral infections as an etiologic factor in male infertility is believed to be underestimated. Data concerning the impact of HIV infection on male fertility are of increasing interest as with the improvement in life expectancy, issues of sexuality and procreation gain importance. Moreover, effects of noninfectious systemic inflammation on the male reproductive tract have to be considered in patients with metabolic syndrome, a disorder of growing relevance worldwide. Finally, microbiological and related diagnostic findings in urine and semen samples are reviewed according to their relevance for male infertility.ConclusionsAvailable data provide sufficient evidence that in men with alterations of the ejaculate, urogenital infections and inflammation have to be considered.

Impact of infection on the secretory capacity of the male accessory glands.

INTRODUCTION Studies that compare the impact of different infectious entities of the male reproductive tract (MRT) on the male accessory gland function are controversial. MATERIALS AND METHODS Semen analyses of 71 patients with proven infections of the MRT were compared with the results of 40 healthy non-infected volunteers. Patients were divided into 3 groups according to their diagnosis: chronic prostatitis NIH type II (n = 38), chronic epididymitis (n = 12), and chronic urethritis (n = 21). RESULTS The bacteriological analysis revealed 9 different types of microorganisms, considered to be the etiological agents, isolated in different secretions, including: urine, expressed prostatic secretions, semen and urethral smears: E. Coli (n = 20), Klebsiella (n = 2), Proteus spp. (n = 1), Enterococcus (n = 20), Staphylococcus spp. (n = 1), M. tuberculosis (n = 2), N. gonorrhea (n = 8), Chlamydia tr. (n = 16) and, Ureaplasma urealyticum (n = 1). The infection group had significantly (p < 0.05) lower: semen volume, alpha-glucosidase, fructose, and zinc in seminal plasma and, higher pH than the control group. None of these parameters was sufficiently accurate in the ROC analysis to discriminate between infected and non-infected men. CONCLUSION Proven bacterial infections of the MRT impact negatively on all the accessory gland function parameters evaluated in semen, suggesting impairment of the secretory capacity of the epididymis, seminal vesicles and prostate. These findings were associated with an infectious related significant increase of semen pH. None of the semen parameters evaluated can be suggested as a diagnostic tool for infection.

Therapeutic challenges of urosepsis

Urosepsis accounts for approximately 25% of all sepsis cases and may develop from a community or nosocomial acquired urinary tract infection (UTI). The underlying UTI is almost exclusively a complicated one with involvement of parenchymatous urogenital organs (e.g. kidneys, prostate). In urosepsis, as in other types of sepsis, the severity of sepsis depends mostly upon the host response. The treatment of urosepsis comprises four major aspects: Early goal directed therapy, early optimal pharmacodynamic exposure to antimicrobials, early control of the complicating factor in the urinary tract and specific sepsis therapy. Following these prerequisites there appear two major challenges that need to be addressed:

Uropathogenic E. coli Induce Different Immune Response in Testicular and Peritoneal Macrophages: Implications for Testicular Immune Privilege

Infertility affects one in seven couples and ascending bacterial infections of the male genitourinary tract by Escherichia coli are an important cause of male factor infertility. Thus understanding mechanisms by which immunocompetent cells such as testicular macrophages (TM) respond to infection and how bacterial pathogens manipulate defense pathways is of importance. Whole genome expression profiling of TM and peritoneal macrophages (PM) infected with uropathogenic E. coli (UPEC) revealed major differences in regulated genes. However, a multitude of genes implicated in calcium signaling pathways was a common feature which indicated a role of calcium-dependent nuclear factor of activated T cells (NFAT) signaling. UPEC-dependent NFAT activation was confirmed in both cultured TM and in TM in an in vivo UPEC infectious rat orchitis model. Elevated expression of NFATC2-regulated anti-inflammatory cytokines was found in TM (IL-4, IL-13) and PM (IL-3, IL-4, IL-13). NFATC2 is activated by rapid influx of calcium, an activity delineated to the pore forming toxin alpha-hemolysin by bacterial mutant analysis. Alpha-hemolysin suppressed IL-6 and TNF-α cytokine release from PM and caused differential activation of MAP kinase and AP-1 signaling pathways in TM and PM leading to reciprocal expression of key pro-inflammatory cytokines in PM (IL-1α, IL-1β, IL-6 downregulated) and TM (IL-1β, IL-6 upregulated). In addition, unlike PM, LPS-treated TM were refractory to NFκB activation shown by the absence of degradation of IκBα and lack of pro-inflammatory cytokine secretion (IL-6, TNF-α). Taken together, these results suggest a mechanism to the conundrum by which TM initiate immune responses to bacteria, while maintaining testicular immune privilege with its ability to tolerate neo-autoantigens expressed on developing spermatogenic cells.

Reducing infection rates after prostate biopsy

Over the years, prostate biopsy has become the gold-standard technique for diagnosing prostate carcinoma. Worldwide, several million prostate biopsies are performed every year, most commonly using the transrectal approach. Preoperative antibiotic prophylaxis with fluoroquinolones has been shown to be effective for reducing infection rates. However, in recent years, an increase in febrile infection rates after transrectal prostate biopsy (from 1% to 4%) has been reported in retrospective and prospective studies. The predominant risk factor for infection seems to be the presence of fluoroquinolone-resistant bacteria in faeces. Patients at risk of fluoroquinolone resistance should receive carefully selected antibiotics at sufficient concentrations to be effective. Targeted prophylaxis after rectal flora swabbing has been shown to be efficacious compared with empirical antibiotic prophylaxis. Several forms of bowel preparations are under investigation, although none have yet been shown to significantly reduce infection rates. Perineal prostate biopsy is currently being evaluated as a strategy for preventing the inoculation of rectal flora, but limited data support this approach at present.

Are Antisperm Antibodies Really Associated with Proven Chronic Inflammatory and Infectious Diseases of the Male Reproductive Tract

BACKGROUND It is debated whether chronic urogenital inflammations and infections may trigger the formation of antisperm antibodies (ASA) in semen. OBJECTIVE To evaluate the formation of ASA in defined chronic inflammatory and infectious diseases of the male reproductive tract (MRT). DESIGN, SETTING, AND PARTICIPANTS Three hundred sixty-five patients retrospectively enrolled in a single center were categorized as having National Institutes of Health (NIH) category II chronic prostatitis (n=38), NIH category IIIa chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) (n=59), NIH category IIIb CP/CPPS (n=213), chronic epididymitis (n=34), and chronic urethritis (n=21). Forty-five age-matched men served as controls. MEASUREMENTS All subjects underwent microbiologic and cytologic analysis for common bacteria, yeasts, and mycoplasma using the four-glass test. Urine samples, ejaculates, and urethral swabs were analyzed with polymerase chain reaction (PCR) for Chlamydia trachomatis and Neisseria gonorrhea. Semen analysis followed World Health Organization (WHO) standards. ASA in seminal plasma were analyzed using the mixed agglutination reaction (MAR) test. RESULTS AND LIMITATIONS The overall positive detection rate of clinically significant levels (> or = 50% of spermatozoa coated by ASA) of IgG and IgA antibodies was 1.8% and 0.8%, respectively, in the patient group. No clinically significant levels of ASA were detected in the control group, and no statistically significant difference was observed between controls and patients (IgG, p=1.0; IgA, p=1.0). No difference was found between the different inflammatory and infectious diseases and the control group in the detection rate of ASA, even when the cut-point value was lowered to > or = 1% (IgG, p=0.4; IgA, p=0.3). Moreover, in one selected subgroup of patients (n=26) with persistent increased inflammatory parameters (peroxidase-positive leukocytes [PPL] > or = 1 x 10(6)/ml and elastase > or = 230 ng/ml), no significant difference in the levels of ASA was observed compared with the controls (IgG, p=0.1; IgA, p=0.8). CONCLUSION There is no association between chronic inflammatory or infectious diseases of the MRT and the presence of ASA in semen.

Urosepsis--from the view of the urologist.

Urosepsis accounts for approximately 25% of all sepsis cases and may develop from a community-or nosocomial-acquired urinary tract infection (UTI). The underlying UTI is almost exclusively a complicated one with involvement of parenchymatous urogenital organs (e.g. kidneys, prostate). In urosepsis, as in other types of sepsis, the severity of sepsis depends mostly upon the host response. The urological management of urosepsis comprises early diagnosis, early fluid and oxygen treatment, early antibiotic therapy and early control of the complicating factor in the urinary tract. Time from admission to therapy is critical. The shorter the time to effective treatment, the higher is the success rate. This aspect has to become incorporated into the organisational process, including urologists, radiologists and intensive care specialists amongst others. Adequate initial antibiotic therapy has to be insured. This goal implies, however, a wide array of measures over time to ensure a rational antibiotic policy, including microbiologists and clinical pharmacologists. Dosage of an antibiotic in the septic patient generally has to be high to ensure adequate pharmacological exposure in the individual patient.

Acute Epididymitis Revisited: Impact of Molecular Diagnostics on Etiology and Contemporary Guideline Recommendations

BACKGROUND Acute epididymitis is a common infectious disease of unknown etiology in about 30% of cases with guidelines based on studies published >15 yr ago. OBJECTIVE To investigate the etiology of acute epididymitis using state-of-the-art methods and to provide rational data for antimicrobial therapy and clinical management. DESIGN, SETTING, AND PARTICIPANTS Between 2007 and 2013, 237 patients (150 antimicrobially naive and 87 antibiotically pretreated) with acute epididymitis underwent comprehensive investigation comprising microbiologic cultures, polymerase chain reaction (PCR) for sexually transmitted infections (STIs), 16S ribosomal DNA (rDNA) analysis, and PCR detection of 23 viruses. Clinical management followed international guidelines. OUTCOME MEASURES AND STATISTICAL ANALYSIS Etiology, clinical management, and outcome after 3 mo were assessed. RESULTS AND LIMITATIONS A causative pathogen, predominantly Escherichia coli (56%), was identified in 132 antibiotic-naive patients (88%) and 44 pretreated patients (51%); 16S rDNA analysis increased the detection rate by 10%. STIs were present in 34 cases (14%) (25 patients with Chlamydia trachomatis) and were not restricted to a specific age group. Enteroviruses were found in only two patients (1%). In naive patients, cultured bacteria were susceptible to fluoroquinolones and group 3 cephalosporins in >85% of cases (preateted patients: 42% and 67%, respectively). Primary empirical therapy was continued in 88% of naive patients for 11 d and in 77% of pretreated patients for 13 d with indwelling urinary catheters, rendering patients as high risk for switching. Only six patients (2.5%) underwent semicastration. Prostate-specific antigen levels halved within 3 mo, except in patients who were antibiotic naive and without detected pathogens. Study limitations included a lack of susceptibility testing in cases of STIs. CONCLUSIONS Even in antimicrobially pretreated patients, acute epididymitis is mainly of bacterial origin. STIs are not limited to patients aged <35 yr. Viral epididymitis seems a rare condition. Current guideline recommendations on empirical antimicrobial therapy are adequate. PATIENT SUMMARY Patients with acute epididymitis should receive appropriate diagnostics and antimicrobial therapy for safe conservative management.

Acute bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: andrological implications.

There is a consensus on the diagnostic management of bacterial prostatitis (acute and chronic). In chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) the diagnostic approach remains unclear, because inflammatory and noninflammatory CP/CPPS might be one entity with varying findings over time. The WHO definition of male accessory gland infection does not differentiate between prostatitis, epididymitis, and other inflammatory alterations of the urethral compartment. The definition therefore cannot be further accepted as a rational tool for the diagnosis of prostatitis and related diseases in urological andrology. Therapy in infectious prostatitis is standardised and antibiotics are the primary agents. Andrological implications are well defined, side‐effects are minimal. CP/CPPS therapy has the goal to reduce pelvic pain. However, treatment regimens are not as standardised. Andrological side‐effects are well defined and mainly due to the functional background of these agents.