Urinary shedding of common DNA viruses and their possible association with bladder cancer: a qPCR-based study.

After a decade of human urinary microbiota research, little is known about the composition of the urinary virome and its association with health and disease. This study aimed to investigate the presence of 10 common DNA viruses in human urine and their putative association with bladder cancer (BC). Catheterized urine samples were collected from patients undergoing endoscopic urological procedures under anesthesia. After DNA extraction from the samples, viral DNA sequences were detected using real-time PCR. Viruria rates were compared between BC patients and controls. A total of 106 patients (89 males and 17 females) were included in the study. Fifty-seven (53.8%) were BC patients and 49 (46.2%) had upper urinary tract stones or bladder outlet obstruction. The viruses detected in the urine were human cytomegalovirus (2.0%), Epstein-Barr virus (6.0%), human herpesvirus-6 (12.5%), human papillomavirus (15.2%), BK polyomavirus (15.5%), torque teno virus (44.2%), and JC polyomavirus (47.6%), while no adenoviruses, herpes simplex virus 1 and 2, or parvoviruses were found. There were statistically significant differences in HPV viruria rates between cancer patients and controls (24.5% vs. 4.3%, p=0.032 after adjustment for age and gender). Viruria rates increased from benign to non-muscle-invasive and muscle-invasive tumors. Patients with a history of BC have higher HPV viruria rates than controls. Whether this relationship is a causal one remains to be established by further research.

Current antibiotic resistance patterns of rare uropathogens: survey from Central European Urology Department 2011-2019.

BACKGROUND: While the resistance rates of commonly detected uropathogens are well described, those of less frequent Gram-negative uropathogenic bacteria have seldom been reported. The aim of this study was to examine the resistance rates of less frequent uropathogenic Gram-negatives in a population of patients treated in a Department of Urology of a tertiary referral centre in Central Europe over a period of 9 years. METHODS: Data on all positive urine samples from urological in- and out-patients were extracted form the Department of Clinical Microbiology database from 2011 to 2019. Numbers of susceptible and resistant isolates per year were calculated for these uropathogens: Acinetobacter spp. (n = 74), Citrobacter spp. (n = 60), Enterobacter spp. (n = 250), Morganella morganii (n = 194), Providencia spp. (n = 53), Serratia spp. (n = 82) and Stenotrophomonas maltophilia (n = 27). Antimicrobial agents selected for the survey included: ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam; cefuroxime, cefotaxime, ceftazidime and cefepime; ciprofloxacin and ofloxacin; gentamicin and amikacin; ertapenem, meropenem and imipenem; trimethoprim-sulfamethoxazole (co-trimoxazole), nitrofurantoin and colistin. RESULTS: Penicillin derivatives have generally poor effect except piperacillin/tazobactam. Cefuroxime is not efficient unlike cefotaxime (except against Acinetobacter spp. and S. maltophilia). Susceptibility to fluoroquinolones is limited. Amikacin is somewhat more efficient than gentamicine but susceptibilities for both safely exceed 80%. Nitrofurantoin shows virtually no efficiency. Cotrimoxazole acts well against Citrobacter spp., Serratia spp. and it is the treatment of choice for S. maltophilia UTIs. Among carbapenems, ertapenem was less efficient than meropenem and imipenem except for S. maltophilia whose isolates were mostly not suceptible to any carbapenems. CONCLUSIONS: Uropathogenic microorganisms covered in this report are noteworthy for their frequently multi-drug resistant phenotypes. Knowledge of resistance patterns helps clinicians choose the right empirical antibiotic treatment when the taxonomical assignment of the isolate is known but sensitivity results are pending.

Information depth of elements affects accuracy of parallel pXRF in situ measurements of soils.

Though not litigable in most European countries, portable X-ray fluorescence spectrometers (pXRF) provide cost- and time-effective as well as prompt information about hot spots of inorganic soil contaminants. The quality of aqua regia analysis of contaminants can be approximated by a thorough sample preparation, i.e., homogenization, grinding, and sieving of the examined soil before pXRF measurement is carried out. However, elaborate sample preparation causes a trade-off in terms of the desired straightforwardness of the pXRF method. For a first assessment of the in situ accuracy of pXRF measurements, two equal pXRF devices were used in parallel to determine the contents of As, Cu, Fe, Mn, Pb, Rb, Sr, Zn, and Zr of 9 identical points of a riparian soil profile. Maximum measurement values were not restricted to one pXRF device, but changed from element to element. Pearson correlation coefficients of the parallel measurements varied between 0.07 (Cu) and 0.80 (Zn), reflecting small-scale heterogeneity of the soil constituents as well as element-specific interferences. For each element, overall deviations between measurement parallels were expressed as the root-mean-square error (RMSE) and contrasted against the element-specific information depth in soil, i.e., the depth interval, from which the received spectral signals originate. From this, a gradual relation could be derived: The greater the information depth, the more stable the measured element value turns out. This context should be taken into account, when interpreting contents of elements with small atomic numbers.

[Vancomycin-resistant enterococci - the nature of resistance and risk of transmission from animals to humans]. / Problematika vankomycín rezistentných enterokokov - podstata rezistencie a riziko prenosu zo zvierat na cloveka.

Enterococci are part of the normal intestinal flora of humans and animals. Under certain circumstances, they are capable of extraintestinal conversion to opportunistic pathogens. They cause endogenous as well as exogenous community and nosocomial infections. The gastrointestinal tract of mammals provides them with favorable conditions for acquisition and spread of resistance genes, for example to vancomycin (van), from other symbiotic bacteria. Thus, vancomycin-resistant enterococci (VRE) become potential reservoirs and vectors of the van genes. Their occurrence in the population of the Czech Republic was first reported by Kolár et al. in 1997. Some variants of the vanA gene cluster carried on Tn1546 which encode resistance to vancomycin are identical in humans and in animals. It means that animals, especially cattle, poultry and pigs, could be an important reservoir of VRE for humans. Kolár and Bardon detected VRE in animals in the Czech Republic for the first time in 2000. In Europe, the glycopeptide antibiotic avoparcin, used as a growth stimulator, is responsible for selection of VRE strains in animals. Strains of Enterococcus faecium from animals may offer genes of antimicrobial resistance to other enterococci or they can be directly dangerous to human. This is demonstrated by finding isolates of E. faecalis from human patients and from pigs having very similar profiles of resistance and virulence genes. The goal of the paper was to point out the similarity between isolates of human and animal strains of enterococci resistant to vancomycin, and the possibility of their bilateral transfer between humans and animals.

Heteroatom-substituted tetra(3,4-pyrido)porphyrazines: a stride toward near-infrared-absorbing macrocycles.

A synthesis procedure for heteroatom-substituted tetra(3,4-pyrido)porphyrazines that absorb light near 800 nm was developed. Based on the observed relationships between the structure and photophysical parameters, a novel highly photodynamically active (IC50 = 0.26 µM) compound was synthesized and biologically characterized.

Bladder cancer is associated with decreased urinary microbiota diversity and alterations in microbial community composition.

INTRODUCTION: Human urine microbiota (UM) research has uncovered associations between composition of microbial communities of the lower urinary tract and various disease states including several reports on the putative link between UM and bladder cancer (BC). The aim of this study was to investigate male UM in patients with BC and controls using catheterised urine specimens unlike in previous studies. METHODS: Urine samples were obtained in theatre after surgical prepping and draping using aseptic catheterisation. DNA was extracted and hypervariable region V4 of the 16S rRNA gene was amplified using 515F and 806R primers. Sequencing was performed on Illumina MiSeq platform. Sequencing data were processed using appropriate software tools. Alpha diversity measures were calculated and compared between groups. Prevalence Interval for Microbiome Evaluation was used to test differences in beta diversity. RESULTS: A total of 63 samples were included in the analysis. Mean age of study subjects was 65.1 years (SD 12.5). Thirty-four men had bladder cancer and 29 participants were undergoing interventions for benign conditions (benign prostate hyperplasia or upper urinary tract stone disease). BC patients had lower UM richness and diversity than controls (83 vs. 139 operational taxonomic units, P = 0.015; Shannon index: 2.46 vs. 2.94, P = 0.049). There were specific taxa enriched in cancer (Veillonella, Varibaculum, Methylobacterium-Methylorubrum) and control groups (Pasteurella, Corynebacterium, Acinetobacter), respectively. CONCLUSION: BC patients had lower bladder microbiota richness and diversity than controls. Specific genera were enriched in cancer and control groups, respectively. These results corroborate some of previous reports while contradicting others. Future microbiota research would benefit from parallel transcriptomic/metabolomic analysis.

Bladder Microbiota Are Associated with Clinical Conditions That Extend beyond the Urinary Tract.

BACKGROUND: Since the discovery of the human urinary microbiota (UM), alterations in microbial community composition have been associated with various genitourinary conditions. The aim of this exploratory study was to examine possible associations of UM with clinical conditions beyond the urinary tract and to test some of the conclusions from previous studies on UM. METHODS: Catheterised urine samples from 87 men were collected prior to endoscopic urological interventions under anaesthesia. The composition of the bacterial community in urine was characterized using the hypervariable V4 region of the 16S rRNA gene. Samples from 58 patients yielded a sufficient amount of bacterial DNA for analysis. Alpha diversity measures (number of operational taxonomic units, ACE, iChao2, Shannon and Simpson indices) were compared with the Kruskal-Wallis test. Beta diversity (differences in microbial community composition) was assessed using non-metric dimensional scaling in combination with the Prevalence in Microbiome Analysis algorithm. RESULTS: Differences in bacterial richness and diversity were observed for the following variables: age, diabetes mellitus, dyslipidemia, smoking status and single-dose preoperative antibiotics. Differences in microbial community composition were observed in the presence of chronic kidney disease, lower urinary tract symptoms and antibiotic prophylaxis. CONCLUSIONS: UM appears to be associated with certain clinical conditions, including those unrelated to the urinary tract. Further investigation is needed before conclusions can be drawn for diagnostics and treatment.

The potential use of blood culture systems for diagnosing intravascular catheter-related infections.

BACKGROUND: A microbiological method for the quantitative analysis of intravascular catheter infections using the BacT/Alert and Bactec blood culture systems is presented. METHODS: The number of bacteria present on an intravascular catheter surface was determined by the time to detection of positivity in a blood culture bottle inoculated with a suspension of bacteria shaken from the catheter surface. RESULTS: The new method was used to examine 573 intravascular catheters. In 94.6% of the cases, the results of microbiological analysis of catheters were in accordance with the patient's clinical condition. Twenty-eight (4.8%) cases were false positive and ten (1.7%) were false negative. Based on clinical signs, 49 cases of catheter-related sepsis were diagnosed. In 39 (79.6%) of those, the microbiological analysis of intravascular catheters was positive (kappa = 0.69). The most frequently detected pathogens were coagulase-negative staphylococci. CONCLUSIONS: In comparison to the current procedures, the new method is easier, faster, and capable of detecting the most common causative agents of catheter-related infections.

Alpha-diversity and microbial community structure of the male urinary microbiota depend on urine sampling method.

Considerable variation exists in the methodology of urinary microbiota studies published so far including the cornerstone of any biomedical analysis: sample collection. The aim of this study was to compare the urinary microbiota of first-catch voided urine (FCU), mid-stream voided urine (MSU) and aseptically catheterised urine in men and define the most suitable urine sampling method. Forty-nine men (mean age 71.3 years) undergoing endoscopic urological procedures were enrolled in the study. Each of them contributed three samples: first-catch urine (FCU), mid-stream urine (MSU) and a catheterised urine sample. The samples were subjected to next-generation sequencing (NGS, n = 35) and expanded quantitative urine culture (EQUC, n = 31). Using NGS, Bacteroidetes, Firmicutes, and Proteobacteria were the most abundant phyla in our population. The most abundant genera (in order of relative abundance) included: Prevotella, Veillonella, Streptococcus, Porphyromonas, Campylobacter, Pseudomonas, Staphylococcus, Ezakiella, Escherichia and Dialister. Eighty-two of 105 samples were dominated by a single genus. FCU, MSU and catheterised urine samples differed significantly in three of five alpha-diversity measures (ANOVA, p < 0.05): estimated number of operational taxonomic units, Chao1 and abundance-based coverage estimators. Beta-diversity comparisons using the PIME method (Prevalence Interval for Microbiome Evaluation) resulted in clustering of urine samples according to the mode of sampling. EQUC detected cultivable bacteria in 30/31 (97%) FCU and 27/31 (87%) MSU samples. Only 4/31 (13%) of catheterised urine samples showed bacterial growth. Urine samples obtained by transurethral catheterisation under aseptic conditions seem to differ from spontaneously voided urine samples. Whether the added value of a more exact reflection of the bladder microbiota free from urethral contamination outweighs the invasiveness of urethral catheterisation remains to be determined.

Strong Antimicrobial Effects of Xanthohumol and Beta-Acids from Hops against Clostridioides difficile Infection In Vivo.

Clostridioides (C.) difficile is an important causative pathogen of nosocomial gastrointestinal infections in humans with an increasing incidence, morbidity, and mortality. The available treatment options against this pathogen are limited. The standard antibiotics are expensive, can promote emerging resistance, and the recurrence rate of the infection is high. Therefore, there is an urgent need for new approaches to meet these challenges. One of the possible treatment alternatives is to use compounds available in commonly used plants. In this study, purified extracts isolated from hops-alpha and beta acids and xanthohumol-were tested in vivo for their inhibitory effect against C. difficile. A rat model of the peroral intestinal infection by C. difficile has been developed. The results show that both xanthohumol and beta acids from hops exert a notable antimicrobial effect in the C. difficile infection. The xanthohumol application showed the most pronounced antimicrobial effect together with an improvement of local inflammatory signs in the large intestine. Thus, the hops compounds represent promising antimicrobial agents for the treatment of intestinal infections caused by C. difficile.

Strong Antimicrobial and Healing Effects of Beta-Acids from Hops in Methicillin-Resistant Staphylococcus aureus-Infected External Wounds In Vivo.

Staphylococcus (S.) aureus is an important causative agent of wound infections with increasing incidence in the past decades. Specifically, the emergence of methicillin-resistant S. aureus (MRSA) causes serious problems, especially in nosocomial infections. Therefore, there is an urgent need to develop of alternative or supportive antimicrobial therapeutic modalities to meet these challenges. Purified compounds from hops have previously shown promising antimicrobial effects against MRSA isolates in vitro. In this study, purified beta-acids from hops were tested for their potential antimicrobial and healing properties using a porcine model of wounds infected by MRSA. The results show highly significant antimicrobial effects of the active substance in both the powder and Ambiderman-based application forms compared to both no-treatment control and treatment with Framycoin. Moreover, the macroscopic evaluation of the wounds during the treatment using the standardized Wound Healing Continuum indicated positive effects of the beta-acids on the overall wound healing. This is further supported by the microscopic data, which showed a clear improvement of the inflammatory parameters in the wounds treated by beta-acids. Thus, using the porcine model, we demonstrate significant therapeutic effects of hops compounds in the management of wounds infected by MRSA. Beta-acids from hops, therefore, represent a suitable candidate for the treatment of non-responsive nosocomial tissue infections by MRSA.

[Tularaemia - an overview of the current knowledge]. / Tulerémie- prehled soucasných poznatku

Francisella tularensis belongs to the family Francisellaceae. It is the aetiological agent of a zoonosis called tularaemia, spread throughout the northern hemisphere. Currently, several subspecies of F. tularensis may be distinguished with various pathogenicity and geographical distribution. In human medicine, only sporadic infections or local epidemics are reported. Given the fact that F. tularensis is highly pathogenic for humans and is easily spread by aerosol, water or food, it may be exploited as a biological weapon. It belongs to fastidious strains requiring specially prepared culture media.

[Detection of Francisella tularensis by blood culture]. / Záchyt Francisella tularensis pomocí hemokultivace.

Francisella tularensis, from the family Francisellaceae, is the aetiological agent of a zoonosis called tularaemia, spread throughout the northern hemisphere. The infectious dose is extremely low (10 CFU/ml) and the infection causes severe diseases or even death if untreated. The transmission to humans is always related to animals, either by a direct contact or by a contact with the environment contaminated by them. Clinical symptoms of the disease can vary depending on the point of entry of the infection. Tularaemia may also occur without any local symptoms or can be manifested by a combination of the symptoms of various typical clinical forms. F. tularensis is a fastidious bacterium and it is rarely diagnosed by blood culture.

Current Antibiotic Resistance Trends of Uropathogens in Central Europe: Survey from a Tertiary Hospital Urology Department 2011-2019.

Monitoring of pathogen resistance profiles is necessary to guide empirical antibiotic therapy before culture and sensitivity results become available. The aim of this study was to describe current antibiotic resistance patterns of five most frequent causative uropathogens in a Department of Urology of a tertiary referral centre in Central Europe over a period of nine years. The Hospital Department of Clinical Microbiology database was used to extract data on all positive urine samples from inpatients in the Department of Urology between 2011 and 2019. Numbers of susceptible and resistant isolates per year were calculated for five most frequent uropathogens: Escherichia coli, Enterococcus spp., Klebsiella spp., Pseudomonas aeruginosa, and Proteus spp. Antimicrobial agents selected for the survey included: ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam; cefuroxime, cefotaxime, ceftazidime and cefepime; ciprofloxacin and ofloxacin; gentamicin and amikacin; ertapenem, meropenem and imipenem; trimethoprim-sulfamethoxazole (co-trimoxazole), nitrofurantoin, colistin, and vancomycin. High resistance rates of Gram-negative uropathogens were demonstrated to most common antimicrobials, with statistically significant increasing or decreasing trends in some cases. No carbapenem-resistant Enterobacteriaceae were isolated. Vancomycin-resistant Enterococcus spp. strains were rare in our population.

Antibiotic Resistance in Nosocomial Bacteria Isolated from Infected Wounds of Hospitalized Patients in Czech Republic.

Hospitalized patients with wounds face an increased risk of infection with multi-drug-resistant nosocomial bacteria. In this study, samples from almost 10,000 patients from big hospitals in Czech Republic with infected wounds were analyzed for the presence of bacterial pathogens. In 7693 patients (78.8%), bacterial etiological agents were identified. Members of the Enterobacterales (37.1%) and Staphyloccus aureus (21.1%) were the most prevalent pathogens. Staphyloccus aureus showed methicillin resistance in 8.6%. Almost half of the Klebsiella pneumoniae isolates were ESBL-positive and 25.6% of the Enterobacter spp. isolates were AmpC-positive. The third most prevalent Pseudomonas aeruginosa showed resistance to 19-32% of the antipseudomonal antibiotics tested. Based on the results, amoxicillin/clavulanic acid, ampicillin/sulbactam or piperacillin/tazobactam combined with gentamicin can be recommended for antibiotic treatment of infected wounds. Once the etiological agent is identified, the therapy should be adjusted according to the species and its resistance.

The association of a reduced susceptibility to moxifloxacin in causative Clostridium (Clostridioides) difficile strain with the clinical outcome of patients.

OBJECTIVES: To investigate the relationship between Clostridium (Clostridioides) difficile strain characteristics and C. difficile infection (CDI) outcome. METHODS: Between October and December 2017, 16 hospitals collected epidemiological data according to the European Centre for Disease Prevention and Control (ECDC) surveillance protocol for CDI. C. difficile isolates were characterized by ribotyping, toxin genes detection and antibiotic susceptibility testing to metronidazole, vancomycin and moxifloxacin. RESULTS: The overall mean CDI incidence density was 4.5 [95% CI 3.6-5.3] cases per 10,000 patient-days. From the 433 CDI cases, 330 (76.2%) were healthcare-associated, 52 (12.0%) cases were community-associated or of unknown origin and 51 (11.8%) CDI cases recurrent; a complicated course of CDI was reported in 65 cases (15.0%). Eighty-eight (20.3%) of patients died and 59 of them within 30 days after the CDI diagnosis. From the 379 C. difficile isolates, the most prevalent PCR ribotypes were 001 (n = 127, 33.5%) and 176 (n = 44, 11.6%). A total of 186 (49.1%) isolates showed a reduced susceptibility to moxifloxacin (> 4 mg/L) and 96.4% of them had Thr82Ile in the GyrA. Nineteen isolates revealed reduced susceptibility to metronidazole and two isolates to vancomycin (> 2 mg/L). A fatal outcome was associated with a reduced susceptibility to moxifloxacin, the advanced age of the patients and a complicated course of CDI (p<0.05). No association between ribotype, binary toxin and a reduced susceptibility to moxifloxacin and complicated course or recurrent CDI was found. CONCLUSIONS: A reduced susceptibility to moxifloxacin, in causative C. difficile strains was associated with fatal outcome of the patients, therefore it is an important marker in surveillance of CDI.

[Detection of urinary tract infection using Uro-Quick system and quantitative dilution method]. / Detekce mocových infekcí systémem Uro-quick a kvantitativní stanovení redicí metodou.

BACKGROUND: Significant bacteriuria is very important marker of urinary tract infection. The standard method for diagnosis of UTI is quantitative urine culture and identification of bacteria. For rapid enumeration of bacteria in urine semiautomatic systems were developed. Aim of the study was to compare the results of the conventional urine culture method with nephelometric enumeration of bacterial cells in urine. MATERIAL AND METHOD: Urine samples were evaluated simultaneously by Uro-Quick and quantitative urine culture. RESULTS: In summary 1 653 urine samples were elaborated, 402 (83.05 %) from 484 positive samples had positive results in Uro-Quick. Sensitivity of Uro-Quick was 0.83, specificity 0.95, positive predictive value 0.85, negative predictive value 0.93 and accuracy 90.68. Culture time extension improved statistical performance characteristic of Uro-Quick. Problem of the method is the detection of the low amounts of microorganisms. Uro-Quick did not detected microbial growth in 16.77 % of samples containing >/= ten to the fourth CFU/ml of microorganisms. The advantage of Uro-Quick is the speed, 73.93 % of the samples with high microbial concentrations (>/= ten to the fifth CFU/ml) were detected in three hours. CONCLUSION: Uro-Quick offers rapid detection of urine samples with high microbial concentrations, but did not replace the quantitative culture of. Nephelometric detection is necessary to complete with agar plate cultivation.

The incidence of subclinical forms of urogenital tuberculosis in patients with pulmonary tuberculosis.

The aim of our study was to determine whether patients with pulmonary tuberculosis may have subclinical forms of urogenital tuberculosis. Between 2011 and 2012, a prospective study was conducted. Basic demographic parameters were recorded and the following investigations were performed: direct bacilloscopy of sputum, evaluation of affected lung fields and presence of cavities on chest X-ray, Mantoux tuberculin skin test II, and interferon gamma release assay. Culture and molecular methods for Mycobacterium tuberculosis in urine were performed. In cases with a positive urine test, an ultrasound examination, computed tomography scan of the abdomen, and endoscopy of the urinary tract were performed. A total of 102 patients (75 men and 27 women) were included in the study, with a median age of 46.8 years. Subclinical forms of urogenital TB were detected in 7 patients; 5 by molecular methods, 1 by urine culture, and 1 with both methods The presence of subclinical forms of genitourinary TB was found in 4 patients without and 3 patients with findings on imaging methods corresponding to TB. A significant number of patients with pulmonary tuberculosis may simultaneously have subclinical forms of urogenital TB.

Emergence of fluoroquinolone resistance in Escherichia coli isolates at the department of clinical hematology.

The aim of this study was to evaluate the dependence of Escherichia coli resistance to fluoroquinolones on their use in the outpatients and inpatients in the Hradec Kralove region of the Czech Republic. Data on inpatient fluoroquinolones use were obtained from the database of the Charles University Teaching Hospital Pharmacy and expressed as defined daily dose per 100 beds - days (DBD). Data on outpatient prescriptions were obtained from the database of the General Health Insurance Company and expressed in defined daily doses per 1000 clients per day (DID). Escherichia coli strains were isolated from samples of urine of both community and hospitalized patients suffering from acute bacterial urinary tract infection, examined using aerobic cultivation, and determined by standard biochemical procedures. The utilization of fluoroquinolones in inpatients has significantly (p < 0.01) increased from 2.73 DBD in 2001 to 4.89 DBD in 2006. In outpatients, fluoroquinolone utilization has also increased significantly from 0.29 DID to 1.15 DID (p < 0.01). In the same period, 11,856 Escherichia coli strains were isolated from inpatients and outpatients with urinary tract infection and tested for the susceptibility to fluoroquinolones. Resistance increased significantly (p < 0.01), both in the hospital (from 2% to 10%) and in the community (from 1% to 11%). The development of Escherichia coli resistance to fluoroquinolones correlates significantly with their utilization both in hospital (r = 0.996, p = 0.005) and in the community (r = 0.878, p = 0.029). Results of this study shows the impact of fluoroquinolone utilization on Escherichia coli resistance, and support the need of controlled use of these effective antibiotics.

Strong antimicrobial activity of xanthohumol and other derivatives from hops (Humulus lupulus L.) on gut anaerobic bacteria.

Anaerobic bacteria, such as Bacteroides fragilis or Clostridium perfringens, are part of indigenous human flora. However, Clostridium difficile represents also an important causative agent of nosocomial infectious antibiotic-associated diarrhoea. Treatment of C. difficile infection is problematic, making it imperative to search for new compounds with antimicrobial properties. Hops (Humulus lupulus L.) contain substances with antibacterial properties. We tested antimicrobial activity of purified hop constituents humulone, lupulone and xanthohumol against anaerobic bacteria. The antimicrobial activity was established against B. fragilis, C. perfringens and C. difficile strains according to standard testing protocols (CLSI, EUCAST), and the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) were calculated. All C. difficile strains were toxigenic and clinically relevant, as they were isolated from patients with diarrhoea. Strongest antimicrobial effects were observed with xanthohumol showing MIC and MBC values of 15-107 µg/mL, which are close to those of conventional antibiotics in the strains of bacteria with increased resistance. Slightly higher MIC and MBC values were obtained with lupulone followed by higher values of humulone. Our study, thus, shows a potential of purified hop compounds, especially xanthohumol, as alternatives for treatment of infections caused by select anaerobic bacteria, namely nosocomial diarrhoea caused by resistant strains.