Antibiotic resistance of urinary tract infection recurrences in a large U.S. integrated health care system.

BACKGROUND: Data on antibiotic resistance of uropathogens for UTI recurrences are lacking. METHODS: In a retrospective cohort of adults at Kaiser Permanente Southern California with culture-confirmed index uncomplicated UTI (uUTI) between 01/2016 and 12/2020, we examined the number and characteristics of subsequent culture-confirmed UTIs through 2021. RESULTS: We identified 148,994 individuals with a culture-confirmed index uUTI (88% female, 44% Hispanic, mean age 51 years [s.d. 19]), of whom 19% developed a subsequent culture-confirmed UTI after a median 300 days (IQR: 126-627). The proportion of UTI due to E. coli was highest for index uUTI (79%) and decreased to 73% for sixth UTI (UTI 6) (p-for trend <0.001), while the proportion due to Klebsiella spp increased from index UTI (7%) to UTI 6 (11%) (p-for-trend <0.001). Non-susceptibility to ≥1 and ≥3 antibiotic classes was observed in 57% and 13% of index uUTIs, respectively, and was higher for subsequent UTIs (65% and 20%, respectively, for UTI 6). Most commonly observed antibiotic non-susceptibility patterns included penicillins alone (12%), and penicillins, trimethoprim-sulfamethoxazole plus ≥1 additional antibiotic class (9%). CONCLUSIONS: Antibiotic non-susceptibility is common in UTIs and increases with subsequent UTIs. Continuous monitoring of UTI recurrences and susceptibility patterns are needed to guide treatment decisions.

Competitive fitness of asymptomatic bacteriuria E. coli strain 83972 against uropathogens in human urine.

Urinary tract infection (UTI) is one of the most common bacterial infections worldwide. The main causative agent of UTI is uropathogenic Escherichia coli (UPEC). There is an immediate need for novel prophylactic and treatment strategies against UTI because of the increasing incidence of antimicrobial resistance among uropathogens. ABU 83972, an asymptomatic bacteriuria-causing E. coli strain, prevents UTI by suppressing the colonization of UPEC. However, the nature of competition and growth repression of UPEC by ABU 83972 is unclear and is the subject of our investigation. Here, we characterized the growth kinetics of ABU 83972 and uropathogens in human urine and laboratory media. Next, we performed a series of competitive co-culture experiments where ABU 83972 and uropathogens were inoculated at a 1:1 ratio in human urine and in various media, and their relative abundance was determined. In human urine, ABU 83972 outcompeted UPEC and additional uropathogens, reaching up to 90% of the total population after 24 hours of incubation. In contrast, UPEC outcompeted ABU 83972 in LB and M9 minimal media and exhibited superior colonization than ABU 83972 in the mouse urinary bladder. Since engineered living materials (ELMs) can be used to retain an organism of interest in a particular location, we developed ABU 83972-containing ELMs that effectively outcompeted UPEC in human urine. In summary, our work establishes that ABU 83972 outcompetes UPEC in a milieu- and cell-density-dependent manner, highlighting the importance of the metabolites and nutrients found in the human urine as determinants of the competitive fitness of ABU 83972.

Biofilm-producing and carbapenems-resistant Escherichia coli nosocomial uropathogens: a cross-sectional study.

OBJECTIVES: This cross-sectional study aims to determine the incidence and potential risk factors associated with biofilm-producing uropathogenic Escherichia coli (UPEC) nosocomial strains from a tertiary care hospital and to examine the prospective correlation between biofilm generation and antibiotic resistance phenotypes and genotypes. METHODS: A total of 130 UPEC nosocomial isolates were identified, their biofilm formation was quantified using a modified microtiter plate assay, and their antibiotic susceptibilities were assessed utilizing the disc diffusion method. Isolates were then subjected to PCR assays targeting blaKPC, blaVIM, blaIMP, and blaOXA48 genes. RESULTS: Over half of the isolates (n = 76, 58.5%) were biofilm producers. Among 17 carbapenem-resistant isolates, 6 (42.9%) isolates harbored the blaOXA48 gene, and only 1 (9.1%) isolate was positive for the blaVIM gene. Prior antibiotic therapy (aOR 15.782, p 0.000) and diabetes mellitus DM (aOR 11.222, p 0.016) were the significant risk factors associated with biofilm production, as determined by logistic regression analysis of the data. In addition, gentamicin resistance was the only statistically significant antibiotic resistance pattern associated with biofilm production (aOR 9.113, p 0.02). CONCLUSIONS: The findings of this study emphasize the significance of implementing proper infection control measures to avoid the horizontal spread of biofilm formation and associated antimicrobial resistance patterns among UPEC nosocomial strains.

Diversity of uropathogens and their antibiotic resistance among diabetic patients presented to MTI-Lady Reading Hospital, Peshawar.

Objective: Our objective was to quantify the number of various bacteria that frequently cause UTI in diabetes patients as well as to gauge their susceptibility and resistance to antibiotics. Method: A cross-sectional study was conducted at the Internal Medicine Ward of Lady Reading Hospital, Peshawar, Pakistan from June 2021 to December 2021, Patients with confirmed diabetes were included in the study; however, participants receiving antimicrobial medications for a maximum of 14 days were excluded from the study. Resistance of Escherichia coli, Candida, Pseudomonas, E. faecalis, Klebsiella, P. mirabilis and Staphylococcus was asssessed using ciprofloxac, ceftazidime and meropenem. Results: The findings highlighted the the prevalence of Escherichia coli in 38.8% of patients, Candida in 19% of patients, Enterococcus faecalis in 11.8% of patients, Pseudomonas in 10%, Klebsiella in 9.5% patients, Proteus mirabilis 6.2% patients and Staphylococcus was found in 5.2% patients. According to the overall sensitivity and resistance of antibiotics in microorganisms, Meropenem showed 89.6% sensitivity and 10.4% resistance. Ciprofloxacin showed 38.9% sensitivity and 61.1% resistance and ceftazidime showed 22.7 sensitivity and 77.3% resistance. Conclusion: UTIs were very common in diabetes patients, and Escherichia coli was the most common uropathogen found. Compared to male patients, more female patients had infections. The uropathogens showed a significant degree of resistance to ceftizidime and ciprofloxacin.

Urinary microbiota and bladder cancer: A systematic review and a focus on uropathogens.

The higher incidence of bladder cancer in men has long been attributed to environmental factors, including smoking. The fact that the sex ratio of bladder cancer remains consistently weighted toward men despite the remarkable increase in the prevalence of smoking among women suggests that other risk factors influence the incidence rates of bladder cancer. These factors may include the urinary microbiota. In this study, we provide a review of recent literature regarding the association between bladder cancer and changes in the urinary microbiota, with a focus on the potential role of uropathogens in the microbiota and sex in bladder cancer. Four databases were systematically searched up to 31 March 2021 to identify human case-controlled studies that evaluated the relationship between urinary microbiota and bladder cancer. We combined bacterial taxa that were significantly higher or lower in the bladder cancer group in each study in the urine (voided and catheterized) and tissue samples. Findings from sixteen eligible studies were analyzed. The total sample size of the included studies was 708 participants, including 449 (63.4 %) bladder cancer patients and 259 (36.6 %) participants in the control group. When considering only the taxa that have been reported in at least two different studies, we observed that with regards to neoplastic tissues, no increased taxa were reported, while Lactobacillus (2/5 of the studies on tissue samples) was increased in nonneoplastic-tissue compared to neoplastic-tissues at the genus level. In catheterized urine, Veillonella (2/3 of the studies on catheterized urine) was increased in bladder cancer patients compared to the control groups at the genus level. In voided urine, Acinetobacter, Actinomyces, Aeromonas, Anaerococcus, Pseudomonas, and Tepidomonas were increased in the bladder cancer patients, while Lactobacillus, Roseomonas, Veillonella were increased in the control groups. Regarding gender, the genus Actinotignum was increased in female participants while Streptococcus was increased in male participants at the genus level. Regarding potential uropathogens in the urinary microbiota, Escherichia-Shigella provided conflicting results, with both showing higher and lower levels in the bladder cancer groups. However, the family Enterobacteriaceae was lower in the bladder cancer groups than in the control groups. In conclusion, there is no consensus on what taxa of the urinary microbiota are associated with bladder cancer according to the sample type. Findings on the potential role of uropathogens in the urinary microbiota in bladder cancer remain inconsistent. Due to the limited number of studies, further studies on urinary microbiota and bladder cancer are needed to address this issue. Given that all publications concerning the urinary microbiota and bladder cancer have been performed using 16S rRNA gene sequencing, we propose that polyphasic approaches, including culture-dependent techniques, may allow for a more comprehensive investigation of the urinary microbiota associated with bladder cancer.

Antibiotic resistance profile of common uropathogens during COVID-19 pandemic: hospital based epidemiologic study.

BACKGROUND: Antimicrobial resistance has a direct impact on the ability to treat common infections, and this was worsened during the COVID-19 pandemic. Worldwide surveillance studies are lacking and resistance rates vary spatially, so frequent local surveillance reports are required to guide antimicrobial stewardship efforts. This study aims to report our common local uropathogens and their antibiogram profiles in our community during the COVID era. METHODS: A retrospective study included patients referred to our urology units with urine culture and sensitivity. All bacterial strains were identified, and their antibiotic susceptibilities were tested. RESULTS: Out of 2581 urine culture results recruited, 30% showed microbiological proof of infection. The majority, 486 (63.4%), were isolated from females. The most frequent isolates were Escherichia coli (44.4%) and Staphylococcus aureus (17.8%). The resistance rates ranged from 26.9 to 79.7%. Piperacillin-tazobactam antibiotic had the lowest resistance rate. The multi-drug resistance pattern was recorded in 181 (23.9%) of the isolates; 159/597 (26.6%) Gram-negative and 22/160 (13.8%) Gram-positive isolates. CONCLUSIONS: Alarming rates of antimicrobial resistance were detected, which stresses the significance of following infection control policies and establishing national antimicrobial stewardship standards.

Prevalence and antimicrobial susceptibility pattern of bacterial uropathogens among adult patients in Madinah, Saudi Arabia.

BACKGROUND: Urinary tract infection (UTI) is considered one of the most prevalent infections that may lead to many renal complications. They account for almost 10% of all infections in Saudi Arabia, making them the second most common cause of emergency department admissions. Bacterial pathogens, primarily Escherichia coli, Klebsiella spp., Enterococcus spp., Proteus spp., and Staphylococcus spp. are the most causative agents of UTI. This study aims to evaluate the prevalence and antimicrobial susceptibility patterns of uropathogens in adult patients from Madinah, Saudi Arabia. METHODS: A retrospective cross-sectional study was performed using data collected from patients who visited King Fahad General Hospital in Madinah, Saudi Arabia. Data included 16,803 urine bacterial cultures and their antimicrobial susceptibility profiles collected between January 2019 and October 2021. RESULTS: Among the 16,803 tested samples, 3937 (23.4%) showed positive results for urine bacterial cultures. UTI prevalence was slightly higher in women (52.1%) than men (47.9%). Escherichia coli (29.8%) was the most prevalent, followed by Klebsiella spp. (23.2%) and Pseudomonas spp. (8.4%). As for Gram-positive bacteria, Enterococcus spp. (10.8%) were most common, followed by Streptococcus spp. (8%) and Staphylococcus spp. (3.3%). Gram-negative bacteria exhibited high resistance rates toward aztreonam (> 83.3%), ampicillin (78.8%), and cephalexin (68.5%). Enterococcus spp. displayed elevated resistance rates (> 62.3%) against ciprofloxacin, gentamicin, and tetracycline. Conversely, Streptococcus spp. showed substantial resistance rates (> 76.6%) toward colistin and trimethoprim/sulfamethoxazole. CONCLUSION: To optimize therapy and minimize the risk of multidrug-resistant uropathogenic infections, physicians should consider the local epidemiological trends and antimicrobial resistance patterns of prevalent uropathogens prior to initiating any empirical antibacterial therapy.

Pediatric community acquired urinary tract infections due to extended-spectrum beta-lactamase versus non-extended-spectrum beta-lactamase producing bacteria.

BACKGROUND: This study aimed to evaluate the demographics, clinical characteristics, risk factors, and antibiotic resistance of pediatric community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing uropathogens. METHODS: This retrospective study was conducted at a tertiary care hospital in Saudi Arabia, among children aged between 0 and 14 years, with a culture-proven diagnosis of community-acquired UTI between February 2019 and September 2021. Patients were divided into two groups based on whether or not their UTI was caused by ESBL-producing bacteria. RESULTS: A total of 383 patients with community-acquired UTI were evaluated. Escherichia coli was detected in 72.6% of cultures. Extended-spectrum beta-lactamase-producing organisms were responsible for 35.7% of UTI episodes. Of these 69% and 31% were caused by E. coli and Klebsiella pneumoniae, respectively. There were no significant differences between the two groups with regard to clinical presentation or urine analysis. The resistance rates in the ESBL-producing group were 39.4% for amoxicillin/clavulanic acid, 65.7% for ciprofloxacin, 72.3% for co-trimoxazole, 32.8% for nitrofurantoin, 21.2% for gentamicin, and 0.7% for amikacin and carbapenems. In the non-ESBL-producing group, it was 22.4% for amoxicillin/clavulanic acid, 22.4% for ciprofloxacin, 38.2% for co-trimoxazole, 23.6% for nitrofurantoin, 6.1% for gentamicin, and zero for amikacin and carbapenems. The presence of renal abnormalities (p = 0.014) and male gender (p = 0.026) were determined to be independent risk factors for ESBL UTIs. CONCLUSIONS: Recognizing risk factors and antibiotic resistance for ESBL-producing bacteria may aid in tailoring an antibiotic regimen for pediatric patients at high risk of ESBL-UTIs.

Frequency Of Uropathogens Showing Resistance To Nitrofurantoin.

Urinary tract infection (UTI) caused by bacteria is the commonest infection accountable for the unforeseen healthcare cost throughout the globe. Nitrofurantoin is being studied as a solution to the perpetually increasing threat of antimicrobial resistance. The objectives of this study were to determine the frequency of urinary isolates causing UTI and their susceptibility pattern against Nitrofurantoin. Data of all isolates reported as uropathogens from April 1, to December 31, 2021, was collected through Electronic Medical Record system of Shalamar Hospital, Lahore. Results of Nitrofurantoin susceptibility were recorded to find the resistance pattern of bacterial isolates. Out of a total of 3,221 samples, 672 (20.9%) were positive with significant bacteriuria. Of the positive samples, 418 (62.2%) were collected from females and 254 (37.8%) from males, with female to male ratio of 1.65:1. The number of female patients was higher in adult age. Of the positive samples, E. coli was the commonest isolate seen in 390 (58%) of samples, followed by Enterococcus spp. 92 (13.7%), Klebsiella spp. 86 (12.8%), Pseudomonas spp. 35 (5.2%), Staphylococcus saprophyticus 24 (3.6%), Proteus spp. 21 (3.1%), Citrobacter spp. 15 (2.2%), and Acinetobacter spp. 9 (1.3%). Overall, 587 (87.4%) isolates were sensitive to Nitrofurantoin. However, it showed increased resistance to 28 (32.6%) isolates of Klebsiella spp. E. coli remains the commonest uropathogen. In conclusion, Nitrofurantoin can be used to treat UTI caused by common bacterial pathogens except Klebsiella spp.

Features of Hemolysin Biosynthesis by Morganella morganii.

We studied the influence of medium composition and aeration on the hemolytic activity of uropathogenic Morganella morganii strain MM 190. The maximum level of hemolysis was observed in LB (59%), DMEM supplemented with fetal bovine serum (62%), and urine (53%) under aeration conditions during the exponential growth phase. The presence of 2% urea in the medium suppressed hemolysin synthesis. Moreover, addition of bacterial culture fluid containing hemolysin to a monolayer of T-24 bladder carcinoma and OKP-GS kidney carcinoma cells led to 25 and 42% cell death, respectively. We found that the maximum expression of the hemolysin gene hlyA was observed in 2-h culture in LB medium, which correlated with the hemolytic activity of the bacteria in this medium and indicated the predominance of the short hlyCA transcript in the cells.

Diversity in the swimming motility and flagellar regulon structure of uropathogenic Morganella morganii strains.

In current times, the opportunistic pathogen Morganella morganii is increasingly becoming a cause of urinary tract infections. The condition has been further complicated by the multiple drug resistance of most isolates. Swimming motility plays an important role in the development of urinary tract infections, allowing bacteria to colonize the upper urinary tract. We determined the differences between the growth, swimming motility, and biofilm formation of two M. morganii strains MM 1 and MM 190 isolated from the urine of patients who had community-acquired urinary tract infections. MM 190 showed a lower growth rate but better-formed biofilms in comparison to MM 1. In addition, MM 190 possessed autoaggregation abilities. It was found that a high temperature (37 °C) inhibits the flagellation of strains and makes MM 190 less motile. At the same time, the MM 1 strain maintained its rate of motility at this temperature. We demonstrated that urea at a concentration of 1.5% suppresses the growth and swimming motility of both strains. Genome analysis showed that MM 1 has a 17.7-kb-long insertion in flagellar regulon between fliE and glycosyltransferase genes, which was not identified in corresponding loci of MM 190 and 9 other M. morganii strains with whole genomes. Both strains carry two genes encoding flagellin, which may indicate flagellar antigen phase variation. However, the fliC2 genes have only 91% identity to each other and exhibit some variability in the regulatory region. We assume that all these differences influence the swimming motility of the strains.

The efficacy and safety of intravesical chondroitin sulphate solution in recurrent urinary tract infections.

BACKGROUND: Urinary tract infections are among the most common indications for antibiotic therapy. The emergence of resistant uropathogens indicates the need for treatment alternatives. Replenishment of the glycosaminoglycan layer of the bladder, achieved by intravesical instillation of e.g. chondroitin sulphate (CS), is described to be a cornerstone in the therapy of cystitis. To retrospectively evaluate the efficacy of a therapy with 0.2% CS in patients suffering recurrent urinary tract infections (rUTI) in comparison to a treatment with low-dose long-term antibiotics (LDLTAB) and a combination of both. METHODS: A total of 151 patients with recurrent UTI who underwent intravesical therapy at Diaconesse hospital in Leiden, The Netherlands were included. 50 patients had been treated with CS, 51 patients had received LDLTAB, and 50 patients had received a combination therapy (LDLTABCS). Data recorded for baseline, after 6, and 12 months of treatment were evaluated. Descriptive statistics were calculated. Exploratory comparisons between groups and within groups were performed by using one-tailed and paired t-tests. Patients filled in a standardized quality of life questionnaire (EQ-5D). RESULTS: We found a statistically significant reduction of number of infections from 7.10 ± 0.50 SEM to 0.45 ± 0.07 SEM after 12 months therapy with CS compared to 12 months therapy with LDLTAB (from 7.04 ± 0.47 SEM to 1.8 ± 0.15 SEM). The number of visits to the urologist significantly decreased in the CS group from 7.46 ± 0.80 SEM to 1.28 ± 0.11 SEM and from 4.10 ± 0.29 SEM to 1.35 ± 0.11 SEM in the LDLTABCS group. In addition, a significant increase in Quality of life (QoL) was seen in the CS-group (from 58.2 ± 0.82 SEM to 80.43 ± 0.82 SEM) and in the LDLTABCS group (from 62.4 ± 0.97 SEM to 76.73 ± 1.06 SEM). There was no improvement in QoL with LDLTAB (from 58.24 ± 1.08 SEM to 58.96 ± 1.19 SEM). Evaluation's evidence is limited due to its retrospective character. CONCLUSIONS: Retrospective analysis of data from patients that underwent therapy for rUTIs confirms the safety and efficacy of CS and indicate a superiority to antibiotic treatment of rUTIs.

Role of Infection and Leukocytes in Male Infertility.

Male infertility is considered as a multifactorial complex reproductive illness, and male urogenital infection and inflammation are crucial etiologies contributing up to 35% of all cases. Mostly triggered by sexually transmitted diseases and uropathogens, chronic manifestation of such infection may cause irreversible infertility in the male. Male urogenital infection involves bacterial, viral, protozoal, and fungal infections many of which remain asymptomatic most of the time and are passed to the sexual partner leading to fertilization failure, pregnancy loss, and even development of illness in the offspring. The abundance of leukocytes in semen can be used as an indicator of urogenital infection. Its contribution in male infertility can be as high as 30% and the clinical condition is referred to as leukocytospermia. Seminal bacterial load together with increased leukocytes contribute to the impairment of male fertility parameters such as, sperm motility, DNA integrity, acrosome reaction, and damage sperm molecular structure. Pathophysiology of bacteriospermia-induced impairment of male infertility is probably mediated by the involvement of bacterial pathogens in the intrinsic apoptotic pathway resulting in sperm death, whereas that of seminal leukocytes operates through excessive generation of ROS. Although the application of antibiotics forms the frontline therapeutic approach, the growing resistance to antibiotics poses a concern in the management of microbes-induced male urogenital infection. Complementary and alternative medicine may offer additional management options in combating such infections. On the other hand, both broad spectrum antibiotics and antioxidant therapy have showed promising results in the management of infertile men with leukocytospermia. Use of herbal medicine may also play a promising role in the management of such patients. However, recent molecular biology techniques have noted the association of elevated levels of IL-8 with both the Chlamydial infection of the male urogenital tract as well as the clinical condition of leukocytospermia. On the basis of such common pathogenesis, further research involving advanced molecular techniques may pave the way towards the development of better diagnostic tools in the clinical management of male urogenital infection and leukocytospermia.

Bacteriospermia and Male Infertility: Role of Oxidative Stress.

Male infertility is one of the major challenging and prevalent diseases having diverse etiologies of which bacteriospermia play a significant role. It has been estimated that approximately 15% of all infertility cases are due to infections caused by uropathogens and in most of the cases bacteria are involved in infection and inflammation leading to the development of bacteriospermia. In response to bacterial load, excess infiltration of leukocytes in the urogenital tract occurs and concomitantly generates oxidative stress (OS). Bacteria may induce infertility either by directly interacting with sperm or by generating reactive oxygen species (ROS) and impair sperm parameters such as motility, volume, capacitation, hyperactivation. They may also induce apoptosis leading to sperm death. Acute bacteriospermia is related with another clinical condition called leukocytospermia and both compromise male fertility potential by OS-mediated damage to sperm leading to male infertility. However, bacteriospermia as a clinical condition as well as the mechanism of action remains poorly understood, necessitating further research in order to understand the role of individual bacterial species and their impact in male infertility.

High burden of ESBL- producing Klebsiella spp., Proteus mirabilis, Enterobacter cloacae and Pseudomonas aeruginosa in diagnosed cases of urinary tract infection in a Nigerian Teaching Hospital.

Infections of the urinary tract have been on the rise globally and these are also worsened by the increasing rate of antibiotic resistance in uropathogens. This study aimed to determine the susceptibility profile of extended spectrum ß-lactamase (ESBL)- producing uropathogens to selected antibiotics and their carriage of ESBL genes. Bacterial uropathogens were obtained from the urine bench of a Microbiology laboratory in a Teaching Hospital in South-West Nigeria. Susceptibility to antibiotics was tested using the disc diffusion method, while detection of ESBL production was done using the double disc synergy test (DDST). Detection of ESBL genes was performed by PCR. A total of 21 ESBL- producing uropathogens were obtained namely: Klebsiella pneumoniae (11), Klebsiella oxytoca (6), Proteus mirabilis (2), Enterobacter cloacae (1) and Pseudomonas aeruginosa (1). The resistance to antibiotics in the uropathogens was: imipenem (0%), gentamicin (38.1%), sulfamethoxazole-trimethoprim (52.4%), amoxicillin-clavulanate (61.9%), aztreonam (66.7%), ceftazidime (66.7%), tetracycline (90.5%), cefpodoxime (100%) and cefotaxime (100%). Altogether, 90.5% (19/21) of the isolates were multidrug resistant (MDR). Of the 21 uropathogens, 61.9% (13/21) carried bla CTX-M, 52.4% (11/21) carried bla TEM while bla SHV was detected in 47.6% (10/21) of the isolates. There was co-carriage of ESBL genes in 12 uropathogens. This study showed a high prevalence of multidrug resistance and a high carriage of ESBL genes in the ESBL- producing isolates obtained over the study period. There is a need for a review of antibiotic options in the treatment of UTI to clamp down on the ever-increasing tide of antibiotic resistance in uropathogens.

Long-term stability of the urogenital microbiota of asymptomatic European women.

BACKGROUND: To date, information on healthy female urinary microbiota is available mostly at genus level and at one time point. However, profound species-level characterization of healthy urinary microbiome and its stability over time are essential for further correct interpretation of its role in healthy urogenital tract. In this study, we investigated female urogenital microbiome (FUM) at two timepoints (within 2.5-year interval) in young asymptomatic European women. We used culturomics with accurate isolates' identification (MALDI-TOF MS and gene markers sequencing) to understand species stability within healthy FUM. RESULTS: Extended culturomics of voided midstream urine sample pairs revealed a mean Shannon diversity index of 1.25 and mean of 19 species/sample (range 5-39 species; total of 115 species; 1830 isolates). High overall species variability between individuals was captured by beta diversity and a variety of community structure types, with the largest cluster characterized by Lactobacillus crispatus, often in combination with Gardnerella vaginalis or Gardnerella genomospecies 3. Significant FUM composition differences, related to Finegoldia magna and Streptococcus anginosus, according to smoking status were found. A high species variability within individuals (Shannon index SD > 0.5 in 7 out of 10 sample pairs) with a mean of 29% of shared species (range 9.1-41.7%) was observed. Moreover, 4 out of 10 sample pairs clustered in the same community structure type. The stable FUM sample pairs presented high abundance of Lactobacillus crispatus, Streptococcus agalactiae or Lactobacillus paragasseri and Bifidobacterium spp.. Moreover, Gardnerella vaginalis, Gardnerella genomospecies 3 or Gardnerella swidsinskii were often maintained within individuals in high abundance. CONCLUSIONS: Shift in species composition at two distant timepoints was frequently observed among urogenital microbiome of European asymptomatic women. This suggests possible interchange of particular species in healthy FUM and the existence of multiple health-associated FUM compositions in certain individuals. Additionally, we provided additional evidence on resilience of particular bacterial communities and identified certain species more prone to persist in urogenital tract. This study revealed important details on the FUM composition complexity relevant for studies aiming to understand microbiota role in the urogenital tract health and for identification of eubiotic and dysbiotic FUM.

Prevalence of bacterial uropathogens and their antimicrobial susceptibility patterns among pregnant women in Eastern Ethiopia: hospital-based cross-sectional study.

BACKGROUND: Urinary tract infection (UTI) is the commonest bacterial infections during pregnancy, leading to significant maternal and prenatal morbidity and mortality. METHOD: This hospital-based cross-sectional study during November 2017 to January 2018 was aimed to determine hospital-based antibacterial susceptibility patterns of bacterial uropathogens among 200 pregnant women in Eastern Ethiopia. ~ 10-20 ml clean-catch midstream urine samples were collected by the study participants. The well-mixed urine samples standardized to 1 µl have inoculated onto Cystine Lactose Electrolyte-Deficient and MacConkey agar. The inoculum was cultured at 37 °C under aerobic conditions for 18-48 h and examined macroscopically to evaluate the colony appearance and size of colonies. The isolate on the plates with pure growth and colonies ≥ 105 CFU/ml were further subjected to biochemical identification and susceptibility testing according to the standard procedures explained in the Clinical and Laboratory Standards Institute guideline. SPSS version 25 was used for data analysis. Descriptive statistics such as frequency, percentage, and cross-tabulation were used to present the findings in the form of graphs and tables. RESULTS: The response rate for this study was 98.04%. Thirty-one bacteria were isolated among the 200 urine samples processed, which gave the overall UTI prevalence of 15.5%. The majority (90.3%) of the isolates were Gram-negative. Escherichia coli (45.2%) was the most frequent isolated uropathogen which followed by Proteus spp. (22.6%), Klebsiella pneumoniae (16.1%), Staphylococcus aureus (9.7%), and Pseudomonas aeruginosa (6.5%). Among the isolates, 96.4% of them were susceptible to amikacin and followed by nitrofurantoin (90.3%), and gentamicin (83.9%). However, high rates of resistance to ampicillin (58.1%), amoxicillin-clavulanate (51.6%), and cotrimoxazole (51.6%) were observed. Overall, 16(51.6%) of the bacterial isolates had developed multiple drug resistance to the selected antimicrobials. CONCLUSION: In general, the overall prevalence of UTI was high, 15.5%. Most of isolated bacterial uropathogens were Gram-negative bacteria, and Escherichia coli was the most frequent isolate. The majority of the isolates were susceptible to amikacin, nitrofurantoin, and gentamicin. However, a high rate of resistance was observed to ampicillin, amoxicillin-clavulanate, and cotrimoxazole. More than half of the isolated bacteria had multiple drug-resistant features. Therefore, periodic and continuous urine culture for screening and diagnosis is mandatory to reduce the consequence of UTI and multidrug resistance bacteria in pregnancy.

Evaluation of the detection ability of uropathogen morphology and vaginal contamination by the Atellica UAS800 automated urine microscopy analyzer and its effectiveness.

BACKGROUND: To help combat the worldwide spread of multidrug-resistant Enterobacterales, which are responsible for many causes of urinary tract infection (UTI), we evaluated the ability of the Atellica UAS800 automated microscopy system, the only one offering the capability of bacterial morphological differentiation, to determine its effectiveness. METHODS: We examined 118 outpatient spot urine samples in which pyuria and bacteriuria were observed using flow cytometry (training set: 81; cross-validation set: 37). The ability of the Atellica UAS800 to differentiate between bacilli and cocci was verified. To improve its ability, multiple logistic regression analysis was used to construct a prediction formula. RESULTS: This instrument's detection sensitivity was 106 CFU/ml, and reproducibility in that range was good, but data reliability for the number of cocci was low. Multiple logistic regression analysis with each explanatory variable (14 items from the Atellica UAS800, age and sex) showed the best prediction formula for discrimination of uropathogen morphology was a model with 5 explanatory variables: number of bacilli (p < 0.001), squamous epithelial cells (p = 0.004), age (p = 0.039), number of cocci (p = 0.107), and erythrocytes (p = 0.111). For a predicted cutoff value of 0.449, sensitivity was 0.879 and specificity was 0.854. In the cross-validation set, sensitivity was 0.813 and specificity was 0.857. CONCLUSIONS: The Atellica UAS800 could detect squamous epithelial cells, an indicator of vaginal contamination, with high sensitivity, which further improved performance. Simultaneous use of this probability prediction formula with urinalysis results may facilitate real-time prediction of uropathogens and vaginal contamination, thus providing helpful information for empiric therapy.

[Rationale for the choice of an antibiotic for urinary tract infections with an emphasis on the environmental safety of therapy].

Difficulties in prescribing antibiotics for lower urinary tract infections (UTI) are associated with a fact that such patients can be treated not only by urologists, but also by general practitioners, internists, pediatricians, and gynecologists. Therefore, it is important to adapt the practical recommendations for the treatment of cystitis for different medical disciplines. When creating clinical guidelines, experts take into account the different factors in choosing antibiotic therapy. First of all, pharmacokinetics is of importance and drugs with renal excretion should be preferred. Secondly, the natural activity of the antibiotic against the pathogens, which cause cystitis, has to be considered. In uncomplicated infections, E. coli predominates, while in complicated and recurrent infections E. coli and other enterobacteria are commonly isolated, as well as Enterococci. In addition, local resistance pattern is reviewed. In the Russian Federation E. coli has minimal resistance to nitrofurans and fosfomycin. Lastly, antibiotics can negatively affect the gastrointestinal and urinary tract microbiota and contribute to the increase of antibiotic resistance and the selection of antibiotic-resistant strains, therefore the environmental safety of therapy should be considered. The effect of antibiotics on the resident flora of the gastrointestinal tract, urinary tract and vagina is called collateral effect, or concomitant (parallel) damage, and it may exceed the therapeutic effect of some antibiotics. Cephalosporins and fluoroquinolones can cause ecologically unfavorable effects with the risk of selection of resistant strains; therefore, these drugs are currently considered as second-line agents for UTI. When choosing an antibiotic, preference should be given to drugs with the narrow spectrum and minimal collateral damage, i.e., the principle of "minimum sufficiency" is of importance. Nitrofurans and fosfomycin trometamol are the optimal drugs in terms of efficiency and environmental safety in UTI. WHO experts consider nitrofurans as the most environmentally safe antibiotics with a minimally sufficient spectrum of activity. The environmental safety of antimicrobial therapy is an important component of preventing antibiotic resistance at the global and local levels.

[Sources of bacterial penetration into the kidney (review part II)].

Kidney and upper urinary tract infections are a serious general medical problem that is the subject of ongoing experimental and clinical research. However, etiological factors and the pathophysiological mechanisms of acute infectious renal inflammation are poorly understood. This also applies to the problem of sources of bacterial penetration into the kidney. The existing hypotheses on this score have "blank spots". This review comprehensively examines the pathways of invasion of microorganisms into the kidney, causing the development of acute inflammation in it. The proofs in favour of the existing views and their criticism are presented. Also, weaknesses in the inference system are determined.