Multidrug-resistant Uropathogens Research Articles

Fosfomycin Susceptibility Among Multidrug-Resistant Extended-Spectrum β-Lactamase and Metallo-β-Lactamase–Producing Uropathogens in a Tertiary Care Hospital

Background Urinary tract infections (UTIs) affect an estimated 150 million people each year worldwide involving women more than men. Because of unrestricted use of antimicrobials and accelerating antimicrobial resistance, therapeutic options for treatment of UTIs are becoming limited. Fosfomycin, a broad-spectrum, rapidly absorbable, antimicrobial agent with good bioavailability and substantial activity against multidrug-resistant (MDR) isolates has antimicrobial activity against a substantial percentage of these MDR isolates. Methods A cross-sectional study over a period of 20 months on urine samples of all patients of all age groups clinically suspected of UTI was conducted in a tertiary care center of southern Rajasthan. Samples were processed immediately as per standard microbiological techniques, followed by culture by a semiquantitative method and antimicrobial susceptibility testing using the Kirby-Bauer disk diffusion method. All gram-negative pathogens were screened for extended-spectrum β-lactamase and further metallo-β-lactamase production using standard disk diffusion tests. Results Of the 1858 positive samples isolated, the most common uropathogen was Escherichia coli (59.96%), with 8.97% confirmed extended-spectrum β-lactamase–producing isolates. Fosfomycin had susceptibility of 96.69%, with its sensitivity and specificity being 98.15% and 6.98% more than nitrofurantoin, respectively. Among the metallo-β-lactamase producers, fosfomycin had susceptibility of 78.58%, with sensitivity and specificity being 91.67% and 25% more than nitrofurantoin, respectively. Conclusion With an increasing threat due to MDR uropathogens in both hospitals and in the community, fosfomycin, with its unique mechanism of action, appears to be a better oral, effective, and safe therapeutic option and a viable potential alternative over other drugs for treatment of UTIs.

Bio-fabrication of ZnONPs using Mimosa pudica Extract to Combat Multidrug Resistant Uropathogens

Zinc oxide nanoparticles (ZnONPs) have been extensively used in therapeutic applications due to their unique physicochemical and biological properties. Meanwhile, urinary tract infection (UTI) is one of the most prevalent infections for which conventional antibiotics are the only treatment option. Unfortunately, improper and overuse of those antibiotics cause antibiotic resistance. Therefore, the current study is about the eco-friendly and cost-effective green synthesis of ZnONPs using Mimosa pudica leaf extract as a reducing, stabilizing, and capping agent that can act as an alternative therapeutics. The structural and optical properties of these M. pudica-based ZnONPs(Mp-ZnONPs), were characterized through various techniques, including UV–Vis spectroscopy, dynamic light scattering (DLS), zeta potential analysis, X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Field Emission Scanning Electron Microscopy (FESEM). From the above characterization, it was demonstrated that these crystalline nearly spherical NPs had an average size of 22.84 nm and a surface charge of −24.6 mV. Furthermore, the antibacterial and antibiofilm activity of MP-ZnONPs was assessed against multidrug-resistant (MDR) uropathogens, including both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) strains with a MIC of 25–400 µg. These NPs also exhibited good hemocompatibility against human blood (hblood) samples. The cytotoxicity assay, reactive oxygen species (ROS) production, and NPs involvement in morphological and intracellular function were also investigated in RAW 264.7 and MCF7 cell lines to understand the in-vitro biocompatibility. These Mp-ZnONPs also showed an anticancer efficiency for cancerous MCF7 cells in comparison with the standard RAW 264.7 cells.

Comprehensive Review of Urinary Tract Infections in Renal Transplant Recipients: Clinical Insights and Management Strategies.

Urinary tract infections (UTIs) pose a significant challenge in the care of renal transplant recipients. This comprehensive review explores this population's multifaceted landscape of UTIs, emphasizing the importance of early diagnosis and tailored management strategies. Renal transplant recipients face an elevated risk of UTIs due to immunosuppression, altered urinary tract anatomy, and complex comorbidities. Complications of UTIs can lead to graft dysfunction and systemic illness, underscoring the need for effective management. The emergence of multidrug-resistant uropathogens adds complexity to treatment, highlighting the importance of targeted antibiotic therapy. Antibiotics are the most commonly prescribed drugs for UTIs, with nitrofurantoin, fosfomycin, amoxicillin, and amoxicillin-clavulanate potassium being some of the commonly used antibiotics. However, the emergence of multidrug-resistant uropathogens has led to the exploration of alternative treatments, such as bacteriophage therapy, as a potential alternative against multidrug-resistant uropathogenic bacteria. Analgesics such as phenazopyridine can be prescribed to relieve discomfort associated with UTIs. Estrogen therapy has also been suggested as a potential treatment option for UTIs, particularly in postmenopausal women. Trimethoprim-sulfamethoxazole or trimethoprim is recommended as first-line therapy for uncomplicated UTIs. The choice of drug and therapy for UTIs depends on the severity of the infection, the causative organism, and the presence of antibiotic resistance.Preventive measures encompass pre-transplant evaluation, perioperative strategies, post-transplant follow-up, and vaccination. A multidisciplinary approach involving transplant specialists, infectious disease experts, pharmacists, and patient engagement is vital for successful care. The future of UTI management lies in ongoing research, exploring personalized medicine, novel therapies, and innovative prevention strategies. By implementing these strategies and advancing research, healthcare providers can improve graft and patient survival, enhancing the quality of care for renal transplant recipients.

BACTERIOPHAGE COCKTAIL EXHIBITED SUPERB ANTIBACTERIAL AND ANTIBIOFILM ACTIVITY AGAINST SELECTED UROPATHOGENS

Urinary tract infections (UTIs) are most abundant bacterial infection worldwide. Approximately 150 million urinary tract infections occur every year globally. The predominant pathogens involved in etiology of UTI are Escherichia coli followed by Staphylococcus spp., Pseudomonas aeruginosa, Proteus spp., Klebsiella spp., Acinetobacter spp., Enterobacter spp., Citrobacter spp., and Enterococcus spp. It is estimated that uropathogenic E. coli (UPEC) cause 80% of UTIs cases. The over use of anti-microbial agents has extraordinarily amplified the rise of multidrug resistant (MDR) uropathogens. Biofilm formation by UPEC is also a major cause of antimicrobial resistance. To curb harmful ripple effects of antibiotic resistance we need to identify alternative treatment procedures. Bacteriophages are bacterial viruses that can invade and infect bacteria. Phage therapy is considered as best alternate to combat several antimicrobial resistant pathogens, including MDR uropathogens. The aim of this research was to isolate and characterize lytic bacteriophages from sewage water and to identify antibacterial and antibiofilm activity of isolated bacteriophage against UPEC. Hazara University Mansehra was the subject of the research. Bacterial samples of UPEC were collected from Ayub Teaching Hospital Abbottabad and Punjab University Lahore. Various biochemical tests including Gram staining, oxidase and catalase test were performed to identify UPEC. The isolated bacteriophages were confirmed by spot assay and plaque assay against the host bacterial strain. The phages were purified by serial dilution up to 5-6 times repeatedly. For morphological studies electron microscopy was performed. The specificity, lytic activity and efficient bacterial growth reduction ability of isolated phages in this study emphasize that these phages could be a suitable therapeutic agents for treatment of MDR infections.

Antimicrobial Resistance and Biofilm Production in Uropathogens from Renal Disease Patients Admitted to Tribhuvan University Teaching Hospital, Nepal

Background. Various antibiotics are prescribed empirically by physicians to cope with infections in renal disease patients. A urinary tract infection (UTI) is often caused by biofilm-forming multidrug-resistant (MDR) uropathogens. This study aimed to analyze the antibiogram of UTI strains from renal disease patients and the biofilm-forming ability of those strains. Methods. 102 patients clinically diagnosed with a UTI and renal disease were recruited into the study from August 2017 to January 2018. Clean-catch midstream urine samples were processed for the isolation and identification of the bacteria following standard methodologies. The antibiogram of the isolates (n = 106) was produced by the Kirby–Bauer disc diffusion method. Detection of biofilm formation was performed in tissue culture plates. Results. The incidence of a UTI in renal disease was 19.1%. Most patients were diagnosed with chronic kidney disease (18.63%), nephrotic syndrome (16.67%), and nephrolithiasis (14.71%). The commonest uropathogens were Escherichia coli (52.8%), Klebsiella pneumoniae (16%), and Enterococcus spp. (15.0%). Ceftriaxone was the most common antibiotic prescribed empirically (37%), whereas nitrofurantoin was the most prescribed antibiotic as adjusted therapy (36.1%). Among the first- and second-line antibiotics, most Gram-negative bacteria were sensitive to amikacin (70.7%), meropenem (70.7%), cefoperazone-sulbactam (70.0%), piperacillin-tazobactam (67.2%), gentamicin (66.7%), and nitrofurantoin (66.7%). Most Gram-positive bacteria were sensitive to doxycycline (90.0%), nitrofurantoin (72.2%), gentamicin (66.7%), and tetracycline (62.5%). All MDR Gram-negative uropathogens were susceptible to colistin sulfate and polymyxin B. Among the 106 isolates, 74.5% produced biofilms and 70.8% were MDR. In 67.0% of cases, including both MDR and biofilm-producing bacteria, the empirical therapy needed adjustment. Conclusions. Aminoglycoside, carbapenem, beta-lactam inhibitor, and nitrofuran group of antibiotics may be the optimal first-line empirical therapies for uropathogens in hospitalized renal disease patients. Regular surveillance of resistance patterns and the study of biofilm formation in uropathogens must be performed to ensure effective management of the patients.

Exploring the Probiotic Proficiency of Dairyderived Lactic Acid Bacteria and Their Antimicrobial Efficacy Against Multi-drug Resistant Diarrheal and Uro-Pathogens

Multidrug resistance (MDR) poses a global health threat, necessitating the exploration of alternative solutions. Probiotics, especially lactic acid bacteria (LAB), offer promising options against the impending crisis due to their recognized safety and potential health benefits. Probiotic potential characterization and selection of candidate LAB strains are highly crucial in probiotic product formulation. This study aimed to identify LAB from dairy product yogurt and evaluate their potential probiotic properties, i.e. aggregation capacity; tolerance to gastric and intestinal conditions; as well as antimicrobial potency. Ten LAB isolates were characterized based on colony characteristics, cellular morphology, and biochemical tests. The LAB isolates, both single and in mixed consortia, displayed a time-dependent increase in auto-aggregation, ranging from 21% to 71% after 5 hours of incubation. Isolate SW2 exhibited the highest auto-aggregative capability (65%). Co-aggregation studies revealed varying degrees of co-aggregation between probiotic LAB and pathogens, with some isolates showing stronger interactions (YD3, SW1, and SW2). Mixed consortia from sample TT demonstrated the highest co-aggregative ability with all tested pathogens. These findings highlight the potential of these isolates to form protective clusters, aiding in their survival and colonization within the gastrointestinal (GI) tract, besides the competitive exclusion of pathogens. The isolates demonstrated good tolerance to simulated gastric and intestinal conditions, as indicated by their non-significant reduction (only 1-2 log) in the bacterial count after 180 minutes of treatment. These findings indicate that LAB isolates can withstand harsh GI conditions, highlighting their suitability as probiotics. Antimicrobial profiles of the LAB isolates were evaluated using radial streak method and turbidimetric microtiter plate assay against eight MDR diarrheal and Uro-pathogens (n=4 for each). LAB isolates SKY1, SW1, SW3 and TT1 exhibited the highest antimicrobial activities; while pathogens DP2, UP41 and UP42 showed the most sensitivity. Exhibited antimicrobial activity of the LAB isolates points to their potential as formidable weapons against MDR infections. Overall, the results indicate that dairy-derived LAB isolates used in this study exhibit potential probiotic traits. Further research is warranted for their mechanisms, safety, efficacy, and use in probiotic supplement development.
 Bioresearch Commu. 9(2): 1340-1350, 2023 (July)

Tissue-resident memory T cells mediate mucosal immunity to recurrent urinary tract infection.

Urinary tract infection (UTI) is one of the most prevalent human bacterial infections. New therapeutic approaches, including vaccination and immunotherapy, are urgently needed to combat the rapid global dissemination of multidrug-resistant uropathogens. Development of therapies is impeded by an incomplete understanding of memory development during UTI. Here, we found that reducing bacterial load early in infection, by reducing the inoculum or with antibiotics after infection, completely abrogated the protective memory response. We observed a mixed T helper (TH) cell polarization, composed of TH1, TH2, and TH17 T cells, among T cells infiltrating the bladder during primary infection. Thus, we hypothesized that reducing antigen load altered TH cell polarization, leading to poor memory. Unexpectedly, however, TH cell polarization was unchanged in these scenarios. Instead, we uncovered a population of tissue-resident memory (TRM) T cells that was significantly reduced in the absence of sufficient antigen. Demonstrating that TRM cells are necessary for immune memory, transfer of lymph node- or spleen-derived infection-experienced T cells to naïve animals did not confer protection against infection. Supporting that TRM cells are sufficient to protect against recurrent UTI, animals depleted of systemic T cells, or treated with FTY720 to block memory lymphocyte migration from lymph nodes to infected tissue, were equally protected compared with unmanipulated mice against a second UTI. Thus, we uncovered an unappreciated key role for TRM cells in the memory response to bacterial infection in the bladder mucosa, providing a target for non-antibiotic-based immunotherapy and/or new vaccine strategies to prevent recurrent UTI.

Occurrence of antibiotic resistant bacteria causing UTIs among children under school age in Soran city, North of Iraq

The current study was carried out to investigate the occurrence of multidrug resistant uropathogens among children under school age (six years old) in Soran city, North of Iraq. A total number of 200 urine samples were taken from children under six years old suffering from UTIs, attending Ashti hospital and Childbirth hospitals in Soran city from July 2017 to march 2018. High frequency of UTIs was among children less than two years old (34.3%) and incidence of UTIs was significantly higher in little girls (57.1%) than in little boys. 70 bacterial uropathogens have benn isolated while 130 samples showed negative culture. The diagnosis of isolates showed that the most common uropathogen was E. coli constituting 27 (38.6%), while others included; Staphylococcus aureus 13 (18.6%), coagulase negative staphylococci 8 (11.4)%, Klebsiella pneumonia 7(10%), Enterococcus faecalis 6 (8.6%), Streptococcus spp. 4 (5.7%), Pseudomonas aeruginosa 2 (2.9%), Staphylococcus saprophyticus 2 (2.9%) and Proteus vulgaris 1 (1.4%). Most of uropathogenic isolates have resisted ampicillin, ceftazidime, ceftriaxone and cefotaxime. Other antibiotics differently showed moderate susceptibilities. The most effective antibiotics were quinolones (ciprofloxacin and levofloxacin) and carbapenems (impenem and meropenem) which showed high susceptibility percentages on all isolates under study. Six multidrug have been chosen resistant isolates to detect the presence of qnrA, qnrB, qnrS and blaKPC responsible for quinolones and carbapenem resistance by using RABD-PCR. The DNA profile showed that only the isolate K 61 (Klebsiella pneumoniae) was bearing qnrB.

Studies on plasmids of multidrug resistant uropathogens isolated from patients with urinary tract infection in a tertiary hospital in Calabar, Nigeria.

Urinary tract Infections caused by multidrug resistant uropathogens have become a significant global public health problem with Nigeria being no exception. This study is aimed at profiling and curing the plasmids of selected multidrug resistant uropathogens isolated from patients with urinary tract infection in a tertiary hospital in Calabar, Nigeria. Isolates were obtained from urine samples of patients using standard microbiological techniques. Multidrug resistant bacterial isolates were then selected for plasmid DNA analysis and curing. The study revealed that E. coli, K. pneumoniae, P. aeruginosa and Proteus mirabilis were resistant to the antibiotics tested. The extracted plasmid DNA showed the presence of TEM, SHV and CTX-M genes in the isolates with sizes of 400-600bp, 300bp and 500-800bp, respectively. All isolates possessed the SHV genes while few had TEM and CTX-M genes. Cells were subjected to curing and plasmid curing was achieved at 200-300µl of ethidium bromide. The reduction in percentage resistance due to plasmid curing observed in this study suggests that the resistance of the isolates to antibiotics were plasmid-mediated. Antibiogram and monitoring of plasmid mediated resistance are necessary for proper management of urinary tract infections.

Emerging Non-Antibiotic Options Targeting Uropathogenic Mechanisms for Recurrent Uncomplicated Urinary Tract Infection.

Urinary tract infections (UTIs) are the most frequent bacterial infections in the clinical setting. Even without underlying anatomic or functional abnormalities, more than 40% of women experience at least one UTI in their lifetime, of which 30% develop recurrent UTIs (rUTIs) within 6 months. Conventional management with antibiotics for rUTIs may eventually lead to the development of multidrug-resistant uropathogens. Targeting of the pathogenicity of rUTIs, the evolution of uropathogenic Escherichia coli (UPEC), and inadequate host defenses by immune responses should be explored to provide non-antibiotic solutions for the management of rUTIs. The adaptive evolution of UPEC has been observed in several aspects, including colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. Focusing on the antivirulence of UPEC and modulating the immunity of susceptible persons, researchers have provided potential alternative solutions in four categories: antiadhesive treatments (i.e., cranberries and D-mannose), immunomodulation therapies, vaccines, and prophylaxis with topical estrogen therapy and probiotics (e.g., Lactobacillus species). Combination therapies targeting multiple pathogenic mechanisms are expected to be a future trend in UTI management, although some of these treatment options have not been well established in terms of their long-term efficacy. Additional clinical trials are warranted to validate the therapeutic efficacy and durability of these techniques.

Is There Any Benefit to the Use of Antibiotics with Indwelling Catheters after Urologic Surgery in Adults.

Antibiotic stewardship in urologic reconstruction is critically important, as many patients will require indwelling catheters for days to weeks following surgery and thus are at risk of both developing catheter-associated urinary tract infections (CAUTI) as well as multi-drug resistant (MDR) uropathogens. Accordingly, limiting antibiotic use, when safe, should help reduce antibiotic resistance and the prevalence of MDR organisms. However, there is significant heterogeneity in how antibiotics are prescribed to patients who need indwelling urethral catheters post-operatively. We performed a literature review to determine if there are benefits in the use of antibiotics for various clinical scenarios that require post-operative indwelling catheters for greater than 24 h. In general, for patients undergoing prostatectomy, transurethral resection of the prostate, and/or urethroplasty, antibiotic administration may be limited without increased risk of CAUTI. However, more work is needed to identify optimal antibiotic regimens for these and alternative urologic procedures, whether certain sub-populations benefit from longer courses of antibiotics, and effective non-antibiotic or non-systemic therapies.

What are the common uropathogens susceptible antimicrobials for nephrostomy patients?

Introduction: Surgical procedures, such as nephrostomy, prone the patient to postoperative infection. Moreover, multidrug-resistant uropathogens emerge due to the inappropriate use of antibiotics and are now a progressive problem worldwide. Distribution mapping of uropathogens and antimicrobial susceptibility patterns in nephrostomy patients gives urologists a clearer picture to aid in better management of their patients. Objectives: To identify the distribution of uropathogens and antimicrobial susceptibility patterns in nephrostomy patients. Materials & methods: We conducted a retrospective observational review of the medical records, including all adult patients undergoing nephrostomy from 1st January 2020 until 31st December 2021 in a tertiary hospital in Yogyakarta, Indonesia. In each patient with a positive urine culture result, uropathogens and antimicrobial susceptibility test reports were recorded and evaluated separately. Results: Of 100 patients, 76 demonstrated positive urine culture (76%), with 78 isolates from 23 strains. Almost all strains were bacterial (22/23; 95.65%), but one was fungi (1/23; 4.35%). Escherichia coli was the most common uropathogens from the isolates (31/78; 39.74%), followed by Pseudomonas aeruginosa (10/78; 12.82%) and Klebsiella pneumoniae (6/78; 7.69%). Antimicrobial susceptibility tests of 33 antibiotics and 2 antifungals were carried out. Most reports showed susceptibility to Meropenem (11.78%), followed by Gentamicin (10.21%), amikacin (8.12%), and Nitrofurantoin (7.07%). Conclusion: The common uropathogens in nephrostomy patients were Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The common susceptible antimicrobials included Meropenem, Gentamicin, amikacin, and Nitrofurantoin.

Multidrug-Resistant Uropathogens Causing Community Acquired Urinary Tract Infections among Patients Attending Health Facilities in Mwanza and Dar es Salaam, Tanzania.

This was a cross-sectional health centre-based survey conducted for a period of five months, from July to November 2021, in the Mwanza and Dar es Salaam regions in Tanzania. We enrolled consecutively a total of 1327 patients aged between 2 and 96 years with a median [IQR] age of 28 [22-39] from Dar es Salaam (n = 649) and Mwanza (n = 678). Significant bacteriuria was observed in 364 (27.4% [95%CI: 25.0-29.9]) patients, from whom 412 urinary pathogens were isolated. Gram-negative bacteria contributed to 57.8% (238) of the 412 uropathogens isolated, of which 221 were Enterobacterales, and Escherichia coli was the most frequent. Staphylococcus aureus and Staphylococcus haemolyticus were the most frequently isolated among Gram-positive uropathogens (n = 156). Generally, resistance among Escherichia coli ranged from 0.7% (meropenem) to 86.0% (ampicillin) and from 0.0% (meropenem) to 75.6% (ampicillin) in other Enterobacterales. Moreover, about 45.4% (108) of Enterobacterales and 22.4% (35) of Gram-positive bacteria were multidrug resistant (MDR), p = 0.008. We observed 33 MDR patterns among Gram-negative bacteria, predominantly AMP-CIP-TCY (23/108; 21.3%), and 10 MDR patterns among Gram-positive bacteria, most commonly CIP-GEN-TCY (22/35; 62.9%). the presence of a high number of wide-ranging uropathogens that are multidrug resistant to a variety of antibiotics points to the need to strengthen the laboratory diagnostic systems for the regular surveillance of the antimicrobial resistance of uropathogens to guide and update empirical treatment guidelines.

Genomic analysis of Fosfomycin resistance in multi-drug resistant uropathogens and comparison of in-vitro susceptibility methods uropathogens.

Urinary tract infection is one of the most common bacterial infections causing high morbidity and mortality. The alarming rise of multidrug-resistant uropathogens worldwide forced the clinician to rethink the old drugs like Fosfomycin for its therapeutic management. Our objective was to compare agar dilution, disc diffusion and E-test method for antimicrobial susceptibility testing of Fosfomycin against different drug-resistant uropathogens. Consecutive 181 uropathogens were tested for Fosfomycin susceptibility using agar dilution, disc diffusion and E-test. Results were interpreted using Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. Whole genome sequencing analysis was done on the 4 XDR/PDR Fosfomycin resistant Klebsiella pneumoniae isolates. Escherichia coli was found as the most common (62.4%) uropathogen followed by Klebsiella pneumoniae (21%). Considering agar dilution as the gold standard, 6.1% of isolates were resistant to Fosfomycin. Following CLSI breakpoints, the susceptibility of Escherichia coli, Klebsiella pneumoniae, other Enterobacterales and Pseudomonas aeruginosa were 92.9%, 92.1%, 100%, 100%; whereas using EUCAST breakpoints the susceptibility rates were 85.7%, 86.9%, 92.9%, and 100%, respectively. The essential agreement, categorical agreement, major error, and very major error for E-test/disc diffusion for all the organisms were 91.2%/Not Applicable, 95%/93.9%, 1.8%/4.7%, 9.1%/9.1%, respectively. Whole-genome sequencing showed mutation UhpT gene as well as the presence of plasmid-mediated fosA5 or fosA6 genes conferring Fosfomycin resistance. This result supports very low resistance of Enterobacterales against Fosfomycin; hence should be considered a valuable option to treat multidrug-resistant uropathogens. Disc diffusion was observed to be a convenient method for Fosfomycin susceptibility testing compared to agar dilution.

Magnitude of Multidrug-resistant Bacterial Uropathogens and Associated Factors in Urinary Tract Infection Suspected Adult HIV-Positive Patients in Southern Ethiopia

Background: Due to the reduction of their immunity, people living with the human immunodeficiency virus (HIV) are more susceptible to acquiring urinary tract infections (UTI). Moreover, the emergence of drug-resistant bacterial uropathogens has grown widely and now constitutes a severe clinical problem among HIV-positive patients. Methods: An institution-based cross-sectional study was conducted at the ART clinic of Arba Minch General Hospital from 1st January to 30th May, 2021. A total of 251 adult HIV-positive patients clinically suspected of having UTIs were systematically recruited. Socio-demographic and other factors were collected by a pre-tested structured questionnaire. A clean-catch mid-stream urine sample was collected and inoculated onto blood agar, MacConkey agar, and cysteine lactose electrolyte deficient agar (CLED). The inoculated culture media were incubated aerobically at 37°C for 24 hrs. After overnight incubation, significant bacteriuria, 105 CFU/ml, was considered. Bacterial identification was made by standard protocols. Antimicrobial susceptibility testing was done by Kirby Bauer’s disk diffusion method. The data was analyzed using SPSS version 25. A P-value less than 0.05 was used as statistical significance. Results: The overall magnitude of multidrug-resistant (MDR) uropathogens was found to be 14.3%, with a 95% CI (10-19.1). Gram-negative bacteria (83.3%) were the predominant MDR isolates, with E. coli (41.7%) followed by K. pneumoniae (22.2%). All isolates of S. aureus and two-thirds of the isolated CoNS were MDR. A total of 30% and 16.7% of Gram-negative isolates were ESBL and carbapenemase producers, respectively, whereas 50% and 33.3% of isolated S. aureus and CoNS were methicillin-resistant, respectively. Antibiotic use in the previous 6 months [AOR = 6.7, 95% CI: (2.53-17.6)], presence of chronic underlying disease [AOR = 7.03, 95% CI: (1.72-28.73)], antibiotic use without a prescription [AOR = 9.7, 95% CI: (3.53-26.675)], CD4+ counts less than 250 cells/mm3 [AOR = 8.05, 95% CI: (2.078–31.154)], and CD4+ count in between 250-500 cells/mm3 [AOR = 2.49, 95% CI: (1.05-5.923)] were found to be statistically significant associated with MDR uropathogens. Conclusion: This study found a significant number of multidrug-resistant uropathogens, indicating that healthcare providers should be aware of this and take urgent action to minimize resistance spread, as well as consider current empirical antibiotic therapy for UTI in HIV-positive patients.

Prevalence, etiology and antibiotic resistance patterns of community-acquired urinary tract infections in Dhaka, Bangladesh.

Urinary tract infection (UTI) accounts for a significant morbidity and mortality across the world and is a leading cause for antibiotic prescriptions in the community especially in developing countries. Empirical choice of antibiotics for treatment of UTI is often discordant with the drug susceptibility of the etiologic agent. This study aimed to estimate the prevalence of community-acquired UTI caused by antibiotic resistant organisms. This was a cross-sectional study where urine samples were prospectively collected from 4,500 patients at the icddr,b diagnostic clinic in Dhaka, Bangladesh during 2016–2018. Urine samples were analyzed by standard culture method and the isolated bacteria were tested for antibiotic susceptibility by using disc diffusion method and VITEK-2. Descriptive statistics were used to estimate the prevalence of community acquired UTI (CA-UTI) by different age groups, sex, and etiology of infection. Relationship between the etiology of CA-UTI and age and sex of patients was analyzed using binary logistic regression analysis. Seasonal trends in the prevalence of CA-UTI, multi-drug resistant (MDR) pathogens and MDR Escherichia coli were also analyzed. Around 81% of patients were adults (≥18y). Of 3,200 (71%) urine samples with bacterial growth, 920 (29%) had a bacterial count of ≥1.0x105 CFU/ml indicating UTI. Women were more likely to have UTI compared to males (OR: 1.48, CI: 1.24–1.76). E. coli (51.6%) was the predominant causative pathogen followed by Streptococcus spp. (15.7%), Klebsiella spp. (12.1%), Enterococcus spp. (6.4%), Pseudomonas spp. (4.4%), coagulase-negative Staphylococcus spp. (2.0%), and other pathogens (7.8%). Both E. coli and Klebsiella spp. were predominantly resistant to penicillin (85%, 95%, respectively) followed by macrolide (70%, 76%), third-generation cephalosporins (69%, 58%), fluoroquinolones (69%, 53%) and carbapenem (5%, 9%). Around 65% of patients tested positive for multi-drug resistant (MDR) uropathogens. A higher number of male patients tested positive for MDR pathogens compared to the female patients (p = 0.015). Overall, 71% of Gram-negative and 46% of Gram-positive bacteria were MDR. The burden of community-acquired UTI caused by MDR organisms was high among the study population. The findings of the study will guide clinicians to be more selective about their antibiotic choice for empirical treatment of UTI and alleviate misuse/overuse of antibiotics in the community.

Targeted Immunomodulation Therapies as New Options to Cure Urinary Tract Infections

Abstract With their high prevalence and predisposition to recurrence, urinary tract infections are important contributors to antibiotic prescription worldwide. Studies involving alternative urinary tract infections treatments emerged as a priority in the last years, developing as a response to rapid global dissemination of multi-drug resistant uropathogens. One of these non-antibiotic strategies is based on the hypothesis that recurrent and severe forms of urinary tract infections have a genetic susceptibility pattern, involving the variability of the innate immune response to germs aggression. Yet insufficient studied, the immunology of urinary tract infections is still a subject for new bold researches. By focusing the precise defect that leads to predisposition towards severe or recurrent evolution of the disease and by targeting to correct them, these new therapies examples outlined in our review can bring a ray of hope in the treatment of UTI and the burden they represent.

Isolation and Identification of Multi-Drug Resistant (MDR) Pathogens from Patients with Urinary Tract Infection (UTI) in Dhaka City, Bangladesh

Urinary tract infection (UTI) is the leading cause of death among patients and majority of people visiting the hospital worldwide. In the current quantitative study, urine samples were obtained using sterile method and 100 isolates, including 60 Escherichia coli, 28 Klebsiella sp., and 12 Proteus sp., were investigated in a laboratory. Current study showed that E. coli 60/100 (60%) was the most common cause of UTI followed by Klebsiella sp. 28/100 (28%) and Proteus sp. 12/100 (12%). Cefotaxime (86.67% sensitive) was found to be the best drug for treating infections with E. coli, ceftazidime (100% sensitive) for infections with Klebsiella sp., and imipenem and levofloxacin (100% sensitive) for infections with Proteus sp. Overall, 51% of the isolated strains showed high multidrug resistance (MDR). Because of the alarming increase in extensively drug-resistant and MDR uropathogens, which is a concern in public health, the rational use of antimicrobial therapy should be implemented.

Comprehensive assessment of holding urine as a behavioral risk factor for UTI in women and reasons for delayed voiding

BackgroundWomen of reproductive age group have greater predilection to urinary tract infections (UTI). Various risk factors increase the prevalence in women. Emergence of multidrug resistant uropathogens make clinical management of UTI challenging. Here we assess holding of urine as risk factor of UTI in women and reasons for delayed voiding. We also investigate the relationship between frequency of UTIs and overall behavioural features, menstrual hygiene and attitude of women towards their own health issues.MethodsA questionnaire based cross-sectional study was performed with 816 hostel residents with written consent. Self-reported data was statistically analysed using SPSS software. Urinalysis and urine culture were done for 50 women by random sampling to obtain the information on leading causative agents of UTI in the study population and their antimicrobial resistance profile.ResultsThe prevalence of UTI among the participants without risk factors was found to be 27.5 (95% CI: 24.4–30.7). Attitude of women towards their own personal health issues and use of public toilets showed a correlation with prevalence of infection. Delay in urination on habitual basis was found to be associated with UTI. Uropathogens isolated by random sampling were resistant to multiple drugs that are generally used to treat UTI.ConclusionsHolding urine for long time had proven to be an important risk factor and amongst different reasons of holding urine, holding due to poor sanitary condition of public toilets was the most common. Higher frequency of self-reported UTIs is related to holding of urine, behavioural features and attitude of women.

Crude metabolites from endophytic fungi inhabiting Cameroonian Annona muricata inhibit the causative agents of urinary tract infections

Urinary tract infections (UTIs) are common bacterial infections. The global emergence of multidrug-resistant uropathogens in the last decade underlines the need to search for new antibiotics with novel mechanisms of action. In this regard, exploring endophytic fungi inhabiting medicinal plants used locally against urinary tract infections could be a promising strategy for novel drug discovery. This study investigates crude metabolites from endophytic fungi isolated from Annona muricata as potential sources of antibiotic drugs to fight against uropathogens and reduce related oxidative stress. Crude ethyl acetate extracts from 41 different endophytic fungi were screened against three bacterial strains using the broth microdilution method, and fungi producing active crude extracts were identified using ITS1-5.8S rRNA-ITS2 nucleotide sequences. The antibacterial modes of action of the five most active extracts were evaluated using Staphylococcus aureus ATCC 43300 and Klebsiella oxytoca strains. The DPPH and FRAP assays were used to investigate their antioxidant activity, and their cytotoxicity against the Vero cell line was evaluated using the MTT assay. Out of the 41 crude extracts tested, 17 were active with minimum inhibitory concentrations (MICs) ranging from 3.125 μg/mL to 100 μg/mL and were not cytotoxic against Vero cell lines with a cytotoxic concentration 50 (CC50) >100 μg/mL. The more potent extracts (from Fusarium waltergamsii AMtw3, Aspergillus sp. AMtf15, Penicillium citrinum AMf6, Curvularia sp. AMf4, and Talaromyces annesophieae AMsb23) significantly inhibited bacterial catalase activity, lysed bacterial cells, increased outer membrane permeability, and inhibited biofilm formation, and the time-kill kinetic assay revealed concentration-dependent bactericidal activity. All seventeen extracts showed weak ferric iron-reducing power (1.06 to 12.37 μg equivalent NH2OH/g of extract). In comparison, seven extracts exhibited DPPH free radical scavenging activity, with RSA50 ranging from 146.05 to 799.75 μg/mL. The molecular identification of the seventeen active fungi revealed that they belong to six distinct genera, including Aspergillus, Curvularia, Fusarium, Meyerozyma, Penicillium, and Talaromyces. This investigation demonstrated that fungal endophytes from Cameroonian Annona muricata, a medicinal plant used locally to treat bacterial infections, might contain potent antibacterial metabolites with multiple modes of action. The antibacterial-guided fractionation of these active extracts is currently ongoing to purify and characterise potential antibacterial active ingredients.