Multidrug-resistant Uropathogens Research Articles

P-1551. Prevalence and Risk Factors of Multidrug Resistance in Patients with Complicated Urinary Tract Infections (cUTIs) and all UTIs: A Systematic Literature Review

Abstract Background Gram-negative pathogens frequently implicated in complicated urinary tract infections (cUTIs) include Enterobacterales (Escherichia coli [E. coli], Klebsiella and Proteus species). These can harbor multidrug resistance mechanisms such as extended-spectrum β-lactamases (ESBLs) limiting the effectiveness of first-line antibiotics. We studied the prevalence of, and risk factors for, multidrug resistant (MDR) infections among patients with cUTI and for all UTIs. Methods Systematic searches were conducted in MEDLINE and Embase, supplemented by conference, bibliography, and keyword-based searches (2013–2024). All US studies reporting data on antimicrobial resistance (AMR) in either confirmed or presumed cUTI and UTI involving bacterial isolates of interest were included (Table 1). A data extraction template was developed a priori and calibrated before use. AMR results were summarized for cUTI and UTIs (uncomplicated UTI [uUTI], mixed uUTI/cUTI, cUTI), as some studies reported a mixture of cUTI and uUTI, or UTI severity not specified. Results We included 44 US primary studies in UTI (13 cUTI, 31 all UTIs), with results summarized for all studies identified for cUTI and all UTIs. The median age range across studies was 3.8–69.0 years (Table 2). Most patients were White/Caucasian (median 53.2%); MDR ≥ 3 was the most commonly reported AMR phenotype. Among cUTI studies, MDR ≥ 3 was seen in 9.9% of E. coli and 10.1% of Klebsiella spp.; for all UTIs studies, it was 6.9% and 4.6%, respectively. The MDR ≥ 3 proportion for Enterobacterales was 12.5% and 11.3% among cUTI/all UTIs, respectively (Table 3). Similar estimates were observed when assessing AMR to individual drug classes with a higher proportion of AMR observed among cUTI isolates vs isolates from all UTIs (Table 4). Within individual studies, resistance rates were generally higher in hospital-acquired vs community-acquired infections, in recurrent vs non-recurrent UTI, in catheter-associated vs non-catheter-associated UTI, in cUTI vs uUTI, and in pyelonephritis vs cystitis. AMR was higher among UTI isolates from men and older patients. Conclusion cUTIs had a higher prevalence of MDR uropathogens vs all UTIs. AMR prevalence in cUTI was higher among men, older patients, and patients with recurrent UTI. Funding: GSK study 221807 Disclosures Fanny S. Mitrani-Gold, MPH, GSK: Employee|GSK: Stocks/Bonds (Public Company) Myriam Drysdale, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Saifuddin Kharawala, DPM, Bridge Medical Consulting Ltd.: Employee of Bridge Medical Consulting Ltd., who received funding from GSK to complete this study|GSK India: Previous employee Pooja Malhotra, MPharm, Bridge Medical Consulting Ltd.: Employee of Bridge Medical Consulting Ltd., who received funding from GSK to complete this study Alanna Farrell-Foster, GSK: Employee|GSK: Stocks/Bonds (Public Company) Jeffrey J. Ellis, PharmD, MS, GSK: Employee|GSK: Stocks/Bonds (Public Company) Emily Lloyd, MSc, GSK: Employee|GSK: Stocks/Bonds (Public Company)

P-1549. Intravenous-line Related Complications in Patients Treated with Short-term Intravenous Antibiotics for Complicated Urinary Tract Infection and Other Infections: A Systematic Literature Review

Abstract Background Complicated urinary tract infections (cUTI) often involve multidrug-resistant uropathogens requiring treatment with intravenous (IV) antibiotics (ABX); risk of IV-line complications increases with longer treatment duration. We studied the occurrence and impact of IV-line complications in patients with cUTI and other infections treated with IV ABX for < 30 days. Methods A systematic literature search for cUTI was conducted in MEDLINE and Embase, supplemented by conference, bibliography, and keyword-based searches (2013–2023). Additional searches on other bacterial infections requiring short term IV ABX were performed due to limited cUTI data. All cUTI primary publications/studies and studies prioritized for other infections were included. Results We identified 130 publications, with 36 eligible primary studies included for evidence synthesis (Table 1). Most publications (n=30) involved patients from the US and/or Europe. Mean/median age range was 5.3–73.6 years (Table 2). Most (median 91.0%) patients were White/Caucasian. At least one IV-line complication was reported in the overall population (median 6.7% [range 0–38.0%]) and in patients with cUTI (median 1.7% [range 0–3.3%]; Table 3). Overall, more serious IV-line complications (median [range]) included bloodstream infections (1.2% [0–3.0%]) and thrombosis/thromboembolism (1.1% [0–3.5%]). For any IV-line complication, the median incidence rate was 3.7 per 1000 catheter days (95% CI, 0.5–15.6; Table 4); the most frequent IV complications were bloodstream infections and displacement/dislodgement (0.6 per 1000 catheter days, each). IV complication rates in patients with cUTI were generally comparable with those in the overall sample and were lower in patients who transitioned from IV to oral ABX, vs those who continued to receive IV ABX. IV complications resulted in increased clinical and economic burden in the form of IV replacement, premature IV removal, emergency department visit, extended hospital stay, readmission, intensive care unit admission, and increased mortality. Conclusion IV-line complications in patients receiving short term IV ABX can result in an increased healthcare burden; complications are less frequent in patients who transition from IV to oral ABX. Funding: GSK study 221810 Disclosures Fanny S. Mitrani-Gold, MPH, GSK: Employee|GSK: Stocks/Bonds (Public Company) Myriam Drysdale, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Saifuddin Kharawala, DPM, Bridge Medical Consulting Ltd.: Employee of Bridge Medical Consulting Ltd., who received funding from GSK to complete this study|GSK India: Previous employee Pooja Malhotra, MPharm, Bridge Medical Consulting Ltd.: Employee of Bridge Medical Consulting Ltd., who received funding from GSK to complete this study Neeti Chana, MPharm, Bridge Medical Consulting Ltd.: Employee of Bridge Medical Consulting Ltd., who received funding from GSK to complete this study Jeffrey J. Ellis, PharmD, MS, GSK: Employee|GSK: Stocks/Bonds (Public Company) Alanna Farrell-Foster, GSK: Employee|GSK: Stocks/Bonds (Public Company) Emily Lloyd, MSc, GSK: Employee|GSK: Stocks/Bonds (Public Company)

The Importance of Antimicrobial Strategies Associated with Clinical Cure and Increased Microbiological Eradication in Patients with Complicated Urinary Tract Infections and High Risk of Relapse.

Complicated urinary tract infections (cUTIs) are serious, potentially life-threatening infections that occur in patients with an increased disease progression risk. Antimicrobial resistance represents an important health issue worldwide, contributing to relapses, which can generate further resistances. It is necessary to clarify the role of microbiological eradication as an additional objective in the management of cUTIs. Some publications suggest that relapses relate to insufficient bacterial suppression in the urinary tract. This study focuses on generating a consensus on how patients with cUTIs would benefit from effective antimicrobial agents associated with higher rates of bacterial eradication. The nominal group technique was followed: systematic literature review, development of a questionnaire, expert panel meeting to discuss results, individual review of draft consensus document, and expert panel meeting to discuss final views and finalise the consensus document. Experts identified risk factors for cUTIs (patients with a higher risk of relapse, physiological obstruction of urinary tract, immune suppression, and previous relapse), and patients who would benefit most from a therapeutic strategy combining clinical cure and aim for microbiological eradication. While experts agreed that the scientific evidence discourages repetition of urine cultures after treatment, they proposed recommendations to prioritise antibiotics with higher evidence of microbiological eradication and close follow-up in patients with a higher risk of relapse, considering any symptoms appearing following clinical cure of the cUTI. Selection of active antimicrobial agents associated with increased microbiological eradication should be prioritised in patients with cUTIs and a high risk of relapse. Complicated urinary tract infections (cUTIs) occur in patients with an increased risk of disease progression or are caused by multidrug-resistant uropathogens. Antimicrobial resistance is of concern as it can result in relapses. Antimicrobial therapeutic strategies associated with increased microbiological eradication in cUTI patients with a high risk of relapse are crucial to prevent relapses and development of antibiotic resistance.

Facile preparation of polyethyleneimine-conjugated silver sulfide nanoparticles as near-infrared-responsive to sterilization of multidrug resistant uropathogens, and cytotoxicity activity.

The online version contains supplementary material available at 10.1007/s13205-024-04168-3.

Patterns of Antimicrobial Resistance in Urinary Tract Infection Pathogens: Analysis in a Provincial Hospital in Zimbabwe

Introduction. Urinary tract infections (UTIs) are among the most common infections globally. Rising multidrug-resistant uropathogens in Zimbabwe underscore the need to review their susceptibility profiles. This study examines antimicrobial susceptibility trends of uropathogens in patients from Victoria Chitepo Provincial Hospital. Methods: This retrospective study included 385 randomly selected UTI-positive patients from 2023. Midstream, clean-catch urine samples were processed using standard microbiological techniques, and statistical analysis was conducted. Results: More females (56.4%) than males (43.6%) had UTIs, with age groups 0–9 and 20–29 years most affected (16.6% each). The predominant uropathogens were E. coli (27.2%), K. pneumoniae (18.4%), Staphylococcus spp. (17.4%), and Enterobacter spp. (12.2%). E. coli was most susceptible to ceftriaxone (93%) and most resistant to doxycycline; K. pneumoniae was most susceptible to chloramphenicol (70.4%). Conclusion: E. coli was the most common uropathogen. Most uropathogens showed susceptibility to ceftriaxone, gentamicin, and chloramphenicol. However, Staphylococcus spp. displayed resistance to norfloxacin, ciprofloxacin, nalidixic acid, and doxycycline. The high resistance rates highlight the need for antimicrobial stewardship and confirmatory testing before prescribing.

Nitrofurantoin susceptibility profile versus other antibiotics tested in uropathogens- a retrospective study from India

Introduction. Urinary Tract Infection (UTI) is one of the most common bacterial infections encountered by clinicians worldwide. The emergence of multidrug-resistant uropathogens necessitates a review of their susceptibility profiles. This study aims to assess the susceptibility trends of uropathogens to a panel of drugs, with special emphasis on Nitrofurantoin (NFT). Methods. A retrospective analysis was conducted on 2,099 mid-stream clean catch urine samples processed by standard microbiological methods. Clinical and Laboratory Standards Institute (CLSI) guidelines (2019) were followed. Statistical analysis was performed. Results. Out of all samples, 212 were culture positive. Escherichia coli (34.9%) and Enterococcus spp. (15.1%) were the most common Gram-negative and Gram-positive organisms, respectively. Gram-negative isolates were most susceptible to Colistin (97.38%), followed by NFT (69.35%). Gram-positive uropathogens were most sensitive to Linezolid (100%), followed by Vancomycin and NFT, each with 92.45% susceptibility. Conclusion. The increase in antibiotic resistance among various uropathogens underscores the need for surveillance data to inform the appropriate selection of antibiotics. Our study highlights that, among the panel of antibiotics tested, NFT appears to be a viable alternative for treating multidrug-resistant uropathogens.

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.