Multidrug-resistant Urinary Tract Infection Research Articles

A cynomolgus monkey E. coli urinary tract infection model confirms efficacy of new FimH vaccine candidates

ABSTRACT The increase in urinary tract infections (UTI) caused by antibiotic-resistant Escherichia coli requires the development of new therapeutic agents and prophylactic vaccines. To evaluate the efficacy of new lead candidates, we implemented a cynomolgus macaque UTI challenge model that mimics human uncomplicated cystitis in response to transurethral challenge with a multidrug-resistant (MDR) E. coli serotype O25b ST131 isolate. E. coli fimbrial adhesin FimH and O-antigens are separately under clinical evaluation by others as vaccine candidates to prevent UTI and invasive urosepsis disease, respectively. Accordingly, we assessed the protective efficacy of three 50-µg intramuscular doses of a novel recombinant FimH antigen adjuvanted with liposomal QS21/MPLA compared with saline placebo in groups of nine animals. A third group was vaccinated with this FimH formulation in combination with 1 µg each of a four-valent mixture of serotype O1a, O2, O6, and O25b O-antigen CRM 197 lattice glycoconjugates. Both vaccines elicited high levels of serum FimH IgG and adhesin blocking antibodies at the time of bacterial challenge and, for the combination group, O-antigen-specific antibodies. Following bacterial challenge, both vaccinated groups showed >200- and >700-fold reduction in bacteriuria at day 2 and day 7 post-infection compared with placebo, respectively. In parallel, both vaccines significantly reduced levels of inflammatory biomarkers IL-8 and myeloperoxidase in the urine at day 2 post-infection relative to placebo. Results provide preclinical proof-of-concept for the prevention of an MDR UTI infection by these new vaccine formulations.

Treatment seeking behaviours, antibiotic use and relationships to multi-drug resistance: A study of urinary tract infection patients in Kenya, Tanzania and Uganda.

Antibacterial resistance (ABR) is a major public health threat. An important accelerating factor is treatment-seeking behaviour, including inappropriate antibiotic (AB) use. In many low- and middle-income countries (LMICs) this includes taking ABs with and without prescription sourced from various providers, including health facilities and community drug sellers. However, investigations of complex treatment-seeking, AB use and drug resistance in LMICs are scarce. The Holistic Approach to Unravel Antibacterial Resistance in East Africa (HATUA) Consortium collected questionnaire and microbiological data from adult outpatients with urinary tract infection (UTI)-like symptoms presenting at healthcare facilities in Kenya, Tanzania and Uganda. Using data from 6,388 patients, we analysed patterns of self-reported treatment seeking behaviours ('patient pathways') using process mining and single-channel sequence analysis. Among those with microbiologically confirmed UTI (n = 1,946), we used logistic regression to assess the relationship between treatment seeking behaviour, AB use, and the likelihood of having a multi-drug resistant (MDR) UTI. The most common treatment pathway for UTI-like symptoms in this sample involved attending health facilities, rather than other providers like drug sellers. Patients from sites in Tanzania and Uganda, where over 50% of patients had an MDR UTI, were more likely to report treatment failures, and have repeat visits to providers than those from Kenyan sites, where MDR UTI proportions were lower (33%). There was no strong or consistent relationship between individual AB use and likelihood of MDR UTI, after accounting for country context. The results highlight the hurdles East African patients face in accessing effective UTI care. These challenges are exacerbated by high rates of MDR UTI, suggesting a vicious cycle of failed treatment attempts and sustained selection for drug resistance. Whilst individual AB use may contribute to the risk of MDR UTI, our data show that factors related to context are stronger drivers of variations in ABR.

Probiotic Limosilactobacillus reuteri KUB-AC5 decreases urothelial cell invasion and enhances macrophage killing of uropathogenic Escherichia coli in vitro study.

Bacterial urinary tract infections (UTI) are among the most common infectious diseases worldwide. The rise of multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) UTI cases is a significant threat to healthcare systems. Several probiotic bacteria have been proposed as an alternative to combat MDR UTI. Lactic acid bacteria in the genus Limosilactobacillus are some of the most studied and used probiotics. However, strain-specific effects play a critical role in probiotic properties. L. reuteri KUB-AC5 (AC5), isolated from the chicken gut, confers antimicrobial and immunobiotic effects against some human pathogens. However, the antibacterial and immune modulatory effects of AC5 on UPEC have never been explored. Here, we investigated both the direct and indirect effects of AC5 against UPEC isolates (UTI89, CFT073, and clinical MDR UPEC AT31) in vitro. Using a spot-on lawn, agar-well diffusion, and competitive growth assays, we found that viable AC5 cells and cell-free components of this probiotic significantly reduced the UPEC growth of all strains tested. The human bladder epithelial cell line UM-UC-3 was used to assess the adhesion and pathogen-attachment inhibition properties of AC5 on UPEC. Our data showed that AC5 can attach to UM-UC-3 and decrease UPEC attachment in a dose-dependent manner. Pretreatment of UPEC-infected murine macrophage RAW264.7 cells with viable AC5 (multiplicity of infection, MOI = 1) for 24 hours enhanced macrophage-killing activity and increased proinflammatory (Nos2, Il6, and Tnfa) and anti-inflammatory (Il10) gene expression. These findings indicate the gut-derived AC5 probiotic could be a potential urogenital probiotic against MDR UTI.

International travel increases risk of urinary tract infection caused by extended-spectrum beta-lactamase-producing Enterobacterales-three-arm case-control study.

Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) have worldwide become increasingly prevalent as pathogens causing urinary tract infections (UTIs), posing challenges in their treatment. Of particular concern are travellers to low- and middle-income countries (LMICs), a substantial proportion of whom become colonized by ESBL-PE, with UTIs as the most common clinical manifestation. Seeking tools for preventing ESBL-PE UTI, we explored factors associated with (i) any UTI (versus control), (ii) ESBL-PE UTI (versus control) and (iii) ESBL-PE versus non-ESBL-PE UTI. During 2015-20, we recruited patients with recent ESBL-PE or non-ESBL-PE UTIs, and controls with no UTI to fill in questionnaires covering potential (ESBL-PE-)UTI risk factors. Of our 430 participants, 130 had ESBL-PE UTI and 187 non-ESBL-PE UTI; 113 were controls. Our three comparisons showed several risk factors as exemplified for any UTI versus controls by female sex, lower education, age, diabetes, antibiotic use, diarrhoea; for ESBL-PE UTI versus controls by travel to LMICs, antibiotic use, swimming; and ESBL-PE versus non-ESBL-PE UTI by male sex, higher education, LMIC travel (participant/household member), pets and antibiotic use. Weekly fish meals appeared protective against both UTI and ESBL-PE UTI. Of the numerous factors predisposing to UTI and/or ESBL-PE UTI, our study highlights antibiotic use and LMIC travel. Household members' LMIC travel appears to pose a risk of ESBL-PE UTI, pointing to household transmission of travel-acquired uropathogens. As predisposing factors to multidrug-resistant UTI, international travel and antibiotic use constitute practical targets for prevention efforts.

Bladder-draining lymph nodes support germinal center B cell responses during urinary tract infection in mice.

Bacterial urinary tract infections (UTIs) are both common and exhibit high recurrence rates in women. UTI healthcare costs are increasing due to the rise of multidrug-resistant (MDR) bacteria, necessitating alternative approaches for infection control. Here, we directly observed host adaptive immune responses in acute UTI. We employed a mouse model in which wild-type C57BL/6J mice were transurethrally inoculated with a clinically relevant MDR UTI strain of uropathogenic Escherichia coli (UPEC). Firstly, we noted that rag1-/- C57BL/6J mice harbored larger bacterial burdens than wild-type counterparts, consistent with a role for adaptive immunity in UTI control. Consistent with this, UTI triggered in the bladders of wild-type mice early increases of myeloid cells, including CD11chi conventional dendritic cells, suggesting possible involvement of these professional antigen-presenting cells. Importantly, germinal center B cell responses developed by 4 weeks post-infection in bladder-draining lymph nodes of wild-type mice and, although modest in magnitude and transient in nature, could not be boosted with a second UTI. Thus, our data reveal for the first time in a mouse model that UPEC UTI induces local B cell immune responses in bladder-draining lymph nodes, which could potentially serve to control infection.

Dissemination of ESBL-producing E. coli ST131 through wastewater and environmental water in Switzerland

The E. coli lineage ST131 is a major cause of multidrug-resistant urinary tract and bloodstream infections worldwide. Recently emerged ST131 sublineages spread globally within few years, but their dissemination routes are incompletely understood. In this study, we investigate the potential role of wastewater and surface water in the spread of extended-spectrum β-lactamase (ESBL)-producing ST131. Streams, lakes, and two wastewater treatment plants (WWTPs) in the canton of Zug, Switzerland, were consecutively sampled over 1.5 years. ST131 was detected in 38% of the samples taken downstream (1–5 km) of WWTP discharge sites, but usually absent in water bodies distant from urban areas or WWTP discharge. Specific strains were repeatedly isolated (≤5 pairwise cgSNP distance) from wastewater or river sites downstream of effluent discharge, indicating their repeated entry or persistence in WWTPs in large concentrations. Genetic characterization of the ESBL-producing water isolates revealed a predominance of clades A and C1 and an emerging ciprofloxacin-resistant sublineage with mutations in quinolone resistance determining regions (QRDR) within clade A. Multiple isolates belonged to internationally circulating sublineages, including C1-M27 and papGII + sublineages with chromosomally encoded ESBLs. This study demonstrates that the clinically relevant E. coli lineage ST131 pollutes river ecosystems, representing a significant challenge to public health and to technologies to minimize their entry into the water environment.

Antimicrobial stewardship program in urinary tract infections due to multiresistant strains in the emergency department

Urinary tract infections (UTI) are a frequent reason for attendance at emergency department (ED). The present study evaluates the impact of a multidisciplinary program for the optimization of antibiotic therapy in patients with UTI caused by multi-drug resistant bacteria treated from the hospital ED. Descriptive study of the implementation of a program in which emergency, microbiology and pharmacy departments participated. Antibiotic treatment of the patients who consulted the ED with positive urine cultures caused by multidrug-resistant bacteria was reviewed upon discharge. In those patients with inappropriate treatment, doctors and/or pharmacists of the next level of healthcare or patients in the case of home discharge were contacted. The impact of the program was evaluated based on new visits to the ED at 30 days after discharge, compared with the results obtained from the usual practice three months prior the intervention. During the first year, 2,474 urine cultures of patients with UTI were reviewed, 533 (21.7%) were caused by multidrug-resistant bacteria. Empirical treatment was inappropriate in 287 (53.4%), making treatment modifications in 243 of them. 73 (19.3%) patients returned to the ED 30 days after discharge, being lower than the results obtained in the three months prior intervention (27.9%; p=0.031), without significant differences in new visits associated with UTI. The implementation of a multidisciplinary program focused on multidrug resistant UTI at discharge form ED correct antibiotic therapy in a large number of patients, being a potentially tool to reduce the number of new ED visits.

Quality indicators for appropriate antibiotic prescribing in urinary tract infections in children

BackgroundThe aim of this study was to define a set of urinary tract infections (UTIs)-specific quality indicators for appropriate prescribing in children and evaluate clinical practices in a district general hospital in Greece.MethodsThe UTIs-specific quality indicators were informed by a review of the existing literature. Quality indicators were selected to describe the overall antibiotics use, prescribing patterns and UTIs clinical management regarding treatment and prophylaxis in a cohort of children admitted with a UTI. Microbiological, clinical and prescribing data about dosing, duration and route of administration were collected from the patients’ electronic health records.ResultsTwelve quality indicators were adapted or developed for prescribing in childhood UTIs. A broad variety of antibiotics were prescribed for UTIs, with a drug utilization (DU) 90% rate of 6 and 9 different antibiotics for febrile and afebrile UTIs, respectively. Despite the low incidence of multi-drug resistant UTIs in the study period (9/261, 3.4%), broad-spectrum antibiotics were prescribed in 33.5% (164/490) of prescriptions. A total of 62.8% (164/261) of patients were started on empiric combined therapies, while opportunities to de-escalate were missed in 37.8% (62/164) of them. One quarter (67/261, 25.7%) of patients did not fulfil the criteria for receiving treatment, while nearly half of those prescribed prophylaxis (82/175, 46.9%) could have avoided having a prophylaxis prescription.ConclusionsOur study identified substantial gaps for improvement in antimicrobial prescribing for UTIs in children. The application of the proposed quality indicators could help to limit unnecessary antibiotics use in children with UTI.

Multidrug-Resistant (MDR) Urinary Tract Infections Associated with Gut Microbiota in CoV and Non-CoV Patients in a Urological Clinic during the Pandemic: A Single Center Experience.

We conducted a case-control study on patients admitted to the urology clinic of the "Parhon" Teaching Hospital in Iasi, Romania, between March 2020 and August 2022. The study group consisted of 22 CoV patients with MDR urinary infections associated with gut microbiota. For the control group, 66 non-CoV patients who developed MDR urinary infections associated with gut microbiota were selected. Electronic medical records were analyzed to determine demographics, characteristics, and risk factors. The types of urinary tract bacteria involved in the occurrence of MDR urinary infections and their sensitivity spectrum were also analyzed. Patients in both groups studied were over 60 years of age, with no differences in gender, environment of origin, and rate of comorbidities. Patients in the CoV group had a higher percentage of urosepsis (54.5% versus 21.2%, p < 0.05) and more hospitalization days (9.27 versus 6.09, p < 0.05). Regarding risk factors, the two groups had similar percentages of previous urologic interventions (95.45% versus 96.97%, p > 0.05), antibiotic therapy (77.3% versus 87.9%, p > 0.05), and the presence of permanent urinary catheters (77.27% versus 84.85%, p > 0.05). Escherichia coli (31.8% versus 42.4%, p > 0.05), Klebsiella spp. (22.7% versus 34.8%, p > 0.05), and Pseudomonas aeruginosa (27.3% versus 9.1%, p > 0.05) were the most common urinary tract bacteria found in the etiology of MDR urinary infections in CoV and non-CoV patients. A high percentage of the involved MDR urinary tract bacteria were resistant to quinolones (71.4-76.2% versus 80.3-82%, p > 0.05) and cephalosporins (61.9-81% versus 63.9-83.6%, p > 0.05), both in CoV and non-CoV patients. Patients with urological interventions who remain on indwelling urinary catheters are at an increased risk of developing MDR urinary infections associated with gut microbiota resistant to quinolones and cephalosporins. Patients with MDR UTIs who have CoV-associated symptoms seem to have a higher rate of urosepsis and a longer hospitalization length.

Evaluating the utility of routine urine culture and antibiotic treatment in children with neurogenic bladder undergoing intradetrusor OnabotulinumtoxinA injection

OnabotulinumtoxinA is used as treatment for refractory idiopathic and neurogenic detrusor overactivity in children. Many patients perform intermittent self-catheterization and therefore have higher rates of asymptomatic bacteriuria, which may increase their risk of symptomatic urinary tract infection (UTI) following treatment. Multiple injections are often needed due to the short-term efficacy of onabotulinumtoxinA treatment, which may also increase the risk of UTI. We aim to evaluate whether a sterile urinary tract is necessary to decrease the risk of postoperative UTI in pediatric patients treated with onabotulinumtoxinA. A retrospective review of patients undergoing intradetrusor onabotulinumtoxinA injection from 2014 to 2021 was performed. Demographic data, clinical characteristics, antibiotic treatment and culture results were collected. A positive urine culture was defined as ≥ 103CFU/ml of uropathogenic bacteria. Our primary outcome was symptomatic UTI within 14 days of the procedure. 103 patients underwent 158 treatments with onabotulinumtoxinA. The incidence of postoperative UTI was 3.2%. The incidence of symptomatic postoperative UTI in patients with asymptomatic bacteriuria compared to those with sterile urine was not significantly different (3.8% vs 0%, p=0.57). Obtaining a preoperative urinalysis or urine culture did not affect the incidence of postoperative UTI (p=0.54). The number needed to treat with antibiotics to prevent one postoperative UTI was 27. The incidence of postoperative UTI was highest in patients with low-risk bladders (p=0.043). Prior history of multi-drug resistant UTI was a risk factor for postoperative UTI (p=0.048). For children undergoing onabotulinumtoxinA injection, there are no evidence-based recommendations regarding antibiotic prophylaxis and the need to screen for and treat asymptomatic bacteruria prior to treatment. Our study addresses this important clinical question, and shows no difference in the rate of postoperative UTI between patients with asymptomatic bacteriuria and those with sterile urine. Patients with a history of multi-drug resistant UTI are at increased risk of symptomatic postoperative UTI and may benefit from preoperative urine testing and treatment. Limitations of our retrospective study include its small sample size in the face of such a low incidence of our primary outcome. The risk of UTI following onabotulinumtoxinA injection in children is low. The presence of sterile urine at the time of surgery does not significantly decrease the risk of postoperative UTI. Routine treatment of asymptomatic bacteriuria prior to surgery results in a large number of patients receiving unnecessary antibiotics. As a result, we recommend against preoperative urine testing for most asymptomatic patients.

Successful management of pelvic urethral strictures with balloon dilation in 3 cats.

To describe the successful management of pelvic urethral strictures in 3 young cats (1 after perineal urethrostomy, 1 after a third-time urethral obstruction, and 1 with prolonged lower urinary tract signs post-urethral obstruction) using balloon dilation and a short-term, indwelling urethral catheter. A 9-month-old neutered male domestic longhair cat with a urethral obstruction and a suspected congenitally narrowed urethra was treated via perineal urethrostomy. The cat later developed acute kidney injury, multidrug-resistant urinary tract infections, and a pelvic urethral stricture. A second case, a 2.3-year-old neutered male domestic shorthair cat, developed a stricture of the pelvic urethra after multiple obstructions and catheterizations. A third case, a 1.2-year-old neutered male domestic shorthair cat, had persistent and prolonged lower urinary tract signs after treatment for a urinary obstruction. The cat also had an abnormally small urethral opening and was ultimately found to have a proximal urethral stricture. The strictures in all 3 cases were successfully treated with a combination of fluoroscopic-guided balloon dilation and short-term indwelling urethral catheterization while managing any present infection. To the authors' knowledge, this is the first published case series of successful balloon dilations paired with the use of a short-term indwelling urethral catheter in cats that developed urethral strictures after catheterization due to urinary obstructions. This procedure appears safe and well tolerated and appears to offer a long-term, cost-effective solution to urethral strictures at the level of the pelvis.

Multipotential use of an old drug, as a new solution for anticancer therapy and multidrug-resistant urinary tract infections

Introduction Nitroxoline (NTX) is a well-known chemotherapeutic agent that has been used to treat urinary tract infections since the 1960s. Today, the incidence of multidrug-resistant (MDR) bacterial strains is on the rise worldwide. This has resulted in repurposing, whereby during the ongoing research on nitroxoline, the possibility of its wide use has been demonstrated, not only in treatment against resistant pathogens, but also potential broad anti-cancer applications. Aim of the study The purpose of our work was to review scientific articles and show the multi-potential - anti-pathogenic and anti-tumor use of nitroxoline. Methods and materials We reviewed the English-language literature in the PubMed database, using the key words: „Nitroxoline”, „Nitroxoline cancer”, „Nitroxoline antibacterial use” Results Analysis of studies has shown that nitroxoline, currently used in benign urinary tract infections, is also applicable in the treatment of urinary tract infections caused by multidrug-resistant bacteria (MRD). It is also active against drug-resistant fungi and mycobacteria. Repurposing has also demonstrated the anticancer effects of nitroxoline through inhibition proliferation, induction apoptosis of tumor cells and other mechanisms, making it likely that nitroxoline will be used in cancer treatment regimens in the future. Conclusion Nitroxoline has found widespread use in the treatment of urinary tract infections caused by multidrug-resistant bacteria (MRD) and by strains of resistant fungi, which in today's world are spreading and increasing their drug resistance. Repurposing has shown promising anticancer activity of nitroxoline in the treatment of urinary tract cancers and more. The data supporting the effects of nitroxoline seem promising, suggesting the rationale for future clinical trials to further our understanding of the exact mechanisms of action and use of nitroxoline in oncology treatment.

The Alarming Situation of Hospital Acquired Multi-drug Resistant Urinary Tract Infections in Pediatric Population in Developing World

Objectives: The aim of this study was to find the magnitude of multi drug resistant UTI in paediatric urology, showing different uropathogenic bacteria, sensitivity pattern, associated urologic pathologies and surgical procedures. Material and Methods: All Paediatric patients with some urologic procedure in this institute who have multi or extensive or pan drug resistant UTI were included, the record retrospectively collected from hospital record system and analysed with SPSS. Results: We total 54 patients included having mean age of 5.4 years and predominantly male patients. The three most common MDR uropathogens were Pseudomonas aueroginosa (63%), E.coli (18.5%) and Kliebsiella spp (9.3%). Other MDR organisms were Enterococcus, Providencia, Serratia marcescens and Staphylococcus. Overall most sensitive drug was colistin (64.8%), followed by Fosfomycin (18.5%), Carbapenems (16.6%), Aminoglycosides (12.9%), Tigecycline (11.1%), Nitrofurantoin (7.4%), Cephalosporin (5.5%), Vancomycin (5.5%), Linzolid ( 5.5%), Septran (3.7%), while Teicoplanin, Fusidic acid and chloramphenicol all 1.8%. We found two culture reports of Pseudomonas aueroginosa as pan drug resistant. The most common urologic pathologies associated with MDR UTI was urinary stone disease, neurogenic bladder and posterior urethral valves. The prevalent surgical procedures were those, underwent for stone diseases. A substantial increase in hospitalization time noted in these patients. Conclusion: The emergence of multi drug resistance is reaching an alarming level in Paeds urology. Pseudomonas aueroginosa causing UTI replacing E.coli with some pan drug resistant species is worrisome. The wide spread use of broad spectrum antibiotics at primary healthcare level and even without culture reports in the tertiary care level needs revision. This has significant impact on the child morbidity, length of hospital stay and finally financiall loss.

Systematic review of antibiotic stewardship interventions for urinary tract infection management in the ambulatory setting

Background: Urinary tract infections (UTIs) are common indications for antibiotics in ambulatory setting, and inappropriate use is prevalent. Fluoroquinolones account for 40% of antibiotics prescribed for uncomplicated UTIs, despite clinical guidance against their use as firstline agents. We conducted a systematic review to determine which antibiotic stewardship intervention(s) are effective in improving antibiotic prescribing for UTIs in the ambulatory setting. Methods: Following PRISMA guidelines, English-language literature from 1995 to September 21, 2021, was searched for articles about antimicrobial stewardship, UTI, and ambulatory setting from PubMed, Embase, and Central. Additional articles were identified from authors’ collections and references of pertinent articles. Studies were included if the authors implemented intervention targeting adults 18 years and older in outpatient setting (excluding emergency departments). Interventions were categorized into Guideline Development and Dissemination (GDD), Audit and Feedback, Clinical Decision Support System (CDSS), and Multimodal Interventions. Results: The literature search identified 1,899 papers; 14 papers were included in this review; and 4 additional papers were identified from other sources. The main interventions were GDD in 6 studies, audit and feedback in 3 studies, CDSS in 4 studies, and multimodal interventions in 5 stidues. These studies had heterogeneity of the practice settings and interventions. Moreover, 11 studies targeted primary care, 2 studies targeted urgent care, 1 study targeted both primary and urgent care, 2 studies were conducted in spinal cord injury clinics, and 2 studies were conducted in hospital-wide outpatient sites. Outcomes included (1) statistically significant increase in guideline-concordant antibiotic prescribing in 12 studies (range, 4.6%–246%); (2) statistically significant decrease in fluoroquinolone prescriptions (range, 9.1%–86.3%) in 7 of 9 studies focusing on fluoroquinolones; (3) significant decreases in drug resistance in urine pathogens in 2 studies that evaluated this. Provider education, in conjunction with passive CDSS tools, such as integrating order sets for UTI prescriptions with prefilled instructions into electronic medical records appeared most beneficial. Several studies have investigated negative impact and have found no increase in retreatment rates or worse outcomes. Conclusions: Our systematic literature review identified a limited number of studies with a variety of interventions that improved antibiotic use for UTIs in the ambulatory care setting. Provider education, in conjunction with CDSS tools, can be less time-consuming than audit and feedback and can target a large number of providers and practices. Future studies need to address sustainability over longer periods and should target specialty clinic populations because they have high burden of patients with multidrug-resistant UTI organisms.Funding: NoneDisclosures: None

Neural Therapy in a multidrug-resistant urinary tract infection in a cat: case report

Urinary tract infection is a frequent condition in companion animals, where several pathogens may be involved, among them, multidrug-resistant agents to antimicrobials, making their treatment difficult. In this context, adjuvant therapies can be indicated to assist in the treatment. Thus, the objective of this study was to report the antimicrobial action of a solution containing procaine hydrochloride associated with sodium bicarbonate, intravesically administered, in a male feline (domestic cat) with urinary tract infection due to multidrug-resistant microorganism. The cat with a history of urinary infection developed after urethrostomy was attended. The animal was receiving treatment with the antimicrobial amoxicillin with clavulanate, however, without positive clinical and laboratory response. After performing urine culture and antibiogram, where the microorganism Proteus mirabilis resistant to 18 classes of tested antimicrobials was isolated, an intravesical application of 2.0 mL of 0.7% procaine solution plus sodium bicarbonate was performed. After seven days of this application, a new urine culture and antibiogram were performed, which did not show any growth of microorganisms. It is concluded that the 0.7% procaine hydrochloride solution associated with intravesical sodium bicarbonate showed antimicrobial action against multi-resistant Proteus mirabilis, which causes urinary infection in a cat.

1417. Fosfomycin Use in the Treatment of Complicated Urinary Tract Infections at a Veterans Affairs Medical Center

BackgroundThe prevalence of multidrug resistant gram-negative urinary tract infections (UTIs) is increasing, often requiring intravenous antimicrobial therapy. Oral fosfomycin is a recommended alternative agent for the treatment of cystitis caused by extended spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli). The primary objective of this study is to evaluate the efficacy of fosfomycin in the treatment of UTIs at the Veterans Affairs Long Beach Healthcare System. The secondary objective is to assess the incidence of adverse drug reactions associated with fosfomycin. MethodsThis is a retrospective, single-center, cohort study. Patients who received fosfomycin between June 1st, 2015 – June 30th, 2020 were included. Data collection was completed by chart review through the Computerized Patient Record System (CPRS). Descriptive analysis was used to evaluate data. Treatment outcomes were analyzed using a composite of clinical and microbiological cure. Clinical cure was defined as resolution of UTI symptoms. Microbiological cure was defined as urine sterilization within 1 month after completing treatment course with fosfomycin.ResultsA total of 62 unique patients were evaluated in this study. The mean age was 71.9 years. 56 patients (90.3%) were male, 31 patients (50.0%) had an indwelling catheter present at the time of treatment, and 48 patients (77.4%) had the presence of genitourinary tract pathology that may increase the risk of developing UTIs. Majority of patients (50%) had a urine culture result positive for E. coli prior to treatment, of which 43.5% were ESBL-producing. 60 patients (96.8%) received more than 1 dose of Fosfomycin. Out of 29 patients who were eligible to be evaluated for clinical outcomes, 20 patients (68.9%) met a positive composite outcome of either microbiological cure, clinical cure, or both. 4 patients (6.5%) experienced an adverse drug reaction of diarrhea that was self-limited. ConclusionFosfomycin is an effective and well-tolerated antimicrobial agent that may be considered for treatment of complicated UTIs without evidence of pyelonephritis or bacteremia caused by multi-drug resistant organisms in the veteran population.Disclosures All Authors: No reported disclosures

Exploring the therapeutic potential of Hibiscus rosa sinensis synthesized cobalt oxide (Co3O4-NPs) and magnesium oxide nanoparticles (MgO-NPs).

Herein, we present a green, economic and ecofriendly protocol for synthesis of cobalt oxide (Co3O4-NPs) and magnesium oxide nanoparticles (MgO-NPs) for multifaceted biomedical applications. In the study, a simple aqueous leaf extract of Hibiscus rosa sinensis, was employed for the facile one pot synthesis of Co3O4-NPs and MgO-NPs. The well characterized NPs were explored for multiple biomedical applications including bactericidal activity against urinary tract infection (UTI) isolates, leishmaniasis, larvicidal, antidiabetic antioxidant and biocompatibility studies. Our results showed that both the NPs were highly active against multidrug resistant UTI isolates as compared to traditional antibiotics and induced significant zone of inhibition against Proteus Vulgaris, Pseudomonas Aurigenosa and E.coli. The NPs, in particular Co3O4-NPs also showed significant larvicidal activity against the Aedes Aegypti, the mosquitoes involve in the transmission of Dengue fever. Similarly, excellent leishmanicidal activity was also observed against both the promastigote and amastigote forms of the parasite. Furthermore, the particles also exhibited considerable antidiabetic activity by inhibiting α-amylase and α-glucosidase enzymes. The biosynthesized NPs were found to be excellent antioxidant and biocompatible nanomaterials. Owing to ecofriendly synthesis, non-toxic and biocompatible nature, the Hibiscus rosa sinensis synthesized Co3O4-NPs and MgO-NPs can be exploited as potential candidates for multiple biomedical applications.

Multi-Drug Resistant Urinary Tract Infection: An Emerging Health Issue

Abstract not available&#x0D; J Bangladesh Coll Phys Surg 2021; 39(2): 76-77

Urinary Tract Infections are becoming Multi-drug Resistant due to Extended Spectrum Beta-lactamases-producing Klebsiella pneumonia

Introduction: Klebsiella pneumoniae are among the most common cause of urinary tract infections such as cystitis and pyelonephritis. These multi-drug resistant K. pneumoniae are producers of extended spectrum beta-lactamases (ESBL) that are capable of hydrolyzing beta-lactams and non-beta-lactams. This laboratory-based study sought to establish the increase of ESBL-producing K. pneumoniae in multi-drug resistant urinary tract infections and determine the effective antibiotic treatment options.&#x0D; Methods: One hundred and seventy five K. pneumoniae isolates obtained from urine cultures were randomly collected and the combined disc synergy method was used to determine the ESBL-producing K. pneumoniae. The Vitek 2 system (bioMérieux, France) was used to perform antimicrobial susceptibility testing of 17 commonly used antibiotics. The data from the work was collated and statistically analysed using the chi-square test and Mann-Whitney U test. P values &lt; 0.05 were considered significant.&#x0D; Results: Of the 175 K. pneumoniae responsible for urinary tract infections, 73.7% were producing ESBL suggesting that most urinary tract infections caused by K. pneumoniae will be multi-drug resistant. The antimicrobial resistance differences between ESBL-producing and non-ESBL-producing Klebsiella pneumoniae indicated a significance difference with p &lt; 0.05. This study indicated that imipenem and amikacin are the antibiotic of choice for the treatment of multi-drug resistant urinary tract infections caused by ESBL-producing K. pneumoniae. Cephalosporins and nitrofurantoin are suitable for the treatment of urinary tract infections due to non-ESBL-producing K. pneumoniae.&#x0D; Conclusion: This study indicated that imipenem (carbapenem) and amikacin are the antibiotic of choice for the treatment of multi-drug resistant urinary tract infections caused by ESBL-producing K. pneumoniae. The third and fourth generation cephalosporins and nitrofurantoin are suitable for the treatment of urinary tract infections due to non-ESBL-producing K. pneumoniae. Rational use of antibiotics and evidence based antibiotic prescription will help to control the spread of resistance by ESBL-producing K. pneumoniae. There is the need to intensify research in the use of natural products to treat multi-drug resistant urinary tract infections emanating from ESBL-producing K. pneumoniae

Rising resistance of urinary tract pathogens in children: a cause for concern.

Urinary tract infection (UTI) is one of the common infections in childhood. Prompt diagnosis and treatment reduces the risk of complications. The choice of antibiotic to treat UTI varies from region to region. Rational use and appropriately chosen antibiotic reduces the emergence of resistant uropathogens. We investigated the resistance pattern of uropathogens for commonly used antibiotics to treat UTI locally. Data was collected between 2009 and 2019 on all infants and children under 16 years of age with culture proven UTI. Results were compared with previously published figures between 2002 and 2008. A total of 1002 samples were analysed (91/year). Male to female ratio was 1:4.6. About 94% of the samples grew E. coli. As before, high resistance rates were recorded to Amoxicillin and Trimethoprim (Z=-0.325: P=0.7452; not significant). Overall, average resistance has decreased for Nitrofurantoin from 10% between 2002 and 2008 to 5.84% between 2009 and 2019 (Z=3.002: P=0.0027). On the other hand, Cefalexin resistance has increased from 7.4 to 14.56% between the two study periods (Z=-4.2: P=<0.0002). Despite rising resistance rates, we recommend that Cefalexin should cautiously remain the antibiotic of choice for empirically treating uncomplicated urinary tract infections in secondary care pending urine culture. Nitrofurantoin should be reserved for treating non-coliform/atypical UTIs or multi-drug resistant UTIs. There is an ongoing need for clinicians in all geographic regions to continue to monitor antibiotic resistance rates every few years.