Nitroxoline resistance is associated with significant fitness loss and diminishes in vivo virulence of Escherichia coli.

IMPORTANCE: Antimicrobial resistance (AMR) poses a global threat and requires the exploration of underestimated treatment options. Nitroxoline, an effective broad-spectrum antibiotic, does not suffer from high resistance rates in the clinics but surprisingly, it is not heavily used yet. Our findings provide compelling evidence that Nitroxoline resistance renders bacteria unable to cause an infection in vivo, thereby reinvigorating the potential of Nitroxoline in combating AMR.

Nitrofurantoin for the treatment of uncomplicated urinary tract infection in female patients: the impact of dosing regimen, age, and renal function on drug exposure.

PURPOSE: The aim of this study is to determine nitrofurantoin exposure in female patients with different age and renal function with complaints of an uncomplicated UTI. Also the nitrofurantoin exposure in relation to the dosage regimen will be studied. METHODS: Eight general practitioners (GP) participated in the study and included 38 patients with symptoms of an uncomplicated UTI, treated either with a dose of 50 mg q6h or 100 mg q12h, upon the discretion of the GP. Nitrofurantoin exposure was quantified in the patient's 24-h urine samples by UHPLC-UV and the area under the curve was calculated. RESULTS: The 38 patients provided a range of 2-17 urine samples. The urine nitrofurantoin exposure was 1028 mg h/L for the patients receiving 50 mg q6h and 1036 mg h/L for those treated with 100 mg q12h (p = 0.97) and was not affected by age and eGFR (p = 0.64 and p = 0.34, respectively). CONCLUSION: The data obtained do not support the discouragement of nitrofurantoin use in the elderly and in patients with impaired renal function. Since only a small number of patients were included, a larger study with more patients is warranted to evaluate nitrofurantoin exposure and adverse effects.

Safety and efficacy of nightly nitrofurantoin as prophylaxis in dogs with recurrent urinary tract infections: 13 cases (2015-2021).

OBJECTIVES: To report the protocol, efficacy and adverse events in dogs receiving nightly nitrofurantoin therapy as antimicrobial prophylaxis for recurrent urinary tract infections. MATERIALS AND METHODS: Retrospective case series of dogs prescribed nitrofurantoin as prophylaxis for recurrent urinary tract infections. Data on urological history, diagnostic investigation, protocol, adverse events and efficacy (through serial urine cultures) were extracted from medical records. RESULTS: Thirteen dogs were included. Before therapy, dogs had a median of 3 (range 3 to 7) positive urine cultures in the past year. In all but one dog, standard antimicrobial therapy was given before starting the nightly nitrofurantoin. The nightly nitrofurantoin was then prescribed at a median dose of 4.1 mg/kg orally every 24 hours for a median of 166 days (range 44 to 1740). The median infection-free interval on therapy was 268 days (95% confidence interval: 165 to undefined). Eight dogs had no positive urine cultures while on therapy. Of these, five (three which discontinued and two which remained on nitrofurantoin) had no return of clinical signs or bacteriuria at time of last follow-up evaluation or death, and three had suspected or confirmed bacteriuria 10 to 70 days after discontinuation. Five dogs developed bacteriuria on therapy, four of which were nitrofurantoin-resistant Proteus spp. Most other adverse events were minor; none were considered likely caused by the drug on causality assessment. CLINICAL SIGNIFICANCE: Based on this small study group, nightly nitrofurantoin appears well tolerated and might be efficacious prophylaxis for recurrent urinary tract infections in dogs. Infection with nitrofurantoin-resistant Proteus spp. was a common reason for treatment failure.

Repurposed drug battles 'brain-eating' amoeba.

A drug for urinary tract infections may also treat Balamuthia mandrillaris.

Devenir de la pose de la sonde double J pour obstruction du haut appareil urinaire Etude documentaire d'une série des cas du Centre National Hospitalo-Universitaire Hubert Koutoukou Mage à Cotonou, Benin / Outcome of the installation of the double J probe for upper urinary tract obstruction: A case series from the Hubert Koutoukou Mage National University Hospital, Cotonou, Benin

Contexte et objectifs. La sonde double J est très utilisée de nos jours dans le drainage des urines du haut appareil. L'objectif de la présente étude était de décrire le devenir de la pose de la sonde double J. Méthodes. Il s'est agi d'une étude documentaire d'une série des cas ayant bénéficié d'un drainage urinaire du haut appareil par une sonde double J au Centre National Hospitalo-Universitaire Hubert Koutoukou Maga de Cotonou, Bénin ; entre les 1er avril 2018 et 31 mars 2021. Résultats. Les dossiers de cent trois patients (âge moyen 48,4 ans, sexe masculin, 58,3 %) ont été colligés. La pose de la sonde double J représentait 84,74 %. La pose de la sonde double J était unilatérale dans 76,7 % des cas avec une prédominance à droite (56,0 %). L'abord par voie endoscopique pour la pose de la sonde double J était la plus pratiquée (89,3 %). La pose de la sonde double J a été effectuée sans guidage fluoroscopique (à l'aveugle) dans 73,7 % et la durée moyenne du port de cette sonde était 118,37 jours. La fonction rénale était perturbée avec un débit de filtration glomérulaire < 60 ml/minute/1,75 m2 chez 33,0 % des patients. Les étiologies à la base d'une obstruction étaient dominées par la pathologie lithiasique (63,1 %). Le taux de réussite de la sonde double J était de 77,6 %. Les échecs de la sonde double J étaient dus aux pathologies tumorales dans 15,53 %. La durée moyenne d'hospitalisation après la pose de la sonde double J par voie endoscopique était de 7,72 jours. Conclusion. Le syndrome obstructif surtout d'origine lithiasique reste la plus importante indication de l'usage de la sonde double J. Sa réalisation sans guidage fluoroscopique (à l'aveugle) est possible dans le milieu ne disposant pas d'amplificateur de brillance.

Exploration of 3D Printing of Anti-Infective Urinary Catheters: Materials and Approaches to Combat Catheter-Associated Urinary Tract Infections (CAUTIs) - A Review.

Three-dimensional (3D) printing is a pioneering technology that has gained increased popularity in the fields of tissue engineering, drug design, drug delivery systems and biomedical devices. Thus, it enables us to explore this technique for fabricating 3D-printed catheters. Owing to its enhanced productivity and cost-efficiency, this technique can be utilized to fabricate any material for manufacturing or designing catheters with antimicrobial properties. From 1930s, Foley's catheter had been widely used to drain the urinary bladder of patients with impaired bladder function. Despite the complications like catheter-associated urinary tract infections (CAUTIs), kidney damage, chronic infections, encrustations and personal discomfort during inflation of the balloon, Foley's catheter was used universally without any changes in product design. Currently, marketed catheters have been reported for reducing CAUTI, but the prevention of limitations by coating drugs onto the catheter is very expensive. Altering the physical properties of the catheter by biopolymer blend might ease the discomfort. Thus, new technologies have to be adopted to manufacture ideal catheters that are biocompatible and provide antimicrobial and anti-fouling properties. Herein, we provide an overview of 3D printing techniques along with different materials opted for manufacturing catheters to overcome the existing challenges and limitations.

Five versus seven days of nitrofurantoin for urinary tract infections in women with diabetes: a retrospective cohort study.

OBJECTIVE: To compare the effectiveness of 5 versus 7 days of nitrofurantoin treatment for urinary tract infection (UTI) in women with diabetes. METHODS: Data were collected retrospectively from Dutch general practitioners between 2013 and 2020. Nitrofurantoin prescriptions with a duration of 5 days (5DN) or 7 days (7DN) in women with diabetes were included. Inverse propensity weighting was performed to calculate adjusted risk differences (RD) for treatment failure within 28 days. Secondary outcomes were 14-day treatment failure, severe treatment failure and 28-day treatment failure in defined risk groups. RESULTS: Nitrofurantoin was prescribed in 6866 episodes, 3247 (47.3%) episodes with 5DN and 3619 (52.7%) episodes with 7DN. Patients in the 7DN group had more co-morbidities, more diabetes-related complications and were more insulin-dependent. There were 517/3247 (15.9%) failures in the 5DN group versus 520/3619 (14.4%) in the 7DN group. The adjusted RD for failure within 28 days was 1.4% (95% CI -0.6 to 3.4). CONCLUSION: We found no clinically significant difference in treatment failure in women with diabetes with UTI treated with either 5DN or 7DN within 28 days. A 5-day treatment should be considered to reduce cumulative nitrofurantoin exposure in DM patients.

Nitrofurantoin 100 mg versus 50 mg prophylaxis for urinary tract infections, a cohort study.

OBJECTIVES: Guidelines do not distinguish between 50 mg or 100 mg nitrofurantoin as daily prophylaxis for recurrent urinary tract infection (UTI), although 50 mg might have a better safety profile. Our objective was to compare the effectiveness and safety of both regimens. METHODS: Data were retrospectively collected from 84 Dutch GP practices between 2013 and 2020. Nitrofurantoin prescriptions of 100 mg and 50 mg every 24 hours in women were included. Cox proportional hazard regression analysis was used to calculate hazard ratios on first episode of UTI, pyelonephritis and (adverse) events. Patients were followed for the duration of consecutive repeated prescriptions, assuming non-informative right censoring, up to 1 year. RESULTS: Nitrofurantoin prophylaxis was prescribed in 1893 patients. Median lengths of follow up were 90 days (interquartile range (IQR) 37-179 days) for 100 mg (n = 551) and 90 days (IQR 30-146 days) for 50 mg (n = 1342) with few differences in baseline characteristics between populations. Under 100 mg and 50 mg, 82/551 (14.9%) and 199/1342 (14.8%) developed UTI and 46/551 (8.3%) and 81/1342 (6.0%) developed pyelonephritis, respectively. Adjusted HRs of 100 mg versus 50 mg were 1.01 (95% CI 0.78-1.30) on first UTI, 1.37 (95% CI 0.95-1.98) on first pyelonephritis episode, 1.82 (95% CI 1.20-2.74) on first consultation for cough, 2.68 for dyspnoea (95% CI 1.11-6.45) and 2.43 for nausea (95% CI 1.03-5.74). CONCLUSION: Daily prophylaxis for recurrent UTI with 100 mg instead of 50 mg nitrofurantoin was associated with an equivalent hazard on UTI or pyelonephritis, and a higher hazard on cough, dyspnoea and nausea. We recommend 50 mg nitrofurantoin as daily prophylaxis.

The Significance of Age and Causative Bacterial Morphology in the Choice of an Antimicrobial Agent to Treat Acute Uncomplicated Cystitis.

Differentiating patients by age and causative bacterial morphology might aid in making the appropriate choice of antimicrobial agent when treating acute uncomplicated cystitis. In this retrospective analysis, the non-susceptibility rates of the causative bacteria to cefcapene-pivoxil (CFPN-PI) and levofloxacin (LVFX) were determined after dividing patients with acute uncomplicated cystitis by age group (15-54 and 55-74 years old) and by bacterial morphology: gram-positive cocci (GPC) or gram-negative rod (GNR). The overall non-susceptibility rates for CFPN-PI and LVFX were 19.4% and 15.3%, respectively. When the subjects were divided by age, only the non-susceptibility rate for LVFX in the younger group significantly decreased (to 8.7%). When the groups were divided by both age and bacterial morphology, the younger GNR group had non-susceptibility rates of 6.9% to CFPN-PI and 7.8% to LVFX, whereas the younger GPC group showed 10.2% non-susceptibility to LVFX. The older GNR group showed 9.8% non-susceptibility to CFPN-PI, while the older GPC group showed 7.2% non-susceptibility to LVFX. All the non-susceptibility rates were lower than 10.2% in the sub-divided groups. Differentiating patients by age and the morphology of causative bacteria can aid in making the appropriate choice of antimicrobial agent and may improve treatment outcomes in patients with acute uncomplicated cystitis.

Resistencia antibiótica de Escherichia coli y Staphylococcus saprophyticus en la infección urinaria de un hospital público / Antibiotic resistance of Escherichia coli and Staphylococcus saprophyticus in urinary tract infection in a public hospital

La resistencia de antibióticos puede llegar a causar una amplia morbilidad y complicaciones. Objetivo: Determinar el perfil de resistencia antimicrobiana de Escherichia Coli y de Staphylococcus Saprophyticus, en pacientes con infección urinaria hospitalizados en el servicio de Medicina Interna del Hospital Municipal Los Olivos. Métodos: Estudio descriptivo, retrospectivo de corte transversal. Se realizó en el servicio de Medicina Interna del Hospital Municipal los Olivos (HMLO). Participantes: historia clínica de pacientes hospitalizados con infección urinaria en el servicio de Medicina Interna. Intervenciones: Según los criterios de inclusión y exclusión se obtuvieron, 96 historias clínicas (HC) del año 2013. Se utilizó un instrumento de recolección validado. Se realizó el análisis descriptivo con software estadístico STATA versión 25. Resultados: De las 96 HC, la edad promedio fue 55,04 años, los agentes microbianos más frecuentes fueron: la Escherichia coli con 85,3%, Staphylococcus saprophyticus 4.2% y Klebsiella pneumoniae 3,1%. La prevalencia de productores de betalactamasa espectro extendido (BLEE) fue 10,4%. Los antibióticos más resistentes fueron: trimetoprim/sulfametoxazol 89,6%, ampicilina 86%, piperacilina 84,6%, tetraciclina 79,2% y ciprofloxacino 70,8%. Los antibióticos más sensibles fueron: amikacina 100%, imipenem 100%, ertapenem 98%, meropenem 96% y piperacilina/tazobactam 96%. Conclusión: El uropatógeno más frecuente en pacientes con ITU hospitalizados fue la E. coli. Los antibióticos que presentaron resistencia a la E. coli fueron: trimetoprim/sulfametoxazol, ampicilina, piperacilina, tetraciclina y ciprofloxacino, y para el S. Saprophyticus fueron: amoxicilina/ ácido clavulánico, trimetoprim/sulfametoxazol, ceftriaxona y ciprofloxacino(AU)

Resistance to antibiotics may actually cause extensive morbidity and complications. Objective: To determine the antimicrobial resistance profile of Escherichia coli and Staphylococcus saprophyticus, in patients with urinary infection hospitalized in the Internal Medicine service of the Los Olivos Municipal Hospital. Methods: Descriptive, retrospective cross-sectional study. It was carried out in the Internal Medicine service of the Los Olivos Municipal Hospital (HMLO). Participants: clinical history of hospitalized patients with urinary infection in the Internal Medicine service. Interventions: According to the inclusion and exclusion criteria, 96 clinical records (HC) from 2013 were obtained. A validated collection instrument was used. Descriptive analysis was performed with STATA version 25 statistical software. Results: Of the 96 CHs, the average age was 55.04 years, the most frequent microbial agents were: Escherichia Coli with 85.3%, Staphylococcus saprophyticus 4.2% and Klebsiella pneumoniae 3.1%. The prevalence of extended spectrum beta-lactamase producers (ESBL) was 10.4%. The most resistant antibiotics were trimethoprim / sulfamethoxazole 89.6 %, ampicillin 86 %, piperacillin 84.6 %, tetracycline 79.2 % and ciprofloxacin 70.8 %. The most sensitive antibiotics were: amikacin 100%, imipenem 100%, ertapenem 98%, meropenem 96% and piperacillin / tazobactam 96%. Conclusion: The most common uropathogen in hospitalized UTI patients was E. coli. The antibiotics that showed resistance to E. coli were: trimethoprim/sulfamethoxazole, ampicillin, piperacillin, tetracycline, and ciprofloxacin, and for S. saprophyticus they were: amoxicillin/clavulanic acid, trimethoprim / sulfamethoxazole, ceftriaxone and ciprofloxacin(AU)

Efficacy of vaccination with StroVac for recurrent urinary tract infections in women: a comparative single-centre study.

PURPOSE: To assess the efficacy of prophylaxis for urinary tract infections (UTI) in a two-year follow-up in women with StroVac compared to a therapy with Nitrofurantoin over three months. MATERIALS AND METHODS: All patients with documented recurrent urinary tract infections (rUTI) were offered vaccination with StroVac or therapy with three months Nitrofurantoin 100 mg once daily for three months at patient's choice. Only patients with a follow-up of at least 24 months were included. All episodes with signs of UTI were documented and urine culture was performed. Success was defined as one or none UTI per 12 months, documented by urine culture. StroVac booster injection was offered 12 months after primary vaccination at patient's choice. RESULTS: 173 patients were included in this study, 124 in the StroVac group, 49 chose Nitrofuratoin. In the first 12 months, 86.8% of patients in the StroVac group and 91.8% in Nitrofurantoin group were successful (p = 0.22). Side effects were noted in 2.3% in the StroVac group causing discontinuation of therapy, whereas in the Nitrofurantoin group 18.4% stopped medication premature, mostly due to mild diarrhoea. In the second year 79.3% of patients in the StroVac group were still successful, most of them had undergone booster injection. In contrast, in the Nitrofurantoin group only 59.2% of patients were still successful (p = 0.03). CONCLUSION: StroVac is an effective and lasting non-antibiotic prophylaxis for rUTI, easy to administer with low rates of adverse events and should be offered to patients with rUTI.

Recurrent acute otitis media: a survey of current management in England.

OBJECTIVE: Recurrent acute otitis media is common in children. The preferred treatment measures for recurrent acute otitis media have a mixed evidence base. This study sought to assess baseline practice across ENT departments in England. METHODS: A national telephone survey of healthcare staff was conducted. Every ENT centre in England was contacted. A telephone script was used to ask about antibiotic and grommet use and duration in recurrent acute otitis media cases. RESULTS: Ninety-six centres (74 per cent) provided complete information. Recurrent acute otitis media treatment across England by ENT departments varied. The antibiotic first- and second-line prophylaxis offered varies, with trimethoprim used in 33 centres and 29 centres not offering any antibiotics. The timing or choice about when to use grommets also varies, but 87 centres (91 per cent) offer grommet surgery at one stage. CONCLUSION: The treatments received by children in England for recurrent acute otitis media vary by centre; collaborative research in this area is advised.

Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-resistant Urothelial Bladder Cancer.

Repeated cycles of first-line chemotherapy drugs such as doxorubicin (DOX) and cisplatin (CIS) trigger frequent chemoresistance in recurrent urothelial bladder cancer (UBC). Nitroxoline (NTX), an antibiotic to treat urinary tract infections, has been recently repurposed for cancer treatment. Here we aimed to investigate whether NTX suppresses drug-resistant UBC and its molecular mechanism. The drug-resistant cell lines T24/DOX and T24/CIS were established by continual exposure of parental cell line T24 to DOX and CIS, respectively. T24/DOX and T24/CIS cells were resistant to DOX and CIS, respectively, but they were sensitive to NTX time- and dose-dependently. Overexpressions of STAT3 and P-glycoprotein (P-gp) were identified in T24/DOX and T24/CIS, which could be reversed by NTX. Western blot revealed that NTX downregulated p-STAT3, c-Myc, Cyclin D1, CDK4, CDK6, Bcl-xL, Mcl-1, and Survivin, which were further confirmed by Stattic, a selective STAT3 inhibitor. In vivo, NTX exhibited the significant anti-tumor effect in T24/DOX and T24/CIS tumor-bearing mice. These results suggested that NTX-induced P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC were mediated by inhibition of STAT3 signaling. Our findings repurpose NTX as a novel STAT3 inhibitor to induce P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC.

Safety and efficacy evaluation of low-dose trimethoprim-sulfamethoxazole for prophylaxis of Pneumocystis pneumonia in HIV uninfected patients undergoing hemodialysis: a retrospective observational study.

BACKGROUND: Pneumocystis pneumonia (PCP) is a potentially life-threatening infection. Trimethoprim-sulfamethoxazole (TMP-SMX) is considered as the first regimen for PCP prophylaxis according to several guidelines. The recommended prophylactic dose of TMP-SMX has been determined based on patients with normal renal function, but the appropriate dosage for patients undergoing hemodialysis is unknown. The aim of this study was to investigate the efficacy and safety of low-dose TMP-SMX in patients undergoing hemodialysis. METHODS: HIV-uninfected adult patients who were undergoing hemodialysis and administered TMP-SMX for PCP prophylaxis, were included, and divided into standard-dose (≥6 single strength (SS, TMP-SMX 80 mg/400 mg tablets/week) and low-dose groups (< 6 SS tablets/week). The endpoints were cumulative incidence of PCP and cumulative discontinuation rate of TMP-SMX due to adverse events. For comparison of the groups, we employed the chi-squared test for categorical variables and the Mann-Whitney U test for continuous variables. Risk factors for the endpoints were evaluated using the Cox Fine and Gray method. RESULTS: The median age of the 81 patients included in the study was 67 years (IQR: 60-76 years), and 52 patients (64.2%) were men. No patients in either group developed PCP during the observation period. The yearly cumulative incidence of discontinuation was 12.1% (95% confidence interval [CI]: 0.027-0.29) in the low-dose group and 35.6% (95% CI: 0.20-0.52) in the standard-dose group (P = 0.019). The adjusted hazard ratio of the low-dose group compared to standard-dose group was 0.18 (95% CI: 0.04-0.86, P = 0.032). CONCLUSIONS: None of the study patients developed PCP, and the cumulative discontinuation rate of TMP-SMX due to adverse events was significantly lower in the low-dose group compared to that in the standard-dose group (P = 0.032). These results indicate that low-dose TMP-SMX is an appropriate regimen to maintain a balance between PCP prophylaxis and prevention of adverse events due to TMP-SMX administration. These findings can guide health care professionals to determine TMP-SMX dosage when considering PCP prophylaxis for patients undergoing hemodialysis.

Pigeon Pea Husk for Removal of Emerging Contaminants Trimethoprim and Atenolol from Water.

The pace of industrialization and rapid population growth in countries such as India entail an increased input of industrial and sanitary organic micropollutants, the so-called emerging contaminants (EC), into the environment. The emission of EC, such as pharmaceuticals, reaching Indian water bodies causes a detrimental effect on aquatic life and ultimately on human health. However, the financial burden of expanding sophisticated water treatment capacities renders complementary, cost-efficient alternatives, such as adsorption, attractive. Here we show the merits of washed and milled pigeon pea husk (PPH) as low-cost adsorbent for the removal of the EC trimethoprim (TMP) and atenolol (ATN) that are among the most detected pharmaceuticals in Indian waters. We found a linear increase in adsorption capacity of PPH for TMP and ATN at concentrations ranging from 10 to 200 µg/L and from 50 to 400 µg/L, respectively, reflecting the concentrations occurring in Indian water bodies. Investigation of adsorption kinetics using the external mass transfer model (EMTM) revealed that film diffusion resistance governed the adsorption process of TMP or ATN onto PPH. Moreover, analysis of the adsorption performance of PPH across an extensive range of pH and temperature illustrated that the highest adsorption loadings achieved concurred with actual conditions of Indian waters. We anticipate our work as starting point towards the development of a feasible adsorbent system aiming at low-cost water treatment.