Objectives: Urinary tract infection (UTI) is common among older women. However, diagnosis is challenging because of frequent chronic lower urinary tract symptoms, cognitive impairment, and a high... Show moreObjectives: Urinary tract infection (UTI) is common among older women. However, diagnosis is challenging because of frequent chronic lower urinary tract symptoms, cognitive impairment, and a high prevalence of asymptomatic bacteriuria (ASB). Current urine diagnostics lack specificity, leading to unnecessary treatment and antimicrobial resistance. This study aimed to evaluate the diagnostic accuracy of 12 urine biomarkers for diagnosing UTI in older women. Methods: In this case -control study, cases were women >= 65 years with >= 2 new -onset lower urinary tract symptoms, pyuria, and one uropathogen >= 104 CFU/mL. Controls were asymptomatic and classified as ASB (one uropathogen >= 105 CFU/mL), negative culture, or mixed flora. Urine biomarker concentrations were measured through liquid chromatography -mass spectrometry and ELISA. Diagnostic accuracy parameters of individual biomarkers and a biomarker model were derived from receiver operating characteristic curves. Results: We included 162 community -dwelling and institutionalized older women. Five urine inflam- matory biomarkers demonstrated high discriminative ability (area under the curve >= 0.80): interleukin 6, azurocidin, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinases 2, and C -X-C motif chemokine 9. Azurocidin exhibited the highest diagnostic accuracy (sensitivity 86% [95% CI 75% -93%] and specificity 89% [95% CI 82%-94%] at 16.7 ng/mmol creatinine). A combined biomarker and pyuria model showed improved diagnostic accuracy in patients with UTI and ASB, compared with pyuria alone. Discussion: We identified several urine biomarkers that accurately differentiated older women with UTI from asymptomatic women, including ASB. These findings represent a potential advancement towards improved diagnostics for UTI in older women and warrant validation in a diverse population. Manu P. Bilsen, Clin Microbiol Infect 2024;30:216 (c) 2023 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/). Show less
Bilsen, M.P.; Treep, M.M.; Aantjes, M.J.; Andel, E. van; Stalenhoef, J.E.; Nieuwkoop, C. van; ... ; Lambregts, M.M.C. 2024
ObjectivesUrinary tract infection (UTI) is common among older women. However, diagnosis is challenging because of frequent chronic lower urinary tract symptoms, cognitive impairment, and a high... Show moreObjectivesUrinary tract infection (UTI) is common among older women. However, diagnosis is challenging because of frequent chronic lower urinary tract symptoms, cognitive impairment, and a high prevalence of asymptomatic bacteriuria (ASB). Current urine diagnostics lack specificity, leading to unnecessary treatment and antimicrobial resistance. This study aimed to evaluate the diagnostic accuracy of 12 urine biomarkers for diagnosing UTI in older women.MethodsIn this case-control study, cases were women ≥65 years with ≥2 new-onset lower urinary tract symptoms, pyuria, and one uropathogen ≥104 CFU/mL. Controls were asymptomatic and classified as ASB (one uropathogen ≥105 CFU/mL), negative culture, or mixed flora. Urine biomarker concentrations were measured through liquid chromatography-mass spectrometry and ELISA. Diagnostic accuracy parameters of individual biomarkers and a biomarker model were derived from receiver operating characteristic curves.ResultsWe included 162 community-dwelling and institutionalized older women. Five urine inflammatory biomarkers demonstrated high discriminative ability (area under the curve ≥0.80): interleukin 6, azurocidin, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinases 2, and C-X-C motif chemokine 9. Azurocidin exhibited the highest diagnostic accuracy (sensitivity 86% [95% CI 75%–93%] and specificity 89% [95% CI 82%–94%] at 16.7 ng/mmol creatinine). A combined biomarker and pyuria model showed improved diagnostic accuracy in patients with UTI and ASB, compared with pyuria alone.DiscussionWe identified several urine biomarkers that accurately differentiated older women with UTI from asymptomatic women, including ASB. These findings represent a potential advancement towards improved diagnostics for UTI in older women and warrant validation in a diverse population. Show less
Background: Recurrent urinary tract infections (UTIs) are common, especially in women. When oral antimicrobial prophylaxis is ineffective or not possible due to allergies or antimicrobial... Show moreBackground: Recurrent urinary tract infections (UTIs) are common, especially in women. When oral antimicrobial prophylaxis is ineffective or not possible due to allergies or antimicrobial resistance, intravesical aminoglycoside instillations (IAIs) are a non-systemic alternative.Objectives: To assess treatment satisfaction, long-term safety and efficacy of IAIs for recurrent UTI.Methods: We conducted a cohort study using data collected between January 2013 and June 2022 at the Leiden University Medical Center. Adult patients with recurrent UTI who received prophylactic IAI were eligible for inclusion. Treatment satisfaction was assessed through a survey. Data on serum aminoglycoside concentrations, cystoscopy results and number of recurrences were obtained through chart review. Number of recurrences and UTI characteristics were compared between patients on and off IAI using Poisson and logistic mixed effects models.Results: Forty-four patients were included (median follow-up time 976 days) and 323 UTIs occurred during follow-up. Overall treatment satisfaction was high (median 79.2/100). All but one patient had undetectable serum aminoglycoside levels and no malignancies were found on follow-up cystoscopy. IAI increased the time to first recurrence (102 days versus 36 days, P = 0.02), reduced the number of recurrences (rate ratio 0.75, 95% CI 0.56-0.99, P = 0.04) and the necessity for systemic antibiotics (OR 0.33, 95% CI 0.13-0.86, P = 0.02). Conclusions: In patients with recurrent UTI, IAI was associated with high treatment satisfaction, and was found to be a safe and effective alternative to oral antimicrobial prophylaxis. Show less
Bilsen, M.P.; Aantjes, M.J.; Andel, E. van; Stalenhoef, J.E.; Nieuwkoop, C. van; Leyten, E.M.S.; ... ; Lambregts, M.M.C. 2023
Background: Pre-existing lower urinary tract symptoms (LUTS), cognitive impairment, and the high prevalence of asymptomatic bacteriuria (ASB) complicate the diagnosis of urinary tract infection ... Show moreBackground: Pre-existing lower urinary tract symptoms (LUTS), cognitive impairment, and the high prevalence of asymptomatic bacteriuria (ASB) complicate the diagnosis of urinary tract infection (UTI) in older women. The presence of pyuria remains the cornerstone of UTI diagnosis. However, > 90% of ASB patients have pyuria, prompting unnecessary treatment. We quantified pyuria by automated microscopy and flowcytometry to determine the diagnostic accuracy for UTI and to derive pyuria thresholds for UTI in older women. Methods: Women >= 65 years with >= 2 new-onset LUTS and 1 uropathogen >= 10(4) colony-forming units (CFU)/mL were included in the UTI group. Controls were asymptomatic and classified as ASB (1 uropathogen >= 10(5) CFU/mL), negative culture, or mixed flora. Patients with an indwelling catheter or antimicrobial pretreatment were excluded. Leukocyte medians were compared and sensitivity-specificity pairs were derived from a receiver operating characteristic curve. Results: We included 164 participants. UTI patients had higher median urinary leukocytes compared with control patients (microscopy: 900 vs 26 leukocytes/mu L; flowcytometry: 1575 vs 23 leukocytes/mu L; P < .001). Area under the curve was 0.93 for both methods. At a cutoff of 264 leukocytes/mu L, sensitivity and specificity of microscopy were 88% (positive and negative likelihood ratio: 7.2 and 0.1, respectively). The commonly used cutoff of 10 leukocytes/mu L had a poor specificity (36%) and a sensitivity of 100%. Conclusions: The degree of pyuria can help to distinguish UTI in older women from ASB and asymptomatic controls with pyuria. Current pyuria cutoffs are too low and promote inappropriate UTI diagnosis in older women. Show less
Bilsen, M.P.; Lambregts, M.M.C.; Prehn, J. van; Kuijper, E.J. 2022
Purpose of review Antimicrobial resistance is a rising threat to global health and is associated with increased mortality. Intestinal colonisation with multidrug-resistant organisms (MDRO) can... Show morePurpose of review Antimicrobial resistance is a rising threat to global health and is associated with increased mortality. Intestinal colonisation with multidrug-resistant organisms (MDRO) can precede invasive infection and facilitates spread within communities and hospitals. Novel decolonisation strategies, such as faecal microbiota transplantation (FMT), are being explored. The purpose of this review is to provide an update on how the field of FMT for MDRO decolonisation has developed during the past year and to assess the efficacy of FMT for intestinal MDRO decolonisation. Recent findings Since 2020, seven highly heterogenous, small, nonrandomised cohort studies and five case reports have been published. In line with previous literature, decolonisation rates ranged from 20 to 90% between studies and were slightly higher for carbapenem-resistant Enterobacteriaceae than vancomycin-resistant Enterococcus. Despite moderate decolonisation rates in two studies, a reduction in MDRO bloodstream and urinary tract infections was observed. Summary and implications Although a number of smaller cohort studies show some effect of FMT for MDRO decolonisation, questions remain regarding the true efficacy of FMT (taking spontaneous decolonisation into account), the optimal route of administration, the role of antibiotics pre and post-FMT and the efficacy in different patient populations. The observed decrease in MDRO infections post-FMT warrants further research. Show less
Nahon, K.J.; Janssen, L.G.M.; Mishre, A.S.D.S.; Bilsen, M.P.; Eijk, J.A. van der; Botani, K.; ... ; Rensen, P.C.N. 2020
Aim To compare the effects of cold exposure and the beta 3-adrenergic receptor agonist mirabegron on plasma lipids, energy expenditure and brown adipose tissue (BAT) activity in South Asians versus... Show moreAim To compare the effects of cold exposure and the beta 3-adrenergic receptor agonist mirabegron on plasma lipids, energy expenditure and brown adipose tissue (BAT) activity in South Asians versus Europids. Materials and Methods Ten lean Dutch South Asian (aged 18-30 years; body mass index [BMI] 18-25 kg/m(2)) and 10 age- and BMI-matched Europid men participated in a randomized, double-blinded, cross-over study consisting of three interventions: short-term (similar to 2 hours) cold exposure, mirabegron (200 mg one dose p.o.) and placebo. Before and after each intervention, we performed lipidomic analysis in serum, assessed resting energy expenditure (REE) and skin temperature, and measured BAT fat fraction by magnetic resonance imaging. Results In both ethnicities, cold exposure increased the levels of several serum lipid species, whereas mirabegron only increased free fatty acids. Cold exposure increased lipid oxidation in both ethnicities, while mirabegron increased lipid oxidation in Europids only. Cold exposure and mirabegron enhanced supraclavicular skin temperature in both ethnicities. Cold exposure decreased BAT fat fraction in both ethnicities. After the combination of data from both ethnicities, mirabegron decreased BAT fat fraction compared with placebo. Conclusions In South Asians and Europids, cold exposure and mirabegron induced beneficial metabolic effects. When combining both ethnicities, cold exposure and mirabegron increased REE and lipid oxidation, coinciding with a higher supraclavicular skin temperature and lower BAT fat fraction. Show less
Intravesical bacillus Calmette-Guerin (BCG) is widely used for high-risk, non-muscle-invasive bladder cancer. This report describes four cases that illustrate the spectrum of BCG-induced... Show moreIntravesical bacillus Calmette-Guerin (BCG) is widely used for high-risk, non-muscle-invasive bladder cancer. This report describes four cases that illustrate the spectrum of BCG-induced complications, varying from granulomatous prostatitis to sepsis. There is considerable debate regarding whether inflammation or infection is the predominant mechanism in the pathogenesis of BCG disease. In two patients with a systemic illness, the symptoms first resolved after adding prednisone, indicating a principal role for inflammation in systemic disease. In vitro testing of T-cell responses and a mycobacterial growth inhibition assay were performed for these patients with systemic disease. The patient with mild symptoms showed more effective in vitro growth reduction of BCG, while the patient with sepsis and organ involvement had high T-cell responses but ineffective killing. While these findings are preliminary, it is believed that immunological assays, as described in this report, may provide a better insight into the pathogenesis of BCG disease in individual patients, justifying further research. (C) 2018 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
