Antibiotic prophylaxis and clinical outcomes among older adults with recurrent urinary tract infection: cohort study.
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ABSTRACT: Background
clinical guidelines recommend antibiotic prophylaxis for preventing recurrent urinary tract infections (UTIs), but there is little evidence for their effectiveness in older adults.Methods
this was a retrospective cohort study of health records from 19,696 adults aged ≥65 with recurrent UTIs. We used prescription records to ascertain ≥3 months' prophylaxis with trimethoprim, cefalexin or nitrofurantoin. We used random effects Cox recurrent event models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risks of clinical recurrence (primary outcome), acute antibiotic prescribing and hospitalisation.Results
of 4,043 men and 15,653 women aged ≥65 with recurrent UTIs, 508 men (12.6%) and 2,229 women (14.2%) were prescribed antibiotic prophylaxis. In men, prophylaxis was associated with a reduced risk of clinical recurrence (HR, 0.49; 95% CI, 0.45-0.54), acute antibiotic prescribing (HR, 0.54; 95% CI, 0.51-0.57) and UTI-related hospitalisation (HR, 0.78; 95% CI, 0.64-0.94). In women, prophylaxis was also associated with a reduced risk of clinical recurrence (HR, 0.57; 95% CI, 0.55-0.59) and acute antibiotic prescribing (HR, 0.61; 95% CI, 0.59-0.62), but estimates of the risk of UTI-related hospitalisation were inconsistent between our main analysis (HR, 1.16; 95% CI, 1.05-1.28) and sensitivity analysis (HR, 0.82; 95% CI, 0.72-0.94).Conclusions
antibiotic prophylaxis was associated with lower rates of UTI recurrence and acute antibiotic prescribing in older adults. To fully understand the benefits and harms of prophylaxis, further research should determine the frequency of antibiotic-related adverse events and the impact on antimicrobial resistance and quality of life.
SUBMITTER: Ahmed H
PROVIDER: S-EPMC6424374 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNitrofurantoin is widely recommended for empirical treatment of urinary tract infection (UTI), but primary care clinicians may prescribe alternative antibiotics to improve prognosis in older, sicker patients. We assessed whether prescribing alternative antibiotics was associated with reduced risk of adverse outcomes in older patients.MethodsThis retrospective cohort study included patients aged ≥65 years empirically treated for a UTI with nitrofurantoin, cefalexin, ciprofloxacin, or co-amoxiclav. We matched patients on their propensity to receive a nitrofurantoin prescription and used mixed-effects logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for reconsultation and represcription (proxy for treatment failure), hospitalization for UTI, sepsis, or acute kidney injury, and death.ResultsWe identified 42 298 patients aged ≥65 years prescribed empirical nitrofurantoin, cefalexin, ciprofloxacin, or co-amoxiclav for a UTI. Compared with nitrofurantoin, patients prescribed cefalexin, ciprofloxacin, or co-amoxiclav had lower odds of reconsultation and represcription (OR for cefalexin = 0.85, 95% CI = 0.75-0.98; OR for ciprofloxacin = 0.48, 95% CI = 0.38-0.61, OR for co-amoxiclav = 0.77, 95% CI = 0.64-0.93). Patients prescribed cefalexin or ciprofloxacin had greater odds of hospitalization for sepsis (OR for cefalexin = 1.89, 95% CI = 1.03-3.47; OR for ciprofloxacin = 3.21, 95% CI = 1.59-6.50), and patients prescribed cefalexin had greater odds of death (OR = 1.44, 95% CI = 1.12-1.85).ConclusionsCompared with nitrofurantoin, prescribing of alternative antibiotics for UTI in older people may be associated with lower rates of treatment failure but was not associated with reduced risk of UTI-related hospitalization or death.
| S-EPMC6411277 | biostudies-literature
Project description:ObjectiveTo understand the relationship between frailty, age, and recurrent urinary tract infections (rUTIs).Materials and methodsThe Timed Up and Go Test (TUGT), a measure of frailty, was administered to all adults aged ≥65 presenting to an academic nononcologic urology practice from December 2015 to January 2018. TUGT was categorized as fast (≤10 seconds), intermediate (11-14 seconds) or slow (≥15 seconds). The TUGT and other clinical data were abstracted from the medical record using direct queries supplemented with chart review. Logistic regression was used to determine the relationship between frailty, age, and the diagnosis of rUTIs in our clinic population.ResultsThere were 136 americans adults with and 2824 americans adults without a diagnosis of rUTIs. Individuals with rUTIs had slower TUGT times (13.8 ± 10.4 seconds compared to 10.8 ± 4.52 seconds, P <.01) and were more likely to be classified as slow, or "frail" (27.2% vs 10.8%). In multivariate analysis, slow TUGT times were associated with a diagnosis of rUTIs (adjusted OR 2.0, 95% CI 1.2-3.3), while age was not a statistically significant predictor of this diagnosis (adjusted OR 1.3, 95% CI 0.7-2.2 for aged ≥81 years).ConclusionOlder adults with a diagnosis of rUTIs are significantly more frail compared to those with other nononcologic urologic diagnoses. Frailty (adjusted for age), was significantly associated with rUTIs, while age (adjusted for frailty) was not. Furthermore, frailty (rather than age) may be important to consider when caring for and treating americans adults with rUTIs.
| S-EPMC8528015 | biostudies-literature
Project description:BackgroundAntibiotic use is associated with several antibiotic-related harms in vulnerable, older long-term care (LTC) residents. Suboptimal antibiotic use may also be associated with harms but has not yet been investigated. The aim of this work was to compare rates of poor clinical outcomes among LTC residents with UTI receiving suboptimal versus optimal antibiotic treatment.MethodsWe conducted a retrospective cohort study among residents with an incident urinary tract infection (UTI) treated in Veterans Affairs LTC units (2013-2018). Potentially suboptimal antibiotic treatment was defined as use of a suboptimal initial antibiotic drug choice, dose frequency, and/or excessive treatment duration. The primary outcome was time to a composite measure of poor clinical outcome, defined as UTI recurrence, acute care hospitalization/emergency department visit, adverse drug event, Clostridioides difficile infection (CDI), or death within 30 days of antibiotic discontinuation. Shared frailty Cox proportional hazard regression models were used to compare the time-to-event between suboptimal and optimal treatment.ResultsAmong 19,701 LTC residents with an incident UTI, 64.6% received potentially suboptimal antibiotic treatment and 35.4% experienced a poor clinical outcome. In adjusted analyses, potentially suboptimal antibiotic treatment was associated with a small increased hazard of poor clinical outcome (aHR 1.06, 95% CI 1.01-1.11) as compared with optimal treatment, driven by an increased hazard of CDI (aHR 1.94, 95% CI 1.54-2.44).ConclusionIn this national cohort study, suboptimal antibiotic treatment was associated with a 6% increased risk of the composite measure of poor clinical outcomes, in particular, a 94% increased risk of CDI. Beyond the decision to use antibiotics, clinicians should also consider the potential harms of suboptimal treatment choices with regards to drug type, dose frequency, and duration used.
| S-EPMC8299613 | biostudies-literature
Project description:OBJECTIVE:To determine if trimethoprim use for urinary tract infection (UTI) is associated with an increased risk of acute kidney injury, hyperkalaemia, or sudden death in the general population. DESIGN:Cohort study. SETTING:UK electronic primary care records from practices contributing to the Clinical Practice Research Datalink linked to the Hospital Episode Statistics database. PARTICIPANTS:Adults aged 65 and over with a prescription for trimethoprim, amoxicillin, cefalexin, ciprofloxacin, or nitrofurantoin prescribed up to three days after a primary care diagnosis of UTI between April 1997 and September 2015. MAIN OUTCOME MEASURES:The outcomes were acute kidney injury, hyperkalaemia, and death within 14 days of a UTI treated with antibiotics. RESULTS:Among a cohort of 1?191?905 patients aged 65 and over, 178?238 individuals were identified with at least one UTI treated with antibiotics, comprising a total of 422?514 episodes of UTIs treated with antibiotics. The odds of acute kidney injury in the 14 days following antibiotic initiation were higher following trimethoprim (adjusted odds ratio 1.72, 95% confidence interval 1.31 to 2.24) and ciprofloxacin (1.48, 1.03 to 2.13) compared with amoxicillin. The odds of hyperkalaemia in the 14 days following antibiotic initiation were only higher following trimethoprim (2.27, 1.49 to 3.45) compared with amoxicillin. However, the odds of death within the 14 days following antibiotic initiation were not higher with trimethoprim than with amoxicillin: in the whole population the adjusted odds ratio was 0.90 (95% confidence interval 0.76 to 1.07) while among users of renin-angiotensin system blockers the odds of death within 14 days of antibiotic initiation was 1.12 (0.80 to 1.57). The results suggest that, for 1000 UTIs treated with antibiotics among people 65 and over, treatment with trimethoprim instead of amoxicillin would result in one to two additional cases of hyperkalaemia and two admissions with acute kidney injury, regardless of renin-angiotensin system blockade. However, for people taking renin-angiotensin system blockers and spironolactone treatment with trimethoprim instead of amoxicillin there were 18 additional cases of hyperkalaemia and 11 admissions with acute kidney injury. CONCLUSION:Trimethoprim is associated with a greater risk of acute kidney injury and hyperkalaemia compared with other antibiotics used to treat UTIs, but not a greater risk of death. The relative risk increase is similar across population groups, but the higher baseline risk among those taking renin-angiotensin system blockers and potassium-sparing diuretics translates into higher absolute risks of acute kidney injury and hyperkalaemia in these groups.
| S-EPMC5806507 | biostudies-literature
Project description:Urinary tract infections (UTI) are an important cause of morbidity and antibiotic use in older adults but there are little data describing disease burden in primary care. The aim of this study was to estimate the incidence of clinically diagnosed UTI and examine associated empirical antibiotic prescribing. We conducted a retrospective observational study using linked health records from almost one million patients aged ?65 years old, registered with 393 primary care practices in England. We estimated incidence of clinically diagnosed UTI between March 2004 and April 2014, and used multilevel logistic regression to examine trends in empiric antibiotic prescribing. Of 931,945 older adults, 196,358 (21%) had at least one clinically diagnosed UTI over the study period. In men, the incidence of clinically diagnosed UTI per 100 person-years at risk increased from 2.81 to 3.05 in those aged 65-74, 5.90 to 6.13 in those aged 75-84, and 8.08 to 10.54 in those aged 85+. In women, incidence increased from 9.03 to 10.96 in those aged 65-74, 11.35 to 14.34 in those aged 75-84, and 14.65 to 19.80 in those aged 85+. Prescribing of broad-spectrum antibiotics decreased over the study period. There were increases in the proportion of older men (from 45% to 74%) and women (from 55% to 82%) with UTI, prescribed a UTI specific antibiotic. There were also increases in the proportion of older men (42% to 69%) and women (15% to 26%) prescribed antibiotics for durations recommended by clinical guidelines. This is the first population-based study describing the burden of UTI in UK primary care. Our findings suggest a need to better understand reasons for increasing rates of clinically diagnosed UTI and consider how best to address this important clinical problem.
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Project description:BackgroundRecurrent 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.ObjectivesTo assess treatment satisfaction, long-term safety and efficacy of IAIs for recurrent UTI.MethodsWe 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.ResultsForty-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).ConclusionsIn 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.
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Project description:The capacity of subinhibitory levels of antibiotics to modulate bacterial virulence in vitro has recently been brought to light, raising concerns over the appropriateness of low-dose therapies, including antibiotic prophylaxis for recurrent urinary tract infection management. However, the mechanisms involved and their relevance in influencing pathogenesis have not been investigated. We characterized the ability of antibiotics to modulate virulence in the uropathogens Staphylococcus saprophyticus and Escherichia coli. Several antibiotics were able to induce the expression of adhesins critical to urothelial colonization, resulting in increased biofilm formation, colonization of murine bladders and kidneys, and promotion of intracellular niche formation. Mice receiving subinhibitory ciprofloxacin treatment were also more susceptible to severe infections and frequent recurrences. A ciprofloxacin prophylaxis model revealed this strategy to be ineffective in reducing recurrences and worsened infection by creating larger intracellular reservoirs at higher frequencies. Our study indicates that certain agents used for antibiotic prophylaxis have the potential to complicate infections.Antibiotics are the mainstay treatment for bacterial infections; however, evidence is emerging that argues these agents may have off-target effects if sublethal concentrations are present. Most studies have focused on changes occurring in vitro, leaving questions regarding the clinical relevance in vivo. We utilized a murine urinary tract infection model to explore the potential impact of low-dose antibiotics on pathogenesis. Using this model, we showed that subinhibitory antibiotics prime uropathogens for adherence and invasion of murine urothelial tissues. These changes in initial colonization promoted the establishment of chronic infection. Furthermore, treatment of chronically infected mice with subtherapeutic ciprofloxacin served to exacerbate infection. A part of these changes was thought to be due to suppression of mucosal immunity, as demonstrated through reductions in cytokine secretion and migration of leukocytes into the urinary tract. This work identifies novel risk factors associated with antibiotic therapy when dosing strategies fall below subtherapeutic levels.
| S-EPMC4453531 | biostudies-other
Project description:ObjectiveTo address clinical uncertainties about the effectiveness and safety of long-term antibiotic therapy for preventing recurrent urinary tract infections (UTIs) in older adults.DesignSystematic review andmeta-analysis of randomised trials.MethodWe searched Medline, Embase, The Cumulative Index to Nursing and Allied Health Literature(CINAHL), and the Cochrane Register of Controlled Trials from inception to August 2016. Eligible studies compared long-term antibiotic therapy with non-antibiotic therapy or placebo in men or women aged over 65, or in postmenopausal women, with recurrent UTIs.ResultsWe did not identify any studies that included older men. Three randomised controlled trials compared long-term antibiotics with vaginal oestrogens (n=150), oral lactobacilli (n=238) and D-mannose powder (n=94) in postmenopausal women. Long-term antibiotics reduced the risk of UTI recurrence by 24% (three trials, n=482; pooled risk ratio (RR) 0.76; 95% CI 0.61 to 0.95, number needed to treat=8.5). There was no statistically significant increase in risk of adverse events (mild adverse events: pooled RR 1.52; 95% CI 0.76 to 3.03; serious adverse events: pooled RR 0.90, 95% CI 0.31 to 2.66). One trial showed 90% of urinary and faecal Escherichia coli isolates were resistant to trimethoprim-sulfamethoxazole after 1 month of prophylaxis.ConclusionsFindings from three small trials with relatively short follow-up periods suggest long-term antibiotic therapy reduces the risk of recurrence in postmenopausal women with recurrent UTI. We did not identify any evidence to inform several clinically important scenarios including, benefits and harms in older men or frail care home residents, optimal duration of prophylaxis, recurrence rates once prophylaxis stops and effects on urinary antibiotic resistance.
| S-EPMC5729980 | biostudies-literature
Project description:We present a 62-year-old woman who developed recurrent urinary tract infections in her early fifties and, after an evaluation by an infectious disease physician, was referred for a neurological consultation. Her history and neurological examination were consistent with spastic paraparesis and there was significant family history of a variety of neurological diagnoses suggesting a genetic disorder. Whole exome genetic testing revealed a novel change, a c.508 C > T variant in the SPAST gene. Our genetic and protein modeling analysis suggest that this is a disease-producing mutation confirming the diagnosis of hereditary spastic paraplegia type 4 (SPG4). This patient expands the spectrum of mutations that can cause this disorder and demonstrate the importance of recognizing the role of neurological disorders in causing neurogenic bladder and recurrent urinary tract infections.
| S-EPMC7427448 | biostudies-literature
Project description:BackgroundRepeated symptomatic urinary tract infections (UTIs) affect 25% of people who use clean intermittent self-catheterisation (CISC) to empty their bladder. We aimed to determine the benefits, harms, and cost-effectiveness of continuous low-dose antibiotic prophylaxis for prevention of recurrent UTIs in adult users of CISC.MethodsIn this randomised, open-label, superiority trial, we enrolled participants from 51 UK National Health Service organisations. These participants were community-dwelling (as opposed to hospital inpatient) users of CISC with recurrent UTIs. We randomly allocated participants (1:1) to receive either antibiotic prophylaxis once daily (prophylaxis group) or no prophylaxis (control group) for 12 months by use of an internet-based system with permuted blocks of variable length. Trial and laboratory staff who assessed outcomes were masked to allocation but participants were aware of their treatment group. The primary outcome was the incidence of symptomatic, antibiotic-treated UTIs over 12 months. Participants who completed at least 6 months of follow-up were assumed to provide a reliable estimate of UTI incidence and were included in the analysis of the primary outcome. Change in antimicrobial resistance of urinary and faecal bacteria was monitored as a secondary outcome. The AnTIC trial is registered at ISRCTN, number 67145101; and EudraCT, number 2013-002556-32.FindingsBetween Nov 25, 2013, and Jan 29, 2016, we screened 1743 adult users of CISC for eligibility, of whom 404 (23%) participants were enrolled between Nov 26, 2013, and Jan 31, 2016. Of these 404 participants, 203 (50%) were allocated to receive prophylaxis and 201 (50%) to receive no prophylaxis. 1339 participants were excluded before randomisation. The primary analysis included 181 (89%) adults allocated to the prophylaxis group and 180 (90%) adults in the no prophylaxis (control) group. 22 participants in the prophylaxis group and 21 participants in the control group were not included in the primary analysis because they were missing follow-up data before 6 months. The incidence of symptomatic antibiotic-treated UTIs over 12 months was 1·3 cases per person-year (95% CI 1·1-1·6) in the prophylaxis group and 2·6 (2·3-2·9) in the control group, giving an incidence rate ratio of 0·52 (0·44-0·61; p<0·0001), indicating a 48% reduction in UTI frequency after treatment with prophylaxis. Use of prophylaxis was well tolerated: we recorded 22 minor adverse events in the prophylaxis group related to antibiotic prophylaxis during the study, predominantly gastrointestinal disturbance (six participants), skin rash (six participants), and candidal infection (four participants). However, resistance against the antibiotics used for UTI treatment was more frequent in urinary isolates from the prophylaxis group than in those from the control group at 9-12 months of trial participation (nitrofurantoin 12 [24%] of 51 participants from the prophylaxis group vs six [9%] of 64 participants from the control group with at least one isolate; p=0·038), trimethoprim (34 [67%] of 51 vs 21 [33%] of 64; p=0·0003), and co-trimoxazole (26 [53%] of 49 vs 15 [24%] of 62; p=0·002).InterpretationContinuous antibiotic prophylaxis is effective in reducing UTI frequency in CISC users with recurrent UTIs, and it is well tolerated in these individuals. However, increased resistance of urinary bacteria is a concern that requires surveillance if prophylaxis is started.FundingUK National Institute for Health Research.
| S-EPMC6105581 | biostudies-literature