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Open Forum Infectious Diseases Jul 2023Defining urinary tract infection (UTI) is complex, as numerous clinical and diagnostic parameters are involved. In this systematic review, we aimed to gain insight into... (Review)
Review
Defining urinary tract infection (UTI) is complex, as numerous clinical and diagnostic parameters are involved. In this systematic review, we aimed to gain insight into how UTI is defined across current studies. We included 47 studies, published between January 2019 and May 2022, investigating therapeutic or prophylactic interventions in adult patients with UTI. Signs and symptoms, pyuria, and a positive urine culture were required in 85%, 28%, and 55% of study definitions, respectively. Five studies (11%) required all 3 categories for the diagnosis of UTI. Thresholds for significant bacteriuria varied from 10 to 10 colony-forming units/mL. None of the 12 studies including acute cystitis and 2 of 12 (17%) defining acute pyelonephritis used identical definitions. Complicated UTI was defined by both host factors and systemic involvement in 9 of 14 (64%) studies. In conclusion, UTI definitions are heterogeneous across recent studies, highlighting the need for a consensus-based, research reference standard for UTI.
PubMed: 37426954
DOI: 10.1093/ofid/ofad332 -
Journal of the American Society of... Feb 2020Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse.
BACKGROUND
Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse.
METHODS
We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI.
RESULTS
Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI.
CONCLUSIONS
This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.
Topics: Acute Kidney Injury; Aged; B7-H1 Antigen; Female; Humans; Kidney; Male; Middle Aged; Nephritis, Interstitial; Programmed Cell Death 1 Receptor; Retrospective Studies; Risk Factors
PubMed: 31896554
DOI: 10.1681/ASN.2019070676 -
International Urology and Nephrology Apr 2022Emphysematous pyelonephritis (EPN) is an acute, severe necrotising infection of the kidney. There has been a shift from early nephrectomy to conservative methods. We... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Emphysematous pyelonephritis (EPN) is an acute, severe necrotising infection of the kidney. There has been a shift from early nephrectomy to conservative methods. We conducted a meta-analysis to assess the impact of risk factors and treatment choices on outcomes in EPN.
METHODS
We conducted a database search of all studies in English, reporting more than 12 patients of EPN from 1980 to 2020. We compiled the demographics, clinical presentations, risk factors, critical diagnostic results, treatment modalities and outcomes, including mortality.
RESULTS
We identified 37 observational studies, 32 retrospective and 5 prospective. The studies reported on 1146 patients, of which 790(68.9%) were female, and 946 (82.5%) were diabetic. In addition, 184 (16.1%) patients had stones, and 235 (20.5%) had obstructive uropathy. Fever and flank pain were the most frequent symptoms. The most common clinical features were pyuria, fever, flank tenderness, and tachycardia. E. coli, Klebsiella pneumoniae and Proteus were the most frequent organisms isolated. X-ray KUB and ultrasound were used as initial diagnostic modalities, but CT scan was the usual diagnostic and confirmatory investigation. Confusion, shock, thrombocytopenia, sepsis, emergency nephrectomy and hyponatremia were significantly associated with mortality. In particular, confusion and hyponatremia were associated with a sevenfold increase in mortality risk. There was no evidence that diabetes, stones, obstructive uropathy, AKI or proteinuria was associated with higher mortality. Nevertheless, 143 of the total 1146 patients died (12.5%). While 26% of the patients who had upfront emergency nephrectomy died, only 9.7% and 10% of patients with medical management and medical management plus minimally invasive treatments died. However, patients that failed medical and minimally invasive treatments and needed salvage emergency nephrectomy had a mortality of upwards of 27%.
CONCLUSION
The risk factors for mortality in emphysematous pyelonephritis are shock, thrombocytopenia, confusion, hyponatremia and emergency nephrectomy. Conservative and minimally invasive treatment should be the initial management strategy for emphysematous pyelonephritis as they carry lesser mortality risks. The presence of risk factors may help predict the subset of patients who need aggressive treatment and minimally invasive treatment modalities or early nephrectomy.
Topics: Emphysema; Escherichia coli; Female; Humans; Prospective Studies; Pyelonephritis; Retrospective Studies; Risk Factors; Treatment Outcome
PubMed: 35103928
DOI: 10.1007/s11255-022-03131-6 -
American Family Physician Sep 2020Urinary tract infections (UTIs) are common in children and are associated with significant short- and long-term morbidity. They have a high recurrence rate and are... (Review)
Review
Urinary tract infections (UTIs) are common in children and are associated with significant short- and long-term morbidity. They have a high recurrence rate and are associated with anatomic and functional abnormalities. The decision to test for UTI is based on risk factors and the child's age. Urinalysis is valuable to rule out UTI and to help decide when to start antibiotics; however, urine culture is needed for definitive diagnosis. Urine specimens collected via perineal bagging should not be used for culture because of high false-positive rates. Diagnosis of UTI requires pyuria and bacterial growth in the urine culture. Prompt treatment of UTIs reduces renal scarring. Antibiotic selection should be based on local sensitivity patterns and adjusted once culture results are available. In most cases, oral antibiotics are as effective as intravenous agents. When intravenous antibiotics are used, early transition to an oral regimen is as effective as longer intravenous courses. Kidney and bladder ultrasonography is helpful to identify acute complications and anatomic abnormalities. Voiding cystourethrography is indicated when ultrasound findings are abnormal and in cases of recurrent febrile UTIs. The use of antibiotic prophylaxis for recurrent UTIs is controversial. Identification and treatment of bowel and bladder dysfunction can prevent UTI recurrence.
Topics: Anti-Bacterial Agents; Child, Preschool; Culture Techniques; Female; Humans; Infant; Kidney; Male; Patient Selection; Recurrence; Ultrasonography; Urinalysis; Urinary Bladder; Urinary Tract Infections; Urography
PubMed: 32866365
DOI: No ID Found -
BMC Urology Mar 2021Our objective was to assess the efficacy of a high dose cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection. (Comparative Study)
Comparative Study Randomized Controlled Trial
High dose versus low dose standardized cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection in healthy women: a double-blind randomized controlled trial.
PURPOSE
Our objective was to assess the efficacy of a high dose cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection.
MATERIAL AND METHODS
We recruited 145 healthy, adult women with a history of recurrent urinary tract infection, defined as ≥ 2 in the past 6 months or ≥ 3 in the past 12 months in this randomized, controlled, double-blind clinical trial. Participants were randomized to receive a high dose of standardized, commercially available cranberry proanthocyanidins (2 × 18.5 mg daily, n = 72) or a control low dose (2 × 1 mg daily, n = 73) for a 24-week period. During follow-up, symptomatic women provided urine samples for detection of pyuria and/or bacteriuria and received an appropriate antibiotic prescription. The primary outcome for the trial was the mean number of new symptomatic urinary tract infections during a 24-week intervention period. Secondary outcomes included symptomatic urinary tract infection with pyuria or bacteriuria.
RESULTS
In response to the intervention, a non-significant 24% decrease in the number of symptomatic urinary tract infections was observed between groups (Incidence rate ratio 0.76, 95%CI 0.51-1.11). Post-hoc analyses indicated that among 97 women who experienced less than 5 infections in the year preceding enrolment, the high dose was associated with a significant decrease in the number of symptomatic urinary tract infections reported compared to the low dose (age-adjusted incidence rate ratio 0.57, 95%CI 0.33-0.99). No major side effects were reported.
CONCLUSION
High dose twice daily proanthocyanidin extract was not associated with a reduction in the number of symptomatic urinary tract infections when compared to a low dose proanthocyanidin extract. Our post-hoc results reveal that this high dose of proanthocyanidins may have a preventive impact on symptomatic urinary tract infection recurrence in women who experienced less than 5 infections per year.
TRIAL REGISTRATION
Clinicaltrials.gov, identifier NCT02572895.
Topics: Adolescent; Adult; Double-Blind Method; Female; Humans; Middle Aged; Phytotherapy; Plant Extracts; Proanthocyanidins; Recurrence; Urinary Tract Infections; Vaccinium macrocarpon; Young Adult
PubMed: 33757474
DOI: 10.1186/s12894-021-00811-w -
Biomedical Reports Aug 2022Several studies, reviews and meta-analyses have documented that D-mannose use lowers the risk of recurrent urinary tract infections (UTI), but its role in the treatment... (Review)
Review
Several studies, reviews and meta-analyses have documented that D-mannose use lowers the risk of recurrent urinary tract infections (UTI), but its role in the treatment of UTI/cystitis-related symptoms is unclear. In particular, no systematic review has analyzed the role of treatment with D-mannose in acute UTI/cystitis. In this paper, we systematically reviewed the published data on the effect of D-mannose, alone or in association with other compounds, on the typical symptoms of UTI/cystitis. PubMed/Medline and EMBASE databases were searched, from 1990 to January 2022, using combinations of the following keywords: 'urinary tract infections', 'cystalgia', 'recurrent next urinary tract infection', 'cystitis', 'mannose', 'mannoside', 'D-mannose', 'bacteriuria', 'pyuria', 'pyelocystitis' with the appropriate Boolean modifiers (Limits: Human, English, full article). Studies were selected for the systematic review if they were clinical studies and reported original data, the number of patients using D-mannose alone or in association with other treatments, and the number of patients with symptoms of UTI/cystitis at trial entry and after the follow-up period. A total of seven studies were identified. D-mannose was given alone in two studies, and was associated with cranberry extract, fruit extract, pomegranate extract, fructo-oligosaccharides, lactobacilli, and N-acetylcysteine in the others. All studies reported that symptoms decreased after treatment with D-mannose. Despite the limitations of the studies, the consistent results observed among all studies give support to the general findings that D-mannose may be useful in the treatment of UTI/cystitis symptoms.
PubMed: 35815191
DOI: 10.3892/br.2022.1552 -
The Lancet. Infectious Diseases Mar 2024The absence of a consensus-based reference standard for urinary tract infection (UTI) research adversely affects the internal and external validity of diagnostic and... (Review)
Review
The absence of a consensus-based reference standard for urinary tract infection (UTI) research adversely affects the internal and external validity of diagnostic and therapeutic studies. This omission hinders the accumulation of evidence for a disease that imposes a substantial burden on patients and society, particularly in an era of increasing antimicrobial resistance. We did a three-round Delphi study involving an international, multidisciplinary panel of UTI experts (n=46) and achieved a high degree of consensus (94%) on the final reference standard. New-onset dysuria, urinary frequency, and urinary urgency were considered major symptoms, and non-specific symptoms in older patients were not deemed indicative of UTI. The reference standard distinguishes between UTI with and without systemic involvement, abandoning the term complicated UTI. Moreover, different levels of pyuria were incorporated in the reference standard, encouraging quantification of pyuria in studies done in all health-care settings. The traditional bacteriuria threshold (10 colony-forming units per mL) was lowered to 10 colony-forming units per mL. This new reference standard can be used for UTI research across many patient populations and has the potential to increase homogeneity between studies.
PubMed: 38458204
DOI: 10.1016/S1473-3099(23)00778-8 -
Clinical Infectious Diseases : An... Jan 2023Sulopenem is a thiopenem antibiotic being developed for the treatment of multidrug-resistant infections. The availability of both intravenous (IV) and oral formulations... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sulopenem is a thiopenem antibiotic being developed for the treatment of multidrug-resistant infections. The availability of both intravenous (IV) and oral formulations will facilitate earlier hospital discharge.
METHODS
Hospitalized adults with pyuria, bacteriuria, and signs and symptoms of complicated urinary tract infection (cUTI) were randomized to 5 days of IV sulopenem followed by oral sulopenem etzadroxil/probenecid or 5 days of IV ertapenem followed by oral ciprofloxacin or amoxicillin-clavulanate, depending on uropathogen susceptibility. The primary end point was overall combined clinical and microbiologic response at the test-of-cure visit (day 21).
RESULTS
Of 1392 treated patients, 444 and 440 treated with sulopenem and ertapenem, respectively, had a positive baseline urine culture and were eligible for the primary efficacy analyses. Extended-spectrum β-lactamase-producing organisms were identified in 26.6% of patients and fluoroquinolone-nonsusceptible pathogens in 38.6%. For the primary end point, noninferiority of sulopenem to the comparator regimen was not demonstrated, 67.8% vs 73.9% (difference, -6.1%; 95% confidence interval, -12.0 to -.1%). The difference was driven by a lower rate of asymptomatic bacteriuria in the subgroup of ertapenem-treated patients who stepped down to ciprofloxacin. No substantial difference in overall response was observed at any other time point. Both IV and oral formulations of sulopenem were well-tolerated and compared favorably to the comparator.
CONCLUSIONS
Sulopenem followed by oral sulopenem-etzadroxil/probenecid was not noninferior to ertapenem followed by oral step-down therapy for the treatment of cUTIs, driven by a lower rate of asymptomatic bacteriuria in those who received ciprofloxacin. Both formulations of sulopenem were well-tolerated.
CLINICAL TRIAL REGISTRATION
NCT03357614.
Topics: Adult; Humans; Ertapenem; Bacteriuria; Urinary Tract Infections; Anti-Bacterial Agents; Pyelonephritis; Ciprofloxacin
PubMed: 36068705
DOI: 10.1093/cid/ciac704