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Cureus Feb 2024species, typically considered commensal organisms of the human urogenital tract, have been implicated in various urinary tract infections (UTIs), including the rare and...
species, typically considered commensal organisms of the human urogenital tract, have been implicated in various urinary tract infections (UTIs), including the rare and challenging presentation of pyelonephritis. This case report describes a unique instance of pyelonephritis induced by , characterized by a negative routine urine culture and a lack of response to empirical antibiotic treatment, highlighting the complexities associated with diagnosing and managing infections caused by atypical pathogens. A 50-year-old female presented to the emergency department with symptoms suggestive of UTI, including fever, vomiting, and dysuria. However, initial urine analysis was notable for pyuria while routine bacterial culture returned negative results, creating a diagnostic dilemma. Empirical treatment with third-generation cephalosporin was initiated. However, the patient's condition failed to improve, raising concerns about antibiotic resistance or atypical pathogens. Subsequent molecular diagnostics, precisely polymerase chain reaction (PCR), identified as the causative agent. This prompted a change in the treatment regimen to doxycycline, to which the patient showed significant clinical improvement. Physicians should be aware of as a potential cause of pyelonephritis, especially in cases of culture-negative UTIs and when patients do not respond to standard empirical treatment. This case emphasizes the importance of considering atypical pathogens in differential diagnosis and the role of molecular diagnostic techniques in guiding appropriate management.
PubMed: 38544616
DOI: 10.7759/cureus.54958 -
JAMA Network Open Mar 2024Guidelines recommend withholding antibiotics in asymptomatic bacteriuria (ASB), including among patients with altered mental status (AMS) and no systemic signs of...
IMPORTANCE
Guidelines recommend withholding antibiotics in asymptomatic bacteriuria (ASB), including among patients with altered mental status (AMS) and no systemic signs of infection. However, ASB treatment remains common.
OBJECTIVES
To determine prevalence and factors associated with bacteremia from a presumed urinary source in inpatients with ASB with or without AMS and estimate antibiotics avoided if a 2% risk of bacteremia were used as a threshold to prompt empiric antibiotic treatment of ASB.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study assessed patients hospitalized to nonintensive care with ASB (no immune compromise or concomitant infections) in 68 Michigan hospitals from July 1, 2017, to June 30, 2022. Data were analyzed from August 2022 to January 2023.
MAIN OUTCOMES AND MEASURES
The primary outcome was prevalence of bacteremia from a presumed urinary source (ie, positive blood culture with matching organisms within 3 days of urine culture). To determine factors associated with bacteremia, we used multivariable logistic regression models. We estimated each patient's risk of bacteremia and determined what percentage of patients empirically treated with antibiotics had less than 2% estimated risk of bacteremia.
RESULTS
Of 11 590 hospitalized patients with ASB (median [IQR] age, 78.2 [67.7-86.6] years; 8595 female patients [74.2%]; 2235 African American or Black patients [19.3%], 184 Hispanic patients [1.6%], and 8897 White patients [76.8%]), 8364 (72.2%) received antimicrobial treatment for UTI, and 161 (1.4%) had bacteremia from a presumed urinary source. Only 17 of 2126 patients with AMS but no systemic signs of infection (0.7%) developed bacteremia. On multivariable analysis, male sex (adjusted odds ratio [aOR], 1.45; 95% CI, 1.02-2.05), hypotension (aOR, 1.86; 95% CI, 1.18-2.93), 2 or more systemic inflammatory response criteria (aOR, 1.72; 95% CI, 1.21-2.46), urinary retention (aOR, 1.87; 95% CI, 1.18-2.96), fatigue (aOR, 1.53; 95% CI, 1.08-2.17), log of serum leukocytosis (aOR, 3.38; 95% CI, 2.48-4.61), and pyuria (aOR, 3.31; 95% CI, 2.10-5.21) were associated with bacteremia. No single factor was associated with more than 2% risk of bacteremia. If 2% or higher risk of bacteremia were used as a cutoff for empiric antibiotics, antibiotic exposure would have been avoided in 78.4% (6323 of 8064) of empirically treated patients with low risk of bacteremia.
CONCLUSIONS AND RELEVANCE
In patients with ASB, bacteremia from a presumed urinary source was rare, occurring in less than 1% of patients with AMS. A personalized, risk-based approach to empiric therapy could decrease unnecessary ASB treatment.
Topics: Adult; Humans; Female; Male; Aged; Bacteriuria; Cohort Studies; Inpatients; Anti-Bacterial Agents; Bacteremia
PubMed: 38477915
DOI: 10.1001/jamanetworkopen.2024.2283 -
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 -
Children (Basel, Switzerland) Feb 2024Hematuria is a worrisome symptom in children and is sometimes associated with urinary tract infections (UTIs). This study aimed to identify useful clinical factors that...
INTRODUCTION
Hematuria is a worrisome symptom in children and is sometimes associated with urinary tract infections (UTIs). This study aimed to identify useful clinical factors that can predict UTIs in hematuria patients without pyuria in the pediatric emergency department (ED).
METHODS
We retrospectively recruited patients with hematuria from the pediatric ED. Clinical symptoms, urine biochemistry and microscopic examination results, and blood laboratory tests were analyzed to identify the predictors of UTIs. Patients were divided into the verbal group (age ≥ 2 years) and non-verbal group (age < 2 years) for identifying predictors of UTIs. Causes of hematuria were also investigated.
RESULTS
A total of 161 patients with hematuria without pyuria were evaluated. Among symptoms, dysuria was significantly correlated with UTIs. Regarding urine biochemistry data, urine esterase and urine protein > 30 mg/dl were found to be significant parameters for predicting UTIs, while urine esterase and urine nitrite showed significant differences in children with age < 2 years. In the urine microscopic examinations, urine red blood cells (RBC) > 373/µL in children aged ≥ 2 years and urine RBC > 8/µL in children aged < 2 years were associated with UTIs. In addition, UTIs and urinary tract stones were found to be the top two causes of hematuria.
CONCLUSIONS
Dysuria, urine esterase, urine nitrite, and urine protein may be useful parameters for predicting UTIs in pediatric patients with hematuria but no pyuria in the ED. In addition, a UTI was the most commonly identified etiology of hematuria without pyuria, followed by urinary tract stones.
PubMed: 38397360
DOI: 10.3390/children11020248 -
Genes Jan 2024The ability to undergo neoangiogenesis is a common feature with all cancers. Signaling related to vascular endothelial growth factors (VEGF) and their receptors (VEGFR)... (Review)
Review
Cardiac and Nephrological Complications Related to the Use of Antiangiogenic and Anti-Programmed Cell Death Protein 1 Receptor/Programmed Cell Death Protein 1 Ligand Therapy.
The ability to undergo neoangiogenesis is a common feature with all cancers. Signaling related to vascular endothelial growth factors (VEGF) and their receptors (VEGFR) plays a key role in the process of tumor neoangiogenesis. A close relationship has been demonstrated between excessive VEGF levels and the induction of immunosuppression in the tumor microenvironment. The use of drugs blocking the VEGF function, apart from the anticancer effect, also result in adverse effects, in particular related to the circulatory system and kidneys. Cardiac toxicity associated with the use of such therapy manifests itself mainly in the form of hypertension, thromboembolic episodes and ischemic heart disease. In the case of renal complications, the most common symptoms include renal arterial hypertension, proteinuria and microangiopathy. Although these complications are reversible in 60-80% of cases after cessation of VSP (VEGF pathway inhibitor) therapy, in some cases they can lead to irreversible changes in renal function, whereas cardiac complications may be fatal. Also, the use of PD-1/PD-L1 inhibitors may result in kidney and heart damage. In the case of cardiac complications, the most common symptoms include myocarditis, pericarditis, arrhythmia, acute coronary syndrome and vasculitis, while kidney damage most often manifests as acute kidney injury (AKI), nephrotic syndrome, pyuria or hematuria. The decision whether to resume treatment after the occurrence of cardiovascular and renal complications remains a problem.
Topics: Humans; Programmed Cell Death 1 Receptor; Vascular Endothelial Growth Factor A; Ligands; Kidney; Neoplasms; Angiogenesis Inhibitors; Hypertension; Tumor Microenvironment
PubMed: 38397167
DOI: 10.3390/genes15020177 -
Journal of Infection and Chemotherapy :... Aug 2024Qualitative urinalysis using the Sternheimer stain is a common method in Japan for identifying bacteriuria, but there is a lack of studies examining its test...
INTRODUCTION
Qualitative urinalysis using the Sternheimer stain is a common method in Japan for identifying bacteriuria, but there is a lack of studies examining its test characteristics. In this study, we aimed to investigate the sensitivity and specificity of the Sternheimer stain for urine culture results and compare it with the sensitivity and specificity of the Gram stain. Our goal was to determine the usefulness of the Sternheimer stain in identifying bacteriuria.
PATIENTS AND METHODS
Among 986 patients aged 16 years or older from whom samples for both urinalysis and urine culture were obtained at the emergency room of Tenri Hospital from January 2019 to December 2019, 342 patients with pyuria, defined as the presence of 10 or more white cells per cubic millimeter in a urine specimen, who had not received prior antimicrobial therapy were included. Urine cultures were used for comparison to determine the sensitivity and specificity of Sternheimer and Gram stain in this patient group. A positive Sternheimer stain result was defined as bacteriuria ≥ (1+), and that of Gram stain was defined as ≥ 1/1 field of high-power ( × 1000) oil immersion.
RESULTS
Using urine culture results for comparison, the sensitivity of Sternheimer stain was 92.2%, the specificity was 48.5%, the positive likelihood ratio was 1.79, and the negative likelihood ratio was 0.16.
DISCUSSION
Sternheimer stain is a rapid and useful method to exclude bacteriuria in a group of patients with pyuria in the emergency department.
Topics: Humans; Emergency Service, Hospital; Retrospective Studies; Male; Female; Gentian Violet; Middle Aged; Sensitivity and Specificity; Phenazines; Urinary Tract Infections; Urinalysis; Adult; Aged; Bacteriuria; Japan; Staining and Labeling; Young Adult; Pyuria; Adolescent; Aged, 80 and over
PubMed: 38387786
DOI: 10.1016/j.jiac.2024.02.019 -
Journal of the American Pharmacists... 2024Pyuria is nonspecific and may result in over-treatment of asymptomatic bacteriuria (ASB). The Infectious Diseases Society of America recommends against antibiotic...
BACKGROUND
Pyuria is nonspecific and may result in over-treatment of asymptomatic bacteriuria (ASB). The Infectious Diseases Society of America recommends against antibiotic treatment of ASB for most patients including those presenting with altered mental status (AMS). Close observation is recommended over treatment to avoid missing alternative causes of AMS and overuse of antibiotics resulting in adverse events and resistance.
OBJECTIVES
The purpose of this study was to evaluate patient outcomes associated with antibiotic treatment of pyuria in patients presenting with AMS at hospital admission without specific urinary tract infection (UTI) symptoms. The primary objective was to compare 30-day readmission rates of patients with pyuria and AMS treated with antibiotics (AMS+Tx) versus those who were not treated (AMS-NoTx). Secondary outcomes included identifying risk factors for antibiotic treatment, comparing alternative diagnoses for AMS, and comparing safety outcomes.
METHODS
This retrospective cohort study evaluated adult patients with AMS and pyuria (10 WBC/hpf) admitted between February 1, 2020 and October 1, 2021, in a 350-bed community teaching hospital. Patients with documented urinary symptoms were excluded. Additional exclusion criteria included admission to critical care, history of renal transplant, urological surgery, coinfections, pregnancy, and neutropenia.
RESULTS
Two-hundred patients were included (AMS+Tx, n = 162; AMS-NoTx, n=38). There was no difference in 30-day hospital readmission rate for AMS between groups (AMS+Tx 16.7% vs AMS-NoTx 23.7%, P = 0.311). An alternative diagnosis of AMS occurred more frequently when antibiotics were withheld (AMS+Tx 66% vs. AMS-NoTx 86.8%, P = 0.012). Urinalyses showing bacteria (odds ratio 2.52; 95% CI, 1.11-5.731) and positive urine culture (OR 3.36; 95% CI, 1.46-7.711) were associated with antibiotic prescribing.
CONCLUSIONS
Inappropriate antibiotic use is common among hospitalized patients presenting with AMS and pyuria; however, treatment of asymptomatic pyuria did not decrease rates of subsequent readmission for AMS or retreatment of symptomatic UTI. Patients who were monitored off antibiotics had higher rates of alternative AMS diagnosis.
Topics: Humans; Anti-Bacterial Agents; Female; Male; Retrospective Studies; Pyuria; Middle Aged; Aged; Patient Readmission; Hospitalization; Adult; Bacteriuria; Risk Factors; Urinary Tract Infections; Mental Disorders; Practice Patterns, Physicians'; Aged, 80 and over
PubMed: 38378100
DOI: 10.1016/j.japh.2024.102043 -
Lancet (London, England) Feb 2024Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action and a... (Randomized Controlled Trial)
Randomized Controlled Trial
Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials.
BACKGROUND
Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action and a unique binding site, providing well balanced inhibition of two type II topoisomerase enzymes. Oral gepotidacin is under investigation to treat uncomplicated urinary tract infections. We aimed to compare the efficacy and safety of oral gepotidacin with that of nitrofurantoin in adolescent and adult female individuals with uncomplicated urinary tract infections.
METHODS
EAGLE-2 and EAGLE-3 were phase 3, randomised, multicentre, double-blind, double-dummy, non-inferiority (10% margin) trials, in which patients were enrolled at 219 centres worldwide. Patients assigned female at birth, non-pregnant, aged 12 years or older, weighing 40 kg or more, with two or more symptoms of dysuria, frequency, urgency, or lower abdominal pain, and with evidence of urinary nitrite, pyuria, or both were eligible for inclusion. Patients were randomly assigned (1:1) centrally by interactive response technology to receive oral gepotidacin (1500 mg twice daily for 5 days) or oral nitrofurantoin (100 mg twice daily for 5 days), with randomisation stratified by age category and history of recurrent uncomplicated urinary tract infections. Patients, investigators, and the sponsor study team were masked to treatment assignment. The primary endpoint, therapeutic response (success or failure) at test-of-cure (ie, day 10-13), was evaluated in randomly assigned patients with nitrofurantoin-susceptible qualifying uropathogens (≥10 colony-forming units [CFU] per mL) and who received at least one dose of study treatment. Conforming to regulatory guidance, therapeutic success was defined as combined clinical success (ie, complete symptom resolution) and microbiological success (ie, reduction of qualifying uropathogens to <10 CFU/mL) without other systemic antimicrobial use. Safety analyses included patients who were randomly assigned and who received at least one dose of study treatment. The trials are registered with ClinicalTrials.gov, NCT04020341 (EAGLE-2) and NCT04187144 (EAGLE-3), and are completed.
FINDINGS
Studies were undertaken from Oct 17, 2019, to Nov 30, 2022 (EAGLE-2), and from April 23, 2020, to Dec 1, 2022 (EAGLE-3). 1680 patients in EAGLE-2 and 1731 patients in EAGLE-3 were screened for eligibility, of whom 1531 and 1605 were randomly assigned, respectively (767 in the gepotidacin group and 764 in the nitrofurantoin group in EAGLE-2, and 805 in the gepotidacin group and 800 in the nitrofurantoin group in EAGLE-3). After an interim analysis, which was prospectively agreed as a protocol amendment, both studies were stopped for efficacy. Thus, the primary analysis population included only patients who, at the time of the interim analysis data cutoff, had the opportunity to reach the test-of-cure visit or were known to not have attained therapeutic success before the test-of-cure visit. In EAGLE-2, 162 (50·6%) of 320 patients assigned gepotidacin and 135 (47·0%) of 287 patients assigned nitrofurantoin had therapeutic success (adjusted difference 4·3%, 95% CI -3·6 to 12·1). In EAGLE-3, 162 (58·5%) of 277 patients assigned gepotidacin and 115 (43·6%) of 264 patients assigned nitrofurantoin had therapeutic success (adjusted difference 14·6%, 95% CI 6·4 to 22·8). Gepotidacin was non-inferior to nitrofurantoin in both studies and superior to nitrofurantoin in EAGLE-3. The most common adverse event with gepotidacin was diarrhoea (observed in 111 [14%] of 766 patients in EAGLE-2 and in 147 [18%] of 804 patients in EAGLE-3), whereas the most common adverse event with nitrofurantoin was nausea (in 29 [4%] of 760 patients in EAGLE-2 and in 35 [4%] of 798 patients in EAGLE-3). Cases were mostly mild or moderate. No life-threatening or fatal events occurred.
INTERPRETATION
Gepotidacin is an efficacious oral antibiotic with acceptable safety and tolerability profiles. As a first-in-class investigational oral antibiotic with activity against common uropathogens, including clinically important drug-resistant phenotypes, gepotidacin has the potential to offer substantial benefit to patients.
FUNDING
GSK and the US Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority.
Topics: Adult; Adolescent; Infant, Newborn; Humans; Female; Nitrofurantoin; Treatment Outcome; Anti-Bacterial Agents; Urinary Tract Infections; Research; Double-Blind Method; Acenaphthenes; Heterocyclic Compounds, 3-Ring
PubMed: 38342126
DOI: 10.1016/S0140-6736(23)02196-7 -
Journal of Neonatal-perinatal Medicine 2024Urinary tract infections (UTIs) and antibiotic overexposure are common neonatal problems. Recently, evidence has emerged that a standardized approach to neonatal UTI can...
BACKGROUND
Urinary tract infections (UTIs) and antibiotic overexposure are common neonatal problems. Recently, evidence has emerged that a standardized approach to neonatal UTI can reduce unnecessary diagnosis without complications. This quality improvement project aimed to achieve those goals in our neonatal intensive care unit (NICU).
METHODS
A UTI diagnosis guideline was adapted from the literature with the goal of maximizing the proportion of diagnosed UTIs that conform to accepted diagnostic criteria: >10,000 CFU/mL of one organism with pyuria, or >50,000 CFU/mL of one organism regardless of pyuria. The guideline was implemented in a level III NICU. Adherence, results, and complications were monitored for 12 months.
RESULTS
Guideline adherence after implementation was favorable, as evidenced by increased adoption of urinalysis with microscopy. There was a non-significant increase in diagnostic adherence to criteria, 87% to 93%, and non-significant decrease in the rate of UTI diagnosis, 39% to 36%. Complications were not significantly changed. Most UTIs were due to gram-negative rods, especially E. coli; Enterococcus was a common contaminant.
CONCLUSIONS
A guideline for diagnosing UTIs can safely increase uniformity. In contrast to previously published results, no significant changes were seen in the rate of UTI or the proportion of diagnoses conforming to the criteria for UTI. It is likely that guideline effects depend on the established practices of NICU providers. Additionally, a consistent pattern was seen in which organisms were more likely to be judged the source of true UTIs or contaminated cultures, meriting further study.
Topics: Infant, Newborn; Humans; Intensive Care Units, Neonatal; Pyuria; Tertiary Care Centers; Escherichia coli; Urinary Tract Infections; Reference Standards
PubMed: 38339942
DOI: 10.3233/NPM-230101 -
NEJM Evidence Sep 2023Antibiotics for Delirium and Pyuria or BacteriuriaDelirium is common among hospitalized older adults, frequently leading to initiation of antibiotics when pyuria or...
Antibiotics for Delirium and Pyuria or BacteriuriaDelirium is common among hospitalized older adults, frequently leading to initiation of antibiotics when pyuria or bacteriuria is detected. However, it is difficult to determine if pyuria or bacteriuria is the cause of delirium or incidentally identified. This article proposes a trial to assess if treatment with antibiotics hastens delirium resolution.
Topics: Humans; Aged; Pyuria; Bacteriuria; Anti-Bacterial Agents; Delirium
PubMed: 38320202
DOI: 10.1056/EVIDtt2300119