ABSTRACT IMPACT: This work seeks to improve the diagnostic accuracy of urinary tract infection among hospitalized older adults and mitigate antibiotic overuse in this population. OBJECTIVES/GOALS: Primary objective: To determine the diagnostic accuracy of serum procalcitonin (PCT) for the diagnosis of symptomatic urinary tract infection (UTI) in hospitalized older adults. Secondary objectives: (1) To develop a predictive model for the diagnosis of UTI; (2) To determine the ability of PCT in discriminating between lower and upper UTI. METHODS/STUDY POPULATION: We performed a prospective observational cohort study of 228 participants from a single institution. The study population included older adults (age 65 or older) who were hospitalized on the general medicine wards with a possible or suspected urinary tract infection (UTI). Upon obtaining informed consent, serum procalcitonin (PCT) was processed on remnant blood samples collected from the emergency department. We performed additional data collection through the electronic health record to obtain demographic information, clinical characteristics, and other laboratory and imaging results. Clinicians were surveyed for the diagnosis of UTI and charts were adjudicated by independent reviews of the medical record by infectious diseases experts to determine the primary endpoint of symptomatic UTI. RESULTS/ANTICIPATED RESULTS: We anticipate that serum procalcitonin predicts the presence of symptomatic urinary tract infection (UTI) by demonstrating an area under the receiver operating characteristic curve of at least 0.85. A predictive model developed in our cohort for the diagnosis of symptomatic UTI will be improved by the addition of serum PCT to the prediction model. Finally, we anticipate the serum PCT will accurately discriminate between upper and lower UTI. DISCUSSION/SIGNIFICANCE OF FINDINGS: Diagnosis of symptomatic UTI in hospitalized older adults is challenging and may lead to overuse of antibiotics and the development of antibiotic resistance in this vulnerable patient population. Serum procalcitonin offers a novel diagnostic strategy in the diagnosis of symptomatic UTI to enable more appropriate antibiotic therapy.
Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer’s disease (AD). Since that time, a subset of people with prior COVID infection continue to report neurological problems more than three months after infection. Blood markers to better characterize LongC are elusive. To further identify neuronal proteins associated with LongC, we maximized the number of nEVs isolated from plasma by developing a hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. We isolated nEVs from people with LongC and neurological complaints, AD, and HIV infection with mild cognitive impairment. Using the OLINK platform that assesses 384 neurological proteins, we identified 11 significant proteins increased in LongC and 2 decreased (BST1, GGT1). Fourteen proteins were increased in AD and forty proteins associated with HIV cognitive impairment were elevated with one decreased (IVD). One common protein (BST1) was decreased in LongC and increased in HIV. Six proteins (MIF, ENO1, MESD, NUDT5, TNFSF14 and FYB1) were expressed in both LongC and AD and no proteins were common to HIV and AD. This study begins to identify differences and similarities in the neuronal response to LongC versus AD and HIV infection.
Community-acquired pneumonia (CAP) accounts for more than 1.5 million adult hospitalizations and 100,000 deaths each year in the United States.1 Antibiotic overuse in the hospital setting is an important contributor to the rise of antibiotic resistance, prompting increased efforts to limit inappropriate antibiotic use in hospitals.2 Procalcitonin, a precursor of the hormone calcitonin, is upregulated in bacterial infections and downregulated in viral infections. The US Food and Drug Administration has approved it as a serum biomarker to assist clinicians with decisions about using antibiotics.3 There is no consensus on how to best use procalcitonin in the management of CAP. We provide a practical update that includes a review of recent literature, added secondary analysis, and expert opinion surrounding the use of procalcitonin in the diagnosis and management of CAP in hospitalized adults.
Antimicrobial resistance (AMR) is a fundamental global concern analogous to climate change threatening both public health and global development progress. Infections caused by antimicrobial-resistant pathogens pose serious threats to healthcare and human capital. If the increasing rate of AMR is left uncontrolled, it is estimated that it will lead to 10 million deaths annually by 2050. This global epidemic of AMR necessitates radical interdisciplinary solutions to better detect antimicrobial susceptibility and manage infections. Rapid diagnostics that can identify antimicrobial-resistant pathogens to assist clinicians and health workers in initiating appropriate treatment are critical for antimicrobial stewardship. In this review, we summarize different technologies applied for the development of rapid diagnostics for AMR and antimicrobial susceptibility testing (AST). We briefly describe the single-cell technologies that were developed to hasten the AST of infectious pathogens. Then, the different types of genotypic and phenotypic techniques and the commercially available rapid diagnostics for AMR are discussed in detail. We conclude by addressing the potential of current rapid diagnostic systems being developed as point-of-care (POC) diagnostic tools and the challenges to adapt them at the POC level. Overall, this review provides an insight into the current status of rapid and POC diagnostic systems for AMR.
Background Although recent World Health Organization (WHO) guidelines recommend withdrawing stavudine (d4T) from first-line antiretroviral therapy (ART), it remains commonly used in resource-limited settings. In 2006, WHO recommended decreasing the dose of d4T from 40 mg to 30 mg to mitigate toxicities. We compared the incidence and severity of peripheral neuropathy by d4T dose in a retrospective cohort study. Methods Patients’ charts from an ART-naive population at a rural clinic in KwaZulu-Natal, South Africa, were retrospectively reviewed for signs and symptoms of incident peripheral neuropathy and were graded for severity using the DAIDS scale. Patients enrolled prior to the WHO guideline change were included in the study if they were on d4T 40 mg for ≥6 months. After the guideline change all patients were initiated on d4T 30 mg. Results A total of 475 patients were analysed, including 235 in the 40 mg cohort (152.7 person-years [py]) and 240 in the 30 mg cohort (244.7 py). Incidence of peripheral neuropathy was 90.4/100 py (95% CI 75.9, 106.8) in the 40 mg cohort versus 40.5/100 py (95% CI 32.9, 49.3) in the 30 mg group (incidence rate ratio 0.45; P<0.0001). There was no difference in proportion of severe peripheral neuropathy cases (grade 3/4) between the cohorts: 8.3% in the 40 mg group and 8.9% in the 30 mg group ( P=1.0). In a multivariate analysis, risk of peripheral neuropathy was associated with increasing age (hazard ratio [HR] 1.65, 95% CI 1.24, 2.19), 40 mg dose (HR 2.1, 95% CI 1.61, 2.74) and concurrent tuberculosis therapy (HR 1.41, 95% CI 1.06, 1.87). Conclusions Incidence of peripheral neuropathy in the 40 mg cohort was extremely high and, although lower, the rate in the 30 mg cohort was nonetheless unacceptably high.
India has the highest rates of tuberculosis (TB) globally and a high prevalence of malnutrition; however, the interplay between host nutritional status, inflammation, and the gut microbiome in active tuberculosis disease (ATBD) is less well-studied. We examined differences in gut microbial composition and diversity based on undernutrition and inflammation status among outpatients with ATBD at the time of treatment initiation. During this exploratory cross-sectional study, outpatients (N = 32) with ATBD (confirmed by Xpert MTB/RIF) were enrolled in anti-TB treatment initiated at a hospital in rural southern India. The 16S rRNA sequencing was used to assess the composition of the gut microbiome. We assessed multiple markers of nutritional status, including micronutrient status concentrations (vitamin D [25(OH)D], vitamin B12, ferritin), anthropometry (body mass index, mid-upper arm circumference, and height), and C-reactive protein (CRP), as indicators of inflammation. We found that 25(OH)D was positively associated with the relative abundance of Oscillospira spp., a butyrate-producing genus linked with anti-inflammation effects, and that ferritin was positively associated with Proteobacteria taxa, which have been associated with worse inflammation in other studies. Finally, we found a greater abundance of inflammation-associated taxa from the Proteobacteria phylum and lower alpha-diversity indices among those who were underweight or who had low mid-upper arm circumference or short stature. In summary, we found differences in the gut microbiota composition and diversity among those with undernutrition compared with those with adequate nutrition status at the time of initiation of treatment among patients with ATBD in India. Clinical implications of these findings will need to be examined by larger longitudinal studies.
The human T cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 infected individuals have increased susceptibility to Mycobacterium tuberculosis infection but the influence of tuberculosis (TB) on the course of HTLV-1 infection is unknown. The aim of this study was to evaluate the influence of TB on immunological, virologic, and neurologic features of HTLV-1 infection. This is a retrospective analysis of individuals enrolled in a cohort study from an HTLV-1 clinic who were evaluated for past or latent tuberculosis (LTB) and classified clinically as HTLV-1 carriers, probable HAM/TSP and definite HAM/TSP. Spontaneous cytokine production (interferon-gamma [IFN-γ], tumor necrosis factor [TNF], and interleukin[IL]-10), serum chemokines (CXCL9 and CXCL10) and HTLV-1 proviral load were evaluated. Of 172 participants, 64 did not have histories of TB (TB- group), 81 had LTB and 27 had TB in the past (TB+ group). In the TB+ group, there was a higher frequency of HAM/TSP patients (35%) than in HTLV-1 carriers (10%) (OR = 3.8, p = .0001). HAM/TSP patients with histories of TB had higher IFN-γ/IL-10 and TNF/IL-10 ratios when compared with HAM/TSP patients without histories of TB. There were no differences in serum chemokine production and proviral load across TB groups stratified on HTLV-1 clinical status. In conclusion, TB may influence the development of HAM/TSP, and patients with these two diseases have an impairment in the modulation of immune response.
To determine if use of antiherpes drugs protects against the development of AIDS-associated Kaposi's sarcoma (KS), data from 935 homosexual men with AIDS from the Multicenter AIDS Cohort Study were analyzed. In nested case-control analysis, neither acyclovir use for human immunodeficiency virus infection (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.56–1.26; P = .39) nor acyclovir use for any indication (OR, 1.02; 95% CI, 0.76–1.38; P = .89) was associated with a reduced risk of KS as initial AIDS diagnosis. In longitudinal analysis, acyclovir was also not protective against developing KS as a late manifestation of AIDS (after initial non-KS AIDS diagnosis). Among men with cytomegalovirus disease, ganciclovir use (relative risk [RR], 0.56; 95% CI, 0.22–1.44; P = .23) and foscarnet use (RR, 0.40; 95% CI, 0.051–3.10; P = .38) were associated (although not significantly) with a reduced risk of KS. Thus, acyclovir use does not appear to reduce the risk of KS, but further study of other antiherpes drugs such as ganciclovir and foscarnet is warranted.
