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The diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-β-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF BDG level was 85 pg/ml for cases, compared to

BackgroundCentral nervous system (CNS) histoplasmosis is a life-threatening condition and represents a diagnostic and therapeutic challenge. Isolation of Histoplasma capsulatum from cerebrospinal fluid (CSF) or brain tissue is diagnostic; however, culture is insensitive and slow growth may result in significant treatment delay. We performed a retrospective multicenter study to evaluate the sensitivity and specificity of a new anti-Histoplasma antibody enzyme immunoassay (EIA) for the detection of IgG and IgM antibody in the CSF for diagnosis of CNS histoplasmosis, the primary objective of the study. The secondary objective was to determine the effect of improvements in the Histoplasma galactomannan antigen detection EIA on the diagnosis of Histoplasma meningitis.MethodsResidual CSF specimens from patients with Histoplasma meningitis and controls were tested for Histoplasma antigen and anti-Histoplasma immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody using assays developed at MiraVista Diagnostics.ResultsA total of 50 cases and 157 controls were evaluated. Fifty percent of patients with CNS histoplasmosis were immunocompromised, 14% had other medical conditions, and 36% were healthy. Histoplasma antigen was detected in CSF in 78% of cases and the specificity was 97%. Anti-Histoplasma IgG or IgM antibody was detected in 82% of cases and the specificity was 93%. The sensitivity of detection of antibody by currently available serologic testing including immunodiffusion and complement fixation was 51% and the specificity was 96%. Testing for both CSF antigen and antibody by EIA was the most sensitive approach, detecting 98% of cases.ConclusionsTesting CSF for anti-Histoplasma IgG and IgM antibody complements antigen detection and improves the sensitivity for diagnosis of Histoplasma meningitis.

Key Points: Question: Does the choice between cefepime and piperacillin-tazobactam affect the risks of acute kidney injury or neurological dysfunction in adults hospitalized with acute infection? Findings: Among 2511 adults hospitalized with acute infection, the highest stage of acute kidney injury or death was not significantly different between patients randomized to cefepime and those randomized to piperacillin-tazobactam. Patients randomized to cefepime experienced more neurological dysfunction, a secondary outcome. Meaning: Among hospitalized adults, the risk of acute kidney injury did not differ between cefepime and piperacillin-tazobactam, but neurological dysfunction was more common with cefepime. Importance: Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial. Objective: To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction. Design, Setting, and Participants: The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022. Interventions: Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam. Main Outcomes and Measures: The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days. Results: There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P =.56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, −1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]). Conclusions and Relevance: Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction. Trial Registration: ClinicalTrials.gov Identifier: NCT05094154 This randomized clinical trial compares the use of cefepime vs piperacillin-tazobactam and the risk of acute kidney injury and neurological dysfunction in adults hospitalized with acute infection. [ABSTRACT FROM AUTHOR]

To the Editor: Infections with nontuberculous mycobacteria (NTM) are being increasingly identified. Several factors may contribute to this finding, including increased awareness of these organisms as pathogens, improved ability of [...]

We describe our approach to addressing a nation-wide supply issue for blood culture bottles. Aerobic blood culture bottles received from our distributor July 1-15, 2024 was <1% of typical usage. Through education and ordering restrictions blood culture designed to minimize risk, orders were reduced by 49% over a one-week period., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Infection is a common mode of failure in lower extremity endoprostheses. The Prophylactic Antibiotic Regimens in Tumor Surgery trial reported that 5 days of cefazolin had no difference in surgical site infection compared with 24 hours of cefazolin. Our purpose was to evaluate infection rates of patients receiving perioperative cefazolin monotherapy, cefazolin-vancomycin dual therapy, or alternative antibiotic regimens., Methods: A single-center retrospective review was conducted on patients who received lower extremity endoprostheses from 2008 to 2021 with minimum 1-year follow-up. Three prophylactic antibiotic regimen groups were compared: cefazolin monotherapy, cefazolin-vancomycin dual therapy, and alternative regimens. The primary outcome was deep infection, defined by a sinus tract, positive culture, or clinical diagnosis. Secondary outcomes were revision surgery, microorganisms isolated, and superficial wound issues., Results: The overall deep infection rate was 10% (30/294) at the median final follow-up of 3.0 years (IQR 1.7 to 5.4). The deep infection rates in the cefazolin, cefazolin-vancomycin, and alternative regimen groups were 8% (6/72), 10% (18/179), and 14% (6/43), respectively (P = 0.625). Patients not receiving cefazolin had an 18% deep infection rate (6/34) and 21% revision surgery rate (7/34) compared with a 9% deep infection rate (24/260) (P = 0.13) and 12% revision surgery rate (31/260) (P = 0.17) in patients receiving cefazolin. In those not receiving cefazolin, 88% (30/34) were due to a documented penicillin allergy, only two being anaphylaxis. All six patients in the alternative regimen group who developed deep infections did not receive cefazolin secondary to nonanaphylactic penicillin allergy., Conclusion: The addition of perioperative vancomycin to cefazolin in lower extremity endoprosthetic reconstructions was not associated with a lower deep infection rate. Patients who did not receive cefazolin trended toward higher rates of deep infection and revision surgery, although not statistically significant. The most common reason for not receiving cefazolin was a nonanaphylactic penicillin allergy, highlighting the continued practice of foregoing cefazolin unnecessarily., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)