Multiplexed gastrointestinal PCR panels for the evaluation of diarrhea in patients with acute leukemia.

Objective: To better delineate multiplexed gastrointestinal polymerase chain reaction (PCR) panel (MGPP) diagnostic and therapeutic stewardship for patients undergoing treatment for acute leukemia including indications and benefits of testing, optimal timing, and interpretation of results.

Study Design: We retrieved all MGPP ordered on 662 consecutive patients admitted with newly diagnosed acute leukemia between June 2015 and May 2024.

Setting: Regional referral center for acute leukemia.

Rapid and Robust Identification of Sepsis Using SeptiCyte RAPID in a Heterogeneous Patient Population.

SeptiCyte RAPID is a transcriptional host response assay that discriminates between sepsis and non-infectious systemic inflammation (SIRS) with a one-hour turnaround time. The overall performance of this test in a cohort of 419 patients has recently been described [Balk et al., J Clin Med 2024, 13, 1194].

Longitudinal associations of plasma amino acid levels with recovery from malarial coma.

Background: Disordered amino acid metabolism is observed in cerebral malaria (CM). This study sought to determine whether abnormal amino acid concentrations were associated with level of consciousness in children recovering from coma. Twenty-one amino acids and coma scores were quantified longitudinally and the data were analysed for associations.

Longitudinal associations of plasma amino acid levels with recovery from malarial coma.

Background: Disordered amino acid metabolism is observed in cerebral malaria (CM). We sought to determine whether abnormal amino acid concentrations were associated with level of consciousness in children recovering from coma. We quantified 21 amino acids and coma scores longitudinally and analyzed data for associations.

Multiplexed Gastrointestinal PCR Panels for the Evaluation of Diarrhea in Hematopoietic Stem Cell Transplantation Recipients.

Multiplexed gastrointestinal PCR panels (MGPPs) are frequently used to aid the diagnosis and management of diarrhea in hematopoietic stem cell transplantation (HCT) recipients. Many issues related to the optimal use of MGPPs in HCT patients remain to be clarified. We aimed to better define MGPP diagnostic and therapeutic stewardship in HCT recipients, including indications for and benefits of testing, optimal timing of tests, and interpretation of results.

Validation of SeptiCyte RAPID to Discriminate Sepsis from Non-Infectious Systemic Inflammation.

(1) SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h.

Syndromic Panel Testing Among Patients With Infectious Diarrhea: The Challenge of Interpreting Positivity on a Multiplex Molecular Panel.

Background: Including (CD) in gastrointestinal multiplex molecular panels (GIPCR) presents a diagnostic challenge. Incidental detection by polymerase chain reaction (PCR) without consideration of pretest probability (PTP) may inadvertently delay diagnoses of other treatable causes of diarrhea and lead to prescription of unnecessary antibiotics.

Methods: We conducted a retrospective study to determine the frequency at which clinicians characterize PTP and disease severity in adult patients who test positive for CD by GIPCR.

An Algorithm Addressing the Problem of Overdiagnosis of Clostridioides difficile Infections in Hematopoietic Stem Cell Transplantation Recipients: Effects on C. difficile Infection Rates and Patient Outcomes.

Diarrhea of other causes and Clostridioides difficile colonization are common in patients hospitalized for hematopoietic stem cell transplantation (HSCT). It has been well recognized that these issues tend to decrease the specificity of stool testing for C. difficile infection (CDI).

Transfer of Extended Spectrum Cephalosporin Resistant Enterobacteriaceae Among Patients on an HSCT Unit and the Value of Surveillance and Contact Isolation.

The mechanism(s) of acquisition of extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCRE) on inpatient hospital units dedicated to hematopoietic stem cell transplantation (HSCT) is unclear. The objectives of this study were to determine whether ESCRE organisms are transmitted among patients housed on a HSCT unit, clarify the mechanisms involved, and determine whether routine surveillance for ESCRE carriage and contact isolation for ESCRE carriers is beneficial. The study was conducted on a 30-bed inpatient unit dedicated to the care of patients with hematologic malignancies and HSCT recipients.

Extended spectrum cephalosporin resistant enterobacteriaceae carriage and infection in patients admitted with newly-diagnosed acute leukemia.

Background: Current information is limited on the incidence, risk factors, and consequences of extended-spectrum cephalosporin resistant Enterobacteriaceae (ESCRE) carriage in patients undergoing therapy for newly-diagnosed acute leukemia.

Methods: We monitored 300 consecutive patients who submitted a first stool within the first week of initial hospitalization for initial and hospital acquired ESCRE carriage. Selected available isolates underwent DNA sequencing for determination of strain typing and resistance genes.

No Implementation Without Representation: Real-Time Pharmacist Intervention Optimizes Rapid Diagnostic Tests for Bacteremia at a Small Community Hospital.

Rapid diagnostic tests (RDTs) for bacteremia allow for early antimicrobial therapy modification based on organism and resistance gene identification. Studies suggest patient outcomes are optimized when infectious disease (ID)-trained antimicrobial stewardship personnel intervene on RDT results. However, data are limited regarding RDT implementation at small community hospitals, which often lack access to on-site ID clinicians.

Evaluation of potential COVID-19 recurrence in patients with late repeat positive SARS-CoV-2 testing.

Background: SARS-CoV-2 reinfection and reactivation has mostly been described in case reports. We therefore investigated the epidemiology of recurrent COVID-19 SARS-CoV-2.

Methods: Among patients testing positive for SARS-CoV-2 between March 11 and July 31, 2020 within an integrated healthcare system, we identified patients with a recurrent positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) assay ≥60 days after an initial positive test.

Clinical evaluation of the acuitas® AMR gene panel for rapid detection of bacteria and genotypic antibiotic resistance determinants.

Urinary tract infections are leading causes of hospital admissions. Accurate and timely diagnosis is important due to increasing morbidity and mortality from antimicrobial resistance. We evaluated a polymerase chain reaction test (Acuitas AMR Gene Panel with the Acuitas Lighthouse Software) for detection of 5 common uropathogens (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Enterococcus faecalis) and antibiotic resistance genes directly from urine for prediction of phenotypic resistance.

Cerebrospinal Fluid Pterins, Pterin-Dependent Neurotransmitters, and Mortality in Pediatric Cerebral Malaria.

Background: Cerebral malaria (CM) pathogenesis remains incompletely understood. Having shown low systemic levels of tetrahydrobiopterin (BH4), an enzymatic cofactor for neurotransmitter synthesis, we hypothesized that BH4 and BH4-dependent neurotransmitters would likewise be low in cerebrospinal fluid (CSF) in CM.

Methods: We prospectively enrolled Tanzanian children with CM and children with nonmalaria central nervous system conditions (NMCs).

Are Clostridioides difficile infections being overdiagnosed in hematopoietic stem cell transplant recipients?

Background: Because both diarrhea due to other causes and gastrointestinal colonization with toxigenic Clostridioides difficile are common in HSCT, there is a possibility of false-positive diagnoses of C difficile infections (CDI).

Methods: We estimated the probability of a patient being colonized by toxigenic C difficile by testing non-diarrheal surveillance stools from 223 HSCT recipients and the probability that a specimen submitted for C difficile testing was not CDI by determining the number of clinical tests that returned negative from this cohort. The number of expected false-positive CDI was estimated using these probabilities and compared with observed clinical test results.

Antimicrobial Stewardship in a Hematological Malignancy Unit: Carbapenem Reduction and Decreased Vancomycin-Resistant Enterococcus Infection.

Background: Antibiotic stewardship is challenging in hematological malignancy patients.

Methods: We performed a quasiexperimental implementation study of 2 antimicrobial stewardship interventions in a hematological malignancy unit: monthly antibiotic cycling for febrile neutropenia that included cefepime (± metronidazole) and piperacillin-tazobactam and a clinical prediction rule to guide anti-vancomycin-resistant Enterococcus faecium (VRE) therapy. We used interrupted time-series analysis to compare antibiotic use and logistic regression in order to adjust observed unit-level changes in resistant infections by background community rates.

Clostridioides difficile colonization and infection in patients admitted for a first autologous transplantation: Incidence, risk factors, and patient outcomes.

Background: More data are needed regarding the incidence, risk factors, and outcomes for Clostridioides difficile infection (CDI) and colonization in patients undergoing an autologous hematopoietic stem cell transplantation (AHSCT).

Methods: We studied 472 consecutive patients admitted for a first AHSCT and conducted a prospective C difficile stool surveillance and ribotyping analysis in a subset of 94 patients.

Results: Clostridioides difficile infection was diagnosed in 7% of patients for an incidence of 3.

Decrease in vancomycin-resistant Enterococcus colonization associated with a reduction in carbapenem use as empiric therapy for febrile neutropenia in patients with acute leukemia.

Objective: To compare the effects of empiric carbapenems versus cycling cefepime and piperacillin/tazobactam on the rates of vancomycin-resistant Enterococcus (VRE) colonization, bloodstream infections, and outcomes of patients admitted with acute leukemia.

Design: Retrospective clinical study with VRE molecular strain typing and gastrointestinal microbiome comparison.

Setting: A regional referral center for acute leukemia.

Predicting Antibiotic Resistance in Gram-Negative Bacilli from Resistance Genes.

We developed a rapid high-throughput PCR test and evaluated highly antibiotic-resistant clinical isolates of ( = 2,919), ( = 1,974), ( = 1,150), and ( = 1,484) for several antibiotic resistance genes for comparison with phenotypic resistance across penicillins, cephalosporins, carbapenems, aminoglycosides, trimethoprim-sulfamethoxazole, fluoroquinolones, and macrolides. The isolates originated from hospitals in North America (34%), Europe (23%), Asia (13%), South America (12%), Africa (7%), or Oceania (1%) or were of unknown origin (9%). We developed statistical methods to predict phenotypic resistance from resistance genes for 49 antibiotic-organism combinations, including gentamicin, tobramycin, ciprofloxacin, levofloxacin, trimethoprim-sulfamethoxazole, ertapenem, imipenem, cefazolin, cefepime, cefotaxime, ceftazidime, ceftriaxone, ampicillin, and aztreonam.

Physician agreement on the diagnosis of sepsis in the intensive care unit: estimation of concordance and analysis of underlying factors in a multicenter cohort.

Background: Differentiating sepsis from the systemic inflammatory response syndrome (SIRS) in critical care patients is challenging, especially before serious organ damage is evident, and with variable clinical presentations of patients and variable training and experience of attending physicians. Our objective was to describe and quantify physician agreement in diagnosing SIRS or sepsis in critical care patients as a function of available clinical information, infection site, and hospital setting.

Methods: We conducted a post hoc analysis of previously collected data from a prospective, observational trial ( = 249 subjects) in intensive care units at seven US hospitals, in which physicians at different stages of patient care were asked to make diagnostic calls of either SIRS, sepsis, or indeterminate, based on varying amounts of available clinical information (clinicaltrials.

Kinetic and Cross-Sectional Studies on the Genesis of Hypoargininemia in Severe Pediatric Malaria.

The low bioavailability of nitric oxide (NO) and its precursor, arginine, contributes to the microvascular pathophysiology of severe falciparum malaria. To better characterize the mechanisms underlying hypoargininemia in severe malaria, we measured the plasma concentrations of amino acids involved in arginine synthesis in children with uncomplicated falciparum malaria (UM;  = 61), children with cerebral falciparum malaria (CM;  = 45), and healthy children (HC;  = 109). We also administered primed infusions of l-arginine uniformly labeled with C and N to 8 children with severe falciparum malaria (SM; age range, 4 to 9 years) and 7 healthy children (HC; age range, 4 to 8 years) to measure the metabolic flux of arginine, hypothesizing that arginine flux is increased in SM.

Clostridioides difficile colonization and infection in patients with newly diagnosed acute leukemia: Incidence, risk factors, and patient outcomes.

Background: The frequency, risk factors, and outcomes for Clostridioides difficile infection (CDI) in patients with newly diagnosed acute leukemia (AL) admitted for induction therapy are unclear.

Methods: We studied 509 consecutive patients with AL admitted between 2006 and 2017 and conducted a prospective C difficile surveillance and ribotyping analysis in a subset of these.

Results: The incidence of CDI was 2.

Fecal Host Transcriptomics for Non-Invasive Human Mucosal Immune Profiling: Proof of Concept in Infection.

Background: Host factors play an important role in pathogenesis and disease outcome in infection (CDI), and characterization of these responses could uncover potential host biomarkers to complement existing microbe-based diagnostics.

Methods: We extracted RNA from fecal samples of patients with CDI and profiled human mRNA using amplicon-based next-generation sequencing (NGS). We compared the fecal host mRNA transcript expression profiles of patients with CDI to controls with non-CDI diarrhea.

Repurposing an Old Drug for a New Epidemic: Ursodeoxycholic Acid to Prevent Recurrent Clostridioides difficile Infection.

Recurrent Clostridioides difficile infection (rCDI) may be mediated in part by secondary bile acids. Here we report salvage therapy with ursodeoxycholic acid (UDCA) to prevent rCDI in 16 high-risk patients. Patients on UDCA had a low observed recurrence rate (12.