In This Issue...
1,3-β-D-Glucan Beats Cultures, Colonization Indices in Identifying Intraabdominal Candidiasis
1,3-β-D-Glucan (βG), a fungal cell wall antigen circulating in the blood of patients with invasive mycoses, is superior to cultures, Candida score (CS), colonization index (CI), and corrected colonization index (CCI) in anticipating the diagnosis of blood culture-negative intraabdominal candidiasis (IAC) (Am J Respir Crit Care Med 2013;188:1100–9). This proof-of-concept study, if validated in other studies, could open the door for individualized management of surgical patients at high-risk for intraabdominal candidiasis, according to the authors.
The researchers were interested in investigating a simple blood test for IAC because of its high morbidity and mortality, and because IAC has non-specific symptoms and culture methods have days-long turnaround times and also lack specificity for differentiating infection from colonization. Yet early antifungal therapy for this condition is an important factor in outcomes.
The study involved 434 consecutive adults with abdominal surgery or acute pancreatitis and stays in intensive care of at least 72 hours. Of these, 89 considered at high risk for IAC were included in the study. For CS, CI, and CCI, cultures were performed twice weekly from samples taken from at least three of five nonsterile sites, such as the mouth, stools, or skin. The researchers defined Candida colonization as recovery of Candida spp. from at least one site and graded as weak, moderate, or heavy by semiquantitative cultures. They defined candidemia as at least one positive blood culture for Candida spp. along with symptoms of infection.
Overall, 921 serum samples were analyzed, a median of nine per patient. βG was at least 80 pg/mL in 50% of patients at the time they entered the study, and at that level in 70% after the seventh day of inclusion. Colonized patients had significantly higher βG levels than those who were not colonized. Among patients with documented IAC, 76% had βG levels ≥80 pg/mL at the time of study inclusion, and 83% at the time of IAC diagnosis. Patients who developed severe sepsis or septic shock had higher βG than those with less severe infection, 313 pg/mL versus 100 pg/mL.
Spectrin N-terminal Fragment Detects Early Mild Traumatic Brain Injury
Calpain-cleaved αll-spectrin N-terminal fragment (SNTF) is associated with both structural and functional outcomes after mild traumatic brain injury (mTBI), and could, upon further assessment and validation, prove useful in assessing and treating mTBI (Front Neurol 2013;4:1–8). The researchers investigated SNTF, which is known to increase in blood after severe TBI but has not been evaluated in mTBI, as part of their search for candidate biomarkers that might identify neurodegeneration following mTBI sooner and with more sensitivity than current imaging techniques, which do not detect up to 30% of long-term and clinically significant mTBI-associated brain dysfunction. Other neurodegenerative biomarkers have been evaluated in mTBI, but none has demonstrated a prognostic relationship with structural brain injury or brain injury symptoms.
The study involved 17 participants with sustained mTBI, 13 with an orthopedic injury, and eight uninjured controls. The researchers obtained plasma samples within 24 hours of the subjects’ injuries. Participants also had neuropsychological and brain imaging assessments at baseline, and 1- and 3-month follow-up visits. The authors used a sandwich immunoassay to detect SNTF in which the enzymatic amplification and detection steps were replaced with next-generation electrochemiluminescence detection chemistry.
The investigators found that increased SNTF on the day of injury correlated significantly with cognitive impairment that persisted for at least 3 months, in both all study participants and in those with mTBI. SNTF levels were at least twice the lower limit of detection in 7 of 17 mTBI cases and in 3 of 13 orthopedic injury cases, but in no uninjured controls. Elevated levels of SNTF also were associated with significant differences in brain structure detected by diffusion tension imaging.
96-Gene Panel Sensitive, Specific in Identifying Eosinophilic Esophagitis
Researchers at the University of Cincinnati College of Medicine in Ohio reported developing a 96-gene quantitative polymerase chain reaction assay and associated algorithm that has high sensitivity and specificity for detecting eosinophilic esophagitis (EoE) (Gastroenterology 2013;145:1289–99). The assay also identified patients with EoE in remission from controls, as well as those exposed to swallowed glucorticoids.
The authors suggested that this novel platform could improve diagnosis and treatment for EoE, an immune-mediated upper gastrointestinal (GI) disorder that has been rising in incidence since it was first characterized 2 decades ago. EoE, typically associated with dysphagia and eosinophilia ≥15 eosinophils/high-power field, accounts for 10–30% of chronic esophagitis refractory to proton pump inhibitor therapy and 7% of patients who undergo upper GI endoscopy. Diagnosis is made by histological analysis of esophageal biopsy, with at least five biopsies needed to achieve sufficient sensitivity, because of the irregularity of EoE pathology.
Recent characterization of the EoE transcriptome consisting of about 500 genes opened up the possibility of diagnosing the disease at the molecular level. The authors developed a 94-gene panel built on a Taqman-qPCR system. They found the panel identified adult and pediatric EoE patients with approximately 96% sensitivity and 98% specificity. The panel also distinguished EoE patients from controls, and from those with reflux esophagitis.
Risk Factors Characterized for Healthcare-Acquired and Community-Associated C. difficile Infection
A retrospective observational cohort study aimed at distinguishing the risk factors, clinical course, and outcomes between healthcare-associated (HA) and community-associated (CA) C. difficile infection (CDI) found that CA-CDI more often is seen in previously healthy children without antibiotic exposure or comorbid conditions (Clin Infect Dis 2013;57:1665–72). The authors also found that in comparison to HA-CDI, children with CA-CDI had a trend toward more episodes of septic shock, toxic megacolon, and recurrences.
The study involved 200 pediatric patients diagnosed with CDI, of whom 38 had had CA-CDI, 144 had HA-CDI, and 20 had indeterminate CDI, meaning their disease started in the community within 4–12 weeks after hospital discharge. In contrast, the researchers defined HA-CDI as disease onset >48 hours after hospital admission, and CD-CDI as symptom onset ≤48 hours after admission and more than 12 weeks since the patient’s last hospitalization.
The researchers found that the risk profiles of children with indeterminate CDI are more similar to HA-CDI, suggesting that these cases should be allocated to HA-CDI rather than CA-CDI. Based on their findings the authors also suggested that the diagnosis of CDI should be considered in healthy children even without recent exposure to antibiotics. They called for additional research to understand why CA-CDI has been increasing, as this trend may not be explained solely by traditional risk factors.