Prolonged silent carriage, genomic virulence potential and transmission between staff and patients characterize a neonatal intensive care unit (NICU) outbreak of methicillin-resistant Staphylococcus aureus (MRSA).

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in neonatal intensive care units (NICU) that confers significant morbidity and mortality. OBJECTIVE: Improving our understanding of MRSA transmission dynamics, especially among high-risk patients, is an infection prevention priority. METHODS: We investigated a cluster of clinical MRSA cases in the NICU using a combination of epidemiologic review and whole-genome sequencing (WGS) of isolates from clinical and surveillance cultures obtained from patients and healthcare personnel (HCP). RESULTS: Phylogenetic analysis identified 2 genetically distinct phylogenetic clades and revealed multiple silent-transmission events between HCP and infants. The predominant outbreak strain harbored multiple virulence factors. Epidemiologic investigation and genomic analysis identified a HCP colonized with the dominant MRSA outbreak strain who cared for most NICU patients who were infected or colonized with the same strain, including 1 NICU patient with severe infection 7 months before the described outbreak. These results guided implementation of infection prevention interventions that prevented further transmission events. CONCLUSIONS: Silent transmission of MRSA between HCP and NICU patients likely contributed to a NICU outbreak involving a virulent MRSA strain. WGS enabled data-driven decision making to inform implementation of infection control policies that mitigated the outbreak. Prospective WGS coupled with epidemiologic analysis can be used to detect transmission events and prompt early implementation of control strategies.

Navigating Clinical Utilization of Direct-from-Specimen Metagenomic Pathogen Detection: Clinical Applications, Limitations, and Testing Recommendations.

BACKGROUND: Metagenomic next generation sequencing (mNGS) is becoming increasingly available for pathogen detection directly from clinical specimens. These tests use target-independent, shotgun sequencing to detect potentially unlimited organisms. The promise of this methodology to aid infection diagnosis is demonstrated through early case reports and clinical studies. However, the optimal role of mNGS in clinical microbiology remains uncertain. CONTENT: We reviewed studies reporting clinical use of mNGS for pathogen detection from various specimen types, including cerebrospinal fluid, plasma, lower respiratory specimens, and others. Published clinical study data were critically evaluated and summarized to identify promising clinical indications for mNGS-based testing, to assess the clinical impact of mNGS for each indication, and to recognize test limitations. Based on these clinical studies, early testing recommendations are made to guide clinical utilization of mNGS for pathogen detection. Finally, current barriers to routine clinical laboratory implementation of mNGS tests are highlighted. SUMMARY: The promise of direct-from-specimen mNGS to enable challenging infection diagnoses has been demonstrated through early clinical studies of patients with meningitis or encephalitis, invasive fungal infections, community acquired pneumonia, and other clinical indications. However, the proportion of patient cases with positive clinical impact due to mNGS testing is low in published studies and the cost of testing is high, emphasizing the importance of improving our understanding of 'when to test' and for which patients mNGS testing is appropriate.

The spectrum of constipation-predominant irritable bowel syndrome and chronic idiopathic constipation: US survey assessing symptoms, care seeking, and disease burden.

INTRODUCTION: The irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are associated with substantial symptom and disease burden. Although typically classified as distinct diseases, symptoms frequently overlap. AIM: The objective of this study was to characterize symptom and disease burden in IBS-C and CIC sufferers and examine a subset of CIC sufferers with abdominal symptoms. METHODS: In a US population-based survey, respondents meeting the Rome III criteria for IBS-C or CIC rated symptom frequency and bothersomeness, missed work and disrupted productivity, and degree of obtaining and satisfaction with physician care. CIC respondents were analyzed in two subgroups: those with abdominal symptoms ≥once weekly (CIC-A) and those without (CIC-NA). RESULTS: Of the 10,030 respondents, 328 met the criteria for IBS-C and 552 for CIC (363 CIC-A; 189 CIC-NA). All symptoms were significantly more frequent in IBS-C vs. CIC respondents (P<0.0001). Constipation was extremely/very bothersome in 72% of IBS-C respondents, 62% of CIC-A, and 40% of CIC-NA (P<0.01 all pairs). All 11 other measured symptoms were significantly more bothersome in IBS-C and CIC-A vs. CIC-NA respondents. In IBS-C vs. CIC-A, abdominal discomfort, bloating, straining, and pellet-like stools were also significantly more bothersome, with other remaining symptoms similar. Gastrointestinal symptoms disrupted productivity a mean of 4.9 days per month in IBS-C respondents, 3.2 in CIC-A, and 1.2 in CIC-NA (P<0.001 all pairs); missed days were similar in IBS-C and CIC-A respondents. CONCLUSION: CIC respondents with abdominal symptoms experience greater disease burden compared with CIC respondents without frequent abdominal symptoms and have a disease burden profile that is similar to IBS-C respondents.

The relationship between wisdom and abstinence behaviors in women in recovery from substance abuse.

BACKGROUND AND AIMS: Wisdom is theorized to be an important construct in recovery from substance abuse. In order to explore the role of wisdom in substance abuse recovery behaviors, the present study had two goals. First, it sought to examine the factor structure of a wisdom scale, the Foundational Value Scale (FVS) in a community sample of women in recovery from substance abuse. Second, the study examined how wisdom predicted the women's beliefs about their ability to abstain from future substance use. METHODS: 116 women in recovery from substance abuse disorders were recruited from self-run recovery homes and a substance abuse recovery convention. RESULTS: Results from an exploratory factor analysis indicated that a modified version of the FVS has good internal consistency reliability and is composed of three wisdom-related dimensions. The three factors were then used to create a higher-order wisdom factor in a structural equation model (SEM) that was used to predict abstinence self-efficacy behaviors. Results from the SEM showed that the wisdom factor was predictive of greater abstinence self-efficacy behaviors. CONCLUSION: The FVS was found to be a reliable measure with women in recovery from substance abuse. In addition, wisdom predicted beliefs about self-efficacy such that those who reported higher levels of wisdom felt more confident in their abilities to abstain from alcohol. SCIENTIFIC SIGNIFICANCE: The results of this study indicate that wisdom is an important construct in the abstinence behaviors of women who are in recovery from substance abuse disorders.

Using a pan-viral microarray assay (Virochip) to screen clinical samples for viral pathogens.

The diagnosis of viral causes of many infectious diseases is difficult due to the inherent sequence diversity of viruses as well as the ongoing emergence of novel viral pathogens, such as SARS coronavirus and 2009 pandemic H1N1 influenza virus, that are not detectable by traditional methods. To address these challenges, we have previously developed and validated a pan-viral microarray platform called the Virochip with the capacity to detect all known viruses as well as novel variants on the basis of conserved sequence homology. Using the Virochip, we have identified the full spectrum of viruses associated with respiratory infections, including cases of unexplained critical illness in hospitalized patients, with a sensitivity equivalent to or superior to conventional clinical testing. The Virochip has also been used to identify novel viruses, including the SARS coronavirus, a novel rhinovirus clade, XMRV (a retrovirus linked to prostate cancer), avian bornavirus (the cause of a wasting disease in parrots), and a novel cardiovirus in children with respiratory and diarrheal illness. The current version of the Virochip has been ported to an Agilent microarray platform and consists of ~36,000 probes derived from over ~1,500 viruses in GenBank as of December of 2009. Here we demonstrate the steps involved in processing a Virochip assay from start to finish (~24 hour turnaround time), including sample nucleic acid extraction, PCR amplification using random primers, fluorescent dye incorporation, and microarray hybridization, scanning, and analysis.

12-Step involvement among a U.S. national sample of Oxford House residents.

A longitudinal analysis was conducted among a U.S. national sample of persons affiliated with Alcoholics Anonymous and Narcotics Anonymous living in self-run recovery homes (Oxford Houses). Categorical involvement in a set of 12-step activities (i.e., having a sponsor, reading 12-step literature, doing service work, and calling other members for help) and averaged summary scores of involvement were examined in relation to abstinence and self-efficacy for abstinence. Participants who were categorically involved in all 12-step activities reported significantly higher levels of abstinence and self-efficacy for abstinence at 1 year compared with those who were less involved, whereas averaged summary scores of involvement were not a significant predictor of abstinence. Participants' number of days in Oxford Houses, but not rates of 12-step meeting attendance, was significantly related to increased abstinence. Findings suggest that categorical involvement in a number of 12-step activities equip persons with substance use disorders with resources for ongoing recovery.

Cytologic evaluation can predict microbial culture results for infectious causes of pulmonary nodules in patients undergoing fine needle aspiration biopsy.

We retrospectively compared cytopathology and microbial culture results for pulmonary fine needle aspiration biopsy specimens over a 10-year period. Eighty samples were submitted for culture, yielding 24 positive cultures with 17 pathogenic organisms. Cytology predicted positive cultures in all cases where organisms were visualized, and it was associated with negative cultures in 24 of 25 cases where inflammatory changes and necrosis were absent.

Thoracic CT findings of novel influenza A (H1N1) infection in immunocompromised patients.

The goal of this study is to describe the spectrum of initial and follow-up CT findings of novel influenza A (H1N1) infection in a series of immunocompromised patients. Eight immunocompromised patients with documented novel influenza A (H1N1) had CT imaging at our institution between May 2009 and August 2009. A total of 20 CTs (initial and follow-up) were reviewed for the presence, severity, and distribution of the following: ground glass opacity, consolidation, interlobular septal thickening, mosaic perfusion, airway wall thickening, airway dilatation, nodules, cysts, pleural effusion, pericardial effusion, lymphadenopathy, and air trapping. The most common findings were airway thickening/dilatation, peribronchial ground glass opacity, centrilobular nodules, and tree-in-bud opacities. Peripheral consolidation involving the lower lobes was also a common pattern. Findings frequently involved all lobes and were closely associated with either large or small airways. Two patients presented with atypical CT findings including focal lobar consolidation and patchy lower lobe consolidation with soft tissue centrilobular nodules. Most survivors showed near complete resolution of findings within 35 days. CT scans in immunocompromised patients with novel influenza H1N1 commonly show a strong airway predominance of findings or peripheral areas of consolidation involving the lower lobes. A subset of patients with novel influenza A (H1N1) will show findings not typical of viral infection.