The spatial and temporal distribution of SARS-CoV-2 from the built environment of COVID-19 patient rooms: A multicentre prospective study.

BACKGROUND: SARS-CoV-2 can be detected from the built environment (e.g., floors), but it is unknown how the viral burden surrounding an infected patient changes over space and time. Characterizing these data can help advance our understanding and interpretation of surface swabs from the built environment. METHODS: We conducted a prospective study at two hospitals in Ontario, Canada between January 19, 2022 and February 11, 2022. We performed serial floor sampling for SARS-CoV-2 in rooms of patients newly hospitalized with COVID-19 in the past 48 hours. We sampled the floor twice daily until the occupant moved to another room, was discharged, or 96 hours had elapsed. Floor sampling locations included 1 metre (m) from the hospital bed, 2 m from the hospital bed, and at the room's threshold to the hallway (typically 3 to 5 m from the hospital bed). The samples were analyzed for the presence of SARS-CoV-2 using quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). We calculated the sensitivity of detecting SARS-CoV-2 in a patient with COVID-19, and we evaluated how the percentage of positive swabs and the cycle threshold of the swabs changed over time. We also compared the cycle threshold between the two hospitals. RESULTS: Over the 6-week study period we collected 164 floor swabs from the rooms of 13 patients. The overall percentage of swabs positive for SARS-CoV-2 was 93% and the median cycle threshold was 33.4 (interquartile range [IQR]: 30.8, 37.2). On day 0 of swabbing the percentage of swabs positive for SARS-CoV-2 was 88% and the median cycle threshold was 33.6 (IQR: 31.8, 38.2) compared to swabs performed on day 2 or later where the percentage of swabs positive for SARS-CoV-2 was 98% and the cycle threshold was 33.2 (IQR: 30.6, 35.6). We found that viral detection did not change with increasing time (since the first sample collection) over the sampling period, Odds Ratio (OR) 1.65 per day (95% CI 0.68, 4.02; p = 0.27). Similarly, viral detection did not change with increasing distance from the patient's bed (1 m, 2 m, or 3 m), OR 0.85 per metre (95% CI 0.38, 1.88; p = 0.69). The cycle threshold was lower (i.e., more virus) in The Ottawa Hospital (median quantification cycle [Cq] 30.8) where floors were cleaned once daily compared to the Toronto hospital (median Cq 37.2) where floors were cleaned twice daily. CONCLUSIONS: We were able to detect SARS-CoV-2 on the floors in rooms of patients with COVID-19. The viral burden did not vary over time or by distance from the patient's bed. These results suggest floor swabbing for the detection of SARS-CoV-2 in a built environment such as a hospital room is both accurate and robust to variation in sampling location and duration of occupancy.

Modified reporting of positive urine cultures to reduce inappropriate antibiotic treatment of catheter-associated asymptomatic bacteriuria (CA-ASB) among inpatients, a randomized controlled trial.

OBJECTIVE: To determine whether modified reporting of positive urine cultures collected from indwelling catheters improved treatment decisions without causing harm. DESIGN: Prospective, unblinded, randomized control trial. SETTING: Two tertiary-care hospitals. PARTICIPANTS: Overall, 100 consecutive positive urine cultures collected from catheterized inpatients were randomized between standard and modified laboratory reporting between November 2018 and June 2019. Exclusion criteria were pregnancy, current antibiotic treatment, ICU or urology admission, or neutropenia. INTERVENTION: The modified report included significant growth without providing identification, quantification, or susceptibility. The standard report included identification, quantitation and susceptibility. Diagnosis of catheter-associated asymptomatic bacteriuria (CA-ASB) and catheter-associated urinary tract infection (CA-UTI) followed published criteria, using prospective chart review. The appropriate antibiotic treatment was defined as treatment of CA-UTI, and no treatment of CA-ASB. Patients were followed for 7 days. RESULTS: Of 543 urine cultures, 443 (82%) were excluded. Of 100 patients, 75 (75%) had CA-ASB and 25 (25%) had CA-UTI. Treatment was given to 45 of 75 CA-ASB patients (60%) and all 25 CA-UTI patients (100%). Appropriate treatment rate was higher in the modified reporting arm than in the standard reporting arm: 57% vs 50% (+7.4%; relative risk [RR], 1.15; P = .45). Untreated CA-ASB was higher in the modified reporting arm: 45% vs 33% (+12%; RR, 1.36; P = .30). The standard report was requested for 33% of modified reports. Furthermore, 4 deaths and 26.9% adverse events occurred in the modified reporting arm, and 3 deaths and 41.3% adverse events occurred in the standard reporting arm. CONCLUSIONS: Modified reporting increased the appropriateness of treatment, and may be safe.Clinical trials identifier: ClinicalTrials.gov#NCT03488355.

Correction: Acute Infectious Gastroenteritis Potentiates a Crohn's Disease Pathobiont to Fuel Ongoing Inflammation in the Post-Infectious Period.

[This corrects the article DOI: 10.1371/journal.ppat.1005907.].

Management of Venous Thromboembolism in Patients with Hereditary Antithrombin Deficiency and Pregnancy: Case Report and Review of the Literature.

Background. Hereditary antithrombin deficiency is a thrombogenic disorder associated with a 50-90% lifetime risk of venous thromboembolism (VTE), which is increased during pregnancy and the puerperium in these patients. We present a case of a woman with antithrombin (AT) deficiency who presented with a VTE despite therapeutic low molecular weight heparin (LMWH). Though the pregnancy was deemed unviable, further maternal complications were mitigated through the combined use of therapeutic anticoagulation and plasma-derived antithrombin concentrate infusions to normalize her functional antithrombin levels. Methods. A review of the literature was conducted for studies on prophylaxis and management of VTE in pregnant patients with hereditary AT deficiency. The search involved a number of electronic databases, using combinations of keywords as described in the text. Only English language studies between 1946 and 2015 were included. Conclusion. Antithrombin concentrate is indicated in pregnant women with hereditary AT deficiency who develop VTE despite being on therapeutic dose anticoagulation. Expert opinion suggests AT concentrate should be used concomitantly with therapeutic dose anticoagulation. However, further high-quality studies on the dose and duration of treatment in the postpartum period are required. Use of AT concentrate for prophylaxis is controversial and should be based on individual VTE risk stratification.

Acute Infectious Gastroenteritis Potentiates a Crohn's Disease Pathobiont to Fuel Ongoing Inflammation in the Post-Infectious Period.

Crohn's disease (CD) is a chronic inflammatory condition of diverse etiology. Exposure to foodborne pathogens causing acute gastroenteritis produces a long-term risk of CD well into the post-infectious period but the mechanistic basis for this ongoing relationship to disease onset is unknown. We developed two novel models to study the comorbidity of acute gastroenteritis caused by Salmonella Typhimurium or Citrobacter rodentium in mice colonized with adherent-invasive Escherichia coli (AIEC), a bacterial pathobiont linked to CD. Here, we show that disease activity in the post-infectious period after gastroenteritis is driven by the tissue-associated expansion of the resident AIEC pathobiont, with an attendant increase in immunopathology, barrier defects, and delays in mucosal restitution following pathogen clearance. These features required AIEC resistance to host defense peptides and a fulminant inflammatory response to the enteric pathogen. Our results suggest that individuals colonized by AIEC at the time of acute infectious gastroenteritis may be at greater risk for CD onset. Importantly, our data identify AIEC as a tractable disease modifier, a finding that could be exploited in the development of therapeutic interventions following infectious gastroenteritis in at-risk individuals.

CXCL9 contributes to antimicrobial protection of the gut during citrobacter rodentium infection independent of chemokine-receptor signaling.

Chemokines have been shown to be effective bactericidal molecules against a variety of bacteria and fungi in vitro. These direct antimicrobial effects are independent of their chemotactic activities involving immunological receptors. However, the direct biological role that these proteins may play in host defense, particularly against intestinal pathogens, is poorly understood. Here, we show that CXCL9, an ELR- chemokine, exhibits direct antimicrobial activity against Citrobacter rodentium, an attaching/effacing pathogen that infects the gut mucosa. Inhibition of this antimicrobial activity in vivo using anti-CXCL9 antibodies increases host susceptibility to C. rodentium infection with pronounced bacterial penetration into crypts, increased bacterial load, and worsened tissue pathology. Using Rag1(-/-) mice and CXCR3(-/-) mice, we demonstrate that the role for CXCL9 in protecting the gut mucosa is independent of an adaptive response or its immunological receptor, CXCR3. Finally, we provide evidence that phagocytes function in tandem with NK cells for robust CXCL9 responses to C. rodentium. These findings identify a novel role for the immune cell-derived CXCL9 chemokine in directing a protective antimicrobial response in the intestinal mucosa.