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Endotracheal aspirate cultures (EACs) help diagnose lower respiratory tract infections in mechanically ventilated patients but are limited by contamination with normal microbiota and variation in laboratory reporting. Increased use of EACs is associated with increased antimicrobial prescribing, but the impact of microbiology reporting on prescribing practices is unclear. This study was a retrospective analysis of EACs from mechanically ventilated patients at Children's Hospital Colorado (CHCO) admitted between 1 January 2019 and 31 December 2019. Chart review was performed to collect all culture and Gram stain components, as well as antibiotic use directed to organisms in culture. Reporting concordance was determined for each organism using American Society for Microbiology guidelines. Days of therapy were calculated for overreported and guideline-concordant organisms. A multivariable model was used to assess the relationship between organism reporting and total days of therapy. Overall, 448 patients with 827 EACs were included in this study. Among patients with tracheostomy, 25 (8%) organisms reported from EACs were overreported and contributed 48 days of excess therapy, while 227 (29%) organisms from the EACs of endotracheally intubated patients were overreported, contributing 472 excess days of therapy. After adjustment, organism overreporting was associated with a >2-fold-higher rate of antimicrobial therapy than guideline-concordant reporting (incident rate ratio [IRR], 2.83; 95% confidence interval [CI], 1.23, 6.53; P < 0.05). Overreported organisms from respiratory cultures contribute to excess antimicrobial therapy exposure in mechanically ventilated patients. Microbiology laboratories have an opportunity to mitigate antimicrobial overuse through standardized reporting practices.

We describe mycobacterial phospholipase A activity (MPLA) and, using reverse genetics, have associated this activity with putative mycobacterial cutinase. PLAs, which hydrolyze fatty acids on phospholipids, play a significant role in human inflammatory states and disease pathogenesis. In prokaryotes, the recognition of their role in virulence is more recent. Cutinases are serine esterases whose primary substrate is cutin, the waxy exterior layer of plants. Mycobacterium tuberculosis has maintained seven putative cutinases, though it should not encounter cutin; we demonstrate that known cutinases and MPLA cleave phospholipids in a PLA-type manner and also hydrolyze Tween. We analyzed cutinase motifs in mycobacteria and found the motif very prevalent. All mycobacteria tested had MPLA activity. These studies suggest an alternative use for putative cutinases by the M. tuberculosis group that is likely related to MPLA activity and lipid metabolism.

Objective. The issue of thimerosal-containing vaccines as a possible cause of autistic spectrum disorders (ASD) and neurodevelopmental disorders (NDDs) has been a controversial topic since 1999. Although most practitioners are familiar with the controversy, many are not familiar with the type or quality of evidence in published articles that have addressed this issue. To assess the quality of evidence assessing a potential association between thimerosal-containing vaccines and autism and evaluate whether that evidence suggests accepting or rejecting the hypothesis, we systematically reviewed published articles that report original data pertinent to the potential association between thimerosal-containing vaccines and ASD/NDDs. Methods. Articles for analysis were identified in the National Library of Medicine&apos;s Medline database using a PubMed search of the English-language literature for articles published between 1966 and 2004, using keywords thimerosal, thiomersal, mercury, methylmercury, or ethylmercury alone and combined with keywords autistic disorder, autistic spectrum disorder, and neurodevelopment. In addition, we used the "related links" option in PubMed and reviewed the reference sections in the identified articles. All original articles that evaluated an association between thimerosal-containing vaccines and ASD/NDDs or pharmacokinetics of ethylmercury in vaccines were included. Results. Twelve publications that met the selection criteria were identified by the literature search: 10 epidemiologic studies and 2 pharmacokinetic studies of ethylmercury. The design and quality of the studies showed significant variation. The preponderance of epidemiologic evidence does not support an association between thimerosal-containing vaccines and ASD. Epidemiologic studies that support an association are of poor quality and cannot be interpreted. Pharmacokinetic studies suggest that the half-life of ethylmercury is significantly shorter when compared with methylmercury. Conclusions. Studies do not demonstrate a link between thimerosal-containing vaccines and ASD, and the pharmacokinetics of ethylmercury make such an association less likely. Epidemiologic studies that support a link demonstrated significant design flaws that invalidate their conclusions. Evidence does not support a change in the standard of practice with regard to administration of thimerosal-containing vaccines in areas of the world where they are used. Pediatrics 2004;114:793-804; thimerosal, thiomersal, mercury, vaccine, methylmercury, ethylmercury, autism, autistic disorder, autistic spectrum disorder, developmental disorder, neurodevelopmental disorder., ABBREVIATIONS. ASD, autistic spectrum disorders; MMR, measles, mumps, rubella; EPA, Environmental Protection Agency; FDA, Food and Drug Administration; NDD, neurodevelopmental disorder; VAERS, Vaccine Adverse Events Reporting System; AE, adverse event; [...]

Objectives: Few studies describe the impact of antimicrobial stewardship programs (ASPs) on recognizing and preventing diagnostic errors. Handshake stewardship (HS-ASP) is a novel ASP model that prospectively reviews hospital-wide antimicrobial usage with recommendations made in person to treatment teams. The purpose of this study was to determine if HS-ASP could identify and intervene on potential diagnostic errors for children hospitalized at a quaternary care children’s hospital. Methods: Previously self-identified “Great Catch” (GC) interventions by the Children’s Hospital Colorado HS-ASP team from 10/2014 through 5/2018 were retrospectively reviewed. Each GC was categorized based on the types of recommendations from HS-ASP, including if any diagnostic recommendations were made to the treatment team. Each GC was independently scored using the “Safer Dx Instrument” to determine presence of diagnostic error based on a previously determined cut-off score of ≤1.50. Interrater reliability for the instrument was measured using a randomized subset of one third of GCs. Results: During the study period, there were 162 GC interventions. Of these, 65 (40%) included diagnostic recommendations by HS-ASP and 19 (12%) had a Safer Dx Score of ≤1.50, (Κ=0.44; moderate agreement). Of those GCs associated with diagnostic errors, the HS-ASP team made a diagnostic recommendation to the primary treatment team 95% of the time. Conclusions: Handshake stewardship has the potential to identify and intervene on diagnostic errors for hospitalized children. [ABSTRACT FROM AUTHOR]

Antimicrobial use (AU) in days of therapy per 1000 patient-days (DOT/1000 pd) varies widely among children's hospitals. We evaluated indirect standardization to adjust AU for case mix, a source of variation inadequately addressed by current measurements. Hospitalizations from the Pediatric Health Information System were grouped into 85 clinical strata. Observed to expected (O:E) ratios were calculated by indirect standardization and compared with DOT/1000 pd. Outliers were defined by O:E z -scores. Antibacterial DOT/1000 pd ranged from 345 to 776 (2.2-fold variation; interquartile range [IQR] 552–679), whereas O:E ratios ranged from 0.8 to 1.14 (1.4-fold variation; IQR 0.93–1.05). O:E ratios were moderately correlated with DOT/1000 pd (correlation estimate 0.44; 95% confidence interval, 0.19–0.64; P  = .0009). Using indirect standardization to adjust for case mix reduces apparent AU variation and may enhance stewardship efforts by providing adjusted comparisons to inform interventions. [ABSTRACT FROM AUTHOR]