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Tracheal Aspirate as an Alternative Biologic Sample for Pharmacogenomics Testing in Mechanically Ventilated Pediatric Patients.

ABSTRACT: Patients in the pediatric intensive care unit are exposed to multiple medications and are at high risk for adverse drug reactions. Pharmacogenomic (PGx) testing could help decrease their risk of adverse reactions. Although whole blood is preferred for PGx testing, blood volume in this population is often limited. However, for patients on mechanical ventilation, tracheal secretions are abundant, frequently suctioned, and discarded. Thus, the aim of this pilot study was to determine if tracheal aspirates could be used as a source of human genomic DNA for PGx testing. We successfully extracted DNA from tracheal secretions of all 23 patients in the study. The samples were successfully genotyped for 10 clinically actionable single nucleotide variants across 3 cytochrome P450 genes (CYP2D6, CYP2C19, and CYP3A5). Using DNA from whole blood samples in 11 of the patients, we confirmed the accuracy of the genotyping with 100% concordance. Therefore, our results support the use of tracheal aspirates from mechanically ventilated children as an adequate biospecimen for clinical genetic testing.

SUBMITTER: Hargreaves KA

PROVIDER: S-EPMC7993287 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Tracheal Aspirate as an Alternative Biologic Sample for Pharmacogenomics Testing in Mechanically Ventilated Pediatric Patients.

Hargreaves Katherine A KA Pratt Victoria M VM Medeiros Elizabeth B EB Lynnes Ty C TC Granfield Caitlin A CA Skaar Todd C TC Iwata-Otsubo Aiko A Tillman Emma M EM

Clinical and translational science 20210125 2

Patients in the pediatric intensive care unit are exposed to multiple medications and are at high risk for adverse drug reactions. Pharmacogenomic (PGx) testing could help decrease their risk of adverse reactions. Although whole blood is preferred for PGx testing, blood volume in this population is often limited. However, for patients on mechanical ventilation, tracheal secretions are abundant, frequently suctioned, and discarded. Thus, the aim of this pilot study was to determine if tracheal as ...[more]

PMID: 32702149

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Project description:ImportanceEndotracheal aspirate cultures are commonly collected from patients with mechanical ventilation to evaluate for ventilator-associated pneumonia or tracheitis. However, the respiratory tract is not sterile, making differentiating between colonization from bacterial infection challenging, and results may be unreliable owing to variable specimen quality and sample processing across laboratories. Despite these limitations, clinicians routinely interpret bacterial growth in endotracheal aspirate cultures as evidence of infection, sometimes regardless of organism significance, prompting antibiotic treatment.ObjectiveTo assess the variability in endotracheal aspirate culture rates and the association between culture rates and antibiotic prescribing among patients with mechanical ventilation across children's hospitals in the US.Design, setting, and participantsCross-sectional retrospective analysis of data obtained from the Children's Hospital Association Pediatric Health Information System database between January 1, 2016, through December 31, 2019. Participants were all patients hospitalized with mechanical ventilation aged less than 18 years.ExposuresA charge for an endotracheal aspirate culture on a ventilated day.Main outcomes and measuresEndotracheal aspirate culture rate and antibiotic days of therapy per ventilated days. For mechanical ventilation, clinical transaction classification codes for mechanical ventilation other unspecified ventilator assistance were used. To identify respiratory cultures, the laboratory test code for aerobic culture was used and relevant keywords (ie, respiratory tract, sputum) were used to identify sources in the hospital charge description master.ResultsA total of 152 132 patients were identified among 31 hospitals. Among these patients, 79 691 endotracheal aspirate cultures were collected on a ventilator-day (patients aged less than 1 year, 44%; 1-4 years, 27%, 5-11 years. 16%, and 12-18 years, 13%; 3% were Asian; 17% Hispanic; 21% non-Hispanic Black; 45% Non-Hispanic White patients; 14% were other; 56% of patients were male, 44% were female). The overall median rate of culture use was 46 per 1000 ventilator-days (IQR, 32-73 cultures per 1000 ventilator-days). The endotracheal aspirate culture rate was positively correlated with the hospital's antibiotic days of therapy rate (R = 0.46; P = .009). In a multivariable model adjusting for patient-level and hospital-level characteristics and among patients with mechanical ventilation, each additional endotracheal aspirate culture was associated with 2.87 (95% CI, 2.74-3.01) higher odds of receiving additional days of therapy compared with patients who did not receive and endotracheal aspirate culture.Conclusions and relevanceIn this study, notable variability was found in endotracheal aspirate culture rates across US pediatric hospitals and pediatric intensive care units, and endotracheal aspirate culture use was associated with increased antibiotic use. These findings suggest an opportunity for diagnostic and antibiotic stewardship to standardize testing and treatment of suspected ventilator-associated infections in pediatric patients with mechanical ventilation pediatric patients.

Project description:BackgroundVentilator-associated pneumonia (VAP) is a well-known, life-threatening disease that persists despite preventative measures and approved antibiotic therapies. This prospective observational study investigated bacterial airway colonization, and whether its detection and quantification in the endotracheal aspirate (ETA) is useful for identifying mechanically ventilated ICU patients who are at risk of developing VAP.Methods240 patients admitted to 3 ICUs at the Lahey Hospital and Medical Center (Burlington, MA) between June 2014 and June 2015 and mechanically ventilated for > 2 days were included. ETA samples and clinical data were collected. Airway colonization was assessed, and subsequently categorized into "heavy" and "light" by semi-quantitative microbiological analysis of ETAs. VAP was diagnosed retrospectively by the study sponsor according to a pre-specified pneumonia definition.ResultsPathogenic bacteria were isolated from ETAs of 125 patients. The most common species isolated was S. aureus (56.8%), followed by K. pneumoniae, P. aeruginosa, and E. coli (35.2% combined). VAP was diagnosed in 85 patients, 44 (51.7%) with no bacterial pathogen, 18 associated with S. aureus and 18 Gram-negative-only cases, and 5 associated with other Gram-positive or mixed species. A higher proportion of patients who were heavily colonized with S. aureus developed VAP (32.4%) associated with S. aureus compared to those lightly colonized (17.6%). The same tendency was seen for patients heavily and lightly colonized with Gram-negative pathogens (30.0 and 0.0%, respectively). Detection of S. aureus in the ETA preceded S. aureus VAP by approximately 4 days, while Gram-negative organisms were first detected 2.5 days prior to Gram-negative VAP. VAP was associated with significantly longer duration of mechanical ventilation and hospitalization regardless of microbiologic cause when compared to patients who did not develop VAP.ConclusionsThe overall VAP rate was 35%. Heavy tracheal colonization supported identification of patients at higher risk of developing a corresponding S. aureus or Gram-negative VAP. Detection of bacterial ETA-positivity tended to precede VAP.

Dataset Information

Tracheal Aspirate as an Alternative Biologic Sample for Pharmacogenomics Testing in Mechanically Ventilated Pediatric Patients.

Publications

Tracheal Aspirate as an Alternative Biologic Sample for Pharmacogenomics Testing in Mechanically Ventilated Pediatric Patients.

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