The rapid detection of respiratory pathogens in critically ill children

Author:

Clark John Alexander1,Morris Andrew Conway1,Curran Martin D2,White Deborah3,Daubney Esther3,Kean Iain RL1,Navapurkar Vilas3,Scott Josefin Bartholdson1,Maes Mailis2,Bousfield Rachel2,Török M. Estée3,Inwald David3,Zhang Zhenguang1,Agrawal Shruti1,Kanaris Constantinos3,Khokhar Fahad1,Gouliouris Theodore3,Baker Stephen1,Pathan Nazima1

Affiliation:

1. University of Cambridge

2. UK Health Security Agency

3. Cambridge University Hospitals NHS Foundation Trust

Abstract

Abstract Purpose Respiratory infections are the most common reason for admission to Paediatric Intensive Care Units (PICU). Most patients with lower respiratory tract infection (LRTI) receive broad-spectrum antimicrobials, despite low rates of bacterial culture confirmation. Here, we evaluated a molecular diagnostic test for LRTI to inform the better use of antimicrobials. Methods The Rapid Assay for Sick Children with Acute Lung infection Study (RASCALS) was a single-centre, prospective, observational cohort study of mechanically ventilated children (> 37/40 weeks corrected gestation to 18 years) with suspected community acquired or ventilator-associated LRTI. We evaluated the use of a 52-pathogen custom TaqMan array card (TAC) to identify pathogens in non-bronchoscopic bronchoalveolar lavage (mini-BAL) samples. TAC results were compared to routine microbiology testing. Primary study outcomes were sensitivity and specificity of TAC, and time to result. Results We enrolled 100 patients; all of whom were tested with TAC and 91 of whom had matching culture samples. TAC had a sensitivity of 89.5% (95% confidence interval (CI95) 66.9–98.7) and specificity of 97.9% (CI95 97.2–98.5) compared to routine bacterial and fungal culture. TAC took a median 25.8 hours (IQR 9.1–29.8 hours) from sample collection to result. Culture was significantly slower; median 110.4 hours (IQR 85.2–141.6 hours) for a positive result and median 69.4 hours (IQR 52.8–78.6) for a negative result. Conclusions TAC is a reliable and rapid adjunct diagnostic approach for LRTI in critically ill children, with the potential to aid early rationalisation of antimicrobial therapy.

Publisher

Research Square Platform LLC

Reference30 articles.

1. (2022) Paediatric Intensive Care Audit Network Annual Report (2021)

2. NHS England (2021) National Schedule of NHS Costs - Year 2020–2021 - NHS trusts and NHS foundation trusts

3. Understanding decisions about antibiotic prescribing in ICU: an application of the Necessity Concerns Framework;Pandolfo AM;BMJ Qual Saf,2021

4. Influence of Antibiotics on the Detection of Bacteria by Culture-Based and Culture-Independent Diagnostic Tests in Patients Hospitalized With Community-Acquired Pneumonia;Harris AM;Open Forum Infect Dis,2017

5. Low diagnostic yield and time to diagnostic confirmation results in prolonged use of antimicrobials in critically ill children;Clark J;Wellcome Open Res,2021

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