The rapid detection of respiratory pathogens in critically ill children

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 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 h (IQR 9.1-29.8 h) from sample collection to result. Culture was significantly slower: median 110.4 h (IQR 85.2-141.6 h) for a positive result and median 69.4 h (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.

Keywords: Critical care; Diagnostic techniques; Healthcare-associated pneumonia; Paediatric; Pneumonia; Respiratory system.

Fig. 1

Study workflow. This figure represents the protocol of the Rapid Assay for Sick Children with Acute Lung infection Study. Critically ill children with suspected respiratory infection underwent non-bronchoscopic bronchoalveolar lavage. Specimens that were obtained underwent both routine microbiology culture and custom TaqMan Array Card. Results were reported back to clinicians, and consultants were surveyed regarding their antimicrobial decision-making

Fig. 2

RASCALS enrolment flowchart. Flowchart of children screened and enrolled into the Rapid Assay for Sick Children with Acute Lung infection Study (RASCALS) April 2020–January 2022. Children aged < 18 years were enrolled if they were commencing or had already commenced antimicrobial therapy for lower respiratory tract infection. mini-BAL: non-bronchoscopic bronchoalveolar lavage

Fig. 3

Performance of TaqMan Array Card (TAC) in the detection of bacterial and fungal micro-organisms compared to routine microbiology culture. A Time to reported result in hours from the time the sample was collected. B Number of detections of bacterial and fungal micro-organisms using TaqMan Array Card (TAC) with cycle threshold result ≤ 32 compared to standard microbiology culture

Fig. 4

Actions of consultants with respect antimicrobial prescribing after reported TAC results. Critically unwell children underwent custom TaqMan Array Card (TAC) for suspected respiratory infection. Paediatric intensive care consultants were surveyed in respect to their prescribing once the results for TAC were documented in the electronic medical record. There were a range of changes made to antimicrobial prescriptions—in both the duration of treatment delivered and the spectrum of antimicrobial therapy