Enhanced diagnosis of severe bacterial and fungal respiratory infection in children using a rapid syndromic array-case report.

Background: A microbiological cause of infection is infrequently identified in critically unwell children with a respiratory infection. Molecular diagnostic arrays provide an alternative. These tests are becoming more broadly available, but little is known about how clinicians interpret the results to impact clinical decision making. Case Description: Here we describe three cases of bacterial and fungal lower respiratory tract infection (LRTI) diagnosed in the paediatric intensive care unit (PICU) using a custom 52 respiratory pathogen TaqMan array card (TAC). Firstly, an early diagnosis of Candida albicans pneumonia was made with the support of the TAC in a trauma patient who received prolonged mechanical ventilation. The pathogen was only identified on microbiological cultures after further clinical deterioration had occurred. Secondly, a rare case of psittacosis was identified in an adolescent with acute respiratory distress, initially suspected to have multisystem inflammatory syndrome in children (MIS-C). Finally, Haemophilus influenzae pneumonia was identified in an infant with recurrent apnoeas, initially treated for meningitis. Two diagnoses would not have been established using commercially available arrays, and pathogen-specific diagnoses were established faster than that of routine microbiological culture. Conclusions: The pathogens included on molecular arrays and interpretation by a multidisciplinary team are crucial in providing value to PICU diagnostic services. Molecular arrays have the potential to enhance early pathogen-specific diagnosis of LRTI in the PICU.

Rapid Detection of Antimicrobial Resistance Genes in Critically Ill Children Using a Custom TaqMan Array Card.

Bacteria are identified in only 22% of critically ill children with respiratory infections treated with antimicrobial therapy. Once an organism is isolated, antimicrobial susceptibility results (phenotypic testing) can take another day. A rapid diagnostic test identifying antimicrobial resistance (AMR) genes could help clinicians make earlier, informed antimicrobial decisions. Here we aimed to validate a custom AMR gene TaqMan Array Card (AMR-TAC) for the first time and assess its feasibility as a screening tool in critically ill children. An AMR-TAC was developed using a combination of commercial and bespoke targets capable of detecting 23 AMR genes. This was validated using isolates with known phenotypic resistance. The card was then tested on lower respiratory tract and faecal samples obtained from mechanically ventilated children in a single-centre observational study of respiratory infection. There were 82 children with samples available, with a median age of 1.2 years. Major comorbidity was present in 29 (35%) children. A bacterial respiratory pathogen was identified in 13/82 (16%) of children, of which 4/13 (31%) had phenotypic AMR. One AMR gene was detected in 49/82 (60%), and multiple AMR genes were detected in 14/82 (17%) children. Most AMR gene detections were not associated with the identification of phenotypic AMR. AMR genes are commonly detected in samples collected from mechanically ventilated children with suspected respiratory infections. AMR-TAC may have a role as an adjunct test in selected children in whom there is a high suspicion of antimicrobial treatment failure.