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16th January 2023
A diagnostic aid based on polymerase chain reactions (PCR), that uses a 52-pathogen custom array card, has been found to provide both rapid (compared to blood culture) and reliable information on respiratory infections in critically ill, mechanically ventilated children, according to a study by UK researchers.
Respiratory tract infections are responsible for a large number of admissions to paediatric intensive care units. Moreover, an intensive care unit is unique environment and for which clinicians often make decisions to use antibiotics with some degree of diagnostic uncertainty. This was clearly illustrated in one study of paediatric intensive care unit children, where despite most critically children receiving antimicrobial therapy, infection was often not microbiologically confirmed. While in many cases, respiratory infections are viral in nature, it is necessary to utilise methods such as quantitative PCR, as a diagnostic aid to identify the presenting pathogens. In fact, a recent study in adults found that multiplex bacterial PCR examination of bronchoalveolar lavage, reduced the duration of inappropriate antibiotic therapy of patients admitted to hospital with pneumonia and who were at risk of Gram-negative infection. In the current study, researchers made use of the TaqMan Array Card (TAC) as a diagnostic aid which is a microfluidic quantitative PCR system comprising of 384 wells containing pre-aliquoted customised primer and probe combinations. The aid has been previously shown to be of value in supporting ventilator-associated pneumonia (VAP) diagnosis in adults. Nevertheless, it has not been examined in critically ill children and therefore, the aim of the present study was to assess the utility of TAC to identify bacterial and fungal respiratory pathogens in critically ill children with suspected community acquired pneumonia or VAP. The study recruited children ≤ 18 years of age and if they were mechanically ventilated and had commenced or were commencing antimicrobial therapy for a lower respiratory tract infection. The researchers determined the sensitivity and specificity of TAC to detect bacterial and fungal pathogens causing lower respiratory tract infections and the time to a result provided by TAC compared to standard microbiology cultures. Secondary objectives included a description of the micro-organisms detected by TAC but not by microbiology culture as well as the impact of TAC on antimicrobial decision-making.
Diagnostic aid and outcomes
A total of 100 children with a median age of 1.2 years (58% male) were included in the study and of whom, 80 had suspected community acquired pneumonia and the remainder, hospital acquired pneumonia.
Bacteria were detected more frequently on TAC compared to microbiology cultures (57% vs 18%, p < 0.001)) and In addition, TAC also identified more fungi (17% vs 2%, p < 0.001).
For the detection of bacterial and fungal species, TAC had a sensitivity of 89.5% (95% CI 66.9 – 98.7) and a specificity of 97.9% (95% CI 97.2 – 98.5). The median time to obtain a result for the diagnostic aid was 25.8 hours compared to 110.4 hours for microbiological cultures and overall, TAC was significantly quicker for both positive and negative results (p < 0.001).
Finally, consultants reported a change of prescription in 47% of cases based upon TAC results. Antimicrobial therapy duration was reduced or stopped in 26% of children, extended in16% and the spectrum of treatment was broadened in 17% of cases and reduced in 17%.
The authors concluded that as a diagnostic aid, TAC can be used to reliably detect pathogens quicker than routine culture in critically ill children with suspected lower respiratory tract infections and called for future studies to incorporate antimicrobial decision support and economic analysis.
Clark JA et al. The rapid detection of respiratory pathogens in critically ill children. Crit Care, 2023
14th June 2022
The use of multiplex PCR for point-of-care testing for respiratory pathogens does not result in a significant reduction of antibiotic use among acutely ill children presenting at an emergency department compared to usual care. This was the conclusion of a randomised, controlled trial by Finnish researchers.
Acute respiratory tract infections are one of the leading causes of emergency department visits and are often due to viral pathogens. Moreover, children suffering from infectious diseases of either bacterial and viral origin, are often treated with empirical antibiotics due to a similarity in the presenting symptoms. For example, in a study of pharyngitis presentations in children, there was evidence of substantial antibiotic overuse and inappropriate antibiotic selection. Such over-prescribing highlights the need for strategies to guide prescribing decisions and one such approach is the use of multiplex PCR point-of-care testing. In fact, one randomised trial in children 3 to 36 months of age with febrile acute respiratory tract infections, found that among those assigned to rapid respiratory viral testing on admission, there was a significant reduction in antibiotic prescription after discharge from the emergency department. Based on these findings, in the present study, the Finnish team hypothesised that the use of a rapid multiplex PCR point-of-care testing panel for respiratory viral and bacterial pathogens would reduce the prescribing of antibiotics in acutely ill children.
Upon arrival at an emergency care department, children aged 0 to 17 years with a fever and or respiratory symptoms including tachycardia, shortness of breath, apnoea, were recruited and randomised 2:1 to either multiplex PCR point-of-care testing (which tested for 18 respiratory viruses and 3 bacteria) or usual care, where the patients were only tested using the multiplex system according to the clinical judgement of the treating physician. For the intervention group, the multiplex PCR test results were available within 70 minutes but not until the following day for the control group. The team set the primary outcome as the proportion of children with any antibiotic therapy that was started or on-going in the emergency department. For their secondary outcome, the team compared the number of diagnostic and radiographic imaging procedures undertaken in the two groups.
Multiplex PCR point-of-care testing and antibiotic use
A total of 1243 children were included of whom, 829 with a mean age of 3 years (55.9% male) were randomised to multiplex PCR testing. Among these children, 18.7% had only fever, where as 41.7% had both a fever and respiratory tract symptoms.
A prescription for antibiotics was given to 27.3% of children assigned to the multiplex PCR testing group and 28.5% of those in the control arm (risk ratio, RR = 0.96, 95% CI 0.79 – 1.16).
For the secondary outcome, there were no differences in either the number of diagnostic tests or imaging and overall emergency department costs were similar.
The authors concluded that systematic testing for respiratory pathogens in an emergency department had limited impacted on clinical decision-making over whether or not to prescribe antimicrobial therapy.
Mattila S et al. Effect of Point-of-Care Testing for Respiratory Pathogens on Antibiotic Use in Children: A Randomized Clinical Trial JAMA Netw Open 2022