Effect of Point-of-Care Testing for Respiratory Pathogens on Antibiotic Use in Children

Key Points Question Does point-of-care testing for respiratory pathogens reduce antibiotic use in acutely ill children? Findings In this randomized clinical trial of 1243 children, multiplex polymerase chain reaction point-of-care testing for respiratory pathogens did not reduce the overall prescribing of antibiotics in the emergency department (27.3% in the intervention group vs 28.5% in the control group). Meaning These findings suggest that testing for respiratory pathogens does not reduce antibiotic use in acutely ill children.


Clinical problem
The field of microbiological diagnostics of respiratory infections has changed dramatically in recent years. There are now several multiplex PCR devices on the market which can provide an accurate diagnosis of the respiratory infection as early as within one hour of sampling. The test panels are able to analyze simultaneously about 20 respiratory pathogens. The multiplex PCR devices can be placed in the emergency room as they can also be used by acute care nurses. This means that the treating doctor can have access to the results during the emergency room visit.
Most pediatric infectious disease doctors consider active and rapid point-of-care (POC) diagnostics relevant because accurate diagnosis of the cause of respiratory infections could reduce the use of unnecessary antibiotics and hospitalizations and provide data to help with prognosis assessment. However, the role of diagnostics in improving patient care has been poorly demonstrated, and the equipment and tests are quite expensive. That is why the clinical benefit of a rapid POC diagnostic device placed in the pediatric emergency room must be investigated compared to current practice before the devices are widely adopted.

Study design
In this study, we investigate the effect of a new rapid POC testing device placed in the pediatric emergency room on the treatment of pediatric patients, the onset of treatment with antibiotics and hospitalization rate compared to current treatment, where the test is prescribed by the doctor and the result is interpreted according to standard practice in the hospital laboratory, and is usually available on the morning of the next working day.

MATERIAL AND METHODS
The inclusion criterion for the trial is the presence of respiratory tract symptoms (at least one of the Because the study is a single-center open trial, randomization is done in 2:1 permuted blocks, the 299 size of which varies randomly between 3, 6, and 9. The randomization is done using computer-   Consent that has already been given can be withdrawn at any stage. Pediatric patients who refuse to 373 take part in the trial are treated in the emergency room according to current normal practice and the 374 refusal has no effect on the child's future care. The trial has been granted a favorable opinion by the 375 Ethics Committee of Northern Ostrobothnia Hospital District and a description of the study register 376 will be drawn up. All trial information will be handled confidentially and a separate assessment of 377 privacy risk concerning the study data will be done. The patients' and controls' data is stored in the     The definition for "Pathogen directed therapy" has been specified as follows:

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"defined as antimicrobial therapy directed against detected pathogen with specific treatment       2. The proportion of participants discharged within 90 minutes after admission to emergency 800 room will be compared.

Hypothesis framework 809
For each of the primary and secondary outcomes, the null hypothesis will be that there is no true difference 810 in effect between the intervention arms. 811 812

Sample size 813
The annual number of visits to the pediatric emergency room at Oulu University Hospital is about 4,000-814 5,000; of these, about 50-70% are related to infections. The main outcome measure in the study is the 815 number of antibiotic treatment courses initiated. We estimate that according to current treatment 816 practice, treatment with antibiotics is started in about 25% of acutely sick children with fever in the 817 emergency room at Oulu University Hospital. A relative reduction of 25% in the number of antibiotic 818 treatment courses initiated was estimated as the lowest clinically significant reduction in antibiotic therapy. 819 In the review of Doan et al.
[1] (2014), a 25% reduction in antibiotic therapy and hospital treatment was 820 considered clinically significant as well. 821 822 When the subjects were randomized to groups at a 2:1 ratio, assuming error probability of 0.05 and 823 power (type 1 error) of 0.8, a sample size of 1,062 subjects in the intervention group and 531 in the 824 control group is needed, resulting in a total sample size of 1,593 subjects. In view of dropouts, we will 825 recruit an additional 50 subjects to the new intervention group and 25 subjects to the control group, 826 yielding a total number of 1,668 subjects recruited. Some patients revisit the emergency room and they can be recruited again if the clinical picture has 828 deteriorated significantly or a new illness is suspected, but only first visits are included in the targeted 829 sample size. 830 831 It is estimated that gathering of data will take 12 months, and the trial ends when the full sample size is 832 reached. If the targeted sample size is reached before 12 months, data gathering will continue for a total of 833 12 months to achieve a sample that covers a whole epidemiological year. No interim analyses will be made. The following characteristics will be described separately for patients randomised to each arm. Differences 912 between groups are not tested statistically. 913 914

Completeness of follow-up 915
Loss to follow-up is expected to be minimal as the most of data for primary and secondary outcomes is 916 manually collected from routine clinical data. 917