Duration of PCR positivity by type of respiratory virus among children using a multiplex PCR test.

Prolonged positive polymerase chain reaction (PCR) results, irrespective of the transmission risk, can lead to prolonged restrictions on daily activities and infection precaution interventions. Studies evaluating the duration of PCR positivity for multiple pathogens in a single patient cohort are scarce. This study aimed to evaluate and compare the durations of PCR positivity for multiple respiratory viruses among children and adolescents. This retrospective study was conducted between April 2018 and March 2024 using a multiplex PCR respiratory panel for symptomatic children and adolescents who had at least two tests within 90 days of study period, with the first PCR test positive. The rate and likelihood of persistent PCR positivity were evaluated for multiple respiratory viruses. For 1325 positive results, repeat tests were conducted within 90 days. The persistent PCR positivity rate at repeat testing decreased over time (60.6%, Days 1-15 and 21.7%, Days 76-90, after the first test). In multivariate logistic regression analysis, an increased likelihood of persistent PCR positivity was observed for rhinovirus/enterovirus and adenovirus, whereas decreased likelihood of persistent positivity was seen in influenza and seasonal coronaviruses, compared with parainfluenza viruses. Persistent PCR positivity is common for multiple respiratory viruses in symptomatic children.

Biallelic loss-of-function variants of EZH1 cause a novel developmental disorder with central precocious puberty.

Pathogenic variants of polycomb repressive complex-2 (PRC2) subunits are associated with overgrowth syndromes and neurological diseases. EZH2 is a major component of PRC2 and mediates the methylation of H3K27 trimethylation (H3K27me3). Germline variants of EZH2 have been identified as a cause of Weaver syndrome (WS), an overgrowth/intellectual disability (OGID) syndrome characterized by overgrowth, macrocephaly, accelerated bone age, intellectual disability (ID), and characteristic facial features. Germline variants of SUZ12 and EED, other components of PRC2, have also been reported in the WS or Weaver-like syndrome. EZH1 is a homolog of EZH2 that interchangeably associates with SUZ12 and EED. Recently, pathogenic variants of EZH1 have been reported in individuals with dominant and recessive neurodevelopmental disorders. We herein present sisters with biallelic loss-of-function variants of EZH1. They showed developmental delay, ID, and central precocious puberty, but not the features of WS or other OGID syndromes.

Pharmacokinetic Models Scaled-up from Humanized-liver Mouse Data Can Account for Drug Monitoring Results of Atomoxetine and Its 4-Hydroxylated and N-Demethylated Metabolites i n Pediatric Patients Genotyped for Cytochrome P450 2D6.

Atomoxetine is a cytochrome P450 (P450) 2D6 probe substrate and an approved medicine for attention-deficit/hyperactivity disorder. In this humanized-liver mouse study, interactions between atomoxetine and the P450 2D6 probe drug paroxetine were observed. Human physiologically based pharmacokinetic (PBPK) models were established by scaling up humanized-liver mouse data obtained in the absence or presence of paroxetine. These models could explain the drug monitoring results of atomoxetine and its primary 4-hydroxylated and N-demethylated metabolites in Japanese children aged 8-14 years and could be used to help establish the correct dosage and for the evaluation of clinical outcomes. The results of simple PBPK models (using input parameters that reflected the subjects' small body size and normal or reduced P450 2D6-dependent clearance) were in general agreement with one-point measured plasma concentrations of atomoxetine and its 4-hydroxylated and N-demethylated metabolites in 13 pediatric participants. Unexpectedly high hepatic exposure, possibly in intermediate-metabolizer patients harboring CYP2D6*10 or 2D6*36 alleles, might in part explain the adverse effects of atomoxetine prescribed alone recorded in a Japanese adverse-event database. The steady-state, one-point drug monitoring data from the participants indicated extensive biotransformation of atomoxetine to 4-hydroxyatomoxetine under individually prescribed doses of atomoxetine. These results also suggest that a relatively narrow range of 4-hydroxyatomoxetine and N-desmethylatomoxetine concentration ratios in spot urine and/or plasma samples from pediatric patients could be a simple semiquantitative determinant factor for P450 2D6 intermediate metabolizers, compared with the wide range of concentrations of the two primary metabolites and substrate in extensive metabolizers. Significance Statement Validated simple pharmacokinetic models are able to predict steady-state plasma concentrations of the approved medicine atomoxetine and its primary metabolites in the majority of pediatric patients. The package insert advises careful dose escalation, especially for poor metabolizers; however, no simple way exists to determine P450 2D6 phenotypes. A relatively narrow range ratio of 4-hydroxyatomoxetine and N-desmethylatomoxetine in spot urine/plasma samples could be a simple semi-quantitative determinant factor for P450 2D6 intermediate metabolizers to optimize or confirm the correct dosage.

The impact analysis of a multiplex PCR respiratory panel for hospitalized pediatric respiratory infections in Japan.

BACKGROUND: Rapid molecular diagnosis of infections has contributed to timely treatments and antimicrobial stewardship. However, the benefit and cost-effectiveness vary in each country or community because they have different standard practices and health care systems. In Japan, rapid antigen tests (RATs) have been frequently used for pediatric respiratory infections. We investigated the impact and cost-effectiveness of a multiplex PCR (mPCR) respiratory panel for pediatric respiratory infections in a Japanese community hospital. METHODS: We replaced RATs with an mPCR respiratory panel (FilmArray®) for admitted pediatric respiratory infections on March 26, 2018. We compared the days of antimicrobial therapy (DOT) and length of stay (LOS) during the mPCR period (March 2018 to April 2019) with those of the RAT period (March 2012 to March 2018). RESULTS: During the RAT and mPCR periods, 1132 and 149 patients were analyzed. The DOT/case was 12.82 vs 8.56 (p < 0.001), and the LOS was 8.18 vs 6.83 days (p = 0.032) in the RAT and mPCR groups, respectively. The total costs during admissions were ∖258,824 ($2331.7) and ∖243,841 ($2196.8)/case, respectively. Pathogen detection rates were 30.2% vs 87.2% (p < 0.001). CONCLUSION: Compared to conventional RATs, the mPCR test contributed to a reduction in the DOT and LOS in a Japanese community hospital for admission-requiring pediatric respiratory infections. However, a proper stewardship program is essential to further reduce the unnecessary usage of antimicrobials.

[A Case of Synchronous Bilateral Neuroendocrine Ductal Carcinoma In Situ].

Neuroendocrine ductal carcinoma in situ(NE-DCIS)is a unique subtype of ductal carcinoma in situ(DCIS)that is not described in the general rules for clinical and pathological recording of breast cancer. NE-DCIS is described as an unusual variant of DCIS in the 2012 World Health Organization(WHO)classification. The chief complaint in NE-DCIS is hemorrhagic nipple discharge. The histological characteristics of NE-DCIS are solid growth of cancer cells with granular and spindle-shaped nuclei. Histologically, NE-DCIS is suggestive of low malignancy but a poor prognosis of neuroendocrine carcinoma of the breast has been reported. The report by Honami et al was the only other report of synchronous bilateral neuroendocrine ductal carcinoma in situ. We report the second case of NE-DCIS diagnosed synchronously in both breasts in a patient who had visited our outpatient clinic with hemorrhagic nipple discharge.

Decreased KLHL3 expression is involved in the pathogenesis of pseudohypoaldosteronism type II caused by cullin 3 mutation in vivo.

BACKGROUND: Pseudohypoaldosteronism type II (PHAII) is a hereditary hypertensive disease caused by mutations in four genes: WNK1, WNK4, Kelch-like3 (KLHL3), and cullin3 (CUL3). Recently, it was revealed that CUL3-KLHL3 E3 ligase complex ubiquitinates WNK1 and WNK4, leading to their degradation, and that a common pathogenesis of PHAII is defective WNK degradation due to CUL3-KLHL3 E3 ligase complex impairment. PHAII-causing CUL3 mutations mediate exon9 skipping, producing a CUL3 protein with a 57-amino acid deletion (Δ403-459). However, the pathogenic effects of KLHL3, an adaptor protein that links WNKs with CUL3, in PHAII caused by CUL3 mutation remain unclear. METHODS: To clarify detailed pathophysiological mechanisms underlying PHAII caused by CUL3 mutation in vivo, we generated and analyzed knock-in mice carrying the same CUL3 exon9 deletion (CUL3WT/Δex9) as that reported in PHAII patients. RESULTS: CUL3WT/Δex9 mice exhibited a PHAII-like phenotype. Interestingly, we confirmed markedly decreased KLHL3 expression in CUL3WT/Δex9 mice by confirming the true KLHL3 band in vivo. However, the expression of other KLHL family proteins, such as KLHL2, was comparable between WT and mutant mice. CONCLUSION: KLHL3 expression was decreased in CUL3WT/Δex9 mice. However, expression levels of other KLHL family proteins were comparable between the wild-type and mutant mice. These findings indicate that the decreased abundance of KLHL3 is a specific phenomenon caused by mutant CUL3 (Δexon9). Our findings would improve our understanding of the pathogenesis of PHAII caused by CUL3 mutation in vivo.

Successful transcatheter arterial antimicrobial and steroid therapy for refractory liver abscess in chronic granulomatous disease: A case report and review of literature.

Hepatic abscess in chronic granulomatous disease (CGD) is very refractory and frequently requires multiple surgeries with frequent morbidities. Although surgical interventions are often required, patients are often not able to have surgery for various reasons. We present the case of a 21-year-old man with recurrent hepatic abscess in CGD. We could not provide surgical interventions due to the lack of a fluid cavity and the patient's refusal, and therefore we administered transcatheter arterial antimicrobial and steroid therapy. He did not have any exacerbation for more than 18 months after the final transcatheter treatment. This is the first reported case of successful transcatheter arterial antimicrobial and steroid therapy for refractory hepatic abscess in CGD. Although the patient's burden and medical cost were not inconsequential, this case shows that the transcatheter arterial antimicrobial and steroid therapy may be a treatment option for patients who are not candidates for surgical interventions.

Questionnaire survey on mumps vaccination for parents in Nara prefecture, Japan.

BACKGROUND: Although the mumps vaccine has not been included in the national immunization program (NIP) in Japan, it has been shown that a two-dose routine vaccine program would be highly cost-effective. In this study, we carried outa questionnaire-based study to investigate how many Japanese parents want the mumps vaccine to be included in the NIP with proper information. METHODS: The questionnaire was given to parents who visited the Pediatrics or neonatal intensive care unit of Nara Prefecture General Medical Center, Nara City, Japan, between 1 March 2017 and 31 August 2017. The questionnaire consisted of information about mumps and six questions, for example (i) do parents know that mumps can be prevented by vaccine; (ii) do they know that they need to pay for mumps vaccines; and (iii) do they hope that the government will resume routine mumps vaccination. RESULTS: In total, 1,224 parents answered the questionnaire. A total of 81% and 75.4% of parents knew that mumps can be prevented by vaccination and that mumps vaccine is not included in the NIP, respectively, before reading the information. After reading the information, 95.0% of parents thought that mumps vaccine should be included in the NIP. While 61.7% of parents answered that they would choose two-dose vaccination without governmental financial support, 92.1% of them would choose two-dose vaccination with governmental financial support (P < 0.0001). CONCLUSION: Japanese parents want the mumps vaccine to be included in the NIP. Japan is able to start routine use of the mumps vaccine now.

[Acute Urinary Retention Caused by Acute Disseminated Encephalomyelitis : A Case Report].

An 11-year-old boy was referred to our department with the chief complaint of acute urinary retention. He had had a history of viral enteritis a few days before the onset of dysuria. He presented with a slight fever, mild headache and weakness of the extremities. A cerebrospinal fluid examination showed the elevation of cell number (cell number : 158/3, polynuclear cells : 29/3, and mononuclear cells : 129/3). Although spinal magnetic resonance imaging (MRI) did not show abnormal findings, fluid attenuated inversion recovery (FLAIR) image of the brain MRI showed a high signal area on the cerebral cortex. Acute disseminated encephalomyelitis (ADEM) was suspected from the clinical course, the cerebrospinal fluid examination, and brain MRI findings. A urethral catheter was indwelled for urinary retention, and steroid pulse therapy was promptly started. After removal of the urethral catheter seven days after the therapy initiation, normal urination without residual urine was observed. Findings of a cerebrospinal fluid test and brain MRI also showed improvement.

[A Case of Encapsulated Papillary Carcinoma of the Breast].

An 84-year-old woman was revealed to have focal asymmetric density(FAD)based on mammography, and ultrasonography showed a 0.5 cm sized cyst in the left breast. It gradually increased in size and contained solid components. A core needle biopsy revealed an intracystic papillary carcinoma of the breast. Partial mastectomy and sentinel lymph node biopsy were performed. Histopathological examination revealed an encapsulated papillary carcinoma and a papillary lesion surrounded by a thick fibrous capsule. Myoepithelial cells were not found at the periphery of the lesion or within fibrovascular cores. Currently, it is classified as non-invasive carcinoma, and the patient has a good prognosis.

[A Case of Occult Breast Cancer].

We report a case of occult breast cancer. A 61-years-old woman underwent tumorectomy of right axillary mass. Pathological diagnosis was adenocarcinoma. Two years after, right axillary mass was discovered again. Wide local excision, axillary lymph node dissection and radiation therapy of the breast was performed. Pathological findings showed lymph node metastasis of breast cancer, or primary cancer of the axially tail of the breast. Ten months after second operation, she presented an axillary mass again. She underwent resection of the axillary tumor. The pathological findings showed lymph node metastasis of breast cancer. There was no evidence of primary tumor of the breast during the period. We suspected lymph node metastasis of occult breast cancer. Irradiation was administered to the right axilla, and she is receiving endocrine therapy.

[A Case of Breast Carcinoma Associated with Osteoclast-Like Giant Cells].

Mammary carcinoma with osteoclast-like giant cells is uncommon, and its onset mechanism and malignancy are unknown. We report a case of mammary carcinoma with osteoclast-like giant cells. A 41-year-old woman noticed a lump in her left breast. Ultrasound sonography findings suggested breast cancer. A core needle biopsy revealed invasive ductal carcinoma of the breast. Modified radicalmastectomy and sentinell ymph node biopsy were performed. Histopathologicalexamination revealed papillotubular carcinoma with osteoclast-like giant cells. Cells were positive for estrogen receptor and progesterone, and negative for HER2. MIB-1 index was under 5%. The giant cells were generally associated with an inflammatory, fibroblastic, hyper-vascular stroma. The carcinomatous part of the lesion was most frequently a well-to moderately differentiated invasive ductalcarcinoma. Immunohistochemicaland ultrastructuralstudies suggested that the osteoclast-like giant cells were of stromalhistiocytic origin. To understand biochemicalfindings of this carcinoma, more case studies are required to be reported.

[A Case of Axillary Arterial Bleeding after Axillary Metastatic Lymph Node Necrosis during Treatment with Paclitaxel and Bevacizumabfor Breast Cancer].

A 44-year-old woman was diagnosed cT4bcN3cM1(LYM), Stage IV triple-negative breast cancer.Enhanced computed tomography revealed ipsilateral axillary lymph node metastasis, 10 cm in diameter.The supraclavicular and cervical lymph nodes also had metastases.She received paclitaxel(90mg/m2, on days 1, 8, and 15 every 4 weeks)in combination with bevacizumab(10mg/kg, on days 1 and 15 every 28 days).Her height was 165 cm, and her body weight was 100 kg.After 1 course of chemotherapy, a metastatic axillary lymph node with necrotic changes was removed spontaneously.A few days later, she experienced severe bleeding from her axillary artery, and she went into hypovolemic shock.Despite undergoing surgical hemostasis, the bleeding recurred twice, so we performed coil embolization of her subclavian artery.Thirty -five days after the first occurrence of bleeding, the patient died of sepsis and ARDS due to left arm necrosis.Bevacizumab is effective for the treatment of large tumors, but when the tumor is close to an artery, clinicians should be wary of fatal bleeding after necrosis.

Co-expression of S100A14 and S100A16 correlates with a poor prognosis in human breast cancer and promotes cancer cell invasion.

BACKGROUND: S100 family proteins have recently been identified as biomarkers in various cancers. Of this protein family, S100A14 and S100A16 are also believed to play an important role in tumor progression. The aim of the present study was to clarify the clinical significance and functional role of these molecules in breast cancer. METHODS: In a clinical study, an immunohistochemical analysis of S100A14 and S100A16 expression in archival specimens of primary tumors of 167 breast cancer patients was performed. The relationship of S100A14 and S100A16 expression to patient survival and clinicopathological variables was statistically analyzed. In an experimental study, the subcellular localization and function of these molecules was examined by using the human breast cancer cell lines MCF7 and SK-BR-3, both of which highly express S100A14 and S100A16 proteins. Cells transfected with expression vectors and siRNA for these genes were characterized using in vitro assays for cancer invasion and metastasis. RESULTS: Immunohistochemical analysis of 167 breast cancer cases showed strong cell membrane staining of S100A14 (53% of cases) and S100A16 (31% of cases) with a significant number of cases with co-expression (p < 0.001). Higher expression levels of these proteins were significantly associated with a younger age (<60 years), ER-negative status, HER2-positive status and a poorer prognosis. Co-expression of the two proteins showed more aggressive features with poorer prognosis. In the human breast cancer cell lines MCF7 and SK-BR-3, both proteins were colocalized on the cell membrane mainly at cell-cell attachment sites. Immunoprecipitation and immunofluorescence analyses demonstrated that the 100A14 protein can bind to actin localized on the cell membrane in a calcium-independent manner. A Boyden chamber assay showed that S100A14 and S100A16 knockdown substantially suppressed the invasive activity of both cell lines. Cell motility was also inhibited by S100A14 knockdown in a modified dual color wound-healing assay. CONCLUSIONS: To our knowledge, this is the first report showing the correlation of expression of S100A14, S100A16, and co-expression of these proteins with poor prognosis of breast cancer patients. In addition, our findings indicate that S100A14 and S100A16 can promote invasive activity of breast cancer cells via an interaction with cytoskeletal dynamics. S100A14 and S100A16 might be prognostic biomarkers and potential therapeutic targets for breast cancer.

In vitro selection of a peptide antagonist of growth hormone secretagogue receptor using cDNA display.

G protein-coupled receptors (GPCRs) are major drug targets, and their ligands are currently being explored and developed by many pharmaceutical companies and independent researchers. Class A (rhodopsin-like) GPCRs compose a predominant GPCR family; therefore, class A GPCR ligands are in demand. Growth hormone secretagogue receptor (GHS-R) is a class A GPCR that stimulates food intake by binding to its peptide ligand, ghrelin. Therefore, antagonists of GHS-R are expected to exert antiobesity function. In this article, we describe the use of cDNA display to screen for successfully and identify an antagonistic peptide of GHS-R. The antagonistic peptide inhibited the ghrelin-induced increase in intracellular Ca(2+) in vitro (IC(50) = approximately 10 µM) and repressed the contraction of isolated animal stomach in response to ghrelin. Furthermore, peripheral administration of the peptide inhibited the food intake of mice. This work provides new insight into the development of antiobesity drugs and describes a method for the discovery of unique peptide ligands for class A GPCRs.

Cilostazol treats transient heart failure caused by ATP1A3 variant-associated polymicrogyria.

BACKGROUND: Some patients with ATP1A3 variant-associated polymicrogyria have recurrent transient heart failure. However, effective treatment for the transient cardiac condition remains to be elucidated. CASE REPORT: The patient started experiencing focal motor onset seizures in 12 h after birth, revealing bilateral diffuse polymicrogyria. The patient also experienced transient bradycardia (sinus bradycardia) attacks from 15 days old. Echocardiography revealed a reduced ejection fraction; however, no obvious electrocorticogram or electroencephalogram abnormalities were observed during the attacks. Initially, the attacks occurred in clusters daily. They later decreased in frequency, occurring at monthly intervals. Repeated episodes of transient bradycardia attacks and polymicrogyria indicated possible ATP1A3 gene abnormality and genetic testing revealed a novel heterozygous ATP1A3 variant (NM_152296: exon22:c.2977_2982del:p.(Glu993_Ile994del)), which was not found in the patient's parents. Cilostazol was administered at 3 months old for recurrent transient bradycardia attacks. Cilostazol significantly shortened the duration of bradycardia episodes and prolonged the interval between attacks. Cilostazol also effectively treats transient symptomatic bradycardia. CONCLUSION: Cilostazol could be a treatment option for recurrent transient bradycardia attacks associated with ATP1A3 gene abnormalities and polymicrogyria.

[Successful maintenance hemodialysis therapy with supplemented growth hormone in a diabetic patient with growth hormone insufficiency].

Growth hormone (GH) insufficiency is difficult to identify especially in adults, because its clinical manifestations overlap with metabolic syndrome and diabetes mellitus. We experienced a case of a 38-year-old woman who abruptly gained weight from the age of five, and was diagnosed as type 2 diabetes mellitus (DM) during her 20s. When the patient visited JA Toride Medical Center at age 38, her renal function had been severely damaged, and caused congestive heart failure. Hemodialysis (HD) therapy was introduced, and GH insufficiency was identified, based on her obesity profile since her childhood and hormone surveillance. GH supplementation was initially avoided, because of her concurrent problems of DM and advanced renal failure. However, because of her restricted activities in daily living (ADL) and frequent hypotension episodes, a decision was taken to start supplementary administration of GH, which consequently succeeded in stabilizing blood pressure and extended her ADL. Although GH supplementation has recently been reported to be effective in improving protein energy malnutrition in dialysis patients without GH insufficiency, there is no report concerning GH insufficiency in dialysis patients. This is the first case report of GH insufficiency, in which GH supplementation enabled the patient to continue HD.

CD8+ Regulatory T Cells Induced by Lipopolysaccharide Improve Mouse Endotoxin Shock.

Sepsis is a systemic inflammatory disease caused by a bacterial infection that leads to severe mortality, especially in elderly patients, because of an excessive immune response and impaired regulatory functions. Antibiotic treatment is widely accepted as the first-line therapy for sepsis; however, its excessive use has led to the emergence of multidrug-resistant bacteria in patients with sepsis. Therefore, immunotherapy may be effective in treating sepsis. Although CD8+ regulatory T cells (Tregs) are known to have immunomodulatory effects in various inflammatory diseases, their role during sepsis remains unclear. In this study, we investigated the role of CD8+ Tregs in an LPS-induced endotoxic shock model in young (8-12 wk old) and aged (18-20 mo old) mice. The adoptive transfer of CD8+ Tregs into LPS-treated young mice improved the survival rate of LPS-induced endotoxic shock. Moreover, the number of CD8+ Tregs in LPS-treated young mice increased through the induction of IL-15 produced by CD11c+ cells. In contrast, LPS-treated aged mice showed a reduced induction of CD8+ Tregs owing to the limited production of IL-15. Furthermore, CD8+ Tregs induced by treatment with the rIL-15/IL-15Rα complex prevented LPS-induced body wight loss and tissue injury in aged mice. In this study, to our knowledge, the induction of CD8+ Tregs as novel immunotherapy or adjuvant therapy for endotoxic shock might reduce the uncontrolled immune response and ultimately improve the outcomes of endotoxic shock.

Epidemiology of respiratory tract infections using multiplex PCR in a Japanese acute care hospital during the COVID19 pandemic.

Introduction: We aimed to investigate the epidemiology of respiratory infections by season and age during the COVID-19 pandemic in a Japanese acute care hospital using multiplex PCR testing. Methods: We detected 21 pathogens in specimens from outpatients with respiratory symptoms at the Nara Prefecture General Medical Center using the multiplex PCR-based FilmArray Respiratory Panel 2.1 (bioMérieux). Results: Of the 3177 cases, 1215 (38.2%) were infected with at least one causative virus, and 1641 viruses were detected. The most common viruses detected were human rhinovirus/enterovirus (n = 655) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 264). Additionally, 321 (10.1%) of these cases were infected with two or more overlapping viruses. There were 23 cases of co-infection with SARS-CoV-2 and other viruses. In the winter months from December 2020 to March 2021, the number of detected viruses was relatively low, followed by the surge of human rhinovirus/enterovirus, respiratory syncytial virus (RSV), and parainfluenza type 3 in the spring and summer of 2021. While the number of human rhinovirus/entero-virus remained relatively high after the 2021 summer, the number of other viruses detected since September 2021 was low. After December 2021, the number of SARS-CoV-2 increased rapidly. Conclusions: Continuous monitoring of the epidemiology of respiratory infection is important to understand the prolonged impact of the COVID-19 pandemic.

Impact of the COVID-19 pandemic and multiplex polymerase chain reaction test on outpatient antibiotic prescriptions for pediatric respiratory infection.

This study aimed to evaluate the impact of the prolonged COVID-19 pandemic on outpatient antibiotic prescriptions for pediatric respiratory infections at an acute care hospital in Japan in order to direct future pediatric outpatient antibiotic stewardship. The impact of the COVID-19 pandemic and the FilmArray Respiratory Panel (RP) on outpatient antibiotic prescriptions was assessed from January 2019 to December 2021 using an interrupted time series analysis of children <20 years. The overall antimicrobial prescription rate decreased from 38.7% to 22.4% from the pre-pandemic period to the pandemic. The pandemic (relative risk [RR] level, 0.97 [0.58-1.61]; P = 0.90; RR slope, 1.05 [0.95-1.17] per month; P = 0.310) and FilmArray RP (RR level, 0.90 [0.46-1.75]; P = 0.75; RR slope, 0.95 [0.85-1.06] per month; P = 0.330) had no significant effect on the monthly antibiotic prescription rates. The COVID-19 pandemic was not significantly related to the antibiotic prescription rate, suggesting that it did not impact physicians' behavior toward antibiotic prescriptions. Replacing rapid antigen tests with the FilmArray RP introduced on December 1, 2020, did not affect the magnitude of the reduction in antibiotic prescription rate for pediatric respiratory infections.