Trend in antibiotic prescription at pediatric primary emergency medical centers in Japan: A multi-center, cross-sectional study.

INTRODUCTION: Antimicrobial resistance is a global issue, and implementation of antimicrobial stewardship programs in outpatient settings is crucial. Japan has also focused on outpatient oral antimicrobial stewardship programs and difficulties in standardizing prescriptions have led to overprescription in primary emergency medical centers. There is a lack of research investigating the antibiotic prescription status of pediatric primary emergency medical centers and the benchmark prescription rates in pediatric outpatient settings. METHODS: We conducted a multi-center, cross-sectional study of seven pediatric primary emergency medical centers located in five prefectures of Japan. We retrospectively extracted data from health claims or directly obtained them from charts at each institution and evaluated trends in the antibiotic prescription rate based on the AWaRe classification between April 2016 and December 2019. RESULTS: Our study included 383,525 encounters, with the most common infectious disease diagnosis being acute upper respiratory tract infection in 93,449 cases (24.4 %). The antibiotic prescription rate during the study period was 7.4 %, representing a decrease of 46 %, from 10.2 % in 2016 to 5.5 % in 2019. The percentage of prescriptions in the Access group increased at all institutions; however, it exceeded 60 % in only three facilities in 2019. The percentage of third-generation cephalosporins varied among facilities, ranging from 1.7 % to 59.4 %, as of 2019. CONCLUSIONS: For pediatric primary emergency medical centers where antimicrobial stewardship programs are implemented, we suggest 5 % as a reasonable benchmark level for the antibiotic prescription rate. Prescribing the antibiotics in the Access groups less frequently remains a domestic challenge in Japan.

Complicated Acute Pericarditis and Peripheral Venous Catheter-Related Bloodstream Infection Caused by Methicillin-Resistant Staphylococcus aureus after Influenza B Virus Infection: A Case Report.

Background: In this study, we report the case of a 14-month-old female patient transferred from another hospital to our hospital with a 9-day history of fever and worsening dyspnea. Case Report. The patient tested positive for influenza type B virus 7 days before being transferred to our hospital but was never treated. The physical examination performed at presentation revealed redness and swelling of the skin at the site of the peripheral venous catheter insertion performed at the previous hospital. Her electrocardiogram revealed ST segment elevations in leads II, III, aVF, and V2-V6. An emergent transthoracic echocardiogram revealed pericardial effusion. As ventricular dysfunction due to pericardial effusion was not present, pericardiocentesis was not performed. Furthermore, blood culture revealed methicillin-resistant Staphylococcus aureus (MRSA). Thus, a diagnosis of acute pericarditis complicated with sepsis and peripheral venous catheter-related bloodstream infection (PVC-BSI) due to MRSA was made. Frequent bedside ultrasound examinations were performed to evaluate the outcomes of the treatment. After administering vancomycin, aspirin, and colchicine, the patient's general condition stabilized. Conclusions: In children, it is crucial to identify the causative organism and provide appropriate targeted therapy to prevent worsening of the condition and mortality due to acute pericarditis. Moreover, it is important to carefully monitor the clinical course for the progression of acute pericarditis to cardiac tamponade and evaluate the treatment outcomes.

Acetaminophen-induced Stevens-Johnson syndrome with lethal lung injury: A case report.

Stevens-Johnson syndrome (SJS) with respiratory distress can lead to fatal outcomes. However, there are a few reports of drug-induced lung injury with diffuse alveolar damage caused by acetaminophen, the most severe type. Here, we describe a fatal case of acetaminophen-induced SJS in a child with irreversible lung lesions.

Two-Year Seroprevalence Surveys of SARS-CoV-2 Antibodies among Outpatients and Healthcare Workers in Ehime, Japan.

We conducted two-year seroprevalence surveys of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies among outpatients and healthcare workers (HCWs) at Ehime University Hospital. Data were collected for outpatients and HCWs in June 2020 (1st survey), December 2020 (2nd survey), July 2021 (3rd survey), and December 2021 (4th survey), focusing on demographics, occupation, and the seroprevalence of anti-SARS-CoV-2 antibodies. Blood samples were obtained from randomly selected outpatients who visited our hospital for medical care and HCWs undergoing regular medical checks with opt-out informed consent. SARS-CoV-2 antibody positivity was evaluated using two laboratory-based quantitative tests. The total number of participants enrolled was 6,369 (1st survey: 1,000 outpatients and 743 HCWs, 2nd survey: 1,000 outpatients and 407 HCWs, 3rd survey: 1,000 outpatients and 804 HCWs, 4th survey: 1,000 outpatients and 415 HCWs). The prevalence of SARS-CoV-2 antibodies among outpatients and HCWs was 0-0.1% and 0-0.124% during the research period, respectively, and changed little over time. These findings suggest that the magnitude of COVID-19 infection during the pandemic among outpatients and HCWs in this rural hospital might have been small.

Rothia mucilaginosa Meningitis in a Child with Myelodysplastic Syndromes.

Rothia mucilaginosa is a Gram-positive coccus and an opportunistic pathogen in immunocompromised hosts. The microorganism has been implicated in serious infections, including bacteremia meningitis or endocarditis. However, there is a dearth of investigations on meningitis, especially in children. As this infection is rare and only a few cases have been recorded, evidence-based guidelines for adequate infection treatment are lacking. We herein report the case of a 12-year-old boy with myelodysplastic syndromes (MDS) presenting with a change in mental status who was diagnosed as having febrile neutropenia and bacterial meningitis caused by R. mucilaginosa at 23 days after unrelated cord blood transplant. In our case, the minimum inhibitory concentrations (MICs) of meropenem and vancomycin (VCM) were both ≤1 µg/mL, whereas the MIC of daptomycin (DAP) was 4 µg/mL. The patient was treated with intravenous antimicrobial therapy due to meropenem for 43 days because he had febrile neutropenia. During follow-up, the patient had no neurological complications. We retrospectively reviewed the antimicrobial susceptibility of all R. mucilaginosa isolates (n = 5) from blood or cerebrospinal fluid cultures at our hospital. The MIC of VCM was <0.5 µg/mL for all strains, whereas the MIC of DAP was ≥2 µg/mL for all strains. The MIC of MEPM was >1 µg/mL for one strain. We recommend choosing VCM as the primary treatment for invasive R. mucilaginosa infections until antimicrobial susceptibility results are known, especially in immunocompromised children.

Properties of Staphylococcus lugdunensis in Children.

Background. Staphylococcus lugdunensis is one of the clinically important coagulase-negative staphylococci. The purpose of this study was to elucidate the microbiological features of S. lugdunensis in hospitalized children. Methods. From January 2012 to December 2019, all isolates were retrospectively screened for S. lugdunensis. Results. Twenty-five children were eligible for study. Nineteen and six children were classified into a critical care unit group (Group A) and a general medical ward group (Group B), respectively. The prevalence of methicillin-resistant S. lugdunensis was significantly higher in Group A than in Group B (68.4% vs 0%; P < .01). Eleven children (44%) had S. lugdunensis infections, while the remaining children were colonized. Six of the 11 infected children (55%) had healthcare-associated infections. Moreover, 3 isolates exhibited the methicillin resistance. Conclusions. The bacteriological characteristics of S. lugdunensis differ depending on patient background. Selection of antibiotic treatment should in part rely on patient background data.

A Catheter-Related Bloodstream Infection by Brevibacterium casei in a Child with Acute Myeloid Leukemia: Case Report and Literature Review.

The most common organisms isolated from pediatric catheter-related bloodstream infections (CRBSIs) are Gram-positive cocci, such as coagulase-negative staphylococci and Staphylococcus aureus. There are few formal reports of Brevibacterium casei infection and even fewer reports of CRBSI due to this Gram-positive rod. Here we report the first case of CRBSI due to B. casei in an 8-year-old girl with acute myeloid leukemia in Japan. The isolate exhibited decreased susceptibility to ß-lactam antibiotics. Antimicrobial therapy with meropenem and vancomycin, in addition to the removal of central venous catheter line, consequently led to a significant clinical improvement of the patient's symptoms. A literature review found available clinical courses in 16 cases (4 pediatric cases including our case) of B. casei infection. Our case and those in literature suggested that B. casei infection often occurs in patients with indwelling central venous catheters; the literature review further suggested that removal of central venous catheters is required in most cases. Special attention should be paid to the detection of opportunistic infections due to Brevibacterium spp. in immunocompromized children who are using a central venous catheter.

Efficacy of bezafibrate for preventing myopathic attacks in patients with very long-chain acyl-CoA dehydrogenase deficiency.

BACKGROUND: Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a mitochondrial fatty acid oxidation disorder that causes episodic attacks, such as general fatigue, hypotonia, myalgia, and rhabdomyolysis accompanied by lack of energy. As yet, there are no preventative drugs for these VLCADD-associated metabolic attacks. PATIENTS AND METHODS: We conducted an open-label, non-randomized, multi-center study into the effects of bezafibrate on five patients with VLCADD. Bezafibrate was administered for 4 years, and we analyzed the number of myopathic attacks requiring hospitalization and treatment infusions. RESULTS: The number of myopathic attacks requiring infusions of 24 h or longer significantly decreased during the study period. The patients' ability to conduct everyday activities was also improved by the treatment. CONCLUSION: Our findings show the potential long-term efficacy of bezafibrate in preventing myopathic attacks for patients with VLCADD.

A novel SOX10 variant in a Japanese girl with Waardenburg syndrome type 4C and Kallmann syndrome.

We report the first case of Waardenburg syndrome type 4C and Kallmann syndrome in the same person. The patient, a Japanese girl, presented with bilateral iris depigmentation, bilateral sensorineural hearing loss, Hirschsprung disease, hypogonadotropic hypogonadism, and anosmia. We identified a novel SOX10 variant, c.124delC, p.Leu42Cysfs*67.

Malignant Ovarian Steroid Cell Tumor, Not Otherwise Specified, Causes Virilization in a 4-Year-Old Girl: A Case Report and Literature Review.

We report a case of a 4-year-old girl with an ovarian steroid cell tumor, not otherwise specified (SCT-NOS). She was admitted to the hospital with progressing virilization and Cushing's syndrome, which included abnormality of the perineum, hirsutism, hypertrichosis, flushing of face, hoarseness, and weight gain. Blood testing showed a significantly increased testosterone level and slightly increased cortisol level. Computed tomography scan revealed an 8.0 × 5.0 × 5.0 cm tumor of the right ovary. The patient underwent right salpingo-oophorectomy, and pathological examination showed malignant potential. Three courses of bleomycin, etoposide, and cisplatin were administered as postoperative chemotherapy. After tumor resection, her testosterone decreased to undetectable levels. However, during the course of the treatment, the patient suffered from adrenal insufficiency resulting in the need for hydrocortisone replacement therapy. Although SCT-NOS in childhood are typically benign, pathological findings should be carefully observed for potential malignancy. In cases of cortisol-producing SCT-NOS, serum levels should be monitored, and hydrocortisone replacement therapy should be considered before resection.

Incidence and Antimicrobial Susceptibilities of Mycoplasma hominis in Pregnant Females, Ehime University Hospital.

OBJECTIVE: Mycoplasma hominis usually colonizes the lower urogenital tract and has been occasionally associated with pelvic inflammatory disease, postpartum fever, preterm labor in pregnant females. The aim of this study was to investigate the incidence and antimicrobial susceptibilities of M. hominis isolated from the urogenital tracts of pregnant females. METHODS: Specimens were obtained from the urogenital tract of pregnant females at Department of Obstetrics and Gynecology, Ehime University Hospital, between November 2014 and December 2017. The identification of M. hominis was confirmed by the polymerase chain reaction (PCR) methods. The minimum inhibitory concentrations (MICs) of antibiotics were measured using a broth microdilution assay. RESULTS: Of the 1074 specimens tested, 63 (5.9%) were positive for M. hominis. The M. hominis-positive rate was highest at 21.3% between 18 and 24 years old. The 21 (25.6%) of 82 patients with bacterial vaginosis were positive for M. hominis. The 17 (40.5%) of 42 patients delivered by cesarean section that occurred infections including of intrauterine infection and pelvic abscess were positive for M. hominis. They were all administered ß-lactam antibiotics before and after cesarean section. All patients recovered immediately following administration of clindamycin (CLDM). ß-lactam antibiotics, macrolides and fosfomycin (FOM) were all resistant against M. hominis strains. In contrast, M. hominis strains were susceptible to CLDM, minocycline (MINO) and quinolones. CONCLUSIONS: Our data suggests that the prevalence of genital M. hominis in pregnant females is high at younger age, bacterial vaginosis and infections after cesarean section with ß-lactam antibiotics administration. CLDM, MINO and quinolones may be recommended against M. hominis infection. Especially, CLDM can be used as the adequate agent for pregnant females because tetracycline and quinolones are undesirable during pregnancy and lactation.

Brain Abscess Associated with Polymicrobial Infection after Intraoral Laceration: A Pediatric Case Report.

Brain abscesses, infections within the brain parenchyma, can arise as complications of various conditions including infections, trauma, and surgery. However, brain abscesses due to polymicrobial organisms have rarely been reported in children. We herein report a case of a 9-year-old girl with unresolved congenital cyanotic heart disease (CCHD) presenting with right hemiplegia who was diagnosed with brain abscess caused by Streptococcus intermedius, Parvimonas micra, and Fusobacterium nucleatum after oropharyngeal injury. She was treated with intravenous antimicrobial therapy, drainage under craniotomy, and antiedema therapy with glycerol and goreisan, which led to the improvement of right hemiplegia to baseline; she was discharged following eight weeks of intravenous antimicrobial therapy. The clinical diagnosis of the brain abscess was difficult due to the nonspecific presentation, highlighting the importance of cranial imaging without haste in patients at increased risk for brain abscesses such as those with CCHD, presenting with fever in the absence of localizing symptoms or fever, accompanied with abnormal neurological findings.

Clinical course in a patient with myopathic VLCAD deficiency during pregnancy with an affected baby.

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive mitochondrial fatty acid oxidation disorder that manifests in three clinical forms: (a) severe, (b) milder, and (c) myopathic. Patients with the myopathic form present intermittent muscular symptoms such as myalgia, muscle weakness, and rhabdomyolysis during adolescence or adulthood. Here, the clinical symptoms and serum creatine kinase (CK) levels of a pregnant 31-year-old woman with the myopathic form of VLCAD deficiency were reduced during pregnancy. Clinical symptoms rarely appeared during pregnancy, although she had sometimes suffered from muscular symptoms before pregnancy. When ritodrine was administered for threatened premature labor at 35 weeks of gestation, her CK level was elevated to over 3900 IU/L. She delivered a full-term baby via cesarean section but suffered from muscle weakness with elevated CK levels soon after delivery. It has been reported that an unaffected placenta and fetus can improve maternal ß-oxidation during pregnancy. However, in our case, the baby was also affected by VLCAD deficiency. These suggest that the clinical symptoms of a woman with VLCAD deficiency might be reduced during pregnancy even if the fetus is affected with VLCAD deficiency.

Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan; 2nd report QOL survey.

INTRODUCTION: Fatty acid oxidation disorders (FAODs) are rare diseases caused by a defective mitochondrial fatty acid oxidation (FAO) enzyme. We recently reported that bezafibrate improved patient quality of life (QOL) based on the SF-36 questionnaire score in patients with FAODs during a 50-week, open-label, clinical trial. Herein we conducted further survey assessments of the trial patients to define the long-term efficacy and safety of bezafibrate. MATERIALS AND METHODS: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in five patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and one patient with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 15.9 years; range, 5.8-26.4 years). The bezafibrate administration was continued for a further 102-174 weeks after the 24-week treatment described in our previous study. QOL was quantitated using the 36-Item Short Form Health Survey (SF-36) questionnaire, which constitutes eight components: physical functioning (PF), role limitation due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitation due to emotional problems, and mental health. RESULTS: PF was elevated in all patients and continued to rise during the study, with the total QOL scores increased from baseline in five of the six cases. In particular, three patients older than 20 years showed treatment efficacy, and all subcategories of QOL were elevated in two of these cases. CONCLUSION: Our findings supported one of the stated benefits of bezafibrate in improving QOL for patients with FAODs.

Mesenchymal Stem Cell Therapy Overcomes Steroid Resistance in Severe Gastrointestinal Acute Graft-Versus-Host Disease.

The authors describe the high effectiveness of human mesenchymal stem cell (hMSC) therapy to treat steroid-refractory gastrointestinal acute graft-versus-host Disease (aGVHD) in a 15-year-old boy with acute lymphoblastic leukemia (ALL). He received allogeneic hematopoietic stem cell transplantation due to high-risk hypodiploid ALL. Around the time of engraftment, he developed severe diarrhea following high-grade fever and erythema. Although methylprednisolone pulse therapy was added to tacrolimus and mycophenolate mofetil, diarrhea progressed up to 5000~6000 ml/day and brought about hypocalcemia, hypoalbuminemia, and edema. Daily fresh frozen plasma (FFP), albumin, and calcium replacements were required to maintain blood circulation. After aGVHD was confirmed by colonoscopic biopsy, MSC therapy was administered. The patient received 8 biweekly intravenous infusions of 2×106 hMSCs/kg for 4 weeks, after which additional 4 weekly infusions were performed. A few weeks after initiation, diarrhea gradually resolved, and at the eighth dose of hMSC, lab data improved without replacements. MSC therapy successfully treated steroid-refractory gastrointestinal GVHD without complications. Despite life-threatening diarrhea, the regeneration potential of children and adolescents undergoing SMC therapy successfully supports restoration of gastrointestinal damage. Even with its high treatment costs, SMC therapy should be proactively considered in cases where young patients suffer from severe gastrointestinal GVHD.

Nonocclusive Mesenteric Ischemia Rescued by Immediate Surgical Exploration in a Boy with Severe Neurodevelopmental Disability.

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI) defines acute mesenteric ischemia without occlusion of the mesenteric arteries. The most common cause of NOMI is vasoconstriction or vasospasm of a mesenteric artery. NOMI generally affects patients >50 years of age, and few cases have been reported in children. CASE PRESENTATION: A 15-year-old boy with severe neurodevelopmental disability developed sudden-onset fever, abdominal distention, and dyspnea. Laboratory and radiological findings indicated acute intestinal obstruction and prerenal failure. He developed transient cardiopulmonary arrest and hypovolemic shock. Emergent laparotomy was performed, which revealed segmentally necrotic intestine from the jejunum to the ascending colon with pulsation of peripheral intestinal arteries, leading to a diagnosis of NOMI. The necrotic intestine was resected, and stomas were created. He was discharged on postoperative day 334 with short bowel syndrome as a complication. CONCLUSIONS: NOMI should be considered a differential diagnosis for intestinal symptoms with severe general conditions in both adults and children with underlying disease. Immediate surgical exploration is essential with NOMI to save a patient's life.

Prolonged adrenal insufficiency after high-dose glucocorticoid in infants with leukemia.

Although outcomes for infant leukemia have improved recently, transient adrenal insufficiency is commonly observed during treatment, especially after glucocorticoid administration. We identified three infants with acute leukemia who suffered from prolonged adrenal insufficiency requiring long-term (from 15 to 66 months) hydrocortisone replacement. All infants showed life-threatening symptoms associated with adrenal crisis after viral infections or other stress. Severe and prolonged damage of hypothalamo-pituitary-adrenal (HPA) axis is likely to occur in early infants with leukemia, therefore routine tolerance testing to evaluate HPA axis and hydrocortisone replacement therapy are recommended for infants with leukemia to avoid life-threatening complications caused by adrenal crisis.

Sepsis and Pleural Empyema Caused by Streptococcus pyogenes after Influenza A Virus Infection.

Streptococcus pyogenes (also referred to as group A streptococci, GAS) causes severe invasive diseases such as bacteremia, necrotizing fasciitis, pneumonia, osteomyelitis, septic arthritis, and toxic shock syndrome in children. However, there are only a few reports on pleural empyema caused by GAS in children. Here, we report the case of a 4-year-old boy who presented with pleural empyema due to GAS after influenza A virus infection. With intravenous antibiotic administration and continuous chest-tube drainage, followed by video-assisted thoracoscopic surgery, his condition improved. During the clinical course, cytokines induced in response to the influenza virus, especially IL-1ß and IL-10, were elevated 1 week after influenza A infection, but these decreased as the symptoms improved. Reportedly, the IL-10 production increases during influenza virus-bacteria superinfection. These observations suggest that the immunological mechanisms induced by the influenza virus can play an important role in influencing the susceptibility to secondary bacterial infections, such as GAS, in children.