Risk factors for liver enzyme elevation with remdesivir use in the treatment of paediatric COVID-19.

AIM: Remdesivir (RDV) causes liver enzyme elevation in adults; however, the frequency of this elevation in children and the associated risk factors are largely unknown. Therefore, we aimed to examine risk factors for liver enzyme elevation in hospitalised paediatric patients who received RDV. METHODS: This was a retrospective case-control study of all patients aged <18 years who were diagnosed with coronavirus disease 2019 and received RDV at a tertiary care hospital between February 2022 and September 2023. Demographic and clinical data were retrieved from the medical records and analysed. Patients with liver enzyme elevation were defined as cases, while those with no liver enzyme elevation were defined as controls. The two groups were compared and analysed for possible risk factors for liver enzyme elevation with RDV use. RESULTS: Sixty-six patients were treated with RDV, 12 (18.2%) of whom developed liver enzyme elevation. Liver enzyme elevation was associated with the median duration of RDV administration (7.5 days vs. 3 days, P = 0.012), median total RDV dose (17.7 mg/kg vs. 10.3 mg/kg, P = 0.017) and acetaminophen use (67% vs. 22%) (odds ratio = 4.34; 95% confidence interval, 1.05-19.97, P = 0.023). All patients showed improvement, except three who had no liver enzyme measurements after having the highest aspartate aminotransferase and alanine aminotransferase values during the observation period. CONCLUSION: Liver enzyme elevation was reversible after discontinuing RDV use. Overall, RDV can be considered safe in children with careful monitoring.

Nosocomial meningitis caused by Staphylococcus haemolyticus in a child with neutropenia in the absence of intracranial devices: a case report.

BACKGROUND: Coagulase-negative staphylococci can cause hospital-acquired infections, especially in immunocompromised hosts. Bacterial meningitis is a potentially fatal infection of the central nervous system, causing high mortality and morbidity. In general, the causative agents of meningitis, coagulase-negative staphylococci, are associated with direct implantation of a foreign body and the presence of a cerebrospinal fluid (CSF) shunt. Here, we describe a case of nosocomial meningitis caused by Staphylococcus haemolyticus in a child with neutropenia who had no intracranial foreign devices. CASE PRESENTATION: A 15-year-old boy with relapsed acute myeloid leukemia undergoing chemotherapy through a central venous catheter developed fever on Day 13 post-initiation of chemotherapy. There was no history of implantation of neurosurgical devices. Two blood cultures obtained on Day 14 were positive for Staphylococcus haemolyticus. Clinical improvement was noted, and treatment with vancomycin and removal of the central venous catheter resulted in negative repeat blood cultures on Day 18. However, the patient developed a tendency for somnolence and improper speech, along with persistent fever on Day 26. A lumber puncture was performed on Day 27, resulting in positive culture of Staphylococcus haemolyticus. He was diagnosed with meningitis and the dosage of vancomycin was increased. A repeat CSF culture was positive for Staphylococcus haemolyticus on Day 40, so oral rifampicin was added. CSF findings on Day 46 revealed a low concentration of vancomycin, and treatment was switched from vancomycin plus rifampicin to linezolid. After Day 46, four subsequent cerebrospinal fluid tests of the CSF showed no growth of Staphylococcus haemolyticus. The patient's symptoms were improved on Day 52. Brain and spinal magnetic resonance images was taken and it showed no abnormalities. Linezolid was continued until Day 72. The patient was discharged without any complications on Day 72. CONCLUSIONS: To the best of our knowledge, this is the first reported case of Staphylococcus haemolyticus meningitis in a patient without a neurosurgical device. Typical symptoms or signs may be absent in a patient with meningitis who also has neutropenia. Repeated tests of the CSF, and prolonged duration of antibiotics should be considered if atypical pathogens are detected in immunocompromised hosts.

Catheter-related bloodstream infection caused by Tsukamurella tyrosinosolvens identified by secA1sequencing in an immunocompromised child: a case report.

BACKGROUND: Tsukamurella spp. are obligate aerobic, gram-positive, non-motile, and slightly acid-fast bacilli belonging to the Actinomycetes family. They share many characteristics with Nocardia, Rhodococcus, Gordonia, and the rapidly growing Mycobacterium species. Therefore, standard testing may misidentify Tsukamurella spp. as another species. Accurate and rapid diagnosis is critical for proper infection management, but identification of this bacterium is difficult in the standard laboratory setting. CASE PRESENTATION: A bloodstream infection caused by a gram-positive bacterium and related to a central venous catheter was identified in an immunocompromised 2-year-old girl. Tsukamurella tyrosinosolvens was identified by modified secA1 sequencing. Antibiotic treatment and removal of the central venous catheter resolved the infection. Inappropriate management of the catheter during an overnight stay outside of the hospital was considered as a possible source of infection. CONCLUSIONS: SecA1 sequencing may be a useful diagnostic tool in the identification of T. tyrosinosolvens. Providing proper central venous catheter care instructions to patients, their families, and medical staff is important for infection prevention.

Treatment optimization by monitoring vancomycin concentration in the serum and cerebrospinal fluid in a child with cystoperitoneal shunt-related infection caused by methicillin-resistant Staphylococcus aureus: a case report and literature review.

BACKGROUND: Cerebral ventricular shunt infections caused by methicillin-resistant Staphylococcus aureus (MRSA), especially strains with elevated minimum inhibitory concentration (MIC) values, have a poor prognosis. Monitoring serum vancomycin (VCM) levels with therapeutic drug monitoring and maintaining high VCM concentrations in the cerebrospinal fluid (CSF) are critical to treatment success. However, there have been a few reports about the CSF penetration and the pharmacokinetics of VCM in children. CASE PRESENTATION: Here, we report the case of a pediatric patient with cysto-peritoneal shunt-related meningitis caused by MRSA with an MIC of 2 µg/mL. The adequate VCM concentration was maintained by monitoring the VCM concentration in the CSF via the external ventricular drain, and frequent blood taking was avoided. VCM showed a good CSF penetration in our patient, and she was discharged without complications. DISCUSSION: Therapeutic drug monitoring of VCM concentration in the CSF may result in successful treatment even if MRSA shows a higher MIC. Therapeutic drug monitoring of VCM concentration in the CSF may also reduce the side effects.

Serologic Evidence of Human Exposure to Ehrlichiosis Agents in Japan.

In retrospective analyses, we report 3 febrile patients in Japan who had seroconversion to antibodies against Ehrlichia chaffeensis antigens detected by using an immunofluorescence and Western blot. Our results provide evidence of autochthonous human ehrlichiosis cases and indicate ehrlichiosis should be considered a potential cause of febrile illness in Japan.

Safety of Remdesivir in 20 Children with COVID-19-Case Series-

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus, has spread worldwide since 2019. Several studies report that adult patients hospitalized with severe COVID-19 can be treated successfully with remdesivir (RDV). However, few studies report the safety and efficacy of RDV for children. This study included 20 hospitalized patients who were diagnosed with COVID-19 and received RDV at Kobe Children's Hospital, Japan, between February and June, 2022. The median age was 2 years (IQR, 1-11 years; range, 5 months to 19 years). Twelve (60%) patients were male. Three (15%) patients were previously healthy, whereas the other 17 had at least one underlying medical condition: five (25%) patients had respiratory disease, four (20%) had cardiac disease, three (15%) had central nervous system disease, four (20%) had hematologic or oncologic disease, and two (10%) had a chromosomal abnormal. All patients recovered without any sequelae, and no serious adverse events were reported. The adverse events were elevated liver enzymes in 4 children (20%), leukopenia (5%), neutropenia (5%), and hypokalemia (5%). Our study may show that the use of RDV for COVID-19 in children led to no serious adverse events.

A case of postpartum thyroiditis following SARS-CoV-2 infection.

Postpartum thyroiditis (PPT) is characterized by mild thyrotoxicosis occurring within one year of parturition commonly followed by transient hypothyroidism. Having genetic background of autoimmune thyroid disorders is a risk factor for it because the immune reactivation during postpartum period is a trigger for PPT. Pandemic of COVID-19: caused by SARS-CoV-2 infection is a global health problem, and occurrence of Graves' disease and Hashimoto's thyroiditis after the viral infection have been reported but occurrence of PPT with COVID-19 has never been reported. A 29-year-old woman developed general fatigue four and a half months after parturition, and was diagnosed as having PPT: one month before, she had COVID-19. Hereafter, we define the date of delivery as Day 0 to make timeline clear. SARS-CoV-2 infection was diagnosed by PCR on Day 103, its disappearance from the upper airway confirmed on Day 124, and the thyroiditis diagnosed on Day 136. She had been euthyroid on Day 0 and 95, but thyrotoxic on Day 136. Serum thyroglobulin (Tg) concentration was normal in the presence of anti-Tg antibody, other thyroid-related autoantibodies were negative, and by ultrasonography, the thyroid gland was normal in size and no evidence of increased vascularity. Thyroid function returned to normal by Day 172 without any specific drug therapy. In conclusion, although a clear causal relationship could not be found, we documented the world's first case of PPT developed following COVID-19.

Clinical Characteristics of Patients With Coronavirus Disease 2019 in Japan: A Single-Center Case Series.

We report a case series of 6 patients with confirmed coronavirus disease 2019 (COVID-19) in Wakayama prefecture, Japan. All 6 of the patients tested positive via pharyngeal swab polymerase chain reaction (PCR) tests, and 2 of the 6 were still positive at 3 weeks after onset. All of the patients exhibited bilateral ground glass opacities on computed tomography (CT). This article also reports narrative information on the spectrum of symptoms collected directly from the patients. It would be difficult to triage patients with COVID-19 based on the typical symptoms of fever and/or cough, although PCR and CT are definitive in diagnosis.

Waterhouse-Friderichsen Syndrome and Central Diabetes Insipidus Due to Escherichia coli Meningitis.

Waterhouse-Friderichsen syndrome and central diabetes insipidus are uncommon but potentially fatal endocrine and metabolic diseases. Waterhouse-Friderichsen syndrome is defined as adrenal insufficiency caused by adrenal hemorrhage, which is typically bilateral and most frequently due to meningococcal infection. It is usually diagnosed by necropsy. Central diabetes insipidus in children is often caused by trauma, intracranial lesions, autoimmune diseases, and infections. In addition, it can be caused by mutations in the AVP-NPII gene, although this occurs typically later in childhood rather than in the neonatal period. This report describes a term infant who developed Escherichia coli meningitis, which resulted in septic shock and disseminated intravascular coagulation. Abdominal ultrasound led to an early diagnosis of bilateral adrenal hemorrhage and appropriate treatment with corticosteroids. Symptomatic central diabetes insipidus developed a few days after the onset of meningitis. Intravenous vasopressin was effective in resolving hemodynamic instability. In conclusion, sepsis and meningitis may have severely affected the endocrine system in this patient. Early diagnosis and appropriate treatment for both diseases may have resulted in better clinical outcomes for this patient.

Hospital burden and characteristics of pediatric COVID-19 based on a multicenter collaborative retrospective study in Japan.

Objectives: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant emergence preceded a wave of pediatric coronavirus disease 2019 (COVID-19) cases, putting considerable strain on hospitals across Japan. Our study evaluated the pediatric disease burden of COVID-19 in pediatric hospitals. Methods: This retrospective study evaluated all pediatric patients (defined as aged < 21 years) hospitalized with SARS-CoV-2 infection, or as close contacts, at four children's hospitals, between January 1 and May 31, 2022. Clinical characteristics, reasons for admission, and outcome data were analyzed. Results: In total, 492 patients (median age 3.0 years; male 58.7%) were included over the study period. Of these, 232 (47.2%) patients had at least one underlying disease. Asymptomatic and mild diseases were common during the study period (n = 451, 91.7%). Social reasons for hospitalization (including a lack of family support at home) accounted for 36.8% (n = 181) of inpatients. The median length of stay was 4.0 days. Fever was the most common symptom (n = 273, 55.5%), followed by upper respiratory (n = 77, 15.7%) and neurological (n = 60, 12.2%) symptoms. Overall, 34 (6.9%) children required invasive mechanical ventilation, 51 (10.4%) were admitted to the pediatric intensive care unit, and two (0.4%) died. COVID-19 vaccination rate was low (n =14/200, 7.0%). Conclusions: The disease burden during the Omicron-predominant period was attributable to asymptomatic and mild infections, and some patients were hospitalized for social reasons. To maintain a medical care system for critically ill patients, each medical facility must play a role according to its function.

Campylobacter jejuni Bacteremia in the Term Infant A Rare Cause of Neonatal Hematochezia.

Early-onset sepsis caused by Gram-negative spiral organisms is rarely reported, with Campylobacter fetus being a better known causative agent than other Campylobacter species. We report the case of a 2-day-old girl who presented with hematochezia and bacteremia caused by Campylobacter jejuni. She was born full-term. Her family ate undercooked chicken, and Campylobacter enteritis was diagnosed before her birth.

Longitudinal analysis of electroencephalography pattern changes in an infant with Schaaf-Yang syndrome and a novel mutation in melanoma antigen L2 (MAGEL2).

BACKGROUND: Schaaf-Yang syndrome (SYS) is a rare hereditary disease caused by truncating point mutations of the paternal allele of melanoma antigen L2 (MAGEL2), one of five protein-coding genes within the Prader-Willi syndrome (PWS) critical domain. SYS shares many clinical and molecular characteristics with PWS but has some distinct features, such as joint contractures and autism. Patients with PWS show abnormal electroencephalography (EEG) patterns. However, there are very few reports on EEG findings in patients with SYS. METHODS: A SYS patient was included in this study. Detailed neurological examinations and EEG were performed from neonate to infant ages. Sanger sequencing was performed. RESULTS: Our patient presented abnormal EEG findings and had diffuse brain dysfunction symptoms including a reduced level of consciousness, diminished spontaneous movements, hypotonia, feeding difficulties, and hypoventilation from early after birth. As she grew older and her background activity of EEG normalized, her neurodevelopmental symptoms remained but improved. Sanger sequencing of this patient revealed a novel, heterozygous c.2005C > T, truncating mutation in the MEGAL2 gene. CONCLUSIONS: We described an SYS-associated, time-dependent, EEG pattern in a patient with SYS. Our findings of longitudinal EEG changes in a patient with SYS revealed a specific pattern of how affected individuals develop brain function.

Case Report: A Domestic Sponge Brush Used to Clean a Milk Feeding Bottle: The Source of Neonatal Meningitis Caused by Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a relatively rare cause of neonatal meningitis, and most patients have serious underlying diseases, prematurity, immunodeficiency, or anatomical abnormalities. We report the case of a 7-day-old girl with meningitis caused by P. aeruginosa. She was born full-term and had no immunodeficiency or anatomical abnormalities as far as our investigation ascertained. Through the use of anti-Pseudomonas antibiotics, she recovered without any complications other than a slight hearing disability revealed by audiology testing. P. aeruginosa was also isolated from a domestic sponge brush used to clean her milk bottle. Physicians should consider P. aeruginosa as a possible pathogen of neonatal meningitis even in full-term infants with no immunodeficiency or anatomical abnormalities. Physicians should give advice concerning appropriate hygiene practices to be applied to the neonate's environment.

Urethral Tuberculosis: A Forgotten Cause of Urethral Stricture.

We describe the clinical features of a 75-year-old man who presented to our hospital with frequent urination for 3 months. Retrograde urethrography showed extended and continuous narrowing of the stricture in the anterior urethra. Cystourethroscopy showed extended narrowing of the urethral lumen without normal membrane. Urine acid-fast bacillus culture and polymerase chain reaction assays indicated a diagnosis of urethral tuberculosis. Anti-tuberculosis therapy was initiated. Urethral tuberculosis is a very rare cause of urethral stricture in developed countries that can be diagnosed by cystourethroscopy. Urethral tuberculosis should be considered in the differential diagnosis of urethral stricture.

Erysipelothrix rhusiopathiae bacteremia following a cat bite.

Erysipelothrix rhusiopathiae is a major causative organism of swine erysipelas, but the infection has rarely occurred in humans. A soft-tissue infection with this organism is described as "erysipeloid." Most reported cases in human are related to occupational exposure. Endocarditis is a common complication of E. rhusiopathiae bacteremia in human. We report the case of a previously healthy 52-year-old Japanese female who presented with fever and an inflamed hand after being bitten by a stray cat. Blood culture was positive for E. rhusiopathiae, but no sign of infective endocarditis was observed. It may be prudent to consider E. rhusiopathiae infection in patients with animal bites.