Pharmacokinetic and Pharmacodynamic Considerations of Novel Antibiotic Agents for Pediatric Infections: A Narrative Review.

Background: Currently, the escalation of microbial resistance poses a significant global challenge. Children are more susceptible to develop infections and therefore are prescribed antibiotics more frequently. The overuse and misuse of antibiotics in pediatric patients can play a considerable role in developing microbial resistance. Accordingly, many policies, including research into new antibiotic agents have been recommended to combat microbial resistance. Recent developments in novel antibiotics have shown promising results against multi-drug resistant (MDR) and extensive drug resistance (XDR) pathogens. However, as pediatric patients are typically excluded from the clinical trials of new medications, labeling and information about approved antibiotics should be improved. This study aimed to evaluate antibiotics having been introduced to the market in the last decade focusing on pediatric population. Methods: This study reviewed the published literatures on novel FDA-approved antibiotics released between 2010 and 2022. Results: Finally, seven newly approved antibiotics including ceftaroline fosamil, ceftazidime-avibactam, ceftolozane-tazobactam, ceftobiprole, imipenem-cilastatin-relebactam, meropenem-vaborbactam, and tedizolid were considered in the present review-article. All relevant data extracted from literatures, were discussed in different subtitles of "Pharmacology", "Mechanism of action", "Indication", "Dosage regimen and pharmacokinetic and pharmacodynamic properties", "Dosage adjustment in renal/liver failure", "Resistance pattern", and "Adverse drug events". Conclusion: This study reviewed available data on seven new antibiotic agents and their pharmacodynamic and pharmacokinetic properties, with a particular focus on their use in pediatric patients. The information presented in this review will be useful for healthcare professionals in selecting appropriate antibiotics for pediatric patients and for researchers in achieving the ideal therapeutic regimens.

Comparing clinical presentation, viremia, and immunological factors at various severity presentations in hospitalized children affected by COVID-19: A cross-sectional study.

Background and Aims: Although SARS-CoV-2 infection usually leads to mild COVID-19 in children, sometimes it causes serious complications, especially in those with underlying diseases. Several factors have been identified in determining disease severity in adults, and limited studies have been conducted in children. The prognostic implications of SARS-CoV-2 RNaemia as an important factor in determining disease severity in children are not well understood. Methods: In this study, we aimed to prospectively assess the relationship between disease severity and immunological factors and viremia in 47 COVID-19 hospitalized children. In this research, 76.5% of children experienced mild and moderate COVID-19, while 23.5% experienced severe and critical forms of the disease. Results: The presence of underlying diseases in different groups of pediatric patients differed significantly from each other. On the other hand, clinical symptoms such as vomiting and chest pain as well as laboratory parameters including erythrocyte sedimentation rate were significantly different in different groups of patients. Viremia was seen in only two children, and this had no significant relationship with the severity of COVID-19. Conclusion: In conclusion, our data confirmed that COVID-19 severity differed in SARS-CoV-2 infected children. Some clinical presentation and lab data parameters were different in various presentation of patients. Viremia was not associated with severity in our study.

Clinical characteristics and outcomes of the multisystem inflammatory syndrome in children (MIS-C) following COVID-19 infection in Iran: A multicenter study.

OBJECTIVES: This study aimed to assess the clinical characteristics, treatment and outcomes of the multisystem inflammatory syndrome in children (MIS-C) following COVID-19 in five different geographical regions of Iran. METHODS: In this multicenter observational study, patients <21 years were included between March 2020 and October 2021. By Disease Control and Prevention (CDC) checklist, demographic characteristics, comorbidities, clinical signs and symptoms, laboratory and radiology findings, and treatment were collected. Statistical analysis was using Chi-square and t-test in STATA14. RESULTS: In total 225 patients with median age of 55 (26-96) months were included that 59.56% boys. 57.33% were admitted to the PICU with a median of 7 days (4-10). 95.56% of patients were discharged with recovery and the rest died. All of the patients in our study were included based on the MIS-C criteria. However, some patients had Kawasaki symptoms, so we compared the clinical and epidemiological characteristics of the two groups. Conjunctival injection, cervical lymphadenopathy>1.5 cm diameter, and strawberry tongue in Kawasaki-like MIS-C patients were higher than of MIS-C patients, and this difference was significant(p<0.001). The most common comorbidity was obesity (24.86%). Most patients tested for COVID-19 and about 60% of the patients had a positive test by serology or reverse transcription-polymerase chain reaction (RT-PCR). Gastrointestinal (88.89%) and hematologic signs (84.44%) were most common. Most drugs used in patients were IVIG and steroids. 88.07% and 61.29% of the patients had at least one problem in echocardiography and lung CT, respectively. CONCLUSIONS: The best outcome was seen in patients who were treated with both IVIG and steroids on the first days of admission. Myocarditis was common in two groups of patients. According to most patients had echocardiography abnormal, screening of heart function is recommended for patients.

Evaluation of the Costs and Outcomes of COVID-19 Therapeutic Regimens in Hospitalized Patients in Shiraz.

COVID-19 patients in critical conditions are hospitalized and treated with various protocols including antiviral drugs, which have been updated repeatedly. This study was aimed to analyze the demographics, costs, and outcomes of drug regimens in COVID-19 patients hospitalized in "Ali Asghar" hospital, affiliated with Shiraz University of Medical Sciences, from March 2019 to December 2020 as a retrospective study, approved by the ethics committee of Shiraz University of Medical Sciences (IR.SUMS.REC.1399.1003) on Dec. 28, 2020. Using hospital information system (HIS) data, 2174 patients receiving favipiravir, remdesivir, interferon-ß, and Kaletra® were analyzed. Descriptive, univariate, and regression analyses were used. The costs and consequences of different drug regimens were significantly different (P value < 0.05); the highest and lowest costs belonged to remdesivir and Kaletra®, respectively. The highest and lowest mean length of stay and mortality were related to remdesivir and favipiravir, respectively. Mortality did not differ significantly with various regimens. Length of stay was significantly shorter with favipiravir and Kaletra® than interferon-ß. Remdesivir had significantly the highest cost. Age presented a significantly positive relationship with mortality and length of stay. Besides, ICU admission significantly increased mortality, length of stay, and costs. Underlying diseases and low blood oxygen saturation contributed to mortality. COVID-19 correlation with age and underlying diseases is accordant with the published data. Given the highest costs and broad usage of remdesivir, besides controversies regarding its outcomes and side effects, a stricter evaluation of remdesivir benefits seems essential. Totally, COVID-19 therapeutic protocols should be selected carefully to optimize costs and outcomes.

Assessment of the HScore as a predictor of disease outcome in patients with COVID-19.

Severe coronavirus disease 2019 (COVID-19) accompanies hypercytokinemia, similar to secondary hemophagocytic lymphohistiocytosis (sHLH). We aimed to find if HScore could predict disease severity in COVID-19. HScore was calculated in hospitalized children and adult patients with a proven diagnosis of COVID-19. The need for intensive care unit (ICU), hospital length of stay (LOS), and in-hospital mortality were recorded. The median HScore was 43.0 (IQR 0.0-63.0), which was higher in those who needed ICU care (59.7, 95% CI 46.4-72.7) compared to those admitted to non-ICU medical wards (38.8, 95% CI 32.2-45.4; P = 0.003). It was also significantly higher in patients who died of COVID-19 (105.1, 95% CI 53.7-156.5) than individuals who survived (41.5, 95% CI 35.8-47.1; P = 0.005). Multivariable logistic regression analysis revealed that higher HScore was associated with a higher risk of ICU admission (adjusted OR = 4.93, 95% CI 1.5-16.17, P = 0.008). The risk of death increased by 20% for every ten units increase in HScore (adjusted OR 1.02, 95% CI 1.00-1.04, P = 0.009). Time to discharge was statistically longer in high HScore levels than low levels (HR = 0.41, 95% CI 0.24-0.69). HScore is much lower in patients with severe COVID-19 than sHLH. Higher HScore is associated with more ICU admission, more extended hospitalization, and a higher mortality rate. A modified HScore with a new cut-off seems more practical in predicting disease severity in patients with severe COVID-19.

A COVID-19 Patient Presenting with Pneumothorax.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus that has affected millions of individuals across the world. It was officially declared as a pandemic on March 11, 2020. Although most patients with COVID-19 manifest as viral pneumonia characterized by symptoms such as fever, dyspnea, and cough, atypical presentations such as acute respiratory distress syndrome (ARDS) and acute kidney or cardiac injury have been reported amongst COVID-19 patients. Bilateral and peripheral ground-glass and opacities are the hallmarks of COVID-19 infection on imaging exams. Herein, we aim to describe a COVID-19 patient who presented with shortness of breath, neck pain, chest pain, and bilateral pneumothorax in his imaging exam.

COVID-19 in Pediatric Granulomatosis with Polyangiitis.

The confirmed cases with COVID-19 in children account for just 1% of the overall confirmed cases. Severe COVID-19 in children is rare. Case Presentation: Our patient was 16 years old with a severe case of COVID-19 and did not survive due to the presence of Granulomatosis with polyangiitis and being treated with immunosuppressive drugs. We used lopinavir, ritonavir, hydroxy chloroquine, intravenous immunoglobulin and continuous veno-venous hemodialysis for treatment. Conclusion: In this patient, an underlying disease and delayed admission to the hospital were two factors complicating his condition.

Status epilepticus as a first presentation of COVID-19 infection in a 3 years old boy; Case report and review the literature.

It was December 2019 that china reported series of patients with respiratory symptoms, a disease that later named COVID-19; and from there spread to other countries around the world; and in February 2020, the world health organization declared COVID-19 as a pandemic. From the beginning, it was assumed that COVID-19 occurrence in pediatric patients is less and has less severity but nowadays; there are a reports that shows severe cases with multiple organ involvement. The most manifestation symptom is fever but convulsion is rare as the first manifestation symptom. Here we describe a 3 years old; previously healthy boy that presented with repeated fever induced seizure and status epilepticus and positive RT-PCR for COVID-19 that in the first day; brain CT scan revealed brain edema and 5 days later, there was intracerebral hemorrhage in brain MRI.

Clinical presentation of paediatric patients with COVID-19 admitted to a single paediatric intensive care unit (PICU) in Iran.

OBJECTIVES: To describe the clinical characteristics of paediatric patients admitted to a single paediatric intensive care unit (PICU) in Iran with COVID-19. METHODS: A cross-sectional study of paediatric patients who were admitted to a COVID-19-dedicated PICU from 16 March 2020 to 21 April 2020 with COVID-19. RESULTS: Six children had confirmed COVID-19 and four had suspected COVID-19. Six had pre-existing chronic medical conditions. Nine had respiratory failure and needed ventilation. Five children, of whom four had chronic medical conditions, died. Four had cardiac arrhythmias. Clinical presentation included fever and cough. CONCLUSION: COVID-19 can be fatal in paediatric patients, especially in those with a chronic medical condition.

A novel mutation in SEPN1 causing rigid spine muscular dystrophy 1: a Case report.

BACKGROUND: Muscular dystrophies are a clinically and genetically heterogeneous group of disorders characterized by variable degrees of progressive muscle degeneration and weakness. There is a wide variability in the age of onset, symptoms and rate of progression in subtypes of these disorders. Herein, we present the results of our study conducted to identify the pathogenic genetic variation involved in our patient affected by rigid spine muscular dystrophy. CASE PRESENTATION: A 14-year-old boy, product of a first-cousin marriage, was enrolled in our study with failure to thrive, fatigue, muscular dystrophy, generalized muscular atrophy, kyphoscoliosis, and flexion contracture of the knees and elbows. Whole-exome sequencing (WES) was carried out on the DNA of the patient to investigate all coding regions and uncovered a novel, homozygous missense mutation in SEPN1 gene (c. 1379 C > T, p.Ser460Phe). This mutation has not been reported before in different public variant databases and also our database (BayanGene), so it is classified as a variation of unknown significance (VUS). Subsequently, it was confirmed that the novel variation was homozygous in our patient and heterozygous in his parents. Different bioinformatics tools showed the damaging effects of the variant on protein. Multiple sequence alignment using BLASTP on ExPASy and WebLogo, revealed the conservation of the mutated residue. CONCLUSION: We reported a novel homozygous mutation in SEPN1 gene that expands our understanding of rigid spine muscular dystrophy. Although bioinformatics analyses of results were in favor of the pathogenicity of the mutation, functional studies are needed to establish the pathogenicity of the variant.

Evaluation of Metabolic Syndrome and Related Factors in Children Affected by Acute Lymphoblastic Leukemia.

INTRODUCTION: Obesity is among the medical problems in survivors of childhood acute lymphoblastic leukemia (ALL). These patients are at risk of metabolic syndrome (MS). The present study aimed to follow the patients with ALL regarding the incidence of MS. PATIENTS AND METHODS: This study was conducted on all patients who referred to the oncology clinic from July 2012 to July 2013. The exclusion criteria of the study were ALL relapse, secondary malignancy, hypothyroidism, Down syndrome, and below 2 years of age. ALL had to be diagnosed at least 12 months before enrollment into this study. MS was assessed by serum triglyceride, cholesterol, fasting blood sugar, leptin, and insulin levels. Besides, body mass index (BMI) and blood pressure (BP) were measured at diagnosis and at the last visit. RESULTS: This study was conducted on 53 patients (male = 35, female = 18). At the end of the study, 13 patients (24.53%) were overweight compared to 3 patients at diagnosis (P = 0.04). The mean blood leptin level was higher in overweight patients compared to the others (P = 0.001). MS was detected in 21 patients (39.6%), including 12 males and 9 females. In addition, the BMI Z-score significantly increased over the study period (P = 0.001). CONCLUSIONS: Being overweight is a complication of ALL treatment, which is associated with elevated blood leptin level and BMI Z-score. Therefore, MS criteria, such as BP, weight, and serum triglyceride level, should be taken into account in each visit.

Leishmaniasis as a Neglected Cause of Isolated Lymphadenopathy: A Case Report.

Leishmaniasis is an endemic parasitic disease in Iran. This paper reports the case of a 5-yr-old boy who presented with multiple isolated cervical lymphadenopathy for several months with no history of fever and no signs or symptoms. In an excisional lymph node biopsy, Leishmania parasites were histologically detected. Thus, leishmaniasis should be included in the differential diagnosis of isolated lymphadenitis in immunocompetent patients, even if the K39 and IFA for kala-azar are reported as negative.

A case of atypical hemolytic uremic syndrome.

A 9-year-old boy presented with fever not responding to antibiotic therapy and elevated blood urea and serum creatinine levels. The patient developed microangiopathic hemolytic anemia and thrombocytopenia during the hospital stay. Kidney biopsy confirmed the diagnosis of atypical hemolytic uremic syndrome (HUS). The patient had sufficient urine output, normal blood pressure, and no evidence of peripheral edema during the whole course of his disease. Serum levels of anti-Epstein-Barr virus immunoglobulin M was elevated, indicating the possible role of Epstein-Barr virus infection in inducing atypical HUS in this patient. The patient underwent hemodialysis with dramatic response. He was discharged with normal kidney function after a few days. Kidney function and platelet count were normal 12 months after the initial presentation. This case report shows that atypical hemolytic uremic syndrome could have unusual presentations such as the absence of oliguria, hypertension, and edema, with rapid recovery and good prognosis.