Variations and National Perspectives on Evaluation and Management of Ventilator-Associated Pneumonia in Neonatal Intensive Care Units: An In-Depth Survey Analysis.

Introduction Infants in the neonatal intensive care unit (NICU) are vulnerable to ventilator-associated pneumonia (VAP), which increases their morbidity and mortality. There is a significant overlap of clinical features of neonatal VAP with other pulmonary pathologies, particularly in preterm infants, which can make the definitive diagnosis and management of VAP challenging. Objective Our study surveyed NICU providers across the United States to understand the perspectives and variations in neonatal VAP diagnostic and management practices. Methods The REDCap survey was distributed to the actively practicing members of the Section on Neonatal-Perinatal Medicine (SoNPM) of the American Academy of Pediatrics (AAP). We used descriptive statistics to analyze the data from the respondents. Results Of 254 respondents, the majority (86.6%, 220) were neonatologists and had a relatively even geographical distribution. Most (75.9%, 193) stated that they would perform a gram stain and respiratory culture as part of a sepsis workup irrespective of the patient's duration on invasive mechanical ventilation (IMV); 224 (88.2%) of providers preferred the endotracheal aspiration (ETA) technique to collect specimens. In cases where a positive respiratory culture was present, VAP (52.4%, 133) was the predominantly assigned diagnosis, followed by pneumonia (27.2%, 69) and ventilator-associated tracheitis (VAT) (9.8%, 25). Respondents reported a prescription of intravenous gentamicin (70%, 178) and vancomycin (41%, 105) as the initial empiric antibiotic drugs, pending final respiratory culture results. Most respondents (55.5%, 141) opted for seven days of antibiotics duration to treat VAP. The reported intra-departmental variation among colleagues in acquiring respiratory cultures and prescribing antibiotics for VAP was 48.8% (124) and 37.4% (95), respectively, with slightly more than half (53.5%, 136) of providers reporting having VAP prevention guidelines in their units. Conclusion The survey study revealed inconsistencies in the investigation, diagnostic nomenclature, choice of antibiotic, and treatment duration for neonatal VAP. Consequently, there is a pressing need for further research to establish a clear definition and evidence-based criteria for VAP.

Cerebral fat embolism syndrome in a patient with homozygous sickle cell disease in the setting of multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a rare progressive inflammatory process temporally associated with exposure to SARS-CoV-2 (COVID-19) in patients 20 years of age and younger. At this time, much of MIS-C is not well understood, including the pathogenesis, long-term implications, and how each variant of the COVID-19 virus affects the progression and severity. We present the unusual case of a 19-year-old man with a history of homozygous sickle cell disease who developed a vaso-occlusive pain crisis and cerebral fat embolism syndrome as a complication of MIS-C secondary to the Omicron variant of COVID-19.

Presentation of cryopyrin-associated periodic fever syndrome as chronic, afebrile urticaria in a 12-month-old female.

A healthy 12-month-old female presented with relapsing and remitting urticaria since birth that was resistant to treatment with antihistamines. A thorough history revealed extensive rheumatic disease on the father's side of the family, and subsequent genetic testing was positive for a missense variant of NLRP3, indicating cryopyrin-associated periodic fever syndrome (CAPS). CAPS encompasses a spectrum of diseases, all related to a defect in the same gene; manifestations vary in severity and presentation, but most are associated with recurrent rash and fever. Because the patient's only presenting symptom was rash, this case highlights the importance of having a high index of suspicion for cryopyrin-associated periodic fever syndrome in infants with persistent, early urticaria.

Retropharyngeal abscess in the setting of multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a potentially severe inflammatory syndrome following recent infection with SARS-CoV-2 (COVID-19). In this report, we describe a 13-year-old boy with a retropharyngeal abscess unresponsive to initial antibiotic therapy who was found to have findings consistent with MIS-C, which included elevated interleukin-6, ferritin, and troponin levels. The patient had COVID-19 infection due to the Omicron variant.

The pharmacokinetics, pharmacodynamics, and clinical role of fixed dose combination of tenofovir disoproxil fumarate, lamivudine and reduced dose efavirenz (TLE-400) in treating HIV-1 infection.

INTRODUCTION: Co-formulated fixed dose combination (FDC) of antiretroviral drugs tenofovir disoproxil fumarate, lamivudine, and reduced dose efavirenz [TDF 300 mg/3TC 300mg/EFV400 mg (TLE-400)] is a single daily tablet recently approved for the treatment of HIV-1 infection. Areas covered: An overview of the pharmacokinetics, pharmacodynamics and role of TLE-400 in the treatment of HIV-1 infection based on the publications from Medline and Pubmed as of February, 2018. Expert opinion: Although TLE-400 has not been formally evaluated in a clinical trial as a new formulation, previous studies have evaluated its components individually and in different doses as other FDCs have shown favorable efficacy and safety results to support continuing its approval and indication in the management of HIV-1 infection. Due to the lower dose of EFV, TLE-400 has a lower rate of toxicity and higher tolerability compared to its predecessor, the TLE-600, which contained a higher 600 mg dose of EFV. Given its low cost and ease of administration, TLE-400 is a promising alternative first line FDC in the management of HIV-1.

Antiretroviral therapy interruptions: impact on HIV treatment and transmission.

INTRODUCTION: Successful management of pediatric and adult human immunodeficiency virus (HIV) disease includes lifelong administration of antiretroviral therapy (ART). The need for the continuous use of antiretroviral drugs throughout the life course poses a challenge to children, adolescents, and adults living with HIV and their caregivers. Historically, treatment interruptions have been viewed as a negative therapeutic strategy. Recently, however, treatment interruptions or treatment reduction strategies have become a focus of investigations as innovative approaches to the long-term management of HIV disease. Current challenges with treatment interruptions include identifying an appropriate timeframe for length of interruptions and identifying HIV patient populations in whom the treatment interruption can be successful. OBJECTIVE: In this review, we aimed at summarizing recent studies of planned and unplanned treatment interruptions in children and adults living with HIV. MATERIALS AND METHODS: We searched two databases (PubMed and Cochrane Controlled Trials Register) using keywords (HIV OR AIDS OR acquired immunodeficiency syndrome OR HIV-1 OR antiretroviral) AND (treatment interruption OR planned interruption OR therapeutic interruption OR unplanned interruption), for published randomized and nonrandomized clinical trials and observational cohort studies in children and adults (from birth to 99 years of age) in global settings covering a period from 2012 to 2018. In this review, only the studies that contained pediatric and adolescent populations with baseline immunological, virological, and clinical characteristics and outcomes after treatment interruption were included. RESULTS: A total of 174 eligible citations from the two databases were identified. We identified 10 prospective treatment interruption studies on children (five studies) and adults (five studies) during 2012-2018 with a total of 863 pediatric and 273 adult subjects. Collectively, recent studies on children and adults with HIV infection suggest that treatment interruptions with proper monitoring can be successful by instituting well-defined immunological and virological parameters or thresholds such as CD4 count, CD4%, and HIV RNA viral load that identify low-risk populations with treatment failure. In addition to standard virological and immunological outcome measurements, selected biomarkers that help detect early immune activation may also be useful in the monitoring of treatment interruption. CONCLUSION: Treatment interruptions in adult and especially pediatric patients with well-controlled HIV disease may provide an alternative opportunity to optimize long-term HIV management by minimizing drug-associated toxicity and improving long-term adherence and quality of life.

Acute development of Cushing syndrome in an HIV-infected child on atazanavir/ritonavir based antiretroviral therapy.

An 11-year-old male with perinatally acquired human immune deficiency virus (HIV) infection on antiretroviral regimen, which included abacavir plus lamivudine (Epzicom), didanosine, ritonavir and atazanavir presented with bilateral axillary striae, increased appetite, fatigue, facial swelling and acute weight gain. Two months prior to presentation, the patient had received a diagnostic and therapeutic intra-articular triamcinolone injection in the knee for pain relief and subsequently became progressively swollen in the face, developed striae bilaterally at the axillae, experienced increased appetite, fatigue and an 8 pound weight gain. During the endocrine workup, suspicion for adrenal insufficiency prompted 24-h urine collection for free cortisol, which was found to be undetectable (below LLQ of 1.0 µg/L). This prompted further evaluation of the hypothalamic-pituitary axis (HPA) by standard dose adrenocorticotropic hormone (ACTH) stimulation test. A 250 µg cosyntropin stimulation test was performed and confirmed HPA axis suppression. Baseline cortisol level was <1 µg/dL and stimulated cortisol level at 30 min was 3.8 µg/dL. The patient was diagnosed with iatrogenic Cushing syndrome and suppression of HPA axis secondary to the drug interaction between ritonavir (RTV) and intra-articular triamcinolone injection. Following endocrine evaluation and workup, the patient was admitted for planned orthopaedic procedure including elective left hamstring lengthening, distal femoral osteotomy and patellar tendon advancement. Taking into consideration the diagnosis of iatrogenic Cushing syndrome, at the start of the surgical procedure, 100 mg IV stress dose of hydrocortisone followed by 50 mg hydrocortisone every 8 h for 24 h was administered. Stress dosing was discontinued 24 h after the procedure. Throughout the hospitalization and upon discharge, the patient continued his ART. From initial presentation, patient has remained clinically stable throughout surgery and postoperative period. LEARNING POINTS: Drug-drug interaction between ritonavir and triamcinolone can cause Cushing syndrome.Although triamcinolone has a half-life of 3 h, an intra-articular injection may be systematically absorbed for 3 weeks after injection, and adrenal suppression may last as long as 30 days.Co-administration of ritonavir and corticosteroids may result in an increase of plasma levels of corticosteroids levels, as they are both eliminated by CYP3A metabolism, and this interaction has the potential to prolong the half-life of triamcinolone several fold.No specific guidelines are available for the management of iatrogenic Cushing syndrome secondary to ritonavir and corticosteroids.One treatment option includes replacing ritonavir with a non-protease inhibitor-based regimen.Initiating hydrocortisone replacement therapy to prevent an adrenal crisis is also an alternate option.

Challenges and Opportunities in the Development of HIV Medications in Pediatric Patients.

Successful management of pediatric HIV disease requires high therapeutic efficacy and adherence, which can be achieved by providing affordable, easy to store, and palatable antiretrovirals. Current challenges in pediatric antiretroviral drug development include poor palatability, large pill size, limited oral liquid formulations, and few incentives for development by drug manufacturers as the number of children with HIV continues to decline due to successful worldwide preventive interventions and improved access to antiretrovirals. This article summarizes the various challenges and opportunities with current pediatric antiretrovirals, recent and ongoing trials, new formulations, and suggestions that may expedite and provide incentives for the development of suitable pediatric formulations.