Influenza vaccines: where we are, where we are going.

PURPOSE OF REVIEW: Influenza vaccines are the most useful strategy for preventing influenza illness, especially in the setting of the COVID-19 pandemic. For the coming year (2021/2022) all vaccines will be quadrivalent and contain two influenza A strains [(H1N1)pdm09-like and (H3N2)-like viruses] and two influenza B strains (Victoria lineage-like and Yamagata lineage-like viruses). However, the currently licensed have suboptimal efficacy due to the emergence of new strains and vaccine production limitations. In this review, we summarize the current recommendations as well as new advancements in influenza vaccinations. RECENT FINDINGS: Recent advances have been aimed at moving away from egg-based vaccines and toward cell culture and recombinant vaccines. This removes egg adaptations that decrease vaccine efficacy, removes the reliance on egg availability and decreases the time necessary to manufacture vaccines. However, even more radical changes are needed if we are to reach the ultimate goal of a universal vaccine capable of providing long-lasting protection against all or at least most influenza strains. We discuss various strategies, including using more stable influenza antigens such as the hemagglutinin stalk and internal proteins as well as new adjuvants, new vaccine formulations, and DNA/RNA-based vaccines that are currently being developed. SUMMARY: The currently available vaccines have suboptimal efficacy and do not provide adequate protection against drifted and shifted strains. Thus, the development of a universal influenza vaccine that induces long-lasing immunity and protects against a broad range of strains is crucial.

Adverse events associated with weekly short course isoniazid and rifapentine therapy in pediatric patients with latent tuberculosis: A chart and literature review.

BACKGROUND: Effective yet safe treatment of latent tuberculosis is important for preventing the spread of tuberculosis and the progression to active disease in pediatric patients. As of 2017, the short course combination regimen of weekly isoniazid and rifapentine (3HP) administered by directly observed therapy (DOT) has replaced 9 months of isoniazid as the standard of treatment for latent tuberculosis in pediatric patients. The literature, limited in size, has established the 3HP regimen's superior safety and adherence. METHODS: We completed a retrospective chart review (n = 22) of pediatric patients at our institution receiving the 3HP regimen via DOT between 2017 and 2019. Frequencies of selected outcomes were compared to previously published data collected in a literature review. RESULTS: In this retrospective chart review, pediatric patients ages 2-20 years receiving 3HP with DOT for latent tuberculosis experienced frequent adverse events, more severe adverse events such as anaphylaxis, and higher treatment discontinuation than that which has been previously reported in the literature. Of note, our cohort's race/ethnicity differed from the cohorts described in the literature. CONCLUSIONS: Our data suggests that the short course combination regimen for pediatric latent tuberculosis patients may have a higher adverse event rate than previously established. Although this sample size is small, this study urges further investigation of more diverse cohorts to better establish the 3HP regimen's safety and tolerability.

Novel Treatment of Infant With COVID-19 With the Sialidase Fusion Protein, DAS181.

We describe the successful treatment of a 10-month-old female with respiratory distress secondary to Coronavirus disease 2019 (COVID-19) with the nebulized investigational drug, DAS181. Therapy was well tolerated, and the patient had minimal side effects. The patient's respiratory distress and positive viral polymerase chain reaction rapidly resolved after initiation of therapy.

Combined Molecular and Phenotypic Antimicrobial Susceptibility Testing Is Beneficial in Detection of ESBL and AmpC Beta-Lactamase Producing Isolates of Enterobacteriaceae in Pediatric Patients with Bloodstream Infections.

Objectives: The aim was to assess the potential advantage of combined genotypic testing with phenotypic antimicrobial susceptibility testing (AST) to detect AmpC ß-lactamases (AmpC) and extended-spectrum ß-lactamases (ESBL) producing Enterobacteriaceae isolated from blood cultures in a pediatric population. Materials and Methods: All first-time Enterobacteriaceae isolates recovered from blood cultures of pediatric patients at the Cincinnati Children's Hospital Medical Center between January 2017 and December 2018 were evaluated. The Check-MDR CT103XL ß-lactamase assay was used to determine the presence of AmpC and ESBL, while AST was performed using the VITEK 2 platform. Phenotypic ESBL resistance was defined by resistance to either ceftriaxone or ceftazidime using Clinical and Laboratory Standards Institute breakpoints, while combined cefoxitin resistance with ceftriaxone or ceftazidime resistance was used to detect AmpCs (as per European Committee on Antimicrobial Susceptibility Testing standards). Results: Overall, there were 170 isolates. Genotypically, 21 (12.4%) had AmpC and 18 (10.6%) had ESBL genes detected. Phenotypically, 11 (6.5%) isolates were AmpC and 26 (15.3%) were ESBL producing organisms. Genotypic testing identified an additional 14 AmpC and two ESBL isolates that failed to meet phenotypic criteria. Conclusions: Using combined genotypic and phenotypic methods to detect AmpC and ESBL producing organisms increased the identification of resistant organism and provided potentially clinical relevant data to guide the treatment of resistant organisms.

Neonatal early onset sepsis in Middle Eastern countries: a systematic review.

BACKGROUND: Early onset neonatal sepsis (EOS) accounts for a significant portion of neonatal mortality, which accounts for 46% of global under five child mortality. OBJECTIVE: This systematic review studies the bacterial aetiology of EOS in the Middle East, susceptibility patterns to recommended empirical antibiotic therapy and whether this differs between high-income and middle-income countries in the region. METHODS: Articles were collected from Medline, Web of Science, the Cochrane Library and Index Medicus for the Eastern Mediterranean Region. The articles included in our systematic review met the following criteria: published after January 2000, data relevant to the Middle East, data specific for early onset sepsis, no language restriction. Data on aetiology and susceptibility were extracted from prospective and retrospective studies. Risk of bias was assessed using the Newcastle-Ottawa Scale. This study focused on EOS but does include data regarding neonatal late-onset sepsis antibiotic susceptibility. The data regarding coagulase-negative Staphylococcus species were excluded from final analysis, as possible contaminants. The protocol for this systematic review was registered on PROSPERO: CRD42017060662. RESULTS: 33 articles from 10 countries were included in the analysis. There were 2215 cases of culture-positive EOS, excluding coagulase-negative Staphylococcus. In middle-income countries, Klebsiella species (26%), Staphylococcus aureus (17%) and Escherichia coli (16%) were the most common pathogens, in contrast to group B Streptococcus (26%), E. coli (24%) and Klebsiella (9%) in high-income countries. Overall susceptibility to ampicillin/gentamicin and third-generation cephalosporin were 40% and 37%, respectively, in middle-income countries versus 93% and 91%, respectively, in high-income countries. CONCLUSIONS: EOS in middle-income countries was more likely to be due to Gram-negative pathogens and less likely to be susceptible to empirical antibiotic therapy. This has important public health implications regarding neonatal mortality in the Middle East region.