Faculty Bibliography

Staphylococcus aureus is a global health concern, resulting in significant disease burden in both hospital and community settings. To establish infection, the bacteria must contend with a multitude of host defense mechanisms, including "nutritional immunity", in which nutrients are sequestered away from invading pathogens. Importantly, S. aureus requires iron for growth during infection, which it acquires through the lysis of erythrocytes (hemolysis). HlgAB, a secreted bi-component pore forming toxin, contributes to the ability of S. aureus to lyse erythrocytes to release heme iron. HlgAB consists of two subunits, the S-subunit HlgA and the F-subunit HlgB. Prior work has shown that the hemolytic activity of HlgAB is dependent on the binding of HlgA to the host receptor Duffy Antigen Receptor for Chemokines (DARC). Here we show that HlgB binds the surface of erythrocytes independently of DARC or HlgA. Our comparative genomic analysis reveals high conservation of hlgA and hlgB genes across S. aureus lineages. By performing structure-function studies, we identified a series of loops within the rim domain of HlgB that are required for the binding of HlgB to erythrocytes and erythrocyte lysis by HlgAB. The importance of HlgB-mediated host targeting was validated in a tissue culture model of S. aureus-mediated lysis of primary human erythrocytes, in an in vivo murine model of intoxication, and during in vivo systemic infection. Altogether, these findings expand our mechanistic insights into how S. aureus overcomes nutritional immunity, and the role of HlgB in S. aureus pathophysiology.

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations for use. The ACIP Work Groups (WG) conduct an in-depth review of the available scientific information regarding specific FDA-licensed vaccines, or important vaccines in advanced stages of clinical development that are under consideration for FDA licensure and then present the information and their recommendation to the ACIP for a vote. If a recommendation receives a majority vote, it moves to the CDC Director for approval and, if approved, it is published in the CDC Morbidity and Mortality Weekly Report (MMWR). At that point the ACIP recommendation represents the official CDC recommendation for U.S. immunizations. The ACIP met on April 16-17, 2025, to discuss influenza vaccines, chikungunya vaccines, coronavirus disease (COVID-19) vaccines, RSV immunizations, meningococcal vaccines, human papillomavirus (HPV) vaccines, Mpox vaccines, and cytomegalovirus (CMV) vaccines. This update summarizes the proceedings of these meetings, with an emphasis on topics that are most relevant to the pediatric population. Major updates for pediatric clinicians include information regarding HPV and meningococcal vaccination considerations, and updates regarding RSV immunization in infants which will likely be voted on during upcoming ACIP meetings.

Vaccine-preventable diseases that have yet to be eliminated are important to review for the practicing clinician. Haemophilus influenzae type b (Hib) was once the leading cause of bacterial meningitis in young children and now causes rare invasive disease in young children and the elderly. Patients with immunodeficiency and impaired complement response to encapsulated organisms (e.g., sickle cell disease; asplenia) are at particular risk of invasive Hib disease. Recognition of a potential case, prompt management and reporting, and inpatient vaccine administration and education are crucial actions for hospitalists in the management of Hib disease and prevention.

Two unvaccinated infants residing in the same borough of New York, New York, USA, had Haemophilus influenzae type b meningitis develop 1 year apart. Whole-genome sequencing and phylogenetic analysis revealed the isolates shared a previously undescribed multilocus sequence type and were more closely related to each other than to other sequenced strains.

INTRODUCTION/BACKGROUND:Current protocols aim to prevent some infant GBS infection through screening and peripartum antibiotics, however such strategies cannot be widely implemented in resource-limited settings. On the other hand, maternal vaccines in development against Group B Streptococcus (GBS) can provide a feasible universal approach. The success of any vaccine will depend on uptake in the population. Rates of maternal GBS colonization in the Dominican Republic (DR) and Caribbean region are among the highest in the world, but little is known about attitudes towards maternal vaccines in this region. METHODS:A cross-sectional, multicenter, mixed-methodology survey evaluated facilitators and barriers to maternal immunization and acceptability of a hypothetical Group B Streptococcus vaccine among pregnant women in three hospitals in the DR. RESULTS:Six-hundred and fifty women completed the survey of whom 85 % had never heard of GBS. Following receipt of information about GBS and a vaccine, 94 % of women stated that they would be likely or very likely to receive a vaccine. Being 18 years or younger was associated with a lower likelihood of GBS vaccine receipt (AOR 0.32, 95 % CI 0.14-0.69). Being born in the DR was associated with a higher likelihood of GBS vaccine receipt (AOR 2.73, 95 % CI 1.25-5.97). Among women who were unlikely to receive the vaccine, uncertainty about potential harm from a novel vaccine was the prominent theme elicited from free text responses. CONCLUSION/CONCLUSIONS:There was a high level of acceptance of a future GBS vaccine among this sample of pregnant women in the DR. However, knowledge of vaccines and vaccine-preventable diseases was low, and most women had concerns about the safety of new vaccines. Interventions that strengthen existing maternal immunisation infrastructures, including increasing education of pregnant women about vaccines, will aid the successful implementation of a future GBS vaccine.

Cefiderocol is a novel cephalosporin antibiotic with activity against multidrug-resistant gram-negative bacteria and limited pediatric experience. This case series describes 3 immunocompromised children receiving blood transfusion who developed benign red or purple urine with administration of cefiderocol. Interaction with iron from blood products is a possible mechanism. It is important to recognize this phenomenon and distinguish it from hematuria to avoid unnecessary diagnostic testing.

Group B Streptococcus (GBS) is a significant global cause of serious infections, most of which affect pregnant women, newborns, and infants. Studying GBS genetic mutant strains is a valuable approach for learning more about how these infections are caused and is a key step toward developing more effective preventative and treatment strategies. In this resource report, we describe a newly created library of defined GBS genetic mutants, containing over 1,900 genetic variants, each with a unique disruption to its chromosome. An indexed library of this scale is unprecedented in the GBS field; it includes strains with mutations in hundreds of genes whose potential functions in human disease remain unknown. We have made this resource freely available to the broader research community through deposition in a publicly funded bacterial maintenance and distribution repository.

In pregnant people colonized with group B Streptococcus (GBS) in Botswana, we report the presence/expansion of sequence types 223 and 109, a low rate of erythromycin resistance, and 3 novel sequence types. These data highlight the importance of local epidemiologic studies of GBS, a significant source of neonatal disease.