Standardizing the approach to late onset sepsis in neonates through antimicrobial stewardship: a quality improvement initiative.

BACKGROUND: Antibiotics are the most prescribed medication in the neonatal intensive care unit (NICU) and there is marked variation in their use. While they are vital for treatment of infections, they put infants at risk for infections with drug resistant organisms, alteration in their microbiome and several other morbidities. Specific guidelines for neonates are often lacking and our NICU is not compliant with late onset sepsis (LOS) guidelines. OBJECTIVE: By January 2019, there will be >75% compliance with our LOS bundle for any infant admitted to Tampa General Hospital's (TGH) NICU undergoing a LOS evaluation at >72 h of life. The bundle includes documented reason for LOS evaluation, appropriate initial antibiotic selection, appropriate initial evaluation considered, and appropriate de-escalation of antibiotics. STUDY DESIGN: The project was implemented in the NICU at TGH, the academic medical center affiliated with the University of South Florida in Tampa, FL. The multidisciplinary antimicrobial stewardship (ASP) team responsible for the project consists of a neonatology attending, three neonatology fellows, a pediatric infectious disease attending, and two NICU pharmacists. The project was started in January 2017 and all data were collected prospectively. We implemented multiple Plan-Do-Study-Act cycles in a stepwise manner; outcome measures included compliance with the LOS bundle and ASP team recommendations. Our process measures were the documented reason for sepsis evaluation, appropriate initial evaluation considered, appropriate antibiotic selection and appropriate antibiotic de-escalation. Patient length of stay was the balancing measure studied. RESULTS: During this 20-month initiative, there were 232 infants who underwent LOS evaluation and there were 98 true positive cultures from blood (28%), urine (35%), and cerebrospinal fluid (3%). Commonly documented rationales for treatment of culture negative sepsis were clinical pneumonia (38%) and necrotizing enterocolitis (38%). Common indications for LOS evaluations were increased respiratory support (51%) and abdominal distension (17%). There was improvement in appropriate initial antibiotic selection (70% vs. 94%); appropriate consideration of initial evaluation (63% vs. 94%, respectively); appropriate de-escalation of antibiotics (86% vs. 100%, respectively) and increase in LOS bundle compliance (44% vs. 87%, respectively). The overall antibiotic utilization rate and length of treatment did not change significantly. CONCLUSIONS: Developing and engaging a NICU ASP team improves compliance with late onset sepsis guidelines through the implementation of a LOS bundle of care.

Staphylococcus aureus Cowan I. Potent stimulus of immunoglobulin M rheumatoid factor production.

These studies demonstrate that Staphylococcus aureus Cowan I (SAC), a protein A-positive Staphylococcal strain, is a potent and consistent inducer of IgM rheumatoid factor production by normal human peripheral blood mononuclear cells. The frequency and magnitude of this response greatly exceeded that of parallel cultures stimulated with pokeweed mitogen or the protein A-negative S. aureus Wood strain, although all three agents induced a similar amount of total IgM. Cell fractionation studies indicated that SAC-induced IgM rheumatoid factor is T cell-dependent. The striking ability of SAC to induce IgM rheumatoid factor may relate to its protein A content, since cultures stimulated with protein A-coupled sepharose beads also consistently produced this autoantibody. Thus SAC is a new probe of in vitro IgM rheumatoid factor production and its use has provided further evidence that most healthy individuals harbor precursors of IgM rheumatoid factor secreting cells. Unlike other polyclonal activators, SAC is unique in its capacity to bind immunoglobulin, a property that may account for its prominent anti-IgG inducing capacity.

Analysis of in vitro polyclonal B cell differentiation responses to bacterial peptidoglycan and pokeweed mitogen in rheumatoid arthritis.

To gain insight into possible determinants of in vivo polyclonal B cell activation seen in rheumatoid arthritis (RA), we enumerated immunoglobulin secreting cells appearing in cultures of peripheral blood mononuclear cells that were stimulated with pokeweed mitogen (PWM) or a newly described polyclonal B cell activator, bacterial peptidoglycan. Peptidoglycan, the major constituent of the cell wall of gram positive bacteria, has properties which warrant its consideration in the pathogenesis of RA; including the ability to induce rheumatoid factor production as well as a RA like syndrome in experimental animals. RA patients as a group had similar immunoglobulin secreting cell responses in PWM stimulated cultures compared to arthritis controls and showed moderately depressed responses compared to healthy volunteers. However, their in vitro responses to peptidoglycan were markedly depressed when compared to those of both control groups. Of note, severely reduced peptidoglycan-induced responses were seen in 26 of 55 rheumatoid patients who demonstrated intact PWM-induced responses. These impaired responses to peptidoglycan were not due to (1) aberrant kinetic response; (2) shift in the dose-response pattern; (3) decreased cell survival in culture or (4) the inability of peptidoglycan to activate RA cells. Cell fractionation studies indicated that peptidoglycan reactive B cells were present in the blood of some patients but their reactivity was abrogated by suppressor T cells. These studies provide evidence of aberrant in vitro polyclonal B cell activation in patients with RA and provide a basis for further investigation of peptidoglycan as an immunopathogenetic agent in this disease.