Abstract
BackgroundObesity, metabolic syndrome (MetS), and diabetes are frequent in surgical populations and can enhance susceptibility to postoperative surgical site infections. Reduced neutrophil function has been linked with diabetes and risk of Staphylococcus aureus infection. Therefore, neutrophil function in diabetic and obese subjects (± MetS) was assessed in this prospective serological and cellular surveillance study to determine whether vaccines administered to protect against infections after surgery could be effective in these populations.MethodsNeutrophil function (chemotaxis, phagocytosis, and opsonophagocytic killing of S. aureus) was assessed in subjects classified according to diabetes status, body mass index, and presence/absence of MetS. Neutrophils were characterized within functional subsets by flow cytometry. A serologic assay was used to measure baseline antibody presence to each antigen in SA4Ag: capsular polysaccharide (CP) type 5, CP8, recombinant mutant Clumping factor A (rmClfA), and recombinant Manganese transport protein C (rMntC).ResultsNeutrophil function was similar for comorbid and healthy cohorts, with no significant between-group differences in cell counts, migration, phagocytosis ability, neutrophil subset proportions, and S. aureus killing ability when neutrophils were isolated 3–6 months apart (Visit 1 [n = 90] and Visit 2 [n = 70]) and assessed. Median pre-existing antibody titers to CP5, CP8, and rmClfA were comparable for all cohorts (insufficient subjects with rMntC titers for determination).ConclusionsMetS, diabetes, and obesity do not impact in vitro neutrophil function with regard to S. aureus killing, suggesting that if an effective S. aureus vaccine is developed it may be effective in individuals with these comorbidities.
Highlights
Obesity, metabolic syndrome (MetS), and diabetes are frequent in surgical populations and can enhance susceptibility to postoperative surgical site infections
The primary defense against gram-positive pathogens such as S. aureus is engulfment and oxidative killing by neutrophils, a process that is dependent on tissue oxygen tension
At Visits 1 and 2, 50 mL blood was drawn for evaluation of immune function, and 10 mL blood was drawn for fasting lipid profile, fasting blood glucose, C-reactive protein (CRP), and HbA1c
Summary
Metabolic syndrome (MetS), and diabetes are frequent in surgical populations and can enhance susceptibility to postoperative surgical site infections. The underlying mechanisms linking these comorbidities to S. aureus infection are not fully defined, but Scully et al Diabetol Metab Syndr (2017) 9:76 may be linked to impairment in several aspects of the immune response to bacterial infections. These aspects include impaired healing, fibroblast and epidermal cell dysfunction, impaired angiogenesis, damage from reactive oxygen species and advanced glycation end products, and decreased host immune resistance [4]. Obese patients have decreased tissue oxygen tension and poor blood supply In those undergoing surgery, this presents a particular problem at the surgical incision site, and increases the risk for surgical site infections [5]. Decreased serum and tissue concentrations of prophylactic antibiotics and increased rates of perioperative hyperglycemia [6] may further increase the risk of postoperative infection
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