Adam C. Schaffer

Immunization with Staphylococcus aureus Clumping Factor B, a Major Determinant in Nasal Carriage, Reduces Nasal Colonization in a Murine Model

ABSTRACT Staphylococcus aureus is responsible for a wide range of infections, including soft tissue infections and potentially fatal bacteremias. The primary niche for S. aureus in humans is the nares, and nasal carriage is a documented risk factor for staphylococcal infection. Previous studies with rodent models of nasal colonization have implicated capsule and teichoic acid as staphylococcal surface factors that promote colonization. In this study, a mouse model of nasal colonization was utilized to demonstrate that S. aureus mutants that lack clumping factor A, collagen binding protein, fibronectin binding proteins A and B, polysaccharide intercellular adhesin, or the accessory gene regulator colonized as well as wild-type strains colonized. In contrast, mutants deficient in sortase A or clumping factor B (ClfB) showed reduced nasal colonization. Mice immunized intranasally with killed S. aureus cells showed reduced nasal colonization compared with control animals. Likewise, mice that were immunized systemically or intranasally with a recombinant vaccine composed of domain A of ClfB exhibited lower levels of colonization than control animals exhibited. A ClfB monoclonal antibody (MAb) inhibited S. aureus binding to mouse cytokeratin 10. Passive immunization of mice with this MAb resulted in reduced nasal colonization compared with the colonization observed after immunization with an isotype-matched control antibody. The mouse immunization studies demonstrate that ClfB is an attractive component for inclusion in a vaccine to reduce S. aureus nasal colonization in humans, which in turn may diminish the risk of staphylococcal infection. As targets for vaccine development and antimicrobial intervention are assessed, rodent nasal colonization models may be invaluable.

Vaccination and passive immunisation against Staphylococcus aureus.

Staphylococcus aureus, an important bacterial pathogen in the hospital and the community, has become increasingly resistant to multiple antibiotics. Non-antimicrobial approaches to controlling S. aureus are clearly needed. Because many individuals who are susceptible to staphylococcal infections are not competent to mount an effective immune response, passive as well as active immunisation strategies have been explored. A capsular polysaccharide-based vaccine (StaphVAX) showed promise in an initial phase III trial in haemodialysis patients, but was found to be ineffective in a confirmatory trial. Likewise, a human immunoglobulin G (IgG) preparation known as INH-A21 (Veronate) with elevated levels of antibodies to the staphylococcal surface adhesins ClfA and SdrG made it into phase III testing, where it failed to show a clinical benefit in neonates. A number of novel antigens are in pre-clinical trials, including cell-wall-anchored adhesins, surface polysaccharides and exotoxoids. Given the multiple and sometimes redundant virulence factors of S. aureus that enable it to be such a crafty pathogen, if a vaccine is to prove effective it will of necessity be multicomponent, incorporating a number of surface proteins, toxoids and surface polysaccharides.

Rates and Characteristics of Paid Malpractice Claims Among US Physicians by Specialty, 1992-2014

Importance Although physician concerns about medical malpractice are substantial, national data are lacking on the rate of claims paid on behalf of US physicians by specialty. Objective To characterize paid malpractice claims by specialty. Design, Setting, and Participants A comprehensive analysis was conducted of all paid malpractice claims, with linkage to physician specialty, from the National Practitioner Data Bank from January 1, 1992, to December 31, 2014, a period including an estimated 19.9 million physician-years. All dollar amounts were inflation adjusted to 2014 dollars using the Consumer Price Index. The dates on which this analysis was performed were from May 1, 2015, to February 20, 2016, and from October 25 to December 16, 2016. Main Outcomes and Measures For malpractice claims (n = 280 368) paid on behalf of physicians (in aggregate and by specialty): rates per physician-year, mean compensation amounts, the concentration of paid claims among a limited number of physicians, the proportion of paid claims that were greater than

Liability impact of the hospitalist model of care

1 million, severity of injury, and type of malpractice alleged. Results From 1992-1996 to 2009-2014, the rate of paid claims decreased by 55.7% (from 20.1 to 8.9 per 1000 physician-years; P < .001), ranging from a 13.5% decrease in cardiology (from 15.6 to 13.5 per 1000 physician-years; P = .15) to a 75.8% decrease in pediatrics (from 9.9 to 2.4 per 1000 physician-years; P < .001). The mean compensation payment was

A Population-Based Care Improvement Initiative for Patients at Risk for Delirium, Alcohol Withdrawal, and Suicide Harm

329 565. The mean payment increased by 23.3%, from

Medical Malpractice Trends: Errors in Automated Speech Recognition

286 751 in 1992-1996 to

Surgical Residents and Medical Malpractice

353 473 in 2009-2014 (P < .001). The increases ranged from

Deep Venous Thrombosis and Pulmonary Embolism

17 431 in general practice (from

Postoperative Renal Failure

218 350 in 1992-1996 to

The Impact of Automated Notification on Follow-up of Actionable Tests Pending at Discharge: a Cluster-Randomized Controlled Trial

235 781 in 2009-2014; P = .36) to