L. Bode

BACKGROUND: Nasal carriers of Staphylococcus aureus are at increased risk for health care-associated infections with this organism. Decolonization of nasal and extranasal sites on hospital admission may reduce this risk. METHODS: In a randomized, double-blind, placebo-controlled, multicenter trial, we assessed whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase-chain-reaction (PCR) assay, followed by treatment with mupirocin nasal ointment and chlorhexidine soap, reduces the risk of hospital-associated S. aureus infection. RESULTS: From October 2005 through June 2007, a total of 6771 patients were screened on admission. A total of 1270 nasal swabs from 1251 patients were positive for S. aureus. We enrolled 917 of these patients in the intention-to-treat analysis, of whom 808 (88.1%) underwent a surgical procedure. All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin. The rate of S. aureus infection was 3.4% (17 of 504 patients) in the mupirocin-chlorhexidine group, as compared with 7.7% (32 of 413 patients) in the placebo group (relative risk of infection, 0.42; 95% confidence interval [CI], 0.23 to 0.75). The effect of mupirocin-chlorhexidine treatment was most pronounced for deep surgical-site infections (relative risk, 0.21; 95% CI, 0.07 to 0.62). There was no significant difference in all-cause in-hospital mortality between the two groups. The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin-chlorhexidine group (P=0.005). CONCLUSIONS: The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission. (Current Controlled Trials number, ISRCTN56186788.)

Expanding knowledge on the humoral immune response in Staphylococcus aureus-infected patients is a mandatory step in the development of vaccines and immunotherapies. Here, we present novel insights into the antibody responses following S. aureus bacteremia. Fifteen bacteremic patients were followed extensively from diagnosis onwards (median 29 days, range 9-74). S. aureus strains (median 3, range 1-6) and serial serum samples (median 16, range 6-27) were collected. Strains were genotyped by pulsed-field gel electrophoresis (PFGE) and genes encoding 19 staphylococcal proteins were detected by polymerase chain reaction (PCR). The levels of IgG, IgA, and IgM directed to these proteins were determined using bead-based flow cytometry. All strains isolated from individual patients were PFGE-identical. The genes encoding clumping factor (Clf) A, ClfB, and iron-responsive surface-determinant (Isd) A were detected in all isolates. Antigen-specific IgG levels increased more frequently than IgA or IgM levels. In individual patients, different proteins induced an immune response and the dynamics clearly differed. Anti-ClfB, anti-IsdH, and anti-fibronectin-binding protein A IgG levels increased in 7 of 13 adult patients (p < 0.05). The anti-IsdA IgG level increased in 12 patients (initial to peak level: 1.13-10.72 fold; p < 0.01). Peak level was reached 7-37 days after diagnosis. In a bacteremic 5-day-old newborn, antistaphylococcal IgG levels declined from diagnosis onwards. In conclusion, each bacteremic patient develops a unique immune response directed to different staphylococcal proteins. Therefore, vaccines should be based on multiple components. IsdA is immunogenic and, therefore, produced in nearly all bacteremic patients. This suggests that IsdA might be a useful component of a multivalent staphylococcal vaccine.

Staphylococcus aureus is both a prominent cause of nosocomial infections with significant morbidity and mortality and a commensal with nasal carriage in around 30% of the population. The rapid spread of multi-resistant strains necessitates novel therapeutic strategies, a challenging task because the species S. aureus and the host response against it are highly variable. In a prospective study among 2023 surgical and non-surgical patients, 12 patients developed S. aureus bacteremia. They were analysed in detail using a personalized approach. For each patient, the extracellular proteins of the infecting S. aureus strain were identified and the developing antibody response was assessed on 2-D immunoblots. S. aureus carriers showed clear evidence of strain-specific pre-immunization. In all immune-competent bacteremia patients, antibody binding increased strongly, in most cases already at diagnosis. In endogenous infections, the pattern of antibody binding was similar to the pre-infection pattern. In exogenous infections, in contrast, the pre-infection pattern was radically altered with the acquisition of new specificities. These were characteristic for individual patients. Nevertheless, a common signature of 11 conserved S. aureus proteins, recognized in at least half of the bacteremic patients, was identified. All patients mounted a dynamic antibody response to a subset of these proteins.

About 25-30% of children with acute idiopathic thrombocytopenia (ITP) develop chronic disease. It is not well known which patient characteristics influence the course of the ITP. A prospective study in 60 children with newly diagnosed ITP was performed. The aim of the study was to identify patient characteristics at the onset of thrombocytopenia that predicts the progression to chronic ITP. Clinical data and blood samples were collected at several time points during the first 6 months of the disease. Variables predicting chronic disease, as calculated in a multivariate logistic regression analysis, were a platelet count >10 x 10(9)/l at the onset [odds ratio (OR) 1.1, 95% confidence interval (CI) 1.01-1.14], the absence of infection shortly before the onset of the disease (OR 4.8, CI 1.16-19.57) and FGR2B-232I/T genotype (OR 7.9, CI 0.96-65.27). The latter may point at an immune-modulating role of Fc gamma RIIb in ITP. Although only three patients had serious bleeds, 35 patients received immune-modulating treatment for low platelet counts only. Seventeen patients were treated with intravenous immunoglobulin (IVIG) and 18 patients received corticosteroids. Patient variables did not differ between these treatment groups. However, patients receiving IVIG had significantly lower risk for chronic disease.