Genetic loci of Staphylococcus aureus associated with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides.

The proteinase 3 (PR3)-positive anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) granulomatosis with polyangiitis (GPA) has been associated with chronic nasal S. aureus carriage, which is a risk factor for disease relapse. The present study was aimed at comparing the genetic make-up of S. aureus isolates from PR3-ANCA-positive GPA patients with that of isolates from patients suffering from myeloperoxidase (MPO)-ANCA-positive AAV, and isolates from healthy controls. Based on a DNA microarray-based approach, we show that not only PR3-ANCA-positive GPA patients, but also MPO-ANCA-positive AAV patients mainly carried S. aureus types that are prevalent in the general population. Nonetheless, our data suggests that MPO-ANCA-associated S. aureus isolates may be distinct from healthy control- and PR3-ANCA-associated isolates. Furthermore, several genetic loci of S. aureus are associated with either PR3-ANCA- or MPO-ANCA-positive AAV, indicating a possible role for pore-forming toxins, such as leukocidins, in PR3-ANCA-positive GPA. Contrary to previous studies, no association between AAV and superantigens was detected. Our findings also show that a lowered humoral immune response to S. aureus is common for PR3-ANCA- and MPO-ANCA-positive AAV. Altogether, our observations imply that the presence or absence of particular virulence genes of S. aureus isolates from AAV patients contributes to disease progression and/or relapse.

Low anti-staphylococcal IgG responses in granulomatosis with polyangiitis patients despite long-term Staphylococcus aureus exposure.

Chronic nasal carriage of the bacterium Staphylococcus aureus in patients with the autoimmune disease granulomatosis with polyangiitis (GPA) is a risk factor for disease relapse. To date, it was neither known whether GPA patients show similar humoral immune responses to S. aureus as healthy carriers, nor whether specific S. aureus types are associated with GPA. Therefore, this study was aimed at assessing humoral immune responses of GPA patients against S. aureus antigens in relation to the genetic diversity of their nasal S. aureus isolates. A retrospective cohort study was conducted, including 85 GPA patients and 18 healthy controls (HC). Humoral immune responses against S. aureus were investigated by determining serum IgG levels against 59 S. aureus antigens. Unexpectedly, patient sera contained lower anti-staphylococcal IgG levels than sera from HC, regardless of the patients' treatment, while total IgG levels were similar or higher. Furthermore, 210 S. aureus isolates obtained from GPA patients were characterized by different typing approaches. This showed that the S. aureus population of GPA patients is highly diverse and mirrors the general S. aureus population. Our combined findings imply that GPA patients are less capable of mounting a potentially protective antibody response to S. aureus than healthy individuals.

Algorithm for pre-emptive glycopeptide treatment in patients with haematologic malignancies and an Enterococcus faecium bloodstream infection.

INTRODUCTION: Nowadays Enterococcus faecium has become one of the most emerging and challenging nosocomial pathogens. The aim of this study was to determine risk factors in haematology patients who are at risk of an Enterococcus faecium bloodstream infection (BSI) and should be considered for pre-emptive glycopeptide treatment. With these identified risk factors a prediction model can be developed for clinical use. METHODS: Retrospectively clinical and microbiological data in 33 patients with an E. faecium BSI were compared to 66 control patients during a 5-year period at the haematology ward. Multivariate logistic regression was used to explore the independent risk factors and a prediction model was developed to determine the risk of an E. faecium BSI. RESULTS: E. faecium BSIs were found to be associated with high mortality rates. Independent risk factors for E. faecium BSI were colonization with E. faecium 30 days prior to blood culture (OR 5.71; CI 1.7-18.7), combination of neutropenia and abdominal focus (4.37; 1.4-13.4), age > 58 years (4.01; 1.3-12.5), hospital stay prior to blood culture > 14 days (3.55; 0.98-12.9) and CRP (C-reactive protein) level >125 mg/L (4.37; 1.1-10.2). CONCLUSION: Using data from this study, risk stratification for the development of an E. faecium BSI in patients with haematological malignancies is possible. Pre-emptive treatment should be considered in those patients who are at high risk. Using a prediction model as designed in this study, antibiotic stewardship in terms of prudent use of glycopeptides can be improved and might be helpful in controlling further spread of VRE (vancomycin resistant enterococci).

Rhodococcus equi infection after alemtuzumab therapy for T-cell prolymphocytic leukemia.

Rhodococcus equi, mainly known from veterinary medicine as a pathogen in domestic animals, can also cause infections in immunocompromised humans, especially in those with defects in cellular immunity. Alemtuzumab, an anti-CD52 monoclonal antibody, causes lymphocytopenia by eliminating CD52-positive cells. We report a patient in whom Rhodococcus equi infection developed after alemtuzumab therapy.