Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus.

To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.

[Periprosthetic infections in systemic inflammatory rheumatic disease. Review article on diagnostics and therapy]. / Periprothetische Infekte bei rheumatisch-entzündlicher Systemerkrankung. Übersichtsartikel zu Diagnostik und Therapie.

BACKGROUND: Patients with an inflammatory disease have an elevated risk for periprosthetic joint infections due to impairment of the immune system caused by the disease itself in combination with disease-modifying antirheumatic drugs (DMARD). These infections can cause life-threatening sepsis. Unfortunately recommendations on the diagnostics and treatment are mostly based on studies with a level of evidence grade IV or V. OBJECTIVES: This article gives an overview of recent publications evaluating the level of evidence of recommendations on diagnostics and treatment of periprosthetic joint infections in patients with inflammatory diseases. METHODS: A systematic literature search was performed in the Medline database in January and February 2014. The search included all articles on diagnostic and/or treatment of periprosthetic joint infections in patients with inflammatory diseases. Articles in languages other than English or German were excluded, as well as case reports, studies with less than 20 patients and articles only referring to patients with inflammatory diseases without periprosthetic infections. RESULTS: Nearly all recommendations are based on retrospective studies or expert opinions (level of evidence IV or V). Conflicting results are common but there is good evidence on preoperative aspiration of joint fluid (level of evidence I) and a doubled risk of joint infections under treatment with anti-tumor necrosis factor (level of evidence II). An increased mortality has been reported in multiple studies. Two-stage revision seems to have a slightly better outcome than retention of prosthesis or one-stage revision. Generally, therapeutic recommendations for periprosthetic joint infections lack a good level of evidence. Future studies are urgently needed.

Is there any rationale for treatment of Staphylococcus aureus infections with antimicrobials that are determined to be ineffective in vitro?

Antimicrobial drug resistance remains a leading problem in modern healthcare, impacting on treatment options, mortality, infection control and economic issues. The introduction of new antimicrobial drugs has consistently been followed by the emergence of resistant bacteria. This review aims to answer the question of whether clinical improvement is likely if treatment of Staphylococcus aureus infections is attempted with an antimicrobial drug against which resistance is expressed in vitro (RD). Over time, S. aureus has acquired a broad range of antimicrobial resistance mechanisms, and methicillin-resistant S. aureus (MRSA) strains have become the most common multidrug-resistant healthcare-related infection-causing bacteria in Europe. As intention-to-treat studies with an RD would be unethical, only observational studies to evaluate the impact of RD therapy have been performed. Most of these studies bolster the assumption that RD therapy offers no benefit to the patient, but some do not show a detrimental effect. Limited antimicrobial treatment options for severe, invasive infections caused by MRSA might tempt physicians to use antimicrobials to which in vitro resistance is reported by the microbiological laboratory. Reasons for this non-evidence-based approach might include better pharmacokinetic/pharmacodynamic parameters, lower toxicity and better bioavailability in specific compartments, and/or the assumption of increased in vivo susceptibility of those microorganisms reported as resistant in vitro. In vitro resistance of a bacterium to a drug implies that exposing this bacterium to that drug should result in a worse clinical outcome than would be obtained with a drug to which resistance has not been observed (SD). As a counterpoint to in vitro resistance breakpoints, the concept of clinical breakpoints is therefore briefly revisited in this review. In a nutshell, no evidence has been published that S. aureus infections can be reliably treated with RDs, either as a single administration or in combination therapy.

The neutralizing effects of hyperimmune antibodies against extracellular fibrinogen-binding protein, Efb, from Staphylococcus aureus.

Staphylococcus aureus is a significant cause of acute and chronic infection and boasts a diverse array of virulence factors. S. aureus produces and secretes a protein, extracellular fibrinogen (Fg)-binding protein (Efb), which contributes to virulence in wound infection. Efb binds to both Fg and platelets and inhibits platelet function in vitro and in vivo. In this study, we have characterized the antibody response against Efb. Antibodies generated in response to immunization with Efb can neutralize the biological effects of Efb. Hyperimmune sheep immunoglobulin (Ig)G against Efb blocked the binding of Efb to Fg and prevented Efb-mediated inhibition of platelet aggregation. Furthermore, these antibodies cross-reacted with coagulase and blocked coagulase activity in plasma. Immunization of mice with Efb resulted in the generation of high titre specific antibodies. When subjected to a foreign-body-associated wound infection, the vaccinated animals developed significantly less severe wound infection than the unvaccinated controls. Also, human IgG against Efb was prepared from commercial IgG pools; however, the monospecific human anti-Efb that was enriched was unable to neutralize Efb. We conclude that immunization with Efb is required in order to generate a protective antibody response to Efb from S. aureus.