Safety of Eosinophil-Depleting Therapy for Severe, Eosinophilic Asthma: Focus on Benralizumab.

Eosinophils play a pivotal role in the inflammatory pathology of asthma and have been the target of new biologic treatments for patients with eosinophilic asthma. Given the central role of interleukin (IL)-5 in the eosinophil lifecycle, several therapies directed against the IL-5 pathway have been developed, including the anti-IL-5 antibodies mepolizumab and reslizumab and the IL-5 receptor α (IL-5Rα)-directed cytolytic antibody benralizumab. Eosinophil-depleting therapies represent a relatively new class of asthma treatment, and it is important to understand their long-term efficacy and safety.

Clinical isolates of Staphylococcus aureus from 1987 and 1989 demonstrating heterogeneous resistance to vancomycin and teicoplanin.

Fifty isolates of Staphylococcus aureus, obtained during a multicenter clinical trial evaluating the efficacy of teicoplanin that was performed between 1987 and 1992, underwent glycopeptide susceptibility testing, and 2 isolates were found to be capable of growth on agar containing 4 or 8 mg/L of vancomycin. Both of these isolates were from patients that had received prolonged teicoplanin therapy and were deemed clinical failures. Extended susceptibility testing combined with mecA gene probing revealed that one isolate was susceptible to oxacillin, the other was resistant, and both were susceptible to a variety of nonglycopeptide agents.

Antimicrobial resistance to linezolid.

Acquired resistance to linezolid, the first approved oxazolidinone, has been selected in laboratory experiments and has been observed in clinical isolates of gram-positive cocci. This resistance has typically been associated with single-nucleotide changes in varying numbers of copies of the genes encoding 23S ribosomal RNA. In the current environment of increasingly prevalent resistance to standard antibiotics, linezolid is an important drug because of its activity against a number of clinically significant gram-positive cocci, including multidrug-resistant staphylococci and enterococci.

Reversion to susceptibility in a linezolid-resistant clinical isolate of Staphylococcus aureus.

Objectives: Linezolid resistance in rare isolates of Staphylococcus aureus has been associated with G2576T mutations in domain V of the 23S rRNA gene. We report the analysis of a clinical S. aureus isolate that developed linezolid resistance (MIC of linezolid of 12 mg/L) after a 25 day course of the drug.

Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein.

Background: The causes of persistent bacteremia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) are poorly understood. This investigation examined potential associations between PB with key clinical features and several in vitro bacterial genotypic and phenotypic characteristics, in isolates from 1 institution.

Methods: Pulsed-field gel electrophoresis (PFGE) relatedness, thrombin-induced platelet microbicidal protein (tPMP)-susceptibility phenotype, accessory gene regulator (agr) genotype and functionality (via delta-lysin production), and autolysis phenotypes were assessed in MRSA isolates from the bloodstream of 21 prospectively identified patients with PB (blood cultures positive after > or =7 days of therapy) and of 18 patients with resolving bacteremia (RB) (sterile blood cultures within the first 2-4 days of therapy) due to MRSA.

Linezolid resistance in sequential Staphylococcus aureus isolates associated with a T2500A mutation in the 23S rRNA gene and loss of a single copy of rRNA.

Linezolid is an important therapeutic option for infections caused by resistant gram-positive bacteria. We report the characterization of sequential methicillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates that developed resistance in a patient treated with a prolonged course of linezolid. Analysis of this series of clinical MRSA isolates detected, in the resistant isolates, the presence of a T2500A mutation in the domain V region of the 23S rRNA gene.

Endocarditis caused by Staphylococcus aureus with reduced susceptibility to vancomycin.

Clinical management of infective endocarditis (IE) is expected to become more difficult with the emergence of Staphylococcus aureus with reduced susceptibility to vancomycin (SARV) in the United States and worldwide. We report the strain characterization and treatment of a patient with SARV IE.