This minireview explores mitochondria as a site for antibiotic-host interactions that lead to pathophysiologic responses manifested as nonantibacterial side effects. Mitochondrion-based side effects are possibly related to the notion that these organelles are archaic bacterial ancestors or commandeered remnants that have co-evolved in eukaryotic cells; thus, this minireview focuses on mitochond...

Clostridium difficile is a leading cause of health care-associated diarrhea with significant morbidity and mortality, and new options for the treatment of C. difficile-associated diarrhea (CDAD) are needed. Cadazolid is a new oxazolidinone-type antibiotic that is currently in clinical development for treatment of CDAD. Here, we report the in vitro and in vivo antibacterial evaluation of cadazol...

BACKGROUND Linezolid is an oxazolidinone antibiotic that is increasingly used to treat drug-resistant, gram-positive pathogens. The mechanism of action is inhibition of bacterial protein synthesis. Optic and/or peripheral neuropathy and lactic acidosis are reported side effects, but the underlying pathophysiological mechanism has not been unravelled. METHODS We studied mitochondrial ultrastru...

The increase in serious gram-positive infections has increased the need for treatment of gram-positive infections in patients with hematologic malignancies. Common gram-positive pathogens exhibit a variety of resistance mechanisms, and this has supported the need for new antibiotics with unique modes of action and no endogenous resistance mechanism(s) directed against them. Linezolid (Zyvox), t...

Linezolid (LZD) is an oxazolidinone antibiotic agent that acts against gram-positive bacteria. It was recently reported that LZD can induce severe hematologic toxicity, which is thought to result in high LZD concentrations in plasma. Although many factors can affect the disposition of drugs, the binding of drug to plasma proteins, such as albumin and alpha1-acid glycoprotein (AGP), is one of th...

OBJECTIVES Linezolid is a new oxazolidinone antibiotic with efficacy against a broad range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). In this study, we have determined the serum and sputum linezolid concentrations in adults with cystic fibrosis (CF) following oral drug administration. METHODS Eleven adult patients with CF were recruited. Subjects ...

Tedizolid phosphate (TR-701), a prodrug of tedizolid (TR-700), is a next-generation oxazolidinone that has shown favorable results in the treatment of acute bacterial skin and skin-structure infections in its first Phase III clinical trial. Tedizolid has high bioavailability, penetration, and tissue distribution when administered orally or intravenously. The activity of tedizolid was greater th...

Obesity, defined as body mass index (BMI) 30 kg/m2, is a growing problem worldwide; the prevalence is 38% in the US adult population.1 Obesity is a risk factor for infection and is associated with antimicrobial treatment failure2 and worse clinical outcomes.3 Communityacquired pneumonia and skin and soft-tissue infections are themost common indications for prescribing outpatient antibiotics for...

Damaging inflammation arising from autoimmune pathology and septic responses results in severe cases of disease. In both instances, anti-inflammatory compounds are used to limit the excessive or deregulated cytokine responses. We used a model of robust T cell stimulation to identify new proteins involved in triggering a cytokine storm. A comparative proteomic mining approach revealed the differ...