Leveraging laboratory and clinical studies to design effective antibiotic combination therapy.

Interest in antibiotic combination therapy is increasing due to antimicrobial resistance and a slowing antibiotic pipeline. However, aside from specific indications, combination therapy in the clinic is often not administered systematically; instead, it is used at the physician's discretion as a bet-hedging mechanism to increase the chances of appropriately targeting a pathogen(s) with an unknown antibiotic resistance profile. Some recent clinical trials have been unable to demonstrate superior efficacy of combination therapy over monotherapy. Other trials have shown a benefit of combination therapy in defined circumstances consistent with recent studies indicating that factors including species, strain, resistance profile, and microenvironment affect drug combination efficacy and drug interactions. In this review, we discuss how a careful study design that takes these factors into account, along with the different drug interaction and potency metrics for assessing combination performance, may provide the necessary insight to understand the best clinical use-cases for combination therapy.

Hypervirulent Klebsiella pneumoniae infection in a woman with a CDH1 gene mutation.

The CDH1 gene, which encodes E-cadherin, may be associated with cancer when mutated, but the significance of mutations in the context of infection is unknown. In this report, we describe a case of disseminated hypervirulent Klebsiella pneumoniae infection in a 49 year old Caucasian woman with a documented CDH1 mutation.