Loss of daptomycin susceptibility in clinical Staphylococcus epidermidis infection coincided with variants in WalK

Abstract

Daptomycin (DAP) is key in treating multidrug-resistant Staphylococcus infections. Diminished susceptibility to DAP is emerging among Staphylococcus epidermidis strains although mechanisms for non-susceptibility (NS) remain poorly understood. We report a case of persistent S. epidermidis bacteremia in which loss of DAP susceptibility arose during prolonged treatment. Whole genome sequencing identified two mutations, Q371del and P415L, in a single-affected gene, WalK, that coincided with the emergence of DAP-NS. Protein modeling of the mutations predicted a disruption of WalK protein configuration. The emergence of mutations in a single-gene during DAP exposure raises concerns in an era of increasingly treatment-resistant infections. Lay summary: Daptomycin is an important antibiotic for fighting Staphylococcus infections. We identified variants in the WalK gene that were coincident with resistance in a clinical Staphylococcus epidermidis infection. Clinicians, hospital epidemiologists, and microbiology laboratories need to be aware of the potential for the evolution of drug resistance during prolonged daptomycin therapy.

Keywords: Staphylococcus epidermidis; antibiotic resistance; daptomycin.

Figure 1.

Timeline of clinical course: The clinical course of the patient (middle) with clinical events demarcated in circles while boxes indicate blood cultures (grey box: no growth; pink box: positive growth). The treatment regimen with days of antibiotic use is included (bottom) alongside the bloodstream isolate collection with susceptibility testing (top). VAD, ventricular assist device; SE, Staphylococcus epidermidis; NG, no growth; S, susceptible; NS, non-susceptible.