Adaptation of Enterococcus faecalis to daptomycin reveals an ordered progression to resistance.

With increasing numbers of hospital-acquired antibiotic resistant infections each year and staggering health care costs, there is a clear need for new antimicrobial agents, as well as novel strategies to extend their clinical efficacy. While genomic studies have provided a wealth of information about the alleles associated with adaptation to antibiotics, they do not provide essential information about the relative importance of genomic changes, their order of appearance, or potential epistatic relationships between adaptive changes. Here we used quantitative experimental evolution of a single polymorphic population in continuous culture with whole-genome sequencing and allelic frequency measurements to study daptomycin (DAP) resistance in the vancomycin-resistant clinical pathogen Enterococcus faecalis S613. Importantly, we sustained both planktonic and nonplanktonic (i.e., biofilm) populations in coculture as the concentration of antibiotic was raised, facilitating the development of more ecological complexity than is typically observed in laboratory evolution. Quantitative experimental evolution revealed a clear order and hierarchy of genetic changes leading to resistance, the signaling and metabolic pathways responsible, and the relative importance of these mutations to the evolution of DAP resistance. Despite the relative simplicity of this ex vivo approach compared to the ecological complexity of the human body, we showed that experimental evolution allows for rapid identification of clinically relevant adaptive molecular pathways and new targets for drug design in pathogens.

A giant cavernous hemangioma of the liver extending into the pelvis.

INTRODUCTION: Giant cavernous hemangiomas are the most common tumors of the liver, ocurring in up to 20% of the general population. Given their benign course, asymptomatic nature and slow growth rate, treatment is rarely indicated. The case presented herein is unique as it describes an uncommon presentation of this common tumor and the circumstances in which surgical treatment is beneficial. PRESENTATION OF CASE: We present a case of a 66 year-old patient with prostate cancer referred for evaluation of a massive 37cm giant liver hemangioma, extending into the pelvis and in the planned field of radiation for prostate cancer, exhibiting rapid growth, and associated with significant symptomatology. Given these clinical characteristics, the patient was offered surgery and underwent a left trisectionectomy with an uneventful recovery. The patient's symptoms resolved and he was able to complete radiation to the pelvis. DISCUSSION: In the context of an unusual presentation, this case presentation reviews the typical clinical and imaging characteristics of giant liver hemangiomas and expands on the current indications for treatment, emphasizing the role of enucleation and resection for patients meeting appropriate indications. CONCLUSION: Although liver hemangiomas are extremely common, surgical treatment is rarely required. With appropriate indications, and when enucleation is not feasible or ideal, major liver resection is a safe alternative approach with excellent outcomes when performed in the right setting.