Antibiotic activity against small-colony variants of Staphylococcus aureus: review of in vitro, animal and clinical data.

The pathogen Staphylococcus aureus uses various strategies for persisting in the host, among which switching to a small-colony variant (SCV) phenotype is of particular biological and therapeutic significance. Phenotypically, SCVs are characterized by a slow growth rate, atypical colony morphology and unusual biochemical features, constituting a real challenge for identification by the clinical microbiology laboratory. Their metabolic defects also alter their susceptibility to antibiotics, which, combined with the ability to survive intracellularly and, for some strains, to form biofilms, largely contributes to therapeutic failures. This paper reviews the available literature on antibiotic activity against SCVs of S. aureus in vitro, in animal models and in clinics. In vitro, aminoglycosides and antifolate agents show high MICs for electron-transport-defective and thymidine-dependent SCVs, respectively. The other antibiotic classes usually show MICs comparable to those measured for the parental strains, but they are less bactericidal. Intracellularly, auxotrophs for thymidine, haemin or menadione show contrasting behaviours with respect to their response to antibiotics, resulting from differences in their intracellular fate. In animal models, SCVs often persist in various locations, including metastatic ones, in spite of the administration of active antibiotics. In healthcare, several case reports mention the selection of SCVs after prolonged administration of not only aminoglycosides and antifolate agents, but also several other antibiotic classes. Apparent eradication requires several weeks or even months of aggressive polytherapy combined, whenever possible, with surgical intervention. Further research is thus warranted for optimizing the treatment of infections caused by SCVs.Journal ArticleResearch Support, Non-U.S. Gov'tReviewSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Improving antiretroviral therapy adherence in resource-limited settings at scale: a discussion of interventions and recommendations

Abstract Introduction:: Successful population-level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale-up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource-limited settings. Methods:: In July 2015, the Bill and Melinda Gates Foundation convened a meeting to discuss the most promising ART adherence interventions for use at scale in resource-limited settings. This article summarizes that discussion with recent updates. It is not a systematic review, but rather provides practical considerations for programme implementation based on evidence from individual studies, systematic reviews, meta-analyses, and the World Health Organization Consolidated Guidelines for HIV, which include evidence from randomized controlled trials in low- and middle-income countries. Interventions are categorized broadly as education and counselling; information and communication technology-enhanced solutions; healthcare delivery restructuring; and economic incentives and social protection interventions. Each category is discussed, including descriptions of interventions, current evidence for effectiveness, and what appears promising for the near future. Approaches to intervention implementation and impact assessment are then described. Results and discussion: The evidence base is promising for currently available, effective, and scalable ART adherence interventions for resource-limited settings. Numerous interventions build on existing health care infrastructure and leverage available resources. Those most widely studied and implemented to date involve peer counselling, adherence clubs, and short message service (SMS). Many additional interventions could have an important impact on ART adherence with further development, including standardized counselling through multi-media technology, electronic dose monitoring, decentralized and differentiated models of care, and livelihood interventions. Optimal targeting and tailoring of interventions will require improved adherence measurement. Conclusions:: The opportunity exists today to address and resolve many of the challenges to effective ART adherence, so that they do not limit the potential of ART to help bring about the end of AIDS