Translational research : the journal of laboratory and clinical medicine
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Wound infections associated with multidrug-resistant (MDR) bacteria are one of the important threats to public health. Bacteriophage (phage) therapy is a promising alternative or supplementary therapeutic approach to conventional antibiotics for combating MDR bacterial infections. In recent years, significant effort has been put into the development of phage formulations and delivery methods for topical applications, along with preclinical and clinical uses of phages for the treatment of acute and chronic wound infections. This paper reviews the application of phages for wound infections, with focus on the current status of phage formulations (including liquid, semi-solid and liposome-encapsulated formulations, phage-immobilized wound dressings), safety and efficacy assessment in clinical settings and major challenges to overcome.
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Clostridioides difficile infection (CDI) is an urgent threat to global public health. Patient susceptibility to C. difficile is highly dependent on host immune status and gut dysbiosis resulting in loss of protective microbiota consortia that prevent spore germination, pathogen colonization, and disease pathogenesis. Recent clinical studies highlight the problems of differentiating symptomatic CDI from asymptomatic C. difficile carriage in patients with diarrhea. In this review, we consider how integration of microbiome and host immune systems biology data may aid in the clinical diagnosis of CDI when validated against gold standard testing and combined with standard microbiology laboratory assays.
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Community acquired pneumonia is a leading cause of mortality in the United States. Along with predisposing comorbid health status, age is an independent risk factor for determining the outcome of pneumonia. Research over the last few decades has contributed to better understanding the underlying immunodysregulation and imbalanced redox homeostasis tied to this aged population group that increases susceptibility to a wide range of pathologies. ⋯ Mitochondria-targeted antioxidants have a number of molecular strategies that include targeting the biophysical properties of mitochondria, mitochondrial localization of catalytic enzymes, and mitigating mitochondrial membrane potential. Results of several antioxidant studies both in vitro and in vivo have demonstrated promising potential as a therapeutic in the treatment of pneumonia in the elderly. More human studies will need to be conducted to evaluate its efficacy in this clinical setting.
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Despite advances in antimicrobial treatments, infection remains a common complication of intensive chemotherapy in patients with acute leukemia. It has become progressively apparent that the current antimicrobial focus has shortcomings that result from disruption of the commensal microbial communities of the gut. ⋯ Several innovative concepts have been proposed and tested in animal models and humans, with the overarching goal of preventing damage to the microbiota and facilitating its recovery. In this review, we discuss these approaches, examine critical knowledge gaps, and explore how they may be filled in future research.
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Antimicrobial resistance poses a significant threat to our ability to treat infections. Especially concerning is the emergence of carbapenem-resistant Enterobacteriaceae (CRE). In the new 2019 United States Centers for Disease Control and Prevention Antibiotic Resistance Report, CRE remain in the most urgent antimicrobial resistance threat category. ⋯ This article reviews recently approved agents with activity against CRE and a range of modalities in the pipeline, from early academic investigation to those in clinical trials, with a focus on structural aspects of new antibiotics. Another article in this series addresses the need to incentive pharmaceutical companies to invest in CRE antimicrobial development and to encourage hospitals to make these agents available in their formularies. This article will also consider the need for change in requirements for antimicrobial susceptibility testing implementation in clinical laboratories to address practical roadblocks that impede our efforts to provide even existing CRE antibiotics to our patients.