Antibiotics2015, 4(3), 309-320; doi:10.3390/antibiotics4030309 (registering DOI) - published 24 July 2015 Show/Hide Abstract
Abstract: Infectious Diseases specialists have used high-dose daptomycin (≥6 mg/kg/day) in select patients with difficult to treat methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) infections to optimize outcomes. Antimicrobial stewardship programs enforce antimicrobial formulary restrictions; however, interventions specifically aimed at Infectious Disease specialists can be particularly challenging. The purpose of this study was to create a high-dose daptomycin algorithm for Infectious Disease specialists that are consistent with best-practices. Daptomycin prescribing habits pre- and post-daptomycin algorithm implementation were evaluated using a quasi-experimental study design. Patients were included if ≥18 years of age and received daptomycin for ≥48 h. Patients were excluded if daptomycin was initiated on an outpatient setting. During the 12-month pre-intervention phase, 112 patients were included, with 73 patients in the 12-month post-intervention phase. A statistically significant decrease in the mean daptomycin dose from 9.01 mg/kg to 7.51 mg/kg (p < 0.005) was observed, resulting in an annual drug cost-savings of over $75,000 without adversely affecting readmission rates due to infection. Creation of a daptomycin algorithm with consideration of pathogen, disease state, and prior treatment, is an effective means of influencing prescribing habits of Infectious Disease specialists.
Abstract: The use of antibiotics in animal husbandry has long been associated with the appearance of antibiotic resistance and virulence factor determinants. Nonetheless, the number of cases of human infection involving resistant or virulent microorganisms that originate in farms is increasing. While many antibiotics have been banned as dietary supplements in some countries, other additives thought to be innocuous in terms of the development and spread of antibiotic resistance are used as growth promoters. In fact, several clay materials are routinely added to animal feed with the aim of improving growth and animal product quality. However, recent findings suggest that sepiolite, a clay additive, mediates the direct transfer of plasmids between different bacterial species. We therefore hypothesize that clays present in animal feed facilitate the horizontal transfer of resistance determinants in the digestive tract of farm animals.
Abstract: Clostridium difficile infection (CDI) remains a substantial burden on healthcare systems and is likely to remain so given our reliance on antimicrobial therapies to treat bacterial infections, especially in an aging population in whom multiple co-morbidities are common. Antimicrobial agents are a key component in the aetiology of CDI, both in the establishment of the infection and also in its treatment. The purpose of this review is to summarise the role of antimicrobial agents in primary and recurrent CDI; assessing why certain antimicrobial classes may predispose to the induction of CDI according to a balance between antimicrobial activity against the gut microflora and C. difficile. Considering these aspects of CDI is important in both the prevention of the infection and in the development of new antimicrobial treatments.
Abstract: Fecal Microbiota Transplantation (FMT) methodology has been progressively refined over the past several years. The procedure has an extensive track record of success curing Clostridium difficile infection (CDI) with remarkably few adverse effects. It achieves similar levels of success whether the CDI occurs in the young or elderly, previously normal or profoundly ill patients, or those with CDI in Inflammatory Bowel Disease (IBD). While using FMT to treat CDI, however, we learned that using the procedure in other gastrointestinal (GI) diseases, such as IBD without CDI, generally fails to effect cure. To improve results in treating other non-CDI diseases, innovatively designed Randomized Controlled Trials (RCTs) will be required to address questions about mechanisms operating within particular diseases. Availability of orally deliverable FMT products, such as capsules containing lyophilised fecal microbiota, will simplify CDI treatment and open the door to convenient, prolonged FMT delivery to the GI tract and will likely deliver improved results in both CDI and non-CDI diseases.
Abstract: Clostridium difficile infection (CDI) is the most important cause of nosocomial diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the structure and diversity of the indigenous intestinal microbiota. These alterations often impair colonization resistance, allowing the establishment and proliferation of C. difficile in the gut. Studies involving animal models have begun to decipher the precise mechanisms by which the intestinal microbiota mediates colonization resistance against C. difficile and numerous investigations have described gut microbiota alterations associated with C. difficile colonization or infection in human subjects. Fecal microbiota transplantation (FMT) is a highly effective approach for the treatment of recurrent CDI that allows the restoration of a healthy intestinal ecosystem via infusion of fecal material from a healthy donor. The recovery of the intestinal microbiota after FMT has been examined in a few reports and work is being done to develop custom bacterial community preparations that could be used as a replacement for fecal material.
Abstract: Clostridium difficile infection (CDI) is known to be associated with prior exposure to many classes of antibiotics. Standard therapy for CDI (i.e., metronidazole and vancomycin) is associated with high recurrence rates. Although tetracycline derivatives such as tetracycline, doxycycline or tigecycline are not the standard therapeutic choices for CDI, they may serve as an alternative or a component of combination therapy. Previous tetracycline or doxycycline usage had been shown to have less association with CDI development. Tigecycline, a broad-spectrum glycylcycline with potency against many gram-positive or gram-negative pathogens, had been successfully used to treat severe or refractory CDI. The in vitro susceptibility of C. difficile clinical isolates to tigecycline in many studies showed low minimal inhibitory concentrations. Tigecycline can suppress in vitro toxin production in both historical and hypervirulent C. difficile strains and reduce spore production in a dose-dependent manner. Tetracycline compounds such as doxycycline, minocycline, and tigecycline possess anti-inflammatory properties that are independent of their antibiotic activity and may contribute to their therapeutic effect for CDI. Although clinical data are limited, doxycycline is less likely to induce CDI, and tigecycline can be considered one of the therapeutic choices for severe or refractory CDI.