Cost-effectiveness analysis of treatment strategies for initial Clostridium difficile infection.

Clostridium difficile infection (CDI) is costly. Current guidelines recommend metronidazole as first-line therapy and vancomycin as an alternative. Recurrence is common. Faecal microbiota transplantation (FMT) is an effective therapy for recurrent CDI (RCDI). This study explores the cost-effectiveness of FMT, vancomycin and metronidazole for initial CDI. We constructed a decision-analytic computer simulation using inputs from published literature to compare FMT with a 10-14-day course of oral metronidazole or vancomycin for initial CDI. Parameters included cure rates (baseline value (range)) for metronidazole (80% (65-85%)), vancomycin (90% (88-92%)) and FMT(91% (83-100%)). Direct costs of metronidazole, vancomycin and FMT, adjusted to 2011 dollars, were $57 ($43-72), $1347 ($1195-1499) and $1086 ($815-1358), respectively. Our effectiveness measure was quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were conducted from the third-party payer perspective. Analysis using baseline values showed that FMT($1669, 0.242 QALYs) dominated (i.e. was less costly and more effective) vancomycin ($1890, 0.241 QALYs). FMT was more costly and more effective than metronidazole ($1167, 0.238 QALYs), yielding an incremental cost-effectiveness ratio (ICER) of $124 964/QALY. One-way sensitivity analyses showed that metronidazole dominated both strategies if its probability of cure were >90%; FMT dominated if it cost <$584. In a probabilistic sensitivity analysis at a willingness-to-pay threshold of $100 000/QALY, metronidazole was favoured in 55% of model iterations; FMT was favoured in 38%. Metronidazole, as the first-line treatment for CDIs, is less costly. FMT and vancomycin are more effective. However, FMT is less likely to be economically favourable, and vancomycin is unlikely to be favourable as first-line therapy when compared with FMT.

Cost-effectiveness of adding decolonization to a surveillance strategy of screening and isolation for methicillin-resistant Staphylococcus aureus carriers.

We compared the cost-effectiveness of a methicillin-resistant Staphylococcus aureus (MRSA) programme of active surveillance plus decolonization with the current Veterans Health Administration (VHA) strategy of active surveillance alone, as well as a common strategy of no surveillance. A decision-analytical model was developed for an inpatient stay time horizon, using the VHA's perspective. Model inputs were taken from published literature where available, and supplemented with expert opinion when necessary. Effectiveness outcomes were hospital-acquired MRSA infections and deaths avoided. One-way and two-way sensitivity analyses and Monte Carlo simulations were performed. In the base-case analysis, the strategy of active surveillance plus decolonization dominated (i.e. lower cost and greater effectiveness) both the comparison strategies of active surveillance and no surveillance. In addition, the active surveillance strategy dominated the strategy of no surveillance. One-way and two-way sensitivity analyses demonstrated that at low levels of direct benefit of decolonization (1-4%), the strategy of active surveillance plus decolonization would no longer be dominant. In the probabilistic sensitivity analysis, active surveillance plus decolonization dominated both the other two strategies, and the active surveillance strategy dominated no surveillance in all of 1000 Monte Carlo simulations. These results provide a strong economic argument for adding an MRSA decolonization protocol to the current VHA active surveillance strategy.

Synthesis and bioaccessibility of Fe-pheophytin derivatives from crude spinach extract.

Heme iron is recognized as a highly bioavailable source of iron suitable for treatment of iron deficiency anemia. However, the animal origin of purified heme limits its broad applicability due to religious, personal, and food safety issues. Development of chlorophyll-derived heme mimetics offers opportunities to expand current iron fortification strategies. The objective of this study was the synthesis of Fe-pheophytin (FePhe) derivatives from natural chlorophyll and subsequent evaluation of their digestive behavior and bioaccessibility in vitro. FePhe a and a' were synthesized from crude spinach extracts by treatment with 1.3 M iron(II)chloride and 0.25 M Na-acetate dissolved in glacial acetic acid at 80 degrees C for 30 min. FePhe-rich extracts (approximately 1 mM) were formulated into corn starch based test meals (7.5% lipid) and subjected to a 2-step in vitro digestion designed to simulate in vivo gastric and small intestinal conditions. Recovery of FePhe following digestion and transfer of FePhe and pheophytins (Phe) from test meal matrix to mixed micelles was assessed by RP C18-HPLC to determine the digestive stability and micellarization efficiency (bioaccessibility). FePhe a and a' derivatives were moderately stable to digestive conditions with recoveries of 52.3% and 58.7%, respectively. Residual Phe a was stable to digestion. Micellarization efficiency of FePhe a (4%) and a' (3.4%) was significantly (P < 0.05) lower than Phe a (25.8%) from test meals. While digestive stability and micellarization efficiency are limiting, the presence of lipophilic FePhe derivatives in mixed micelles suggests that these compounds would be available for subsequent absorption in the intestinal tract.