Cost-effectiveness analysis of rivaroxaban plus aspirin versus aspirin alone in secondary prevention among patients with chronic cardiovascular diseases.

PURPOSE: This study aimed to investigate the cost-effectiveness of low-dose rivaroxaban plus aspirin versus aspirin alone for patients with stable cardiovascular diseases in the Taiwan setting. METHODS: We constructed a Markov model to project the lifetime direct medical costs and quality-adjusted life-years of both therapies. Transitional probabilities were derived from the COMPASS trial, and the costs and utilities were obtained from the Taiwan National Health Insurance Database and published studies. One-way, scenario, subgroup, and probabilistic sensitivity analyses were performed to assess the uncertainty. Incremental cost-effectiveness ratio was presented as the outcome. The threshold of willingness-to-pay was set at US$76,368 (3 times the gross domestic product per capita of Taiwan). All analyses were operated by TreeAge 2019 and Microsoft Excel. RESULTS: The incremental cost-effectiveness ratios of rivaroxaban plus aspirin versus aspirin alone in the patients with stable cardiovascular diseases, coronary artery diseases, and peripheral artery diseases were US$83,459, US$69,852 and -US$13,823 per quality-adjusted life-year gained, respectively. The probabilistic sensitivity analyses showed that the probabilities of cost-effectiveness for the regimen with rivaroxaban among those with cardiovascular diseases and coronary artery diseases were 44.1% and 65.3% at US$76,368. CONCLUSION: Low-dose rivaroxaban plus aspirin is less likely to be a cost-effective alternative to aspirin in secondary prevention for the patients with stable cardiovascular diseases; however, among these patients, the regimen may have pharmacoeconomic incentives for the group merely having chronic coronary artery diseases from the Taiwan national payer's perspective. The pharmacoeconomic incentives are influenced by the drug price, event treatment fees, and willingness-to-pay threshold.

In vitro and in vivo antibacterial activity of tigecycline against Vibrio vulnificus.

BACKGROUND/PURPOSE: The aim of this study is to investigate the role of tigecycline in Vibrio vulnificus infection. METHODS: Eight randomly selected clinical V. vulnificus isolates were studied to obtain the minimal inhibitory concentrations (MICs) of minocycline, cefotaxime, and tigecycline, and the time-kill curves of tigecycline alone or in combination with other drugs. A peritonitis mouse model was used for the evaluation of the therapeutic efficacy of tigecycline alone or cefotaxime in combination with minocycline or tigecycline. RESULTS: The MIC of minocycline, cefotaxime, and tigecycline for eight clinical V. vulnificus isolates was 0.06-0.12 µg/mL, 0.03-0.06 µg/mL, and 0.03-0.06 µg/mL, respectively. In time-killing studies, at the concentration of 1 × MIC, the inhibitory effect of tigecycline persisted for 24 hours in five of eight isolates. With 2 × MIC and trough level, the inhibitory effect was noted in all isolates for 24 hours. With the combination of minocycline plus cefotaxime and tigecycline plus cefotaxime at 1/2 × MIC, the bactericidal effect was noted in 25% and 62.5% of eight isolates and synergism in 50% and 75% of isolates. With a low (1.25 × 105 CFU/mL) inoculum, all infected mice survived with tigecycline alone, tigecycline plus cefotaxime, or minocycline plus cefotaxime on the 14th day. At the inoculum of 1.25 × 106 CFU, the survival rate was 33.3% on the 14th day in the tigecycline plus cefotaxime-treated group, but none of the mice treated by tigecycline alone or minocycline plus cefotaxime survived (33.3% vs. 0%, p = 0.01 by Fisher's exact test). CONCLUSION: Our in vitro combination and animal studies indicate that tigecycline could be an option for the treatment of invasive V. vulnificus infections.

RNA polymerase B subunit gene mutations in biofilm-embedded methicillin-resistant Staphylococcus aureus following rifampin treatment.

BACKGROUND/PURPOSE: This study was conducted to compare the mutation rates of different rpoB sites and rifampin minimum inhibitory concentration (MIC) changes prior to and after rifampin therapy for biofilm-embedded methicillin-resistant Staphylococcus aureus (MRSA) isolates. METHODS: The screening of rifampin-resistant MRSA isolates, from the biofilm at Day 5 with or without exposure to the susceptible breakpoint concentration of rifampin recommended by the Clinical and Laboratory Standards Institute (1 mg/L), was conducted using agar plates containing rifampin. A partial fragment of RNA polymerase B subunit gene (rpoB), including clusters I and II, was amplified and sequenced. The rifampin MIC values and mutation frequencies at different sites of rpoB were measured and evaluated in rifampicin-resistant isolates. RESULTS: Rifampin-resistant mutants could be selected from all of 39 randomly selected rifampin-susceptible MRSA isolates in the biofilm model. The spontaneous mutation frequency ranged from 1.00 × 10(-4) to 3.85 × 10(-7). Mutation at codon 481 was most commonly found at 35 (89.7%) of 39 MRSA isolates. Without rifampin induction, the MIC ranged between 0.125 mg/L and1024 mg/L and mutation sites included cluster I 464, 466, 468, 471, 474, 477, 481, 484, 486 and cluster II 519, 527, 529 with the percentage of 471 (35.9%), 477 (33.3%), 481 (53.8%), and 484 (35.9%). Conversely, with the induction of rifampin, the MIC value ranged ∼256-1024 mg/L. The mutation sites that were more concentrated included 468 (17.9%), 477 (30.8%), 481 (89.7%), 484 (17.9%), and 486 (33.3%). CONCLUSION: We documented high rifampin resistance induction activity when MRSA was engaged in biofilm with rifampin exposure. Monotherapy seems to be inadequate for MRSA in biofilm. There is an urgent need for developing effective combination therapies with less rifampin resistance-inducing activities for treating MRSA in biofilms.

Correlation between carbapenem consumption and resistance to carbapenems among Enterobacteriaceae isolates collected from patients with intra-abdominal infections at five medical centers in Taiwan, 2006-2010.

We investigated the trend in resistance to carbapenems among isolates of Enterobacteriaceae that had been collected from patients with intra-abdominal infections at five medical centers in Taiwan from 2006 to 2010 and evaluated the correlation between resistance to carbapenems and consumption of said agents as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). During the study period, the usage of ertapenem and that of total carbapenems (ertapenem, imipenem, and meropenem) increased significantly from 6.13 to 13.38 defined daily doses per 1000 patient-days for ertapenem and from 20.43 to 34.25 defined daily doses per 1000 patient-days for total carbapenems. The most common species were Escherichia coli (n = 1095), Klebsiella spp. (n = 663), and Enterobacter spp. (n = 202). The susceptibility of all isolates to ertapenem and to imipenem varied during the study period. For ertapenem, the rates of nonsusceptibility ranged from 3.5% to 10.3% and those for imipenem ranged from 3.5% to 10.7%. Although the use of carbapenems increased during the study period, there was no marked increase in resistance to carbapenems. Continuous monitoring of resistance trends is necessary so that antimicrobial prescription policies can be adjusted and infection control intervention programs can be implemented.