Jack Brown

Vancomycin AUC24/MIC Ratio in Patients with Complicated Bacteremia and Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus and Its Association with Attributable Mortality during Hospitalization

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of complicated bacteremia (CB) and infective endocarditis (IE). The gold standard treatment for these infections is vancomycin. A vancomycin area under the concentration-time curve from 0 to 24 h (AUC24)/MIC ratio of >400 has been suggested as a target to achieve clinical effectiveness, and yet to date no study has quantitatively investigated the AUC24/MIC ratio and its association with attributable mortality (AM). We performed a review of patients treated for MRSA CB and IE from 1 July 2006 to 30 June 2008. AM was defined as deaths where CB or IE was documented as the main cause or was mentioned as the main diagnosis. Classification and regression tree analysis (CART) was used to identify the AUC24/MIC ratio associated with AM. Mann-Whitney and Fisher exact tests were used for univariate analysis, and logistic regression was used for multivariate modeling. The MICs were determined by Etest, and the AUC24 was determined using a maximum a posteriori probability-Bayesian estimator. A total of 32 CB and 18 IE patients were enrolled. The overall crude mortality and AM were 24 and 16%, respectively. The CART-derived partition for the AUC24/MIC ratio and AM was <211. Patients with an AUC24/MIC ratio of <211 had a >4-fold increase in AM than patients who received vancomycin doses that achieved an AUC24/MIC ratio of ≥211 (38 and 8%, respectively; P = 0.02). In bivariate analysis the APACHE-II score and an AUC24/MIC ratio of <211 were significantly associated with AM. In the multivariate model, the APACHE-II score (odds ratio, 1.24; P = 0.04) and a vancomycin AUC/MIC ratio of <211 (odds ratio, 10.4; P = 0.01) were independent predictors of AM. In our analysis, independent predictors of AM were the APACHE-II score and an AUC24/MIC ratio of <211. We believe further investigations are warranted.

Consensus summary of aerosolized antimicrobial agents: application of guideline criteria. Insights from the Society of Infectious Diseases Pharmacists.

Aerosolized delivery of antimicrobial agents is an attractive option for management of pulmonary infections, as this is an ideal method of providing high local drug concentrations while minimizing systemic exposure. With the paucity of consensus regarding the safety, efficacy, and means with which to use aerosolized antimicrobials, a task force was created by the Society of Infectious Diseases Pharmacists to critically review and evaluate the literature on the use of aerosolized antiinfective agents. This article summarizes key findings and statements for preventing or treating a variety of infectious diseases, including cystic fibrosis, bronchiecstasis, hospital acquired pneumonia, fungal infections, nontuberculosis mycobacterial infection, and Pneumocystis jiroveci pneumonia. Our intention was to provide guidance for clinicians on the use of aerosolized antibiotics through evidence based pharmacotherapy. Further research with well designed clinical trials is necessary to elucidate the optimal dosage and duration of therapy and, of equal importance, to appreciate the true risks associated with the use of aerosolized delivery systems.

Colon-Targeted Oral Drug Delivery Systems: Design Trends and Approaches

Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn’s disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

Impact of rapid methicillin-resistant Staphylococcus aureus polymerase chain reaction testing on mortality and cost effectiveness in hospitalized patients with bacteraemia: a decision model.

AbstractBackground: Patients hospitalized with Staphylococcus aureus bacteraemia have an unacceptably high mortality rate. Literature available to date has shown that timely selection of the most appropriate antibacterial may reduce mortality. One tool that may help with this selection is a polymerase chain reaction (PCR) assay that distinguishes methicillin (meticillin)-resistant S. aureus (MRSA) from methicillin-susceptible S. aureus (MSSA) in less than 1 hour. To date, no information is available evaluating the impact of this PCR technique on clinical or economic outcomes. Objective: To evaluate the effect of a rapid PCR assay on mortality and economics compared with traditional empiric therapy, using a literaturederived model. Methods: A literature search for peer-reviewed European (EU) and US publications regarding treatment regimens, outcomes and costs was conducted. Information detailing the rates of infection, as well as the specificity and sensitivity of a rapid PCR assay (Xpert MRSA/SA Blood Culture PCR®) were obtained from the peer-reviewed literature. Sensitivity analysis varied the prevalence rate of MRSA from 5% to 80%, while threshold analysis was applied to the cost of the PCR test. Hospital and testing resource consumption were valued with direct medical costs, adjusted to year 2009 values. Adjusted life-years were determined using US and WHO life tables. The cost-effectiveness ratio was defined as the cost per life-year saved. Incremental cost-effectiveness ratios (ICERs) were calculated to determine the additional cost necessary to produce additional effectiveness. All analyses were performed using TreeAge Software (2008). Results: The mean mortality rates were 23% for patients receiving empiric vancomycin subsequently switched to semi-synthetic penicillin (SSP) for MSSA, 36% for patients receiving empiric vancomycin treatment for MRSA, 59% for patients receiving empiric SSP subsequently switched to vancomycin for MRSA and 12% for patients receiving empiric SSP for MSSA. Furthermore, with an MRSA prevalence of 30%, the numbers of patients needed to test in order to save one life were 14 and 16 compared with empiric vancomycin and SSP, respectively. The absolute mortality difference for MRSA prevalence rates of 80% and 5% favoured the PCR testing group at 2% and 10%, respectively, compared with empiric vancomycin and 18% and 1%, respectively, compared with empiric SSP. In the EU, the cost-effectiveness ratios for empiric vancomycin- and SSP-treated patients were h695 and h687 per life-year saved, respectively, compared with h636 per life-year saved for rapid PCR testing. In the US, the cost-effectiveness ratio was

Inpatient costs, mortality and 30-day re-admission in patients with central-line-associated bloodstream infections.

US898 per life-year saved for empiric vancomycin and

Differential risk of Clostridium difficile infection with proton pump inhibitor use by level of antibiotic exposure

US820 per life-year saved for rapid PCR testing. ICERs demonstrated dominance of the PCR test in all instances. Threshold analysis revealed that PCR testing would be less costly overall, even at greatly inflated assay prices. Conclusion: Rapid PCR testing for MRSA appears to have the potential to reduce mortality rates while being less costly than empiric therapy in the EU and US, across a wide range of MRSA prevalence rates and PCR test costs.

Cost Effectiveness of Respiratory Syncytial Virus Prophylaxis: A Critical and Systematic Review

Previous work has suggested that central-line-associated bloodstream infection (CLABSI) is associated with increased costs and risk of mortality; however, no studies have looked at both total and variable costs, and information on outcomes outside of the intensive-care unit (ICU) is sparse. The aim of this study was to determine the excess in-hospital mortality and costs attributable to CLABSI in ICU and non-ICU patients. We conducted a retrospective cohort and cost-of-illness study from the hospital perspective of 398 patients at a tertiary-care academic medical centre from 1 January 2008 to 31 December 2010. All CLABSI patients and a simple random sample drawn from a list of all central lines inserted during the study period were included. Generalized linear models with log link and gamma distribution were used to model costs as a function of CLABSI and important covariates. Costs were adjusted to 2010 US dollars by use of the personal consumption expenditures for medical care index. We used multivariable logistic regression to identify independent predictors of in-hospital mortality. Among both ICU and non-ICU patients, adjusted variable costs for patients with CLABSI were c.

Alternative Therapies for Clostridium difficile Infections

32 000 (2010 US dollars) higher on average than for patients without CLABSI. After we controlled for severity of illness and other healthcare-associated infections, CLABSI was associated with a 2.27-fold (95% CI 1.15-4.46) increased risk of mortality. Other healthcare-associated infections were also significantly associated with greater costs and mortality. Overall, CLABSI was associated with significantly higher adjusted in-hospital mortality and total and variable costs than those for patients without CLABSI.

Predictors of agr Dysfunction in Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates among Patients with MRSA Bloodstream Infections

Clostridium difficile infection (CDI) is a major cause of hospital‐acquired diarrhea worldwide. We examined the risk of CDI associated with the use of acid‐suppressive agents (proton pump inhibitors [PPI] and histamine‐2 receptor blockers) and determined whether this risk varied by number or type of antibiotic (high or low CDI risk) received during hospitalization.

Impact of pharmacist intervention on clinical outcomes in the palliative care setting.

Respiratory syncytial virus (RSV) is the leading cause of infant hospitalization in the US. The economic burden of severe disease is substantial, including hospitalization costs and out-of-pocket expenses. RSV prophylaxis with either RSV immune globulin intravenous (RSV-IGIV) or palivizumab has been shown to be effective in reducing RSV-related hospitalizations. Motavizumab, a new enhanced-potency humanized RSV monoclonal antibody, is presently in clinical trials. RSV-IGIV and palivizumab are associated with high acquisition costs. Cost-effectiveness analyses are therefore of great importance in helping to determine who should receive RSV prophylaxis. Six studies have analysed the cost effectiveness of RSV-IGIV, 14 have analysed the cost effectiveness of palivizumab and five have analysed the cost effectiveness of both agents, two of which directly compared palivizumab with RSV-IGIV. The cost effectiveness of motavizumab has not been studied.Significant variation exists in the modelling used in these analyses. Many studies have examined short-term benefits such as reducing hospitalizations and associated costs, while fewer studies have examined long-term benefits such as QALYs or life-years gained. The payer and society have been the most common perspectives used. The endpoints examined varied and generally did not account for the potential impact of RSV prophylaxis on RSV-related complications such as asthma. While some studies have reported acceptable cost-effectiveness ratios for RSV prophylaxis, the majority failed to show cost savings or cost-effectiveness ratios below commonly accepted thresholds for either RSV-IGIV or palivizumab. Cost effectiveness of RSV prophylaxis tended to be more favourable in populations with specific risk factors, including premature infants ≤32 weeks’ gestational age, and infants or children aged <2 years with chronic lung disease or congenital heart disease.Comparing the results of economic analyses of the two agents suggests palivizumab may be the more cost-effective option in the population for which RSV prophylaxis is recommended. Over time, the acquisition cost of RSV prophylaxis agents, a major cost driver, may decrease, and more acceptable outcomes of economic analyses may result. Albeit important, the results of economic analyses are not the only tool that decision makers rely on, as population-specific risk factors, and efficacy and safety data must be considered when developing treatment guidelines and making clinical decisions.