Clearance Confusion: An Exploratory Analysis of Inpatient Dosing Discordances Between Renal Estimating Equations.

BACKGROUND: Numerous equations exist for estimating renal clearance for drug dosing, and discordance rates may be as high as 40% in certain populations. However, the populations and types of equations used in these studies may not be generalizable to broader pharmacy practice. OBJECTIVES: To determine the dosing discordance rate between Cockcroft-Gault (C-G), Chronic Kidney Disease Epidemiology (CKD-EPI), and Modification of Diet in Renal Disease (MDRD) equations in a community hospital population. METHODS: This was a cross-sectional analysis of inpatients who had documented renal function assessment over a 6-month period. Renal estimation was calculated using 5 equations (MDRD, CKD-EPI, and 3 C-G variants). Differences between equations were assessed using mean bias, dosing discordance, and agreement (κ statistic). Patients with acute kidney injury and those requiring renal replacement therapy were excluded. RESULTS: A total of 466 patients were eligible for inclusion. Dosing discordance was evident between C-G variants and both MDRD and CKD-EPI equations in greater than 20% of patients. Agreement was highest between MDRD and CKD-EPI (κ = 0.93) and lowest between MDRD and C-G calculated using ideal body weight (κ = 0.33). The majority of discordant instances led to higher dosing recommendations when using MDRD and CKD-EPI equations compared with C-G variants. Dosing discordance exceeded 18% between the different C-G variants, with the highest discordance (36%) observed between total body weight and ideal body weight variants. CONCLUSION AND RELEVANCE: Dosing discordance between renal estimating equations is widespread. Practitioners and institutions should be aware of these differences when dosing medications and implementing renal dosing policies.

Relationship between day 1 and day 2 Vancomycin area under the curve values and emergence of heterogeneous Vancomycin-intermediate Staphylococcus aureus (hVISA) by Etest® macromethod among patients with MRSA bloodstream infections: a pilot study.

BACKGROUND: In vitro data suggests that suboptimal initial vancomycin exposure may select for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections. However, no clinical studies have evaluated the relationship between initial vancomycin exposure and emergence of hVISA. This pilot study seeks to assess the relationship between day 1 and day 2 vancomycin area under the curve (AUC) and emergence of hVISA bloodstream infections (BSIs) by Etest® macromethod among patients with a non-hVISA BSI at baseline. METHODS: This was a retrospective cohort study of patients with methicillin-resistant Staphylococcus aureus (MRSA) BSIs at Albany Medical Center Hospital (AMCH) between January 2005 and June 2009. The vancomycin AUC exposure variables on day 1 (AUC0-24h) and day 2 (AUC24-48h) were estimated using the maximal a posteriori probability (MAP) procedure in ADAPT 5. RESULTS: There were 238 unique episodes of MRSA BSIs during the study period, 119 of which met inclusion criteria. Overall, hVISA emerged in 7/119 (5.9%) of patients. All 7 cases of hVISA involved patients who did not achieve area under the curve over broth microdilution minimum inhibitory concentration (AUC0-24h/MICBMD) ratio of 521 or an AUC24-48h/MICBMD ratio of 650. No associations between other day 1 and day 2 AUC variables and emergence of hVISA were noted. CONCLUSIONS: Although more data are needed to draw definitive conclusions, these findings suggest that hVISA emergence among patients with non-hVISA MRSA BSIs at baseline may be partially explained by suboptimal exposure to vancomycin in the first 1 to 2 days of therapy. At a minimum, these findings support further study of the relationship between initial vancomycin exposure and hVISA emergence among patients with MRSA BSIs in a well-powered, multi-center, prospective trial.

Emerging trends in epidemiology and management of infections caused by carbapenem-resistant Enterobacteriaceae.

The recent emergence and spread of infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are concerning because carbapenems have represented a last line of defense against resistant strains of gram-negative pathogens. Existing therapies against CRE include tigecycline, the recently approved drug ceftazidime-avibactam, and older drugs not widely used in recent years, such as colistin, fosfomycin, and aminoglycosides. Best practices for use of the available drugs are not well defined. New therapeutic options with activity against CRE offer the opportunity to enhance our current approach to managing patients with infections due to CRE. The purpose of this report is to review the evolving epidemiology and treatment of infections due to CRE. As part of the treatment overview, this manuscript will discuss supportive data for antibiotics currently being used in the treatment of infections due to CRE, as well as those recently approved and in late-stage development.