Edward H. Eiland

Comparison of the Modification of Diet in Renal Disease and Cockcroft-Gault Equations for Antimicrobial Dosage Adjustments

Background: Direct measurement of glomerular filtration rate (GFR) is considered to be the most accurate method of assessing kidney function, albeit difficult and costly. With the derivation of the Modification of Diet in Renal Disease (MDRD) equation to estimate GFR in patients with chronic kidney disease, questions exist as to whether this method should be preferred over the Cockcroft–Gault (CG) equation when making dosage adjustments for renally eliminated antimicrobials. Objective: To determine whether a difference exists when making antimicrobial dosage adjustments in patients with chronic kidney disease based on estimation of GFR using the MDRD and CG equations. Methods: We conducted an observational analysis of 409 patients with chronic kidney disease who were admitted to a tertiary care facility with an inpatient dialysis center and nephrology unit. GFR was calculated using both the 4- or 6-variable MDRD equation and the CG equation and compared using correlation and Bland–Altman methodology. Dosage discordance rates of the selected antimicrobials were determined on the basis of manufacturer renal dose recommendations. Results: Average ± SD GFR for all patients using the CG equation was 34.8 ± 12 mL/min and, using the MDRD equation, was 40.2 ± 12 mL/min (absolute mean difference 5.40; 95% CI 4.66 to 6.15; p < 0.001). The correlation coefficient between the 2 estimations, among all patients, was excellent (r=0.80). The Bland–Altman plot yielded limits of agreement of -9.8 and 20.6; thus, the MDRD estimation may range from 9.8 mL/min below to 20.6 mL/min above the CG estimation for 95% of the cases. A discordance rate of 21–37% (p < 0.001) existed among the recommended dosing adjustments of the selected antimicrobials. Conclusions: This analysis demonstrated statistically significant differences between the CG and MDRD equations, resulting in different dosing recommendations in 21–37% of patients. The clinical significance of these differences is uncertain in the absence of data regarding clinical outcomes that would result from the use of the discordant doses.

Assessment of Vancomycin Dosing and Subsequent Serum Concentrations in Pediatric Patients

Background Because of concerns regarding increasing microbial resistance to vancomycin, adult treatment guidelines recommend higher trough concentrations based on the type of infectious process. Although these recommendations are not specific to pediatrics, the principles can be extrapolated. Desired higher trough serum concentrations will require escalated dosages of vancomycin in children. Objective: To evaluate current dosing regimens and subsequent trough serum concentrations of vancomycin in children, compare these to reference recommended dosages and guidelines, and predict a dosing equation to achieve desired serum concentrations. Methods: Pharmacokinetic parameters of children in a community teaching hospital who were prescribed vancomycin from January 2005 to May 2010 were evaluated in this retrospective chart review. Vancomycin dosing and subsequent serum concentrations were analyzed. Therapeutic serum concentrations were evaluated and compared to vancomycin prescribing and monitoring guidelines by year. Results: Four hundred thirty-five trough serum concentrations determined in 295 patients were analyzed. The average dosages, when evaluated by year, were 48 mg/kg/day (2005-2008) and 59 mg/kg/day (2009-2010). Using trough concentration recommendations of 5-15 mg/L, vancomycin regimens provided therapeutic trough concentrations 78% of the time from 2005 to 2008. Using 10-20 mg/L as the trough recommendations in 2009-2010, only 49% of serum concentrations reached a therapeutic level. Based on our predictive equation for children aged 1 month-18 years with normal renal function, a vancomycin dosage of 70 mg/kg/day is required to provide trough serum concentrations of 10 mg/L; a dosage of 85 mg/kg/day is required to provide trough serum concentrations of 15 mg/L. Conclusions: Our institution was primarily using vancomycin dosing regimens that were recommended in pediatric references (40-60 mg/kg/day), which resulted in subtherapeutic serum concentrations in our population based on new monitoring recommendations. Considering that the currently desired therapeutic trough concentrations of vancomycin are 10-20 mg/L, the total daily dosage should be increased.

Augmentation with Atypical Antipsychotics for Depression: A Review of Evidence‐Based Support from the Medical Literature

Major depressive disorder (MDD) is a chronic mental illness that affects an estimated 5–26% of adults at some time in their lives. Treatment is often started as pharmacotherapy using a single drug such as a selective serotonin reuptake inhibitor. If a patient fails to respond adequately to the initial antidepressant, typically three pharmacotherapy options are available to the practitioner. The dose of the current therapy can be maximized, a change can be made to a different drug, or the current regimen can be augmented with another drug. Atypical antipsychotics have recently become a major focus for augmentation of traditional antidepressant therapy.

Demonstrating the Value of Antimicrobial Stewardship Programs to Hospital Administrators

The movement away from fee-for-service models to those that emphasize quality of care and patient outcomes affords a unique opportunity for antimicrobial stewardship programs to expand their value for hospital administration. Antimicrobial stewardship participants must collaborate with administrators and key stakeholders to position themselves to improve economic, process, and outcomes measures. This will allow the establishment of antimicrobial stewardship programs as essential components of the present and future healthcare quality journey.

Assessing Appropriateness of Antimicrobial Therapy: In the Eye of the Interpreter

To address the increase of drug-resistant bacteria and widespread inappropriate use of antimicrobials, many healthcare institutions have implemented antimicrobial stewardship programs to promote appropriate use of antimicrobials and optimize patient outcomes. However, a consensus definition of appropriate use is lacking. We conducted a multicenter observational study to compare 4 definitions of appropriateness--a study site-specific definition, use supported by susceptibility data, use supported by electronic drug information resources (Clinical Pharmacology/Micromedex), or study site principal investigator (PI) opinion-among patients receiving 1 or more of 13 identified antimicrobials. Data were collected for 262 patients. Overall, appropriateness with the 4 definitions ranged from 79% based on PI opinion to 94% based on susceptibility data. No single definition resulted in consistently high appropriate use for all target antimicrobials. For individual antimicrobials, the definitions with the highest rate of appropriate use were Clinical Pharmacology/Micromedex support (6 of 7 antimicrobials) and susceptibility data (5 of 7 antimicrobials). For specific indications, support from susceptibility data resulted in the highest rate of appropriate use (4 of 7 indications). Overall comparisons showed that appropriateness assessed by PI opinion differed significantly compared with other definitions when stratified by either target antimicrobial or indication. The significant variability in the rate of appropriate use highlights the difficulty in developing a standardized definition that can be used to benchmark judicious antimicrobial use.

Fidaxomicin Use and Clinical Outcomes for Clostridium difficile-Associated Diarrhea.

BackgroundFidaxomicin has been scrutinized because of its high acquisition cost. Real-world experience is needed to determine whether fidaxomicin has value in patients with Clostridium difficile–associated diarrhea (CDAD) and certain risk factors. MethodsIn this single-center, retrospective cohort study, patients 18 years or older with diarrheal symptoms and positive polymerase chain reaction assay for C. difficile toxin B gene or pseudomembranes were administered fidaxomicin between August 2011 and March 2013. Clinical success was defined as the resolution of signs and symptoms of disease and no further therapy required for CDAD as of the second day after cessation of fidaxomicin therapy. The recurrence of CDAD was defined by the reappearance of signs and symptoms of disease after the cessation of therapy, a new positive C. difficile polymerase chain reaction result, and the need for CDAD retreatment. Readmissions were tracked for 90 days after hospital discharge. ResultsOf the 60 patients who received fidaxomicin, 58 (96.7%) achieved clinical success. Twenty-six (43.3%) of the 60 patients were being treated for a second or greater episode. Six (10.3%) of the 58 patients had recurrence within 90 days after the initial treatment course, and 4 (6.9%) were readmitted within 30 days after hospital discharge. ConclusionsIn this real-world setting, fidaxomicin resulted in a high rate of clinical success, a low rate of recurrence, and a low readmission rate.

Retrospective Analysis of Clinical and Cost Outcomes Associated with Methicillin-Resistant Staphylococcus aureus Complicated Skin and Skin Structure Infections Treated with Daptomycin, Vancomycin, or Linezolid

Objective. The objective of this analysis was to compare clinical and cost outcomes associated with patients who had suspected or documented methicillin-resistant Staphylococcus aureus (MRSA) infections treated with daptomycin, vancomycin, or linezolid in complicated skin and skin structure infections (cSSSIs). Design. This was a retrospective analysis conducted from February to June of 2007. Appropriate data was collected, collated, and subsequently evaluated with the purpose of quantifying length of stay, antibiotic therapy duration, clinical cure rates, adverse drug events, and cost of hospitalization. Results. All 82 patients included in the analysis experienced clinical cure. The duration of antibiotic therapy was similar among the three groups yet the length of hospitalization was slightly shorter in the daptomycin group. Conclusions. The incidence of resistant staphylococcal infections is increasing; therefore, judicious use of MRSA active agents is paramount. Future studies are necessary to determine if MRSA treatment options can be stratified based on the severity of the infectious process.

Linezolid-Induced Lactic Acidosis Corrected With Sustained Low-Efficiency Dialysis: A Case Report

Linezolid, an oxazolidinone antibiotic, has been reported to increase the risk of lactic acidosis and peripheral neuropathy because it disrupts mitochondrial function. This case report describes the development of lactic acidosis in a 63-year-old man who had received 3 months of treatment with intravenous linezolid for pulmonary nocardiasis, and correction of the acidotic state with sustained low-efficiency dialysis. This case demonstrates that renal replacement therapy can be an alternative to discontinuation alone for rapid reversal of linezolid-induced lactic acidosis.

Forecast of Antibiotic Development in an Era of Increasing Bacterial Resistance

Over the last decade there has been a decreased number of novel antimicrobial agents introduced to the market due to multiple factors including reduced governmental funding, marginal research and development interest by the pharmaceutical industry, lack of return on investment relative to medications used for chronic illnesses, and spiking microbial resistance trends. In an effort to most judiciously use the available armamentarium of anti-infectives available, many hospitals are implementing stewardship programs to re-direct inappropriate antibiotic use, which is estimated to account for up to 50% of all antibiotics prescribed. These efforts make it increasingly evident that the best defense against inappropriate antimicrobial use is accurate diagnosis of infectious diseases. Both the public and federal government must recognize the need for new and improved antimicrobials, as well as augmented infection control strategies and diagnostic techniques, to appropriately aid in the facilitation of bacterial control or eradication.

The Utility of Rapid Microbiological and Molecular Techniques in Optimizing Antimicrobial Therapy

Early treatment of bloodstream infections with appropriate, definitive antimicrobial therapy has proven to reduce mortality, length of hospital stay, and healthcare costs. Culture-based testing methods require up to five days for final pathogen identification and susceptibility reporting, forcing use of broad spectrum empiric therapy. Recently, multiple rapid microbiological and molecular testing methods have been developed that reduce the time to identify the pathogen and susceptibility, allowing optimal antimicrobial therapy to be prescribed earlier. Real-time polymerase chain reaction and gene microarray have been described in literature, yet only peptide nucleic acid fluorescent in-situ hybridization has published data justifying its use based on clinical outcomes and cost savings. Target enriched multiplex polymerase chain reaction was developed to identify both the pathogen and multiple genes associated with resistance from blood within 6 hours and this methodology was studied in our hospital to assess effectiveness at optimizing antimicrobials in staphylococcal bloodstream infections.