Optimal vancomycin dose in the treatment of Clostridium difficile infection, antimicrobial stewardship initiative

Abstract

C. difficile infections (CDI) are increasingly recognized as a leading cause of infectious diarrhea, with increasing morbidity and mortality. Treatment primarily centers around oral vancomycin treatment. A wide range of dosing regimens exist in clinical practice, with little evidence to help distinguish the therapeutic benefit between them. This is a retrospective cohort study conducted at an academic medical center that enrolled adult patients admitted with CDI. The primary outcome was a composite of complete or partial cure at the end of treatment and was assessed using a test of equivalency with a 20% equivalency limit. Subjects were divided into low dose (125 mg) or high dose (250 mg or 500 mg) of oral vancomycin dosed every 6 hours. Overall, 78 patients were included who received low dose vancomycin and 33 who received high dose. Generally, the two groups were similar, except the low dose group had significantly more leukocytosis and less ICU admission or hypotension compared to the high dose group. Equivalency between the two treatment groups was demonstrated (Absolute Risk Difference −0.022, 90% confidence interval: −0.13 to 0.18, p = 0.03). A stepwise logistic regression identified gender, baseline albumin, and ICU admission as significant predictors of the chance for complete or partial cure. No differences between groups for the secondary outcomes of 90-day readmission/recurrence, 30-day all-cause mortality, or time to resolution of diarrhea were demonstrated. Low dose oral vancomycin was demonstrated to result in equivalent outcomes compared to high dose vancomycin for the treatment of CDI.

Keywords:

• Vancomycin dose
• Clostridioides difficile infection
• stewardship

Additional information

Notes on contributors

Benjamin J. Ereshefsky

Benjamin J. Ereshefsky, PharmD, BCPS is an infectious diseases specialist who serves as the antimicrobial stewardship pharmacist at Kaweah Delta Health Care District. He serves as a preceptor for PGY1 pharmacy practice residents who take an ID/antimicrobial stewardship rotation. Dr. Ereshefsky received his Doctor of Pharmacy from the University of Texas College of Pharmacy in 2010. He completed both his PGY1 residency and PGY2 Infectious Diseases Pharmacy residency at UK HealthCare in Lexington, KY in 2012. Dr. Ereshefsky comes to KDHCD after spending 4 years in academia at the Philadelphia College of Pharmacy. His current clinical practice and research interests include optimizing antimicrobial therapy, treating antibiotic resistant infections, and management of Clostridium difficile infections. Dr. Ereshefsky currently serves as the Social Media Subcommittee chair for the Society of Infectious Diseases Pharmacists.

Diaa Alrahmany

Pharmacist Diaa Alrahmany, Registered pharmacotherapy pharmacist since 1998, with almost 22 years' experience in different aspects of pharmacy practice. Working for Ministry of health – Sultanate of Oman since 2002 till now. Currently running an active antimicrobial stewardship program in Suhar hospital – a referral hospital serving one third of Omani population – with the responsibility of conducting surveillance and observational studies, as well as the construction and periodical update of hospital antibiogram. Participated on the national project of implementation of antimicrobial stewardship program in Omani healthcare facilities. Also running a multi-phasic research project in collaboration with overseas colleagues about antimicrobial resistance in Oman, started by a comprehensive surveillance study of microbial resistance and continued by detailed evaluation of treatment outcomes of some resistant phenotypes, in order to provide targeted interventions to treatment protocols. Authors of journal publications, international conference poster presentations, in addition to book chapters in the field of antimicrobial stewardship. Furthermore; a speaker and tutor in the national antimicrobial stewardship program, as well as the online British society of antimicrobial chemotherapy AMS program directed for the middle east and northern Africa.

Wasim S. El Nekidy

Dr. Wasim S. El Nekidy is a senior pharmacotherapy specialist at Cleveland Clinic Abu Dhabi, UAE and Clinical Associate Professor of Medicine at Cleveland Clinic Lerner College of Medicine of Case Wester Reserve University, Cleveland, OH, USA. Dr. El Nekidy's clinical practice is focused on pharmacokinetics and pharmacodynamics (PK/PD) of antimicrobials and itsdosinginpatients utilizing different renal replacement therapies (IHD, PD, CRRT, and PIRRT). Additionally, Dr. El Nekidy has a well versedexperiencein designingand execution of research projects investigating PK/PD and outcomes in patients utilizing different modalities of renal replacement therapy.He is the primary investigator in different research modalities (randomized clinical trials, prospective observational, retrospective analysis, and case reports) as well as performing computer-based PK/PD predictionsuch asMonte Carlo simulations.He is also the primary author and co-author of a multitude of publications including journal articles,and book chapters, and international conference proceedings.Dr. El Nekidy also serve as a scientificreviewer of multiple U.S., Canadian, and international journals.

Laura Pontiggia

Dr. Wasim S. El Nekidy is a senior pharmacotherapy specialist at Cleveland Clinic Abu Dhabi, UAE and Clinical Associate Professor of Medicine at Cleveland Clinic Lerner College of Medicine of Case Wester Reserve University, Cleveland, OH, USA. Dr. El Nekidy's clinical practice is focused on pharmacokinetics and pharmacodynamics (PK/PD) of antimicrobials and itsdosinginpatients utilizing different renal replacement therapies (IHD, PD, CRRT, and PIRRT). Additionally, Dr. El Nekidy has a well versedexperiencein designingand execution of research projects investigating PK/PD and outcomes in patients utilizing different modalities of renal replacement therapy.He is the primary investigator in different research modalities (randomized clinical trials, prospective observational, retrospective analysis, and case reports) as well as performing computer-based PK/PD predictionsuch asMonte Carlo simulations.He is also the primary author and co-author of a multitude of publications including journal articles,and book chapters, and international conference proceedings.Dr. El Nekidy also serve as a scientificreviewer of multiple U.S., Canadian, and international journals.Dr. Laura Pontiggia is an accomplished teacher, researcher and higher education administrator. She earned a Ph.D. and M.S. in Statistics from the University of Minnesota and currently serves as the Director of Academic Programs at the Institute of Emerging Health Professions at Thomas Jefferson University in Philadelphia.She has been a very active faculty, teaching a variety of undergraduate and graduate courses and leading the development of new programs in data science and statistics.Dr. Pontiggia main research interests and expertise liesin statistical methodological development as well as general statistical applicationsof novel, intuitive and practical statistical methods that contribute to solving real life problems.She has participated in a multitude of collaborative research projects that resulted in more than 40 publications.

Islam M. Ghazi

Dr. Islam Ghazi is a professor, researcher and clinician of infectious diseases with broad range of interests, pharmacokinetics and pharmacodynamics of antimicrobials using in vivo animal modeling designed experimentally to simulate various human infections, characterization of pharmacologic activity of drugs utilizing dynamic in vitro models constructed to mimic the humanized exposure in terms of changing concentrations and clearance, bench-top microbiological testing such as determination of minimum inhibitory concentration, time kill experiments, antibiotic synergy and phenotypic enzyme production, computer-based pharmacokinetic/pharmacodynamic modeling and prediction (population drug profiling and Monte Carlo simulations) along with statistical analysis. Dr. Ghazi is an author of over 45 publications including; conference presentations, book chapters and peer reviewed articles.