Hospital Pharmacy - October 2019 - 294

787439
research-article2018

HPXXXX10.1177/0018578718787439Hospital PharmacyShah et al

Original Article

Impact of Delayed Oral Vancomycin for
Severe Clostridium difficile Infection

Hospital Pharmacy
2019, Vol. 54(5) 294-299
© The Author(s) 2018
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DOI: 10.1177/0018578718787439
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Sunish Shah1, Benjamin Ereshefsky1,2, Laura Pontiggia1,
and Michael Cawley1

Abstract
Background: Treatment of severe Clostridium difficile infection (CDI) with oral vancomycin (VAN) is known to be superior
to treatment with metronidazole (MDZ). However, previous studies have not evaluated the impact on patients when oral
VAN therapy is delayed after diagnosis of severe CDI. Materials and Methods: This was a single-center, retrospective
study of adult patients who were diagnosed with severe CDI. The objective was to compare clinical outcomes for patients
treated initially with oral VAN versus patients receiving delayed oral VAN after at least 48 hours of initial treatment with
MDZ. The primary outcome was all-cause in-hospital mortality. Results: There were 101 patients who comprised the initial
oral VAN group, while 20 patients comprised the delayed oral VAN group. There was no significant difference in all-cause
in-hospital mortality for patients in the initial oral VAN treatment group compared to those who had delayed oral VAN
therapy (4.95% vs 15.00%, P = 0.13). Patients who were initially treated with oral VAN experienced a significantly higher rate
of clinical cure (49.50% vs 20.00%, P = 0.02), shorter median postinfection length of hospitalization (7.0 days vs 13.0 days,
P < 0.001), shorter median time to resolution of leukocytosis (3.9 days vs 10.4 days, P = 0.01), and were less likely to have
an end of treatment serum creatinine greater than 1.5 times their baseline (8.7% vs 29.4%, P = 0.03). Conclusion: Patients
who receive oral VAN as their initial treatment for severe CDI experience improved clinical outcomes compared to patients
receiving delayed oral VAN after being initially treated with MDZ.
Keywords
infectious diseases, gastrointestinal disorders, antiinfectives

Introduction
Severe Clostridium difficile infection (CDI) is a common
community-acquired and nosocomial infection associated
with electrolyte abnormalities, renal failure, sepsis, and in
severe cases, toxic megacolon, bowel perforation, and death.1
Even more concerning is that in recent years, the incidence,
morbidity, and mortality of CDI has increased at an exponential rate, which corresponds with the rise of strains with
increased virulence, such as NAP1/B1/027.2,3 Furthermore,
it is also estimated that CDI has a recurrence rate of 20%.4,5
Several regimens are used to treat this highly infectious
disease. Oral vancomycin (VAN) and metronidazole (MDZ)
remain the cornerstone of CDI treatment and have been studied for the past 30 years.6 Proposed treatment options that
have failed to find a place in primary CDI therapy include
nitazoxanide, rifaximin, tigecycline, bacitracin, and fusidic
acid.7 In 2011, fidaxomicin was shown to be noninferior to
oral VAN for the treatment of CDI.8 It is currently the only
other antibiotic besides oral VAN to be approved by the FDA
for the treatment of CDI. Bezlotuxumab was recently
approved by the FDA to reduce the recurrence of CDI, but is
not intended for active treatment.9 The Infectious Diseases

Society of America guideline recommends oral VAN 125mg
every 6 hours for nonsevere and severe CDI, and oral or rectal
VAN 500mg every 6 hours with or without intravenous (IV)
MDZ 500mg every 8 hours for fulminant CDI.1 Oral MDZ is
only recommended as an alternative for nonsevere CDI.1
Guidelines from the American Journal of Gastroenterology
and the European Society of Clinical Microbiology and
Infectious Diseases have similar recommendations.10,11
Previous studies comparing the clinical outcomes of patients
treated with either oral VAN or MDZ for CDI have shown the
superiority of oral VAN for severe infections.12,13,14
Despite the demonstration of superiority of oral VAN compared to MDZ for severe CDI, initial inappropriate therapy is
common.15,16 Furthermore, It has been shown that in patients
with CDI, undertreated patients experienced worse clinical
outcomes and overtreated patients failed to show significant
1

University of the Sciences, Philadelphia, PA, USA
Cooper University Hospital, Camden, NJ, USA

2

Corresponding Author:
Sunish Shah, Philadelphia College of Pharmacy, University of the Sciences,
600 South 43rd Street, Philadelphia, PA 19104, USA.
Email: Sunishshah93@gmail.com
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