Enhanced Efficacy of High Dose Oral Vancomycin Therapy in Clostridium difficile Diarrhea for Hospitalized Adults Not Responsive to Conventional Oral Vancomycin Therapy: Antibiotic Stewardship Implications

Abstract

Current therapy of Clostridium difficile diarrhea (CDD) is problematic. Optimal treatment for CDD remains oral vancomycin, but there is little data on oral vancomycin dosing regimens. The objective of this C. difficile diarrhea study was to compare the efficacy of “high dose” vancomycin, 500 mg (PO) q6h, as sole treatment and in those who after 72 h failed to respond to conventional doses of oral vancomycin, 125–250 mg (PO) q6h. Hospitalized adults with CDD were evaluated by various oral vancomycin regimens, i.e., a conventional dose group (125–250 mg (PO) q6h), a “high dose escalation” dose group (250 mg → 500 mg (PO) q6h), and a “high dose” group (500 mg (PO) q6h). Oral vancomycin treatment groups were compared by time to improvement, i.e., decrease in >50% of watery stools/day and duration of therapy. The high dose escalation and high dose oral vancomycin groups showed the most rapid resolution of diarrhea. There was marked decrease in stools/day after “high dose” vancomycin escalation from conventional dosing, i.e., 250 mg (PO) q6h → 500 mg (PO) q6h. This study demonstrated that “high dose” escalation or initial high dose oral vancomycin, i.e., 500 mg (PO) q6h was the most efficacious regimen for CDD.

Effective Dosage of Oral Vancomycin in Treatment for Initial Episode of Clostridioides difficile Infection: A Systematic Review and Meta-Analysis

“…We retrieved 1069 non-duplicated citations for a review of their title and abstracts, and included 10 articles for meticulous evaluation after eliminating references based on our inclusion criteria ( Figure 1). We contacted the corresponding authors of three studies to request additional data [22][23][24] and received replies from the authors of two studies [22,24]. In addition, one study is a conference poster [23].…”

“…In addition, one study is a conference poster [23]. Of those two studies, one author replied that the requested recurrence rate data was not available but provided additional detailed standard deviation data according to each group of antibiotic agents [22]. Characteristics of the studies included are summarized in Table 1.…”

“…Characteristics of the studies included are summarized in Table 1. In total, the study included one randomized controlled trial [12] and three retrospective cohort studies [11,22,24]. One retrospective cohort study was designed to compare escalated vancomycin dose to 500 mg 4 times per day in patients who failed to respond to conventional dose of vancomycin.…”

“…One retrospective cohort study was designed to compare escalated vancomycin dose to 500 mg 4 times per day in patients who failed to respond to conventional dose of vancomycin. In that retrospective cohort study, there was a group of patients who received high dose vancomycin 500 mg given 4 times per day (14 patients) for an initial episode CDI [22]. The pooled OR of recurrence in the low dose vancomycin arm compared with the high dose vancomycin arm was 2.058 (95% CI: 0.653 to 6.489, p = 0.958), indicating a reduced incidence of The pooled OR of recurrence in the low dose vancomycin arm compared with the high dose vancomycin arm was 2.058 (95% CI: 0.653 to 6.489, p = 0.958), indicating a reduced incidence of recurrence following high dose vancomycin (Figure 2, Table A2).…”

“…In one retrospective study published by Cunha et al, they escalated vancomycin from 250 mg to 500 mg 4 times per day when the patient did not have a clinical response in three days [22]. They saw improvement when escalating the dose.…”