Effectiveness of oral antibiotics for definitive therapy of non-Staphylococcal Gram-positive bacterial bloodstream infections

Abstract

Background: Data on the effectiveness of definitive oral (PO) antibiotics for BSIs in preparation for discharge from hospital are lacking, particularly for Gram-positive bacterial BSIs (GP-BSI). The objective of this study was to determine rates of treatment failure based on bioavailability of PO antimicrobial agents used for GP-BSI. Methods: This was a single-center, retrospective cohort study of adult inpatients admitted to an academic medical center over a three-year period. Patients with a non-staphylococcal GP-BSI who received intravenous antibiotics and were then switched to PO antibiotics for at least a third of their treatment course were included. The cohort was stratified into high (⩾90%) and low (<90%) bioavailability groups. The primary endpoint was the proportion of patients experiencing clinical failure in each group. Secondary endpoints included clinical failure stratified by antibiotic group, bactericidal versus bacteriostatic PO agents, and organism. Results: A total of 103 patients met criteria for inclusion, which failed to reach the a priori power calculation. Of the patients included, 26 received high bioavailability agents and 77 received low bioavailability agents. Infections originated largely from a pulmonary source (30%) and were caused primarily by streptococcal species (75%). Treatment failure rates were 19.2% in the high bioavailability group and 23.4% in the low bioavailability group ( p = 0.66). Clinical failure stratified by subgroups also did not yield statistically significant differences. Conclusions: Clinical failure rates were similar among patients definitively treated with high or low bioavailability agents for GP-BSI, though the study was underpowered to detect such a difference.

Fluoroquinolone versus Beta-Lactam Oral Step-Down Therapy for Uncomplicated Streptococcal Bloodstream Infections

“…No difference in the incidence of CDAD was seen in our cohort, although the study was not powered to evaluate this outcome. Our findings are similar to those of Quinn et al, who evaluated oral step-down therapy for nonstaphylococcal Gram-positive BSIs, a majority of which were caused by streptococcal species (15). Those authors found no difference in clinical failure when comparing high-and low-bioavailability agents, although that study was underpowered to detect such a difference.…”

“…A sample size of 100 was calculated to evaluate noninferiority of the two oral step-down groups regarding clinical success using an ␣ value of 0.05, a ␤ value of 0.2 (80% power), an estimated clinical success rate of 90% for both groups, and a noninferiority margin of 15%. The estimated rate of clinical success and the noninferiority margin were based on previous studies of oral step-down therapy for Gram-negative and nonstaphylococcal Gram-positive BSI (10,12,13,15). SAS statistical software (version 9.4; SAS Institute, Cary, NC) was used to conduct all analyses.…”

“…Studies comparing the efficacies of FQs and BLs for BSI oral step-down therapy have almost exclusively been conducted in the setting of Gram-negative BSI, with some studies finding no difference in clinical outcomes and others showing an increased rate of treatment failure with BLs (12)(13)(14). Quinn et al examined oral step-down for nonstaphylococcal Gram-positive BSIs, comparing the efficacy of high-bioavailability agents, including FQs, to that of BLs (15). No difference was seen in the rates of clinical failure, although that study was underpowered to detect such a difference.…”

Evaluation of step-down oral antibiotic therapy for uncomplicated streptococcal bloodstream infections on clinical outcomes

“…From a pharmacokinetic/pharmacodynamic standpoint, Streptococcus spp is unique with lower minimum inhibitory concentrations (MICs) compared with other organisms, which makes the oral option very attractive, even for some of the beta-lactam agents that may not have high bioavailability. Recent studies have evaluated oral antibiotics of high (fluoroquinolones, clindamycin, and doxycycline) versus low bioavailability (beta-lactam) 28 and fluoroquinolones versus oral beta-lactams 29 and found comparable outcomes in the beta-lactam group. In our study, beta-lactam agents were the second most commonly utilized oral agents (32%) after fluoroquinolones (40%), although we could not make meaningful comparisons based on oral antibiotic choice on its effect on outcomes due to the small sample size.…”

Significant Publications on Infectious Diseases Pharmacotherapy in 2020

“…[39][40][41] Studies evaluating oral step-down therapy in the treatment of Gram-positive BSI have been underpowered to detect a difference in clinical failure, warranting additional, adequately-powered studies. 42 Arensman et al conducted a multicenter, retrospective cohort study to compare clinical outcomes between patients treated with either FQs or β-lactams for oral step-down therapy in streptococcal BSIs. The primary outcome of the study was clinical success, defined as the absence of all-cause mortality, BSI recurrence, and infection-related readmission at 90 days from the first positive blood culture.…”