Variability in oral antibiotic step-down therapy in the management of Gram-negative bloodstream infections

Abstract

There are important gaps in the literature regarding the role and timing of oral therapy for Gram-negative bloodstream infections (GN-BSIs). To better understand contemporary management practices involving oral step-down in GN-BSI, we conducted an international survey of infectious diseases (ID) specialists. We developed and disseminated an online survey to ID specialists to assess practice patterns involving oral step-down in GN-BSIs, including providers from six continents and 28 countries. χ² tests and generalised estimating equations were used to identify factors associated with oral step-down. In total, 277 ID specialists completed the survey (64% physicians, 31% pharmacists). Relative to a line source, oral step-down was more common in abdominal [OR = 1.96 (95% CI 1.48-2.61); P < 0.001], pneumonia [2.24 (1.67-2.99); P < 0.001], skin [7.26 (4.71-11.20); P < 0.001] and urinary [9.15 (5.73-14.60); P < 0.001] sources of GN-BSI. US providers were more likely to practice oral step-down than non-US providers (OR = 4.35, 95% CI 2.57-7.36; P < 0.001). Moreover, 40% of providers practice oral step-down for some, but not all, sources of GN-BSI. Among all providers, 23-53% (depending on GN-BSI source) recommend extended (≥5 days) intravenous (IV) therapy before oral step-down or ongoing IV therapy. Most respondents (76% of all providers; 80% of ID physicians) expressed interest in enrolling patients in a trial of full IV versus early oral step-down for GN-BSI. There is extensive heterogeneity in oral step-down practices for GN-BSI. The optimal role of oral step-down in managing GN-BSIs warrants further investigation.

Keywords: Bacteraemia; Bloodstream infection; Gram-negative; Oral step-down.

Figure 1.

Percentage of survey respondents that typically step-down to oral antibiotic therapy in managing gram-negative bloodstream infections (A). The data were stratified by location of practice (within United States [US] versus outside US [ex-US]) (B) and years of experience since terminal degree (e.g., M.D., PharmD, etc.) (C). Abbreviations: IAI, intra-abdominal infection; IV, intravenous; PNA, pneumonia; SSTI, skin/soft tissue infection.

Figure 2.. Distribution of number of oral step-down responses for each provider.

For each provider, the number of gram-negative bloodstream infection (GN-BSI) sources in which oral antibiotic step-down is practiced was calculated. This number can range from 0 (no oral step-down practiced in any of the five GN-BSI sources) to 5 (oral step-down is practiced for all five GN-BSI sources). A histogram of the responses for the providers (n=270) is presented here.

Figure 3.. Minimum duration of intravenous (IV) antibiotics prescribed in bacteremic pneumonia (A), bacteremic central line infection (B), bacteremic urinary tract infection/pyelonephritis (C), bacteremic intra-abdominal infection (D), and bacteremic skin/soft tissue infection (E).

All data are from providers who stated that they typically step-down to oral antibiotic therapy for the respective infections. Among such providers, the percentage that have a minimum duration of IV antibiotics prior to oral step-down is shown in the graphs on the left. For providers that have a minimum number of days of IV antibiotics they provide, the graphs on the right show the distribution of the minimum days of IV antibiotics.

Figure 4.. Factors that influence decision to step-down to oral antibiotic therapy.

Providers that step-down to oral antibiotics were surveyed on how strongly they consider each listed variable before transitioning to oral therapy.