Jean Huang, Pharm.D., Alyssa Divens, Pharm.D., Heba El-Ghoroury, Pharm.D., Kelsey Olmack, Pharm.D., St. Joseph Mercy Hospital, Ann Arbor
Bacteremia remains a major contributor to morbidity and mortality, accounting for approximately 80,000 deaths each year.1 With a cost of nearly $17,000 per patient, there is also a large financial burden.2 While initial use of intravenous antibiotics remains the standard of care, there has been a general lack of published data to support an optimal treatment duration and use of oral versus intravenous antibiotics with regard to patient outcomes. In the absence of treatment guidelines, patients often experience prolonged lengths of stay, are recommended longer durations of therapy and are placed at higher risk of nosocomial complications in order to continue inpatient intravenous antibiotic treatment. Over the last few years, new data has become available that supports shorter treatment durations and de-escalation to oral antibiotics, most notably for enterobacteriaceae bloodstream infections secondary to urinary sources. In light of increasing antimicrobial resistance, it is more important than ever to reduce unnecessary use of antibiotics.
A recent meta-analysis conducted by Tansarli et al. reviewed five studies that compared durations of therapy for enterobacteriaceae bacteremia, four of which were retrospective analyses and one randomized controlled trial.3 First, the authors examined all-cause mortality differences between ≤10 days of treatment versus >10 days of treatment. At 30 days, they found no difference in all-cause mortality between the treatment courses (1,374 patients; RR = 0.99; 95 percent CI, 0.69 to 1.43). Similarly, 90-day mortality showed no difference between treatment durations (1,750 patients; RR = 1.16; 95 percent CI, 0.81 to 1.66). When discussing clinical cure, there was also no significant difference between the two treatments when studies were pooled (81.6 percent versus 81.4 percent, respectively; 1,080 patients; RR = 1.02; 95 percent CI, 0.96 to 1.08). Additionally, four of the studies provided data on relapse of bacteremia at 30 or 90 days from the completion of antibiotic therapy. At 90 days there was no significant difference between treatment durations (1,750 patients; RR = 1.08; 95 percent CI, 0.69 to 1.67) as well as at 30 days (RR = 0.56; 95 percent CI, 0.19 to 1.64).
Coinciding with the recent evidence suggesting shorter treatment durations for gram-negative bacteremia, the literature also seems to support de-escalation from intravenous to oral antibiotics. In a recently published systematic review and meta-analysis, Punjabi et al. reviewed eight retrospective studies that compared step-down oral therapy for enterobacteriaceae bacteremia.4 The study included data for 2,289 patients, 65 percent of whom were transitioned to oral fluoroquinolones, 7.7 percent to trimethoprim-sulfamethoxazole, and 27.2 percent to beta-lactams. The authors found no significant difference in all-cause mortality in patients de-escalated to either group of oral antibiotics (OR = 1.13; 95 percent CI, 0.69 to 1.87), but they did find an increased risk of infection recurrence in patients transitioned to oral beta-lactams versus fluoroquinolones (OR = 2.05; 95 percent CI, 1.17 to 3.61). Of note, factors such as underdosing of and decreased adherence due to frequency of dosing of beta-lactams may have contributed to the increased recurrence. Although the optimal oral antibiotic upon de-escalation still requires further investigation, recent evidence supports the use of step-down oral therapy for enterobacteriaceae bacteremia in regard to patient outcomes.
Bacteremia is a high risk infection that leads to increased mortality, healthcare costs and utilization of hospital resources. Without clear direction from national guidelines, practitioners must evaluate available literature in order to optimize patient care. Two main areas of interest in bacteremia treatment include length of treatment and transitioning from intravenous to oral therapy. As described, the literature supports limiting treatment to 10 days of therapy as well as transitioning to oral antibiotics when medically appropriate. Since literature updates focus on bacteremia caused by enterobacteriaceae from urinary sources, clinicians should continue to evaluate a variety of resources to determine the most effective treatment of all types of bacteremia.
- Goto M, Al-Hasan MN. (2013). Overall burden of bloodstream infection and nosocomial bloodstream infection in North America and Europe. Clin Microbiol Infect, 19, 501-9.
- Riu M, Chiarello P, Terradas R, et al. (2017). Incremental cost of nosocomial bacteremia according to the focus of infection and antibiotic sensitivity of the causative microorganism in a university hospital. Medicine (Baltimore), 96(17):e6645.
- Tansarli G, Andreatos N, Pliakos E, et al. (2019). A Systematic Review and Meta-analysis of Antibiotic Treatment Duration for Bacteremia Due to Enterobacteriaceae. Antimicrob Agents Chemother, 63(5):e02495-18.
- Punjabi C, Tien V, Meng L, et al. (2019). Oral Fluoroquinolone or Trimethoprim-sulfamethoxazole vs. ß-lactams as Step-Down Therapy for Enterobacteriaceae Bacteremia: Systematic Review and Meta-analysis. Open Forum Infect Dis, 6(10):ofz364.