Oral Is the New IV. Challenging Decades of Blood and Bone Infection Dogma: A Systematic Review

Abstract

Background: We sought to determine if controlled, prospective clinical data validate the long-standing belief that intravenous (IV) antibiotic therapy is required for the full duration of treatment for 3 invasive bacterial infections: osteomyelitis, bacteremia, and infective endocarditis.

Methods: We performed a systematic review of published, prospective, controlled trials that compared IV-only to oral stepdown regimens in the treatment of these diseases. Using the PubMed database, we identified 7 relevant randomized controlled trials (RCTs) of osteomyelitis, 9 of bacteremia, 1 including both osteomyelitis and bacteremia, and 3 of endocarditis, as well as one quasi-experimental endocarditis study. Study results were synthesized via forest plots and funnel charts (for risk of study bias), using RevMan 5.4.1 and Meta-Essentials freeware, respectively.

Results: The 21 studies demonstrated either no difference in clinical efficacy, or superiority of oral versus IV-only antimicrobial therapy, including for mortality; in no study was IV-only treatment superior in efficacy. The frequency of catheter-related adverse events and duration of inpatient hospitalization were both greater in IV-only groups.

Discussion: Numerous prospective, controlled investigations demonstrate that oral antibiotics are at least as effective, safer, and lead to shorter hospitalizations than IV-only therapy; no contrary data were identified. Treatment guidelines should be modified to indicate that oral therapy is appropriate for reasonably selected patients with osteomyelitis, bacteremia, and endocarditis.

Keywords: Bacteremia; Endocarditis; Meta-analysis; Oral antibiotics; Osteomyelitis.

Figure 1.. Flow Chart for Study Inclusion.

One RCT (Schrenzel 2004) was included in both the osteomyelitis and bacteremia sections as both patient populations were studied in the trial. *Excluded based on being retrospective or observational studies, non-interventional prospective studies (in which treatment with oral or IV was left to the discretion of the treating physician rather than being assigned by the protocol), studies of prophylaxis, studies of infections caused by non-bacterial pathogens, and single arm or non-controlled studies.

Figure 2.. Meta-Analysis Forest Plot of Osteomyelitis Treatment Success.

Overall treatment success was not significantly different.

Figure 3.. Meta-Analysis Forest Plot of Bacteremia Treatment Success.

Overall treatment success was not significantly different, although the confidence interval favored oral therapy.

Figure 4.. Meta-Analysis Forest Plot of Endocarditis Treatment Success.

Oral therapy was significantly more effective.