Oral Antibiotics for Bacteremia and Infective Endocarditis: Current Evidence and Future Perspectives

Abstract

Bacteremia and endocarditis are two clinical syndromes that, for decades, were managed exclusively with parenteral antimicrobials, irrespective of a given patient's clinical condition, causative pathogen, or its antibiotic susceptibility profile. This clinical approach, however, was based on low-quality data and outdated expert opinions. When a patient's condition has improved, gastrointestinal absorption is not compromised, and an oral antibiotic regimen reaching adequate serum concentrations is available, a switch to oral antibacterials can be applied. Although available evidence has reduced the timing of the oral switch in bacteremia to three days/until clinical improvement, there are only scarce data regarding less than 10-day intravenous antibiotic therapy in endocarditis. Many standard or studied oral antimicrobial dosages are smaller than the approved doses for parenteral administration, which is a risk factor for treatment failure; in addition, the gastrointestinal barrier may affect drug bioavailability, especially when the causative pathogen has a minimum inhibitory concentration that is close to the susceptibility breakpoint. A considerable number of patients infected by such near-breakpoint strains may not be potential candidates for oral step-down therapy to non-highly bioavailable antibiotics like beta-lactams; different breakpoints should be determined for this setting. This review will focus on summarizing findings about pathogen-specific tailoring of oral step-down therapy for bacteremia and endocarditis, but will also present laboratory and clinical data about antibiotics such as beta-lactams, linezolid, and fosfomycin that should be studied more in order to elucidate their role and optimal dosage in this context.

Keywords: Enterobacterales; Enterococcus; Pseudomonas; Staphylococcus; Streptococcus; bacteremia; endocarditis; oral treatment.

Figure 2

Chemical structure of certain commonly used oral antibiotics (adapted from PubChem): (A), amoxicillin; (B), cloxacillin sodium; (C), cefalexin; (D), cefuroxime axetil; (E), cefixime; (F), ciprofloxacin hydrochloride; (G), levofloxacin hemihydrate; (H), moxifloxacin hydrochloride; (I) sulfamethoxazole/trimethoprim; (J), clindamycin; (K) linezolid; (L) fosfomycin trometamol [180,181,182,183,184,185,186,187,188,189,190,191].

Figure 1

Oral antibiotic options for bacteremia and endocarditis according to causative pathogen, provided that PK/PD targets can be achieved given the MIC. * Only combined with another active antibiotic. † Only as an adjunct treatment against E. faecalis. List of abbreviations: TMP/SMX, trimethoprim/sulfamethoxazole; PK/PD, pharmacokinetic/pharmacodynamic; MIC, minimum inhibitory concentration.