When are Oral Antibiotics a Safe and Effective Choice for Bacterial Bloodstream Infections? An Evidence-Based Narrative Review
Bacterial bloodstream infections (BSIs) are a major cause of morbidity and mortality in the United States. Traditionally, BSIs have been managed with intravenous antimicrobials. However, whether intravenous antimicrobials are necessary for the entirety of the treatment course in BSIs, especially for uncomplicated episodes, is a more controversial matter. Patients that are clinically stable, without signs of shock, or have been stabilized after an initial septic presentation, may be appropriate candidates for treatment of BSIs with oral antimicrobials. There are risks and costs associated with extended courses of intravenous agents, such as the necessity for long-term intravenous catheters, which entail risks for procedural complications, secondary infections, and thrombosis. Oral antimicrobial therapy for bacterial BSIs offers several potential benefits. When selected appropriately, oral antibiotics offer lower cost, fewer side effects, promote antimicrobial stewardship, and are easier for patients. The decision to use oral versus intravenous antibiotics must consider the characteristics of the pathogen, the patient, and the drug. In this narrative review, the authors highlight areas where oral therapy is a safe and effective choice to treat bloodstream infection, and offer guidance and cautions to clinicians managing patients experiencing BSI.
© 2018 Society of Hospital Medicine
Gram-Positive Cocci, Enterococcus
E. faecium and E. faecalis are commonly implicated in BSI.1 Similar to S. aureus, infective endocarditis must be ruled out when treating enterococcus BSI; a scoring system has been proposed to assist in deciding if such patients require echocardiography.62 Intravenous ampicillin is a preferred, highly effective agent for enterococci treatment when the organism is susceptible.44 However, oral ampicillin has poor bioavailability (50%), and data for its use in BSI are lacking. For susceptible strains, amoxicillin has comparable efficacy for enterococci and enhanced bioavailability (85%); high dose oral amoxicillin could be considered, but there is minimal clinical trial data to support this approach. Fluoroquinolones exhibit only modest activity against enterococci and would be an inferior choice for BSI.63 Although often sensitive to oral tetracyclines, data on their use in enterococcal BSI are insufficient. Nitrofurantoin can be used for susceptible enterococcal urinary tract infection; however, it does not achieve high blood concentrations and should not be used for BSI.
There is significant data comparing oral linezolid with intravenous daptomycin for vancomycin-resistant enterococci (VRE) BSI. In a systematic review including 10 trials using 30-day all-cause mortality as the primary outcome, patients treated with daptomycin demonstrated higher odds of death (OR 1.61, 95% CI 1.08–2.40) compared with those treated with linezolid.64 However, more recent data suggested that higher daptomycin doses than those used in these earlier trials resulted in improved VRE BSI outcomes.65 A subsequent study reported that VRE BSI treatment with linezolid is associated with significantly higher treatment failure and mortality compared with daptomycin therapy.66 Further research is needed, but should the side-effect profile of linezolid be tolerable, it remains an effective option for oral treatment of enterococcal BSIs.
Evidence Regarding Anaerobic Bacterial Blood Stream Infection
Anaerobic bacteria include Bacteroides, Prevotella, Porphyromonas, Fusobacterium, Peptostreptococcus, Veillonella, and Clostridium. Anaerobes account for approximately 4% of bacterial BSIs, and are often seen in the context of polymicrobial infection.67 Given that anaerobes are difficult to recover, and that antimicrobial resistance testing is more labor intensive, antibiotic therapy choices are often made empirically.67 Unfortunately, antibiotic resistance amongst anaerobes is increasing.68 However, metronidazole remains highly active against a majority of anaerobes, with only a handful of treatment failures reported,69 and has a highly favorable pharmacokinetic profile for oral treatment. Oral metronidazole remains an effective choice for many anaerobic BSIs. Considering the polymicrobial nature of many anaerobic infections, source control is important, and concomitant GNR infection must be ruled out before using metronidazole monotherapy.
Clindamycin has significant anaerobic activity, but Bacteroides resistance has increased significantly in recent years, as high as 26%-44%.70 Amoxicillin-clavulanate has good anaerobic coverage, but bioavailability of clavulanate is limited (50%), making it inferior for BSI. Bioavailability is also limited for cephalosporins with anaerobic activity, such as cefuroxime. Moxifloxacin is a fluoroquinolone with some anaerobic coverage and a good oral pharmacokinetic profile, but Bacteroides resistance can be as high as 50%, making it a risky empiric choice.68
Conclusions
Bacterial BSIs are common and result in significant morbidity and mortality, with high associated healthcare costs. Although BSIs are traditionally treated with intravenous antimicrobials, many BSIs can be safely and effectively cured using oral antibiotics. When appropriately selected, oral antibiotics offer lower costs, fewer side effects, promote antimicrobial stewardship, and are easier for patients. Ultimately, the decision to use oral versus intravenous antibiotics must consider the characteristics of the pathogen, patient, and drug.
Disclosures
None of the authors report any conflicts of interest.
