Using Intravenous Antibiotics to Treat Infective Endocarditis Lacks Convincing Evidence

The prolonged use of intravenous antibiotics to treat infective endocarditis (IE) is a well-known and widely followed medical regimen. However, a review published in the JAMA Internal Medicine has demonstrated the therapeutic efficacy of oral step-down antibiotic therapy as an alternative and safer treatment method. According to researchers at the University of California, these highly bioavailable antibiotics should be incorporated as a step-down therapy for IE after removing bacteremia and attaining clinical stability with intravenous procedures.

Antimicrobial History of Infective Endocarditis Treatment

A wide belief in medicine has been the effectiveness of extensive intravenous antibiotic therapy for treating infective endocarditis or IE (bacterial or fungal infection of the endocardium). This philosophy developed in the 1950s when penicillin was regarded as the most effective antibiotic for IE treatment. The rationale behind the philosophy was the understanding that a large number of bacteria lie ‘deep’ within the cardiac muscle, limiting access of antimicrobial medicines and also any effective host inflammatory response.

Source: The BMJ

The sulfonamides, which arrived in mid-1930, were the first truly effective antibacterial agents. However, early treatment regimens using these oral supplements were disappointing in treating IE – a 99% mortality rate in 2,596 patients before using sulfa drugs as compared to a 96% mortality rate among patients treated with oral sulfa drugs, according to a study. Next came the oral tetracyclines and macrolides in the late 1940s to early 1950s, which also showed unfavorable results of less than 30% cure rates in most patients.

With the availability of parenteral penicillin G in the 1940s, improved cure rates were seen – 1% before parenteral penicillin G to 85% after its administration – and it soon became the standard cure for IE. Oral penicillin formulations arrived in the mid-1950s but were viewed as unreliable for IE treatment due to apprehensions about bioavailability and the previous experiences of failure with oral antimicrobial agents.

Evaluating the Possibility of Using Oral Antibiotics for IE Treatment

The researchers highlighted various points for considering an alternate oral treatment regime for treating IE. To begin with, bacteria are incapable of recognizing the route via which antibiotics are administered to a patient. They are only affected by the dosage of medicine that reaches the site of infection and whether it is sufficient enough to eradicate them. Secondly, the levels attained by older oral sulfonamides, tetracyclines and macrolides in blood and tissue were most likely to be below the concentrations required to kill most bacteria causing IE, as compared to modern oral antimicrobial agents. Thirdly, oral regimes avoid the need for prolonged intravenous catheterization, which itself has a 10% to 60% rate of potentially severe adverse events, such as central line infection, deep venous thrombosis, central venous stenosis and catheter fracture and/or migration. Apart from these pharmacokinetic observations, intravenous treatment is also more expensive and requires more labor as compared to oral supplementation. Moreover, intravenous measures obligate a longer inpatient stay with increased risks of developing additional infections.

Source: AIMST University

Keeping this framework as their foundation, researchers evaluated medical literature to find substantial evidence for the efficacy of prolonged intravenous therapy in comparison to oral step-down therapy for infective endocarditis. In October 2019, with an update in February 2020, scientists reviewed literature available on PubMed (free search engine accessing mainly the MEDLINE database of references and abstracts on life sciences and biomedical topics) searching for titles that included ‘endocarditis’ and ‘oral’. They identified 169 research articles. Studies involving the pathogenesis or epidemiology of IE, single patient outcomes, prophylaxis for dental or other procedures, editorials, reviews, and those evaluating oral agents other than antibiotics were excluded. Ultimately, 24 studies – 21 observational or quasi-experimental studies and three randomized controlled trials (RCTs) – were examined.

Clinical Proof in Support of Oral Treatments for Infective Endocarditis

According to scientists, none of the published literature demonstrated that only intravenous antibiotic therapy was more effective than the alternative existing, oral antibiotic step-down regimes. The three randomized control trials showed that oral step-down antibiotic therapy was almost as effective as intravenous therapy in left-sided, right-sided or prosthetic valve infections. In the largest trial examined with a 3.5-year follow-up, patients receiving oral step-down therapy showed a significantly better cure and mortality rate as compared to those who received only intravenous therapy. Multiple observational studies also showed similar conclusions.

The belief that intravenous antibiotics regimes are best for treating IE appear to reflect non-evidence based practice rather than a clinically conclusive one. Ample data is now available to conclude that oral step-down antibiotic therapy is as effective as intravenous therapy for IE patients, after clearance of bacteremia and achievement of clinical stability. The review calls for a practical consideration of using oral therapy for treating IE in well-selected patients.

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