Evaluation of a Paradigm Shift From Intravenous Antibiotics to Oral Step-Down Therapy for the Treatment of Infective Endocarditis

Abstract

dogma in medicine has long been that effective treatment of infective endocarditis (IE) requires prolonged intravenous antibiotic therapy. This dogma developed during an era when penicillin was the most effective antibiotic to treat IE, for which it was only administered intravenously because its oral absorption was regarded as unreliable. The underpinning of this dogma was the rationalization that a high number of bacteria are "buried" deep within cardiac vegetations, limiting both antimicrobial access and an effective host inflammatory response.The first truly effective antibacterial agents were the sulfonamides, which became available in the mid-1930s. 1 Early experiences with oral sulfonamides in the treatment of IE were disappointing. A 1943 pre-post study reported a 99% mortality rate among 2596 patients with IE prior to sulfa drugs compared with a 96% mortality rate among subsequent patients with IE treated with oral sulfa drugs. 2 Other case series reported similar mortality rates. 3 When parenteral penicillin G became available in the 1940s and achieved better cure rates among patients with IE (from 1% before parenteral penicillin G to 85% after its introduction), it quickly became the standard of care for this infection. 3 Nevertheless, interest in the possibility of using oral therapy for IE continued owing to the difficulties inherent in prolonged intravenous therapy. When oral tetracyclines and macrolides became available in the late 1940s to early 1950s, they too were administered to patients with IE, also with unfavorable outcomes (eg, cure rates of <30% in case series). 4 Oral formulations of penicillin became available in the mid-1950s but were not viewed as reliable options for IE therapy, given concerns about bioavailability and the preceding high rates of failure of other oral agents. In 1954, a preeminent authority of infectious diseases, Maxwell Finland, published a 2-part review article on the treatment of IE. 3,4 He wrote, "in this disease, oral administra-tion…has generally been discarded as inadequate. Presumably, the oral route is at times successful…it is more likely, however, that such usage is responsible for many therapeutic failures…However, little of this type of experience is recorded, and therefore this assump-IMPORTANCE The requirement of prolonged intravenous antibiotic courses to treat infective endocarditis (IE) is a time-honored dogma of medicine. However, numerous antibiotics are now available that achieve adequate levels in the blood after oral administration to kill bacteria. Moreover, prolonged intravenous antibiotic regimens are associated with high rates of adverse events. Accordingly, recent studies of oral step-down antibiotic treatment have stimulated a reevaluation of the need for intravenous-only therapy for IE.OBSERVATIONS PubMed was reviewed in October 2019, with an update in February 2020, to determine whether evidence supports the notion that oral step-down antibiotic therapy for IE is associated with inferior outcomes compared with intravenous-only therapy. ...

1,2-Diarylethanols—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains

“…For the synthesis of target molecules 4, palladium nanoparticles catalysed reaction was selected [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ], ( Figure 2 ). Preliminary studies on reaction between phenylboronic acid and vinyl acetate showed that commercially available palladium nanoparticles Pd0 EnCat 30NP in the presence of benzoquinone ( 3 ) proceed in water at room temperature in 1% yield.…”

“…This compound was found to have antioxidant and anti-inflammatory properties [ 11 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. Recently special attention was paid on combrestatin for its antimicrobial activity [ 11 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. Due to its biological activity, combre...…”

“…Analysing the structure of Combrestatin, we have found that the core of the combrostatine structure (marked in red in Figure 1 ) is similar to the structure of di-1,2-diphenylethanol derivatives, which may have different R functional groups. It is known from literature that 1,2-diphenylethanol derivatives are proved to be effective antifungal agents [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], inhibitors of rhinovirus infection [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] and potential ligands of oestrogen receptors [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , ...…”

Enterococcus faecalis Endocarditis and Outpatient Treatment: A Systematic Review of Current Alternatives

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Advances in 3D bioprinting technology for cardiac tissue engineering and regeneration

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