Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis

Kasper Iversen; Nikolaj Ihlemann; Sabine U Gill; Trine Madsen; Hanne Elming; Kaare T Jensen; Niels E Bruun; Dan E Høfsten; Kurt Fursted; Jens J Christensen; Martin Schultz; Christine F Klein; Emil L Fosbøll; Flemming Rosenvinge; Henrik C Schønheyder; Lars Køber; Christian Torp-Pedersen; Jannik Helweg-Larsen; Niels Tønder; Claus Moser; Henning Bundgaard

doi:10.1056/nejmoa1808312

Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis

Kasper Iversen, Nikolaj Ihlemann, Sabine U Gill, Trine Madsen, Hanne Elming, Kaare T Jensen, Niels E Bruun, Dan E Høfsten, Kurt Fursted, Jens J Christensen, Martin Schultz, Christine F Klein, Emil L Fosbøll, Flemming Rosenvinge, Henrik C Schønheyder, Lars Køber, Christian Torp-Pedersen, Jannik Helweg-Larsen, Niels Tønder, Claus MoserHenning Bundgaard

187 Citations (Scopus)

Abstract

BACKGROUND Patients with infective endocarditis on the left side of the heart are typically treated with intravenous antibiotic agents for up to 6 weeks. Whether a shift from intravenous to oral antibiotics once the patient is in stable condition would result in efficacy and safety similar to those with continued intravenous treatment is unknown. METHODS In a randomized, noninferiority, multicenter trial, we assigned 400 adults in stable condition who had endocarditis on the left side of the heart caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci and who were being treated with intravenous antibiotics to continue intravenous treatment (199 patients) or to switch to oral antibiotic treatment (201 patients). In all patients, antibiotic treatment was administered intravenously for at least 10 days. If feasible, patients in the orally treated group were discharged to outpatient treatment. The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen, from the time of randomization until 6 months after antibiotic treatment was completed. RESULTS After randomization, antibiotic treatment was completed after a median of 19 days (interquartile range, 14 to 25) in the intravenously treated group and 17 days (interquartile range, 14 to 25) in the orally treated group (P=0.48). The primary composite outcome occurred in 24 patients (12.1%) in the intravenously treated group and in 18 (9.0%) in the orally treated group (between-group difference, 3.1 percentage points; 95% confidence interval, −3.4 to 9.6; P=0.40), which met noninferiority criteria. CONCLUSIONS In patients with endocarditis on the left side of the heart who were in stable condition, changing to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment.

Original language	English
Journal	The New England Journal of Medicine
Volume	380
Issue number	5
Pages (from-to)	415-424
Number of pages	10
ISSN	0028-4793
DOIs	https://doi.org/10.1056/nejmoa1808312
Publication status	Published - 31 Jan 2019

Keywords

Administration, Intravenous
Administration, Oral
Aged
Anti-Bacterial Agents/administration & dosage
Bacteremia/drug therapy
Endocarditis, Bacterial/drug therapy
Female
Heart Valve Prosthesis/microbiology
Humans
Intention to Treat Analysis
Kaplan-Meier Estimate
Length of Stay
Male
Middle Aged
Recurrence

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Iversen, K., Ihlemann, N., Gill, S. U., Madsen, T., Elming, H., Jensen, K. T., Bruun, N. E., Høfsten, D. E., Fursted, K., Christensen, J. J., Schultz, M., Klein, C. F., Fosbøll, E. L., Rosenvinge, F., Schønheyder, H. C., Køber, L., Torp-Pedersen, C., Helweg-Larsen, J., Tønder, N., ... Bundgaard, H. (2019). Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. The New England Journal of Medicine, 380(5), 415-424. https://doi.org/10.1056/nejmoa1808312

Iversen, K, Ihlemann, N, Gill, SU, Madsen, T, Elming, H, Jensen, KT, Bruun, NE , Høfsten, DE, Fursted, K, Christensen, JJ, Schultz, M, Klein, CF, Fosbøll, EL, Rosenvinge, F, Schønheyder, HC, Køber, L , Torp-Pedersen, C, Helweg-Larsen, J, Tønder, N, Moser, C & Bundgaard, H 2019, 'Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis', The New England Journal of Medicine, vol. 380, no. 5, pp. 415-424. https://doi.org/10.1056/nejmoa1808312

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abstract = "BACKGROUND Patients with infective endocarditis on the left side of the heart are typically treated with intravenous antibiotic agents for up to 6 weeks. Whether a shift from intravenous to oral antibiotics once the patient is in stable condition would result in efficacy and safety similar to those with continued intravenous treatment is unknown. METHODS In a randomized, noninferiority, multicenter trial, we assigned 400 adults in stable condition who had endocarditis on the left side of the heart caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci and who were being treated with intravenous antibiotics to continue intravenous treatment (199 patients) or to switch to oral antibiotic treatment (201 patients). In all patients, antibiotic treatment was administered intravenously for at least 10 days. If feasible, patients in the orally treated group were discharged to outpatient treatment. The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen, from the time of randomization until 6 months after antibiotic treatment was completed. RESULTS After randomization, antibiotic treatment was completed after a median of 19 days (interquartile range, 14 to 25) in the intravenously treated group and 17 days (interquartile range, 14 to 25) in the orally treated group (P=0.48). The primary composite outcome occurred in 24 patients (12.1%) in the intravenously treated group and in 18 (9.0%) in the orally treated group (between-group difference, 3.1 percentage points; 95% confidence interval, −3.4 to 9.6; P=0.40), which met noninferiority criteria. CONCLUSIONS In patients with endocarditis on the left side of the heart who were in stable condition, changing to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment.",

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author = "Kasper Iversen and Nikolaj Ihlemann and Gill, {Sabine U} and Trine Madsen and Hanne Elming and Jensen, {Kaare T} and Bruun, {Niels E} and H{\o}fsten, {Dan E} and Kurt Fursted and Christensen, {Jens J} and Martin Schultz and Klein, {Christine F} and Fosb{\o}ll, {Emil L} and Flemming Rosenvinge and Sch{\o}nheyder, {Henrik C} and Lars K{\o}ber and Christian Torp-Pedersen and Jannik Helweg-Larsen and Niels T{\o}nder and Claus Moser and Henning Bundgaard",

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day = "31",

doi = "10.1056/nejmoa1808312",

language = "English",

volume = "380",

pages = "415--424",

journal = "The New England Journal of Medicine",

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T1 - Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis

AU - Iversen, Kasper

AU - Ihlemann, Nikolaj

AU - Gill, Sabine U

AU - Madsen, Trine

AU - Elming, Hanne

AU - Jensen, Kaare T

AU - Bruun, Niels E

AU - Høfsten, Dan E

AU - Fursted, Kurt

AU - Christensen, Jens J

AU - Schultz, Martin

AU - Klein, Christine F

AU - Fosbøll, Emil L

AU - Rosenvinge, Flemming

AU - Schønheyder, Henrik C

AU - Køber, Lars

AU - Torp-Pedersen, Christian

AU - Helweg-Larsen, Jannik

AU - Tønder, Niels

AU - Moser, Claus

AU - Bundgaard, Henning

PY - 2019/1/31

Y1 - 2019/1/31

N2 - BACKGROUND Patients with infective endocarditis on the left side of the heart are typically treated with intravenous antibiotic agents for up to 6 weeks. Whether a shift from intravenous to oral antibiotics once the patient is in stable condition would result in efficacy and safety similar to those with continued intravenous treatment is unknown. METHODS In a randomized, noninferiority, multicenter trial, we assigned 400 adults in stable condition who had endocarditis on the left side of the heart caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci and who were being treated with intravenous antibiotics to continue intravenous treatment (199 patients) or to switch to oral antibiotic treatment (201 patients). In all patients, antibiotic treatment was administered intravenously for at least 10 days. If feasible, patients in the orally treated group were discharged to outpatient treatment. The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen, from the time of randomization until 6 months after antibiotic treatment was completed. RESULTS After randomization, antibiotic treatment was completed after a median of 19 days (interquartile range, 14 to 25) in the intravenously treated group and 17 days (interquartile range, 14 to 25) in the orally treated group (P=0.48). The primary composite outcome occurred in 24 patients (12.1%) in the intravenously treated group and in 18 (9.0%) in the orally treated group (between-group difference, 3.1 percentage points; 95% confidence interval, −3.4 to 9.6; P=0.40), which met noninferiority criteria. CONCLUSIONS In patients with endocarditis on the left side of the heart who were in stable condition, changing to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment.

AB - BACKGROUND Patients with infective endocarditis on the left side of the heart are typically treated with intravenous antibiotic agents for up to 6 weeks. Whether a shift from intravenous to oral antibiotics once the patient is in stable condition would result in efficacy and safety similar to those with continued intravenous treatment is unknown. METHODS In a randomized, noninferiority, multicenter trial, we assigned 400 adults in stable condition who had endocarditis on the left side of the heart caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci and who were being treated with intravenous antibiotics to continue intravenous treatment (199 patients) or to switch to oral antibiotic treatment (201 patients). In all patients, antibiotic treatment was administered intravenously for at least 10 days. If feasible, patients in the orally treated group were discharged to outpatient treatment. The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen, from the time of randomization until 6 months after antibiotic treatment was completed. RESULTS After randomization, antibiotic treatment was completed after a median of 19 days (interquartile range, 14 to 25) in the intravenously treated group and 17 days (interquartile range, 14 to 25) in the orally treated group (P=0.48). The primary composite outcome occurred in 24 patients (12.1%) in the intravenously treated group and in 18 (9.0%) in the orally treated group (between-group difference, 3.1 percentage points; 95% confidence interval, −3.4 to 9.6; P=0.40), which met noninferiority criteria. CONCLUSIONS In patients with endocarditis on the left side of the heart who were in stable condition, changing to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment.

KW - Administration, Intravenous

KW - Administration, Oral

KW - Aged

KW - Anti-Bacterial Agents/administration & dosage

KW - Bacteremia/drug therapy

KW - Endocarditis, Bacterial/drug therapy

KW - Female

KW - Heart Valve Prosthesis/microbiology

KW - Humans

KW - Intention to Treat Analysis

KW - Kaplan-Meier Estimate

KW - Length of Stay

KW - Male

KW - Middle Aged

KW - Recurrence

U2 - 10.1056/nejmoa1808312

DO - 10.1056/nejmoa1808312

M3 - Journal article

C2 - 30152252

SN - 0028-4793

VL - 380

SP - 415

EP - 424

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

IS - 5

ER -

Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis

Abstract

Keywords

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