LB3. Daptomycin plus Fosfomycin versus Daptomycin Monotherapy for Methicillin-resistant Staphylococcus aureus Bacteremia. A Multicenter, Randomized, Clinical Trial
Session: Oral Abstract Session: Late Breaker Oral Abstracts: HIV and Antibiotic Trials
Thursday, October 4, 2018: 10:50 AM
Room: S 151-153
Background: Daptomycin plus fosfomycin combination has demonstrated synergistic and bactericidal effect in animal models of methicillin-resistant Staphylococcus aureus bacteremia (MRSAB), but there is lack of data in humans.

Method: A randomized (1:1), open-label, clinical trial involving adults with MRSAB was conducted at 18 medical centers in Spain. Patients were assigned to receive daptomycin, 10mg/kg IV daily plus fosfomycin, 2g IV/6h (combination-therapy) or to receive daptomycin 10mg/kg/24h IV (monotherapy) during 10 up to 14 days for uncomplicated bacteremia and 28 up to 42 days for complicated bacteremia. The primary efficacy endpoints were: a) treatment success at Test-of-Cure visit (ToC: 6 weeks after end of therapy) and b) treatment success at 7 days (defined as alive at day 7 and clearance of bacteremia without relapse from 8 to 90 days after randomization), according with the proposed primary endpoints for use in clinical trials in bloodstream infections in adults.

Result: Between December 2013 and November 2017, 674 patients with MRSAB were evaluated and 155 patients were randomized: 74 received combination therapy and 81 monotherapy. In intention-to-treat analysis, (a) at ToC visit successful outcome was achieved in 40 of 74 patients (54,1%) who received combination therapy as compared with 34 of 81 patients (42%) who were given monotherapy (54.1% vs. 42.0%; absolute difference, 12.1%; 95% confidence interval, 0%-27.0%); (b) at seven days after starting the therapy: a successful outcome was achieved in 69 of 74 patients who received combination therapy as compared with 62 out of 81 patients who received monotherapy (93.2% vs. 76.5%; absolute difference, 16.7%; 95% confidence interval, 5.4%-27.7%). Combination therapy was associated with lower rates of microbiologic failure than monotherapy at ToC visit (0 vs. 9 patients, p-value 0.009). Combination therapy, as compared with daptomycin monotherapy, was associated with a non-significantly higher rate of adverse events due to study medication leading to treatment failure and discontinuation of therapy: 6/74 (8.1%) vs 3/81 (3.7%) (p-value 0.31).

Conclusion: The combination of daptomycin plus fosfomycin was more effective than daptomycin alone for treating MRSAB. (NCT01898338)

Miquel Pujol, MD, PhD1, Jose-Maria Miro, MD, PhD2, Evelyn Shaw, MD, PhD3, Jose Maria Aguado, MD, PhD4, Rafael San-Juan Garrido, MD, PhD5, Mireia Puig, MD, PhD6, Carle Pigrau, MD, PhD6, Esther Calbo, MD, PhD7, Jose Miguel Montejo, MD, PhD8, Regino Rodriguez, MD8, Maria Jose Garcia-Pais, MD9, Vicente Pintado, MD, PhD10, Rosa Escudero, MD10, Joaquin Lopez-Contreras, MD, PhD11, Laura Morata, MD12, Milagro Montero, MD, PhD13, Marta Andres, MD14, Juan Pasquau, MD, PhD15, Belen Padilla, MD, PhD16, Javier Murillas, MD, PhD17, Alfredo Jover, MD, PhD18, Luis Eduardo Lopez-Cortes, MD, PhD19, Graciano Garcia-Pardo, MD20, Oriol Gasch, MD, PhD21, Sebastian Videla, MD, PhD3, Cristian Tebe, MSc22, Natalia Pallares, MSc23, Pilar Hereu, MD, PhD3, Mireia Sanllorente, MSc3, Maria Angeles Dominguez, MD, PhD3, Jordi Camara, MD3, Ariadna Padulles, MD, PhD3 and Jordi Carratala, MD, PhD3, (1)Infectious Diseases Department, Hospital de Bellvitge, L'Hospitalet llobregat, Spain, (2)Infectious Diseases, Hospital Clínic, BARCELONA, Spain, (3)Hospital de Bellvitge, L'Hospitalet llobregat, Spain, (4)Hospital 12 de Octubre, MADRID, Spain, (5)Hospital 12 Octubre, MADRID, Spain, (6)Hospital Vall d'Hebron, BARCELONA, Spain, (7)Hospital Mútua de Terrassa, TERRASSA, Spain, (8)Hospital de Cruces, BILBAO, Spain, (9)Hospital Lucus Augusti, LUGO, Spain, (10)Hospital Ramón y Cajal, MADRID, Spain, (11)Hospital de la Santa Creu i Sant Pau, BARCELONA, Spain, (12)Hospital Clínic, BARCELONA, Spain, (13)Hospital del Mar, B, Spain, (14)Consorci Sanitari de Terrassa, TERRASSA, Spain, (15)Hospital Virgen de las Nieves, GRANADA, Spain, (16)Hospital Gregorio Marañón, MADRID, Spain, (17)Hospital Son Espases, MALLORCA, Spain, (18)Hospital Arnau de Vilanova, LLEIDA, Spain, (19)Hospital Virgen Macarena, SEVILLA, Spain, (20)Hospital Joan XXIII, TARRAGONA, Spain, (21)Hospital del Parc Taulí, SABADELL, Spain, (22)Institut d'Investigacions Biomèdiques de Bellvitge (IDIBELL), L'Hospitalet llobregat, Spain, (23)Institud d'Investigacions Biomèdiques de Bellvitge (IDIBELL), L'Hospitalet llobregat, Spain

Disclosures:

M. Pujol, None

J. M. Miro, None

E. Shaw, None

J. M. Aguado, None

R. San-Juan Garrido, None

M. Puig, None

C. Pigrau, None

E. Calbo, None

J. M. Montejo, None

R. Rodriguez, None

M. J. Garcia-Pais, None

V. Pintado, None

R. Escudero, None

J. Lopez-Contreras, None

L. Morata, None

M. Montero, None

M. Andres, None

J. Pasquau, None

B. Padilla, None

J. Murillas, None

A. Jover, None

L. E. Lopez-Cortes, None

G. Garcia-Pardo, None

O. Gasch, None

S. Videla, None

C. Tebe, None

N. Pallares, None

P. Hereu, None

M. Sanllorente, None

M. A. Dominguez, None

J. Camara, None

A. Padulles, None

J. Carratala, None

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