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Daptomycin, fosfomycin combination more effective against MRSA

Miquel Pujol
Miquel Pujol

SAN FRANCISCO — The combination of daptomycin and fosfomycin was more effective in treating MRSA bacteremia than daptomycin alone, according to a recent study.

“MRSA bacteremia has a devastating effect because it affects the most fragile and critical patients of the health care system and carries a mortality rate as high as 30%,” Miquel Pujol, MD, PhD, from the infectious diseases department at Bellvitge University Hospital in Barcelona, Spain, told Infectious Disease News. “Although there have been numerous efforts in recent years to reduce this mortality through new combinations or new antibiotics, the results have been disappointing. Therefore, the treatment of MRSA bacteremia remains a very significant problem for clinicians.”

To examine the efficacy of the combination of daptomycin and fosfomycin, researchers conducted a randomized, open-label clinical trial in adults with MRSA bacteremia at 18 medical centers in Spain. Patients were assigned to receive either daptomycin plus fosfomycin or monotherapy with daptomycin for 10 to 14 days for uncomplicated bacteremia and 28 to 42 days for complicated bacteremia. Efficacy endpoints were treatment success at the test-of-cure visit, which was 6 weeks after end of therapy, and treatment success at 7 days, defined as survival at day 7 and clearance of bacteremia without relapse 8 to 90 days after randomization.

The researchers evaluated 674 patients between December 2013 and November 2017. One hundred and fifty-five patients were randomly assigned to the two cohorts — 74 who received the combination therapy and 81 who received monotherapy. According to the study, at the test-of-cure visit successful treatment was achieved in 40 of 74 patients (54.1%) who received combination therapy vs. 34 of 81 (42%) who were given monotherapy (absolute difference = 12.1%; 95% CI, 0%-27%). At the 7-day mark, a successful outcome was achieved in 69 of 74 patients (93.2%) who received combination therapy, compared with 62 of 81 patients (76.5%) who received monotherapy (absolute difference = 16.7%; 95% CI, 5.4% to 27.7%).

Additionally, researchers determined that combination therapy was associated with significantly lower rates of microbiologic failure than monotherapy at the test-of-cure visit (0 vs. 9 patients).

The researchers added that the combination therapy was associated with a higher rate of adverse events leading to treatment failure and discontinuation of therapy, but this finding was not statistically significant.

“The results show that the combination has a very important bactericidal effect, avoids persistent bacteremia in all who received the combination and significantly reduces complicated bacteremia at the end of treatment, reducing mortality at 7 days,” Pujol said. “With the combination, we have increased the chances of success of treatment and reduced mortality at 7 days of treatment, although this effect is diluted 6 weeks after the end of the treatment, probably due to different reasons not related to the infection but mainly due to the characteristics of the patients.” – by Caitlyn Stulpin

Reference:

Pujol, M, et al. Abstract LB3. Presented at ID Week; Oct. 3-7, 2018; San Francisco.

Disclosures: The authors report no relevant financial disclosures.

Miquel Pujol
Miquel Pujol

SAN FRANCISCO — The combination of daptomycin and fosfomycin was more effective in treating MRSA bacteremia than daptomycin alone, according to a recent study.

“MRSA bacteremia has a devastating effect because it affects the most fragile and critical patients of the health care system and carries a mortality rate as high as 30%,” Miquel Pujol, MD, PhD, from the infectious diseases department at Bellvitge University Hospital in Barcelona, Spain, told Infectious Disease News. “Although there have been numerous efforts in recent years to reduce this mortality through new combinations or new antibiotics, the results have been disappointing. Therefore, the treatment of MRSA bacteremia remains a very significant problem for clinicians.”

To examine the efficacy of the combination of daptomycin and fosfomycin, researchers conducted a randomized, open-label clinical trial in adults with MRSA bacteremia at 18 medical centers in Spain. Patients were assigned to receive either daptomycin plus fosfomycin or monotherapy with daptomycin for 10 to 14 days for uncomplicated bacteremia and 28 to 42 days for complicated bacteremia. Efficacy endpoints were treatment success at the test-of-cure visit, which was 6 weeks after end of therapy, and treatment success at 7 days, defined as survival at day 7 and clearance of bacteremia without relapse 8 to 90 days after randomization.

The researchers evaluated 674 patients between December 2013 and November 2017. One hundred and fifty-five patients were randomly assigned to the two cohorts — 74 who received the combination therapy and 81 who received monotherapy. According to the study, at the test-of-cure visit successful treatment was achieved in 40 of 74 patients (54.1%) who received combination therapy vs. 34 of 81 (42%) who were given monotherapy (absolute difference = 12.1%; 95% CI, 0%-27%). At the 7-day mark, a successful outcome was achieved in 69 of 74 patients (93.2%) who received combination therapy, compared with 62 of 81 patients (76.5%) who received monotherapy (absolute difference = 16.7%; 95% CI, 5.4% to 27.7%).

Additionally, researchers determined that combination therapy was associated with significantly lower rates of microbiologic failure than monotherapy at the test-of-cure visit (0 vs. 9 patients).

The researchers added that the combination therapy was associated with a higher rate of adverse events leading to treatment failure and discontinuation of therapy, but this finding was not statistically significant.

“The results show that the combination has a very important bactericidal effect, avoids persistent bacteremia in all who received the combination and significantly reduces complicated bacteremia at the end of treatment, reducing mortality at 7 days,” Pujol said. “With the combination, we have increased the chances of success of treatment and reduced mortality at 7 days of treatment, although this effect is diluted 6 weeks after the end of the treatment, probably due to different reasons not related to the infection but mainly due to the characteristics of the patients.” – by Caitlyn Stulpin

Reference:

Pujol, M, et al. Abstract LB3. Presented at ID Week; Oct. 3-7, 2018; San Francisco.

Disclosures: The authors report no relevant financial disclosures.

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