Combination of Beta-lactams and Daptomycin Does Not Reduce MSSA Bacteremia Mortality

An antibiotic combination therapy failed to reduce mortality rates in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, a new study from Spain reports.

S aureus is the leading cause of both community and health care-associated bacteremia in the United States and treatment presents dangerous and costly challenges. Cases have a 30-day mortality rate of 20%, with health care costs averaging more than $50,000 per case.

For decades, mortality rates from blood infections caused by S aureus have remained high with only modest reductions, with serious and fatal infections continuing to pose a clinical challenge in health care settings. A study recently published in the journal Clinical Infectious Diseases builds on previous small studies and compares beta-lactams in combination with daptomycin with beta-lactam monotherapy as treatment for bacteremia caused by MSSA.

The study is based on a retrospective cohort analysis of prospectively collected data on patients with cases of MSSA bacteremia confirmed by at least one positive blood culture from Bellvitge University Hospital in Barcelona. Patients included adults ages 18 years and older admitted between January 2011 and December 2017.

Excluded from the study were patients who received different antibiotic combinations; those who received antibiotics more than 72 hours after onset of bacteremia; those who were diagnosed with pneumonia; those who had a treatment duration of less than 72 hours; and those who died during the first 48 hours.

Of the 514 episodes of MSSA bacteremia recorded during the study period, 350 cases met inclusion criteria and were included and followed up on for up to 90 days. Of the patients included, 70% were male with a mean age of 63.1 years. Overall, 136 patients received the combination therapy and 214 received monotherapy.

Treatment began within the first 24 hours in 131 patients in the combination treatment group, and 81.6% of those in the group received the antibiotic cloxacillin in combination with daptomycin.

Catheter-related bacteremia was the cause of 31.1% of cases and 14% of patients had septic shock at diagnosis. While the patients on combination therapy had persistent bacteremia more often than monotherapy patients, the raw analysis showed that there were no differences in mortality rates between the 2 groups.

“We separately analyzed only the patients with high-risk sources of infection to determine if BL/D-C could have an impact on mortality in this subgroup of patients. However, this subgroup had the worst prognosis,” write the authors. “In this sub-analysis, no differences were found between the BL/D-C and BL-M patients. We also performed the analysis by excluding patients with catheter-related bacteremia, again finding no differences in mortality rates between the groups.”

The authors note that their study is the largest cohort study to date to analyze patients treated with this combination therapy and the first to evaluate the impact of the combination therapy on clinical outcomes for MSSA bacteremia, though the main limitation of the study was its retrospective design.

In an interview with Contagion®, study co-author Sara Grillo, MD, of the Department of Infectious Diseases at Bellvitge University Hospital in Barcelona, noted that increasing life expectancy, health care exposure, and the use of invasive devices have increased the burden of MSSA bacteremia.

“Although in our study BL/D-C did not improve outcomes, we believe that antibiotic combination may be the clue to deal with this pathology,” said Dr. Grillo. “The high incidence of S aureus bacteremia and its extremely high mortality rate make mandatory to investigate this important issue. Randomized controlled trials testing different combination therapies are warranted.”