Combo Tx Doesn't Improve Survival in Patients with Gram-Negative Bloodstream Infections

Combo Tx Doesn't Improve Survival in Patients with Gram-Negative Bloodstream Infections
Combo Tx Doesn't Improve Survival in Patients with Gram-Negative Bloodstream Infections

SAN DIEGO, CA—Combination therapy does not improve survival over beta-lactam monotherapy for gram-negative bloodstream infection (GN BSI), according to a single healthcare system cohort study findings reported at IDWeek 2015.

Regardless of patient stratified predicted prognosis on presentation using the Bloodstream Infection Mortality Risk Score (BSIMRS), 28-day morality, the primary end point, was not statistically significant (P=0.51) between the two groups, said Julie Ann Justo, PharmD, MS, BCPS, AAHIVP, Clinical Assistant Professor, South Carolina College of Pharmacy, USC Campus, and Infectious Diseases Clinical Specialist at Palmetto Health Richland, Columbia, SC.

Overall, 28-day mortality was 12.9% (95% confidence interval [CI] 8.0%, 17.8%) in patients who received combination therapy and 15.3% (95% CI 10.0%, 20.6%) in those who received combination therapy.

In North America, bloodstream infection is the leading cause of death due to infections. However, “utility of combination antibiotic therapy v.s monotherapy is a long-standing controversy,” Dr. Justo pointed out.

The study compared outcomes for monotherapy and combination therapy for 190 pairs of patients matched by BSIMRS-predicted prognoses among adults hospitalized for first episodes of GN BSI between 2010 and 2013 at Palmetto Health Richland and Baptist Hospitals in Columbia, SC. Each BSIMRS-matched pair included one patient receiving monotherapy and one receiving combination therapy. A total of 212 (56%) of patients had a BSIMR Score of <5 and 168 (44%) had a score of ≥5.

In the monotherapy group, patients had to have received a beta-lactam within the first 24 hours of index blood culture collection, with treatment continued for at least 48 hours. Those in the combination therapy group had both a beta-lactam plus a fluoroquinolone or an aminoglycoside initiated within 24 hours of index blood culture collection, with the beta-lactam continued for at least 48 hours and the combination agent continued for at least 24 hours.

Within the combination therapy group, 128 patients (67%) received fluoroquinolones and 62 (33%), aminoglycosides, with duration of therapy a median of 2.6 days.

Patients receiving empirical combination therapy were matched 1:1 to those receiving empiric monotherapy based on age range (±10 years), sex, exact BSIMRS, and beta-lactam type (anti-pseudomonal or non-pseudomonal). Multivariate Cox proportional hazards regression tests with propensity score adjustment was used to examine 28-day mortality overall and within BSIMRS categories, with a score of <5 a “good prognosis” and one of ≥5 a “guarded/poor prognosis,” she said.

Median age was 66 years, and 54% of the cohort was female. A total of 246 patients (65%) received anti-pseudomonal beta-lactams. In both group, Escherichia coli was most frequently cultured, followed by Klebsiella spp.

After stratification by BSIMRS, mortality in both the combination therapy and monotherapy groups was 1.1% in patients with BSIMR Scores <5 (P=0.98) and 27.0% and 32.4%, respectively, in patients with BSIMR Scores ≥5 (P=0.47), Dr. Justo said. After adjusting for the propensity to receive combination therapy, risk of mortality was not significantly different for combination therapy compared to monotherapy (hazard ratio [HR] 0.90; 95% CI: 0.51, 1.60; P=0.73).”

Those findings did not change significantly in subgroup analyses of BSIMR Scores: <5 vs. ≥5: HRs 0.96 (95% CI: 0.04, 24.29; P=0.98) and 0.83 (95% CI: 0.46–1.48; P=0.52), respectively, she reported.

“Future studies should focus on the impact of combination therapy in niched subgroups,” Dr. Justo concluded, such as in “patients with high risk of antimicrobial resistance, particularly among those with high BSIMRS.”

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