Considering a Beta Lactam as Adjunctive Therapy for Staphylococcus aureus Early in Treatment
This bacteremia can present heterogeneously and be difficult to contain, especially in an older patient population. Daniel B. Chastain, PharmD, BCIDP, AAHIVP, FIDSA, reviews the data of this class of therapies and how it may be clinically beneficial in combination with other antimicrobials.
It has been documented that the incidence rates for Staphylococcus aureus bacteremia (SAB) ranges from 20 to 50 cases/100,000 population per year, and the mortality rates are between 10% and 30%.1 According to one study, this accounts for a greater number of deaths than for several other infectious diseases including AIDS, tuberculosis, and viral hepatitis combined.1
This infection can be particularly challenging on seniors as age is the largest factor for mortality with older patients more than twice as likely to expire from SAB.1
“One of the things that I've always heard and always been taught is respect Staph aureus bacteremia, in that it's always challenging, and it's certainly a difficult process [treating it], said Daniel B. Chastain, PharmD, BCIDP, AAHIVP, FIDSA clinical associate professor University of Georgia College of Pharmacy.
Staphylococcus aureus can also be heterogenous in presentation and lead to patient management issues.
Chastain reviewed the literature looking at the use of beta-lactams as adjunctive therapy for Staphylococcus aureus, and presented his findings at IDWeek last month.2
One of the novel approaches is to consider prescribing combination therapy earlier in the treatment cycle.
“Given the presentation, given the severity of the illness, why not add combination therapy up front? Once you have a blood culture that has staphylococcus species before you know that it's MSSA or MRSA, there are certainly some older data that supports a beta-lactams from start to finish, having improved outcomes compared to deescalating from vancomycin to a beta-lactam,” Chastain said. “So if we could start with vancomycin, adaptomycin, in addition to either a cefazolin or an antistaphylococci penicillin, perhaps we're able to better impact that patient's care up front and maybe decrease the risk of complicated Staph aureus bacteria later on down the road.”
He sees another potential benefit in risk stratification looking at patient presentation, which may help identify who would be a better candidate for combination therapy. Chastain notes there does not appear to be a reduction in mortality in the literature. “Most of them don't result in mortality benefit, which is really interesting, despite improvements in time to blood culture sterilization or decreased risk of recurrence or persistent Staph aureus bacteremia.”
“I think the lack of mortality benefit is largely from the fact that most of our clinical trials that we have now include a wide variety of patients with diverse sources. So some may have catheter-related infections; whereas others may have bone or joint involvement. Some may have endovascular [infections], so if we're able to better risk stratify, perhaps upfront, through biomarkers or certain sub phenotypes, then perhaps, maybe we can better affect their care overall, and actually figure out who could benefit from that combination therapy.”
He does believe in exercising caution when considering adjunctive therapy.
“I think that of the data that we have, early combination therapy for patients that are at high risk for poor outcomes, so high risk for complicated Staph aureus bacteremia or high risk for mortality, will hopefully certainly improve patient outcomes,” Chastain said. “And then the only thing I would add is that there are some door framework and radar analysis that have been done to suggest that perhaps patients don't always have the greatest experience with combination therapy. So, I think it's important that we balance being a little bit more aggressive with treatment as well as what the patient experiences, and taking that whole entire process into account as we try to treat these patients.”
