AT ASM MICROBE 2017
NEW ORLEANS (FRONTLINE MEDICAL NEWS) – Ceftaroline fosamil reduced the median duration of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia by 2 days in Veterans Administration patients, a retrospective study showed.
Investigators identified 219 patients with MRSA within the Veterans Affairs (VA) medical system nationwide from 2011 to 2015. All patients received at least 48 hours of ceftaroline fosamil (Teflaro) therapy to treat MRSA bacteremia. “We know it has good activity against MRSA in vitro. We use it in bacteremia, but we don’t have a lot of clinical data to support or refute its use,” said Nicholas S. Britt, PharmD, a PGY2 infectious diseases resident at Barnes-Jewish Hospital in St. Louis.
“Most of these patients had bacteremia about 3 days before ceftaroline, and patients cleared in about 1 day afterward. Median duration of MRSA bacteremia before ceftaroline initiation was 2.79 days, compared with a significantly shorter 1.18 days afterward (P less than.001). So the microbiologic outcomes were pretty good,” Dr. Britt said during a poster presentation at the annual meeting of the American Society for Microbiology.
“Ceftaroline was primarily used as second-line or salvage therapy … which is basically what we expected, based on how it’s used in clinical practice,” Dr. Britt said.
A total of 88 of the 219 (40%) patients experienced treatment failure. This rate “seems kind of high, but, if you look at some of the other MRSA agents for bacteremia (vancomycin, for example), it usually has a treatment failure rate around 60%,” Dr. Britt said. “The outcomes were not as poor as I would expect with [patients] using it for second- and third-line therapy.”
Hospital-acquired infection (odds ratio, 2.11; P = .013), ICU admission (OR, 3.95; P less than .001) and infective endocarditis (OR, 4.77; P = .002) were significantly associated with treatment failure in a univariate analysis. “Admissions to the ICU and endocarditis were the big ones, factors you would associate with failure for most antibiotics,” Dr. Britt said. In a multivariate analysis, only ICU admission remained significantly associated with treatment failure (adjusted OR, 2.24; P = .028).
The investigators also looked at treatment failure with ceftaroline monotherapy, compared with its use in combination. There is in vitro data showing synergy when you add ceftaroline to daptomycin, vancomycin, or some of these other agents,” Dr. Britt said. However, he added, “We didn’t find any significant difference in outcomes when you added another agent.” Treatment failure with monotherapy was 35%, versus 46%, with combination treatment (P = .107).
“This could be because the sicker patients are the ones getting combination therapy.”
No observed differences by dosing
Dr. Britt and his colleagues also looked for any differences by dosing interval, “which hasn’t been evaluated extensively.”
The Food and Drug Administration labeled it for use every 12 hours, but treatment of MRSA bacteremia is an off-label use, Dr. Britt explained. Dosing every 8 hours instead improves the achievement of pharmacokinetic and pharmacodynamic parameters in in vitro studies. “Clinically, we’re almost always using it q8. They’re sick patients, so you don’t want to under-dose them. And ceftaroline is pretty well tolerated overall.”
“But, we didn’t really see any difference between the q8 and the q12” in terms of treatment failure. The rates were 36% and 42%, respectively, and not significantly different (P = .440). “Granted, patients who are sicker are probably going to get treated more aggressively,” Dr. Britt added.
The current research only focused on outcomes associated with ceftaroline. Going forward, Dr. Britt said, “We’re hoping to use this data to compare ceftaroline to other agents as well, probably as second-line therapy, since that’s how it’s used most often.”
Dr. Britt had no relevant financial disclosures.