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Shorter antibiotic treatment may increase long-term cellulitis relapse risk

Roshini Claire Anthony
14 May 2018

While a 6-day course of flucloxacillin appeared as effective as a 12-day course in curing and reducing short-term risk of relapse among patients hospitalized for cellulitis, the 6-day course led to a greater risk of relapse at 90 days, according to a study from The Netherlands.

“After initial cure without relapse, relapse rates at day 90 were higher in the 6-day group than in the 12-day group. Patients with a shorter course of therapy showed significantly faster and more frequent relapses by day 90,” said study investigator Dr Duncan Rowan Cranendonk from the Academic Medical Center in Amsterdam, The Netherlands, who presented the results of the study at ECCMID 2018.

For this multicentre (11 hospitals in The Netherlands), double-blind, non-inferiority trial, Cranendonk and co-investigators recruited 248 adult inpatients with cellulitis who had undergone treatment with intravenous flucloxacillin for 6 days. Patients who were afebrile and had a reduced cellulitis severity score on day 6 (n=151, mean age 63 years, 66 percent male, 24 percent with diabetes) were randomized to receive either intravenous flucloxacillin for an additional 6 days (n=77) or placebo (n=74). The intention-to-treat population comprised patients who took at least one dose of the study drug (n=71 and 69 in the 12-and 6-day treatment groups, respectively).

The primary outcome, cure by day 14 with no relapse by day 28, was comparable between patients who received 12 days and 6 days of flucloxacillin (49.3 percent vs 50.7 percent, absolute risk reduction, 1.4, 95 percent confidence interval, -14.8 to 17.5). [ECCMID 2018, abstract O1122]

However, the relapse rate at 90 days was significantly higher among patients who received antibiotics for 6 days compared with 12 days (p=0.04).

According to the researchers, an antibiotic treatment duration of 10–14 days is recommended for patients hospitalized with cellulitis, though this recommendation is mainly based on expert advice.

“We know that antibiotic consumption in general drives the development of antimicrobial resistance. If you can shorten or reduce consumption, you can hopefully reduce resistance rates,” said Cranendonk.

“Over the last few years, many studies have shown that many infections can be treated for a shorter duration of therapy which proved to be equally safe to the standard durations.”

“Our trial is the exact opposite; we had elderly hospitalized patients with a lot of comorbidity. This is the population clinicians are likely to see, but unfortunately, therapy cannot be shortened within this population,” he said.

The results were surprising as we started the trial thinking that the results would show that the shorter duration of treatment would be equally effective to the standard duration, he said.

According to Cranendonk, while these results will not change treatment duration recommendations for cellulitis, it might be beneficial to examine the long-term outcomes of shorter treatment periods on other infections seeing as how this increased risk of cellulitis relapse would not have been detected should the protocol have set the assessment at day 30 instead of day 90.

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