Lessons Learned From a Randomized Controlled Trial of Short-Course Intravenous Antibiotic Therapy for Erysipelas and Cellulitis of the Lower Limb (Switch Trial)

Abstract

BackgroundThe diagnosis of cellulitis is made clinically without a gold standard diagnostic test, and cellulitis has many disease mimics. There is currently no consensus for optimal antimicrobial treatment duration or method of antimicrobial delivery.MethodsThis was a randomized controlled open-label multicenter trial to determine the safety and efficacy of 24 hours of intravenous (IV) therapy compared with ≥72 hours of IV therapy, both followed by oral therapy to a maximum of 7–10 days’ duration for the treatment of lower limb cellulitis.ResultsOver 40 months, 80 patients were recruited. Thirty-nine patients were assigned to 24 hours of IV antibiotics and 41 to ≥72 hours of IV antibiotics. The mean duration (range) of IV antibiotics in the 24-hour group was 25.5 (17–40) hours, and in the ≥72-hour group it was 78 (41.5–210) hours. Three patients in the 24-hour arm and 4 patients in the ≥72-hour arm were excluded from the analysis due to withdrawal from the trial. Analysis of the remaining patients revealed that 6 patients (4 in the intervention arm and 2 in the control arm) did not achieve an adequate response to therapy. Only 1 patient experienced self-limiting adverse effects of treatment.ConclusionsThe noninferiority of short-course IV therapy cannot be determined from this trial. Challenges included resource limitations for recruitment, misdiagnosis, participant withdrawal, and subjective responses to therapy based on visual assessment by treating clinicians. Further studies are needed to determine if short-course IV therapy is a suitable treatment option.Australia Council of Clinical Trials Registry NoACTRN12613001366741.

Route and duration of antibiotic therapy in acute cellulitis: A systematic review and meta-analysis of the effectiveness and harms of antibiotic treatment

“…A single RCT compared efficacy of early (24h) versus later (≥72h) switch to oral antibiotics in uncomplicated cellulitis requiring IV antibiotics (table 2). 28 Resolution of cellulitis was achieved in 79% and 84% of patients in the of shorter (24h and longer (>72 hour) treatment groups respectively but the study sample size was too small to demonstrate non-inferiority. Decreases in patient-reported pain scores were similar between groups.…”

“…Inter-observer agreement was moderate at title and abstract screening (Kappa=0•66, 95%CI 0•59-0•73). Among the 47 included articles, one described two RCTs yielding a total of 48 studies (figure 1): 16 RCTs (including one quasi-RCT), [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] two non-randomised interventional studies 38,39 and 30 observational studies. Eleven RCTs were included in two separate meta-analyses.…”

“…The question of timing of IV-to-oral switch has been addressed in only a single trial which was too small to demonstrate non-inferiority and again included only a subset of patients with uncomplicated cellulitis. 28 Although we identified ten randomised trials providing evidence on duration of therapy, a major limitation of this evidence base is that eight of the trials use short-course treatment with agents anticipated to have longer durations of action compared to the longer-course agent used. For instance, azithromycin is used as the short-course agent in half of the trials on duration but is known to have a longer serum half-life than the other antibiotics.…”

Serological Responses to Streptococcus pyogenes Vaccine Candidate Antigens Suggests That Streptococcus dysgalactiae Is the Predominant Cause of Lower Limb Cellulitis

“…This study has limitations. The lack of a gold standard diagnostic test remains a challenge in cellulitis trials [ 31 ]. Although all patients received a clinical assessment by a study member working in the infectious diseases department to confirm a diagnosis of cellulitis, there is small possibility that some patients with a noncellulitis diagnosis may have been inadvertently included.…”

Cellulitis in the Emergency Department: A prospective cohort study with patient‐centred follow‐up

“…The clinical course of ED diagnosed cellulitis is reported poorly, with few prospective studies describing clinical response after diagnosis, [3][4][5][6] and none…”