Baseline Characteristics and Outcomes Among Patients with Complicated Skin and Soft Tissue Infections Admitted to the Intensive Care Unit: Analysis of the Phase 3 COVERS Randomized Trial of Ceftaroline Fosamil Versus Vancomycin Plus Aztreonam

Abstract

Aim: Exploratory analyses evaluated patient characteristics and outcomes among patients with complicated skin and soft tissue infection (cSSTI) in the phase 3 COVERS study who were admitted to an intensive care unit (ICU).

Methods: Adults with cSSTI (surface area ≥ 75 cm2) and evidence of systemic inflammation and/or underlying comorbidities were randomized 2:1 to intravenous ceftaroline fosamil (600 mg every 8 h [q8h]) or vancomycin (15 mg/kg every 12 h) plus aztreonam (1 g q8h) for 5-14 days. Clinical response and ICU length of stay (LOS) within first hospitalization were evaluated in the modified intent-to-treat (MITT) and clinically evaluable (CE) populations; a Cox proportional hazards model identified factors associated with increased hospital LOS.

Results: Overall, 42 of 761 randomized patients were admitted to the ICU (ceftaroline fosamil, n = 32; vancomycin plus aztreonam, n = 10) prior to, or at start of, study treatment. Baseline differences between the ICU and non-ICU populations were indicative of more severe disease in ICU patients; within this subset, there were also some notable imbalances between treatment groups. Clinical cure rates at test-of-cure (ceftaroline fosamil vs. vancomycin plus aztreonam) were generally similar in the non-ICU and ICU subsets (MITT population 79% vs. 79% and 69% vs. 90.0%, respectively; CE population 87% vs. 85% and 80% vs. 89%, respectively). Median ICU LOS was 8 vs. 13 days, respectively. ICU admission was a risk factor predicting increased hospital LOS (P < 0.001).

Conclusions: Clinical outcomes for patients admitted to the ICU were generally similar to non-ICU patients, despite more severe baseline disease, with shorter median treatment duration in the ceftaroline fosamil group. ICU admission was associated with longer hospital LOS. Given the small sample size and unbalanced patient and disease characteristics within the ICU subgroup, differences between treatment groups should be interpreted with caution.

Trial registration: ClinicalTrials.gov identifier, NCT01499277.

Keywords: Antimicrobial resistance; Ceftaroline fosamil; Complicated skin and soft tissue infections; Healthcare resource use; Intensive care unit.

Figures

Fig. 1

Kaplan–Meier curves for a length of first hospital stay; b length of ICU stay.aCE clinically evaluable, ICU intensive care unit, LFU late follow-up, MITT modified intent-to-treat. aThe length of first hospital stay is calculated as number of days from randomization until when the patient is no longer recorded as being in one of the hospital wards (including ICU) for the first admission. The length of ICU stay is calculated as number of days from randomization until when the patient is no longer recorded as being in ICU for the first admission. For patients who stay in hospital (including ICU) beyond the LFU visit, the length of stay is censored at the LFU visit. For patients lost to follow-up while in a hospital ward (including ICU), the length of stay is censored at the last recorded visit