Table 2 Summary of FDA guidance document issued in 2013 and potential issues in implementation

Definitions of ABSSSI

Cellulitis or erysipelas, wound infections, and abscesses with at least 75 cm² area of redness, edema, or induration.

Lesion size >75 cm² is arbitrary [26].

Minimum lesion size of 75 cm² differentiates ‘minor’ cutaneous abscess from ‘major’ abscess.

Minimum lesion size may exclude key groups (pediatric, small adults) and body parts (face, hand, genitalia) [28].

Measurement of induration and edema is subjective [28].

Depth of involvement may be more important than diameter [26].

Clinical trial design, populations, and entry criteria

Mixture of ABSSSI entities.

Conflicting evidence regarding the efficacy of drug therapy for ‘minor’ abscess.

Limit on number of major abscesses to ≤30% of total enrolled.

No requirement for elevated body temperature at enrollment.

Abscess less common in European ED settings than in North America due to lower prevalence of CA-MRSA.

Prior antibacterial drug therapy

Encourage prompt enrollment procedures.

Prompt enrollment is difficult to achieve in many ED settings.

Allow enrollment of small number of patients who have received a single dose of a short-acting antibacterial drug within the previous 24 h.

Many ED patients have commenced therapy on presentation in areas with developed primary care services.

Allow enrollment of patients with objective documentation of clinical progression while on antibacterial therapy (i.e. not based on history alone).

Difficult to obtain objective evidence of clinical progression of previously treated ABSSSI, where treatment commenced in primary care.

Outcome measures and timing of assessments

Primary outcome measure of lesion response at 48 to 72 h (≥20% reduction in lesion size when measured compared to baseline).

Achieving reliable endpoint measurement in trials of outpatient oral therapy may be difficult in ED setting, with higher loss to follow-up rate.

Secondary efficacy endpoint is a resolution of ABSSSI 7 to 14 days after completion of therapy.

No evidence that reduction in the size of lesion represents how patients feel or function [28].