Delafloxacin on par with current SSI therapies

Delafloxacin is noninferior to best available therapies (BAT) for acute bacterial skin and skin structure infections (ABSSSI), particularly in the subset of surgical site infections (SSI), according to the results of the phase IIIb/IV, observer-blinded DRESS study presented at ECCMID 2021.

“ABSSSI represent one of the most challenging to treat infections due to suboptimal spectrum coverage, potential toxicities, limited options for oral formulations, which can result in prolonged hospitalizations,” said Dr Giuseppe Mangialardi from Menarini Ricerche SpA, Pomezia, Italy, during his virtual presentation.

“[Given the ‘enriched’ microflora in SSIs, we] aimed to demonstrate [the potential of delafloxacin to] provide a valuable therapeutic alternative in [this] challenging scenario,” he continued. A new fluoroquinolone approved for ABSSSI in the US and EU, delafloxacin may expand the current ABSSSI therapeutic armamentarium.

DRESS enrolled 266 patients (mean age 64.9 years, 57 percent male, superficial SSI 60 percent) who had surgery within 30 days and a diagnosis of SSI requiring IV treatment and hospitalization. They were randomized 1:1 to receive either delafloxacin 300 mg IV Q12H (may be switched to 450 mg tablets) or a reference* treatment for 5–14 days. [ECCMID 2021, abstract 4845]

The team chose two SSI settings – abdominal and cardiothoracic/related leg SSI – to explore the efficacy of delafloxacin against Gram-negative (abdominal) and Gram-positive bacteria, including multiresistant Staphylococcus aureus (cardiothoracic). There were more abdominal vs cardiothoracic SSI cases (n=246 vs 20) owing to early trial termination due to the COVID-19 pandemic.

 

Comparable clinical, cure success

Delafloxacin was comparable to BAT in terms of clinical success across all timepoints (94 percent vs 92 percent, 92 percent vs 90 percent, and 92 percent vs 88 percent for EOT, TOC, and LFU/EOS**, respectively), as well as EOT (average 7.7 vs 6.7 days) and sustained clinical success (91 percent vs 87 percent).

In terms of cure*** success, delafloxacin was also noninferior to BAT across the three timepoints (51 percent vs 54 percent, 75 percent vs 73 percent, and 89 percent vs 83 percent, respectively).

“Despite the early termination, the primary endpoint was met … In the scatter plots, delafloxacin fell within the 10 percent noninferiority margin,” said Mangialardi.

 

Shorter IV treatment duration

There were similar fractions of participants between the delafloxacin and BAT arms who were eligible for switching (96 percent vs 98 percent) and discharge (89 percent vs 87 percent). Looking at the actual switch and discharge however, delafloxacin fared quite better than BAT (72 percent vs 63 percent [switch] and 69 percent vs 54 percent [discharge]).

IV treatment duration was shorter with delafloxacin at a little over 4 days, as opposed to BAT which ran for about 6 days, noted Mangialardi. “This means that patients on delafloxacin had the opportunity to be discharged before EOT because they can continue the therapy orally at home.”

 

Favourable safety

There were more adverse events (AEs) with delafloxacin than BAT (26 vs 21 percent), but fewer serious AEs (7 percent vs 10 percent). The most common treatment-emergent AEs with delafloxacin are gastrointestinal disorders (5 percent), infections and infestations (4 percent), and metabolism and nutrition disorders (4 percent). “The safety profile [of delafloxacin] is comparable to BAT and is in line with previous studies,” said Mangialardi.

 

As effective as BAT

Taken together, the findings suggest that delafloxacin is equally as effective as BAT in terms of success in improving clinical conditions, and allows for the possibility of switch to an oral formulation and potential early discharge in this patient setting.

“[Delafloxacin offers] the advantage of an IV/oral formulation covering the need for an effective empiric treatment against the wide spectrum of pathogens involved in difficult-to-treat ABSSSI,” concluded Mangialardi.