Advice
Advisory statement on likely place in therapy
Delafloxacin may be an option for adults needing hospital treatment for severe acute bacterial skin and skin structure infections (ABSSSI), primarily cellulitis or erysipelas, abscesses and wound infections, when standard oral and intravenous treatments are not suitable. Evidence supports the use of intravenous delafloxacin in these circumstances, with a switch to oral treatment after 3 days if possible. Take account of local antimicrobial resistance and seek specialist microbiological advice. Follow the recommendations on new antimicrobials in the NICE guideline on antimicrobial stewardship.
Rationale
The European Public Assessment Report (EPAR) for delafloxacin states that most ABSSSI remain susceptible to penicillin and beta-lactam antibiotics, but antibiotic resistance is becoming more common. ABSSSI can be caused by several pathogens, with gram-negative and anaerobic pathogens found alongside gram-positive organisms, particularly in people with comorbidities and those previously treated with antibiotics.
Two phase 3 randomised controlled trials in over 1,500 adults with ABSSSI attending non-UK hospitals found that delafloxacin was non-inferior to vancomycin plus aztreonam for reducing lesion size (erythema) by at least 20% after 48 hours to 72 hours, and resolving signs and symptoms at 14 days.
One of the studies investigated intravenous delafloxacin only and the other investigated intravenous delafloxacin for 3 days followed by oral delafloxacin. There is no direct evidence to support using the oral formulation alone. Delafloxacin has not been compared with other treatments in phase 3 studies.
The infections treated in the studies were cellulitis or erysipelas, abscesses and wound infections. The mean erythema size of the lesion was around 300 cm2 or more in both studies and participants had at least 2 signs of systemic infection, showing that the infections were severe.
Delafloxacin offers the potential for treating infections caused by gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), and gram-negative pathogens, without the need for combination therapy. It appears to be well-tolerated, but its full adverse effect profile is not yet known. In the MHRA drug safety update in March 2019, the MHRA issued new restrictions and precautions for fluoroquinolone antibiotics because of very rare reports of disabling and potentially long-lasting or irreversible adverse effects affecting musculoskeletal and nervous systems. The EPAR states that the possibility of class effects of fluoroquinolones (such as tendon rupture) with delafloxacin cannot be excluded, although some data suggest a possible safety benefit of delafloxacin compared to other fluoroquinolones, in particular for QT prolongation and phototoxicity. Suspected adverse reactions associated with delafloxacin should be reported via the Yellow Card Scheme.
The NICE guideline on antimicrobial stewardship makes recommendations on the effective use of new antimicrobials. Delafloxacin should be reserved for those people most likely to benefit from it, after specialist microbiological advice to help monitor use and limit antimicrobial resistance.