Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin

Figures & data

Table 1 Characteristics of antimicrobials that are available or in late stage of development for the treatment of ABSSSI

	Bactericidal	Prolonged	MRSA	Equal activity on	Oral and IV	Gram-negative
	activity	half-life	activity	MRSA and MSSA	formulation	activity
Ideal drug	Yes	Yes	Yes	Yes	Yes	Yes
Available for use
Oxacillin	Yes	No	No	No	Yes	Limited
Moxifloxacin	Yes	Yes (OD)	No	No	Yes	Moderate
Levofloxacin	Yes	No	No	No	Yes	Moderate
Trimethoprim/	Yes	No	Yes/No	No	Yes	Limited
sulfamethoxazole
Clindamycin	Yes	No	Yes/No	No	Yes	Limited
Daptomycin	Yes	Yes (OD)	Yes	Yes	No	No
Tigecycline	No	No	Yes	Yes	No	Yes
Vancomycin	Yes	No	Yes	No	No	No
Linezolid	No	No	Yes	Yes	Yes	No
Ceftaroline	Yes	No	Yes	Yes	No	Moderate
Dalbavancin	Yes	Yes (OW)	Yes	Yes	No	No
Oritavancin	Yes	Yes (OW)	Yes	Yes	No	No
Tedizolid	No	Yes (OD)	Yes	Yes	Yes	No
Phase III trials completed
Telavancin	Yes	Yes (OD)	Yes	Yes	No	No
Delafloxacin	Yes	No	Yes	Yes	Yes	Yes

Abbreviations: ABSSSI, acute bacterial skin and skin structure infections; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus; OD, once daily; OW, once weekly.

Figure 1 Chemical structure of delafloxacin.

Notes: Three characteristics differentiate delafloxacin from other quinolones: 1) the lack of a protonable substituent group in position 7 that confers a weak acid character to the molecule; 2) the presence of a chlorine atom in position 8 that reduces the reactivity of the heterocycle, stabilizing the molecule; and 3) the aromatic ring attached to N1 that increases the surface of the molecule.

Table 2 Phase II and III clinical trials analyzing the efficacy of IV delafloxacin in ABSSSI

Study type	Patients (n)	Delafloxacin arm	Comparator(s)	Outcome	Reference
Phase II	150	Two IV doses (300 and 450 mg q12h)	Tigecycline (100 mg first dose, then 50 mg ql2h)	Cure rates: 94.3% delafloxacin 300 mg, 92.5% 450 mg, 91.2% tigecycline	48
Phase II	256	300 mg q12h	Linezolid (600 mg IV q12h); vancomycin (15 mg/kg q12h)	Cure rates: 70.4% delafloxacin, 64.9% linezolid, 54.1% vancomycin	49
Phase III	660	300 mg ql2h	Vancomycin (15 mg/kg q12h) ± aztreonam	Objective response: 78.2% delafloxacin, 80.9% vancomycin/aztreonam Investigator-assessed cure: 52.0% delafloxacin, 50.5% vancomycin/ aztreonam Late follow-up: 70.4% delafloxacin, 66.6% vancomycin/aztreonam	57

Abbreviations: ABSSSI, acute bacterial skin and skin structure infections; IV, intravenous; q12h, every 12 hours.

Table 3 Delafloxacin unique characteristics compared to older quinolones

Characteristic	Potential effect in clinical practice
Weak acid character	Enhanced activity in low pH environments including inflammatory cells and infected tissues such as biofilm-associated infections, abscesses, skin and urinary infections
Dual target (gyrase and topoisomerase IV)	Broader spectrum of action (gram-positive and gram-negative bacteria) and reduced selection of resistance
In vitro activity against MRSA, fluoroquinolone-	Empirical and targeted use in ABSSSI and potential use in other infections (e.g., respiratory
resistant gram-negative anaerobes	infections, intra-abdominal infections, urinary tract infections)
Mild CYP3A4 induction	No clinically relevant drug-drug interactions
Favorable safety profile in clinical trials	Potential use in infections requiring prolonged treatment (e.g., >2 weeks)

Abbreviations: ABSSSI, acute bacterial skin and skin structure infections; CYP, cytochrome P450; MRSA, methicillin-resistant Staphylococcus aureus.