Clinical and pharmacokinetic drug evaluation of delafloxacin for the treatment of acute bacterial skin and skin structure infections

Figures & data

Table 1. Pros and cons of new and old antimicrobials for complicated skin and skin structure infections.

Drug	Pros	Cons
Delafloxacin	● Broad spectrum of activity ● Bactericidal activity ● Anti-biofilm activity ● Improved activity in acid mediums ● Oral formulation allows treatment of outpatients and early oral switch ● Good tolerability profile ● Few drug interactions	● Twice-daily administration ● Risk of tendinopathy and tendon rupture ● Risk of arthropathy
Daptomycin	● Rapid bactericidal activity ● Anti-biofilm activity ● Good tolerability profile ● Low drug interactions	● Only intravenous ● Spectrum limited to gram positives ● Dosage not well established
Tigecycline	● Broad spectrum of activity ● Good tissue penetration	● Only intravenous ● Twice-daily administration ● Frequent nausea ● FDA black box warning
Linezolid	● Oral formulation allows treatment of outpatients and early oral switch ● Good penetration in the tissue (skin and bone)	● Spectrum limited to gram positives ● Drug–drug interactions ● Important adverse effects ● Twice-daily administration
Tedizolid	● Oral formulation allows treatment of outpatients and early oral switch ● Good penetration in the tissue (skin and bone) ● Once-daily administration ● Few drug interactions ● Low myelotoxicity	● Spectrum limited to gram positives
Dalbavancin	● Once-weekly administration ● Single injection for skin infections ● Good penetration into cortical bone and articular tissues ● Good tolerability profile	● Spectrum limited to Gram positives ● Only intravenous
Oritavancin	● Single-dose treatment ● Good tolerability profile ● Bactericidal	● Spectrum limited to gram positives ● Only intravenous
Ceftaroline	● Broad-spectrum activity ● Good tolerability profile	● Only intravenous ● Twice-daily administration

Adapted from Bassetti et al., 2017 [42].

Table 2. Summary of pharmacokinetic parameters after single-dose fluoroquinolones.

	Dose (mg)	Cmax (mg/L)	tmax (min)	Vd (L/kg)	Pb (%)	CL (L/h)	t1/2β (h)	AUC0-∞ (mgh/L)	Fos (%)	fe (%)	Ref.
Levofloxacin	500 PO	5.2	78 ± 30	1.3^a	30	10.5^b	6.5	47.7		69	[18]
	500 IV	6.3		1.2		9.4	6.6	55.3		61	[18]
Moxifloxacin	400 PO	2.5	120	3.1^c	45	11.6^b	15.6	29.8	86.2	19.3	[19]
	400 IV	3.6		2.1		11.6	15.4	34.6		22.1	[19]
Delafloxacin	450 PO	6.12	49		84			24.2	58.8		[16]
	300 IV	8.98	60	0.43		12.53	2.35	24.8		38.9	[17]

^a V_β/F.

^b CL/F.

^c V_ss/F.

AUC_0−∞: area under the concentration–time curve to infinity; CL: total body clearance; C_max: peak plasma concentration; F_os: oral bioavailability; f_e: fraction of unchanged drug excreted in the urine; IV: intravenous; OS: oral; P_b: protein binding; t_1/2β: elimination half-life; t_max: time to peak plasma concentration; V_d: volume of distribution; V_ss: volume of distribution at steady state; V_β: volume of distribution determined during the β-elimination phase.

Box 1. Drug summary.

(Adapted from Bassetti M et al, 2015 [15])
Drug name	Delafloxacin
Phase	III
Indication	Acute bacterial skin and skin structure infections
Pharmacology description/mechanism of action	Inhibition of DNA gyrase and topoisomerase IV activity
Route of administration	Injectable/oral
Chemical structure
Pivotal trials	NCT01811732 [30], NCT01984684 [31]

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cited 2017 Sep 1. Available from: https://clinicaltrials.gov/ct2/show/NCT01811732

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cited 2017 Sep 1. Available from: https://clinicaltrials.gov/ct2/show/NCT01984684

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