In Vitro Activity of Delafloxacin and Microbiological Response Against Fluoroquinolone Susceptible and Non-Susceptible S. aureus Isolates from Two Phase 3 Studies of Acute Bacterial Skin and Skin Structure Infections (ABSSSIs)
Abstract
DLX is a novel investigational anionic fluoroquinolone antibiotic with broad-spectrum activity, including Gram-positive organisms, Gram-negative organisms, atypical organisms, and anaerobes. DLX can be administered by either an intravenous (IV) infusion route or orally as a tablet for the treatment ABSSSI. Two global Phase 3 studies of DLX vs VAN/AZ in ABSSSI have been completed (RX-3341-302 and RX-3341-303). DLX is more active than levofloxacin against most Gram-positive pathogens. Notably, the MIC50 is at least 32‐fold lower for DLX compared to levofloxacin and ciprofloxacin for methicillin-resistant Staphylococcus aureus (MRSA).1 The increased potency of DLX relative to other fluoroquinolones against Gram-positive bacteria and the enhanced activity of DLX at acidic pH are largely due to its structure-activity relationships profile. The collaboration between a large N1 substitution and a weakly‐polar group at C8 results in increased potency against quinolone-resistant Gram‐positive bacteria, a phenotype common among MRSA. The basicity at C7 leads to increased potency at acidic pH.2 DLX is equally effective at stabilizing cleavable complexes by binding either gyrase or topoisomerase IV in both S. aureus and E. coli and, as such, is considered dual-targeting fluoroquinolone. Due to enhanced potency of DLX against MRSA, it was of interest to further investigate the in vitro activity of DLX and the percent microbiological response in Phase 3 clinical trial subjects infected…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 1,042 participants or records.
Read the paper
Related studies
- Pharmacokinetic aspects of retinal drug delivery
- A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis
- From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics
- Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus
- In Vitro Pharmacodynamic Evaluation of the Mutant Selection Window Hypothesis Using Four Fluoroquinolones against Staphylococcus aureus
- Discovery of Potent, Selective Multidrug and Toxin Extrusion Transporter 1 (MATE1, SLC47A1) Inhibitors Through Prescription Drug Profiling and Computational Modeling
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.