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Delafloxacin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Rekha Pai Mangalore, Jason Kwong, M. Lindsay Grayson
Delafloxacin has greater in vitro activity against multidrug-resistant S. pneumoniae (including penicillin- and macrolide-resistant strains) than trovafloxacin, levofloxacin, or ciprofloxacin (Bassetti et al., 2015; see section 2, Antimicrobial activity and Table 108.1). The drug also has excellent activity against many other respiratory pathogens, including Moraxella catarrhalis, H. influenzae, Legionella spp., and Chlamydia spp. (Nilius et al., 2003; Bassetti et al., 2015; Zhanel et al., 2003a; Zhanel et al., 2003b; Hammerschlag and Roblin, 2004; Table 108.1). For this reason, a number of authors have suggested a potential role for delafloxacin in the treatment of community-acquired pneumonia (Bassetti et al., 2015; Bassetti et al., 2016). A phase III study of delafloxacin therapy for hCABP is currently underway (NIH, 2016b).
Delafloxacin as a treatment option for community-acquired pneumonia infection
Published in Expert Opinion on Pharmacotherapy, 2021
Cristiana M. Nascimento-Carvalho
Adulthood community-acquired pneumonia imposes a major burden on the health care system all over the world as it is responsible for high morbidity and mortality rates [1]. Bacterial pathogens are recognized to be frequent causative agents, which makes antibacterial treatment crucial for the good prognosis of these patients. There are several antimicrobial options available in daily practice. However, bacterial resistance is a problem to be faced. In vitro data showed that delafloxacin is active against a wide range of bacteria, including the majority of community-acquired pneumonia bacterial agents among adults. Besides that, results from phase 2 and phase 3 have demonstrated that delafloxacin use is safe. Nonetheless, the judicious use of such a broad-spectrum antibacterial drug is imperative once it comes to market to prevent the development of resistance [54]. In 2017, 22% of MRSA isolates, associated either with healthcare-related infections or community-associated infections, from seven hospitals in New York, were nonsusceptible to delafloxacin [55].
Overcoming problems of poor drug penetration into bacteria: challenges and strategies for medicinal chemists
Published in Expert Opinion on Drug Discovery, 2018
Davide Benedetto Tiz, Danijel Kikelj, Nace Zidar
Recent success in the discovery of novel antibacterials is represented by delafloxacin (Figure 2), a FQ indicated for treating acute bacterial skin and skin structure infections caused by both Gram-positive and Gram-negative bacteria [78,79]. Delafloxacin has shown higher antibacterial activities than other FQs against several pathogens such as methicillin-resistant S. aureus [80]. Three structural features, different from other FQs, seem to be the reason for its superior potency: (i) the lack of a strong basic group in position C7 which renders delafloxacin an anion at physiological pH (and not a zwitterion as in other FQs), (ii) the presence of a chlorine atom in position C8 which stabilizes the heterocycle, and (iii) the aromatic ring on the N1 which increases the molecular surface compared to other FQs. The anionic character of delafloxacin culminates in its better accumulation in bacteria at acidic pH. Inside of a phagolysosome where pH is from 5 to 5.5, delafloxacin is mainly found in its neutral form and is thus able to traverse through the transmembrane region of the phagolysosome into the bacterium cell. Once inside the bacteria, where the pH becomes neutral, it is deprotonated into its anionic form which is trapped inside and thus accumulates. Delafloxacin has shown a potential role in the treatment of respiratory, urinary, and sexually transmitted infections. It does not appear to be a substrate for EPs [80].
A profile of delafloxacin in the treatment of adults with community-acquired bacterial pneumonia
Published in Expert Review of Clinical Pharmacology, 2022
Silvia Gómez-Zorrilla, Elena Sendra, Juan P. Horcajada
Delafloxacin is a concentration-dependent bactericidal agent. The pharmacokinetic/pharmacodynamic (PK/PD) parameter most closely associated with its activity is the ratio of the area under the free drug concentration-time curve to the minimum inhibitory concentration of the infecting organism (fAUC24/MIC), as in other FQs [44,45]. The pharmacodynamics of delafloxacin have been studied in a series of experiments using the murine lung and thigh infection models [46–48]. As discussed below in the section on ‘Animal models,’ these studies demonstrated high penetration into the lung compartment, since concentrations in the epithelial lining fluid were significantly higher than those of free drug in plasma (mean penetration ratio 13:1) [46,47].