Quinolones in 2005: an update

Bambeke, Françoise Van; Michot, Jean-Michel; Eldere, J. Van; Tulkens, Paul M.

doi:10.1111/j.1469-0691.2005.01131.x

Cited by 329 publications

(288 citation statements)

References 273 publications

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“…This suggests a capacity to rapidly redistribute inside the cell to reach their target, which is consistent with their capacity to easily diffuse through membranes (29) and to their strong binding to the DNA-topoisomerase complex in bacteria (45). In infected cells incubated in neutral medium, delafloxacin shows a very low static concentration and reaches a nearbactericidal effect, making it one of the most active drugs against intracellular S. aureus in this model.…”

Section: Discussionmentioning

confidence: 53%

Contrasting Effects of Acidic pH on the Extracellular and Intracellular Activities of the Anti-Gram-Positive Fluoroquinolones Moxifloxacin and Delafloxacin againstStaphylococcus aureus

Lemaire

Tulkens

Bambeke

2011

Antimicrob Agents Chemother

166

140

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In contrast to currently marketed fluoroquinolones, which are zwitterionic, delafloxacin is an investigational fluoroquinolone with an anionic character that is highly active against Gram-positive bacteria. We have examined the effect of acidic pH on its accumulation in Staphylococcus aureus and in human THP-1 cells, in parallel with its activity against extracellular and intracellular S. aureus. Moxifloxacin was used as a comparator. Delafloxacin showed MICs 3 to 5 log 2 dilutions lower than those of moxifloxacin for a collection of 35 strains with relevant resistance mechanisms and also proved to be 10-fold more potent against intracellular S. aureus ATCC 25923. In medium at pH 5.5, this difference was further enhanced, with the MIC decreasing by 5 log 2 dilutions. In infected cells incubated in acidic medium, the relative potency was 10-fold higher than that at neutral pH and the maximal relative efficacy reached a bactericidal effect at 24 h. These results can be explained by a 10-fold increase in delafloxacin accumulation in both bacteria and cells at acidic pH, making delafloxacin one of the most efficient drugs tested in this model. Opposite effects were seen for moxifloxacin with respect to both activity and accumulation. As reported for zwitterionic fluoroquinolones, delafloxacin was found associated with the soluble fraction in homogenates of eukaryotic cells. Taken together, these properties may confer to delafloxacin an advantage for the eradication of S. aureus in acidic environments, including intracellular infections.Fluoroquinolones are one of the first families of fully synthetic antibiotics with large clinical use, and they represent a wide range of molecules, which permits the establishment of in-depth structure-activity relationships (16,17). Over the last 20 years, most fluoroquinolone research efforts have been focused on new molecules with improved activity toward Grampositive cocci because of the increasing spread of multiresistant staphylococci and streptococci. The 8-methoxy fluoroquinolone moxifloxacin is the first example of this new generation to reach the commercial market. It combines many desirable microbiological and pharmacokinetic properties (rapid bactericidal activity, a spectrum covering pertinent pathogens, excellent oral bioavailability, a large tissue distribution, and a propensity to accumulate within eukaryotic cells [see reference 45 for a review]). Moxifloxacin shows extensive activity toward bacteria thriving in the cytosol (Listeria monocytogenes [14]), phagosomes (Legionella pneumophila, Mycobacterium avium, and Mycobacterium tuberculosis [5,9,46]), and phagolysosomes (Staphylococcus aureus [6]), suggesting that it easily diffuses between different subcellular compartments. Yet moxifloxacin activity is partially defeated by the acidic pH prevailing in vacuolar subcellular compartments (6).Delafloxacin [RX-3341; 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid] is an investigational fluoro...

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Section: Discussionmentioning

confidence: 53%

Contrasting Effects of Acidic pH on the Extracellular and Intracellular Activities of the Anti-Gram-Positive Fluoroquinolones Moxifloxacin and Delafloxacin againstStaphylococcus aureus

Lemaire

Tulkens

Bambeke

2011

Antimicrob Agents Chemother

166

140

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“…Comparing Microkit SL laboratories strains to those isolated from hospitals and to ATCC, it was observed through absorbance performed by turbidimetry tests, that hospital strains had the highest cellular Tables 9 and 10. Overall, the MIC of different levofloxacin drugs against S. aureus and E coli evaluated were found much lower than that reported by Martínez et al (2004) and Van Bambeke (2005). On the other hand, MIC of levofloxacin was determined against to E. coli tropically and S. luteums, for the first time in Colombia.…”

Section: Hospital Strains Growth Curvescontrasting

confidence: 42%

In vitro antimicrobial activity of generic and brand-name Levofloxacin against clinical and ATCC strains E. coli and S. aureus

Sanchez-Hoyos¹,

Alvíz‐Amador²,

Duran-Lengua³

2018

Afr. J. Pharm. Pharmacol.

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In vitro antimicrobial activity between generic and brand-name Levofloxacin was evaluated against isolated strains collected in 3 Colombia hospitals: Staphylococcus aureus and Escherichia coli. Initially, active substance was quantified using the methodologies identified by the United States Pharmacopeia (USP) 38 NF 32, chromatographic conditions were validated and standardized. The minimum inhibitory concentration (MIC) of Levofloxacin was determined in accordance with the Clinical and Laboratory Standards Institute (CLSI). Growth curves were then performed to determine the maximum growth time of the bacteria in order to determine the MIC at the maximum growth time. Different brands evaluated did not present any difference with MIC of 0.125, 0.062, 0.031, 0.062 and 0.125 µg/ml for E. Coli ATCC, E. Coli Tropical, S aureus sensible ATCC, S aureus resistant ATCC and S. luteum, respectively. The in vitro antibacterial activity of levofloxacin against E coli Tropically and S luteum are reported for the first time.

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“…The cyclopropyl-substituted fluoroquinolones, namely ciprofloxacin, moxifloxacin and gatifloxacin, make up the clinically most relevant compounds [36]. Each of these groups …”

Section: Structure -Activity Relationsmentioning

confidence: 99%

“…In particular, the prominent role of gatifloxacin is not sufficiently explained. Up to a fluoroquinolone concentration of at least 100 µM, which is 20fold above the peak plasma concentrations [36,37], the presence of a basal glucose concentration precludes the depolarization of metabolically intact B-cells and the ensuing stimulation of insulin secretion. We hypothesize that at therapeutically relevant concentrations of the fluoroquinolones, their K ATP channelblocking effect has to be potentiated by as yet unidentified factors to stimulate insulin secretion in the presence of a basal glucose concentration and to finally induce hypoglycemia.…”

Section: Correlation With Risk Of Hypoglycemiamentioning

confidence: 99%