Comparative In Vitro Activities of Ciprofloxacin, Gemifloxacin, Grepafloxacin, Moxifloxacin, Ofloxacin, Sparfloxacin, Trovafloxacin, and Other Antimicrobial Agents against Bloodstream Isolates of Gram-Positive Cocci

Hardy, Dwight J.; Amsterdam, Daniel; Mandell, Lionel A.; Rotstein, Coleman

doi:10.1128/aac.44.3.802-805.2000

Cited by 49 publications

(24 citation statements)

References 7 publications

(1 reference statement)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This result is comparable to those of previous studies, which have shown 8-to 32-fold greater activity for clinical isolates of methicillin-sensitive S. aureus (6,14,15,19,20,28,(30)(31)(32). The fact that in genetically defined mutants of S. aureus single mutations in either subunit of topoisomerase IV caused a twoto fourfold increase and a mutation in DNA gyrase caused a twofold increase in the MIC of gemifloxacin suggested similar targeting of the two enzymes.…”

Section: Discussionsupporting

confidence: 80%

“…It has been reported to have enhanced activity compared to that of older-generation fluoroquinolones against gram-positive aerobic bacteria (15,19,32) while retaining an activity similar to that of ciprofloxacin against gramnegative species (6,31). Similar to other quinolones, it is less potent against methicillin-resistant staphylococci (19), but recent work has shown that it might retain activity against some ciprofloxacin-resistant S. aureus strains (30,44).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Topoisomerase Targeting with and Resistance to Gemifloxacin in Staphylococcus aureus

İnce

Zhang

Silver

et al. 2003

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Gemifloxacin, a novel quinolone with potent activity against Staphylococcus aureus, was 8-to 16-fold more active against wild-type S. aureus than ciprofloxacin. The two-to fourfold increase in the MIC of gemifloxacin in genetically defined grlBA mutants and the twofold increase in a single gyrA mutant, supported by the low frequency of selection of resistant mutants at twice the MIC (7.4 ؋ 10 ؊11 to 1.1 ؋ 10 ؊10 ), suggested similar targeting of the two enzymes by gemifloxacin. Dual mutations in both gyrase and topoisomerase IV caused a 64-to 128-fold increase in the MIC of gemifloxacin, similar to that seen with ciprofloxacin. Gemifloxacin also had similar activity in vitro against topoisomerase IV and gyrase purified from S. aureus (50% inhibitory concentrations of 0.25 and 0.31 g/ml, respectively). This activity was 10-to 20-fold higher than that of ciprofloxacin for topoisomerase IV and 33-fold higher than that for gyrase. In contrast to the in vitro findings, only topoisomerase IV mutants were selected in first-step mutants. Overexpression of the NorA efflux pump had a minimal effect on resistance to gemifloxacin, and a mutation in the promoter region of the gene for NorA was selected only in the sixth step of serial selection of mutants. Our data show that although gemifloxacin targets purified topoisomerase IV and gyrase similarly in vitro, topoisomerase IV is the preferred target in the bacteria. Selection of novel resistance mutations in grlA requires further expansion of quinolone-resistancedetermining regions, and their study may provide increased insight into enzyme-quinolone interactions.

show abstract

Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

Topoisomerase Targeting with and Resistance to Gemifloxacin in Staphylococcus aureus

İnce

Zhang

Silver

et al. 2003

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…The compound has a broad spectrum of activity against Gram-positive and Gram-negative bacteria. [1][2][3] It is particularly active against Gram-positive organisms including penicillin-, macrolide-, and quinolone-resistant Streptococcus pneumoniae, 4 4-folds more potent than moxifloxacin against S. pneumoniae. 5 Gemifloxacin has also shown potent activity against other major pathogens involved in respiratory tract infections, including Haemophilus influenzae and Moraxella catarrhalis and the atypical organisms, Legionella pneumophila,Chlamydia spp., and Mycoplasma spp.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of gemifloxacin and diuretics in bulk, pharmaceutical dosage forms and human serum by RP-HPLC

et al. 2010

View full text Add to dashboard Cite

Recebido em 25/11/09; aceito em 16/3/10; publicado na web em 20/7/10 An isocratic reversed phase high-performance liquid chromatographic (RP-HPLC) method has been developed for the simultaneous determination of gemifloxacin and diuretics (hydrochlorothiazide and furosemide) in bulk, dosage formulations and human serum at 232 nm. Chromatographic separation was achieved on Purospher Start C 18 (250 mm x 4.6 mm, 5 µm) column using mobile phase, methanol: water: acetonitrile (70:25:5 v/v/v) adjusted to pH 3.0 via phosphoric acid 85% having flow rate of 0.8 mL min -1 at room temperature. Calibration curves were linear over range of 0.5-10 µg mL -1 with a correlation coefficient ± 0.999. LOD and LOQ were in the ranges of 0.75-2.56 µg mL -1. Intra and inter-run precision and accuracy results were 98.26 to 100.9.

show abstract

“…These species make up the heterogeneous group of CoNS that are less susceptible to antibacterials than S. epidermidis is. CoNS were in the past and are at present more resistant to the antibacterials studied than S. epidermidis is (73,(80)(81)(82)(83). This holds true for methicillin-susceptible and -resistant isolates, respectively.…”

Section: Pd Effects On the Human Resident Microflora As A Model Of A mentioning

confidence: 76%

“…To address these questions, publications were reviewed in which the MICs of all of the relevant antibacterial agents in different drug classes for S. aureus were compared to those for S. epidermidis (73)(74)(75)(76)(77)(78) and those for S. aureus were compared to those for CoNS (74)(75)(76)(77)(78)(79)(80)(81)(82)(83). Only those publications in which the activities of the agents against both species were compared directly with each other were selected.…”

Section: Pd Effects On the Human Resident Microflora As A Model Of A mentioning

confidence: 99%

Alternative Strategies for Proof-of-Principle Studies of Antibacterial Agents

Dalhoff¹,

Weintraub²,

Nord³

2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The proof that a new antibacterial agent is not only active in vitro but also effective in vivo under clinically relevant conditions is currently provided (i) by using appropriate nonclinical models of infection and pharmacokinetic-pharmacodynamic (PK-PD) analysis providing evidence of the likelihood of clinical efficacy and (ii) by examining the study drug in exploratory clinical trials, as well as dose and schedule finding during phase II of clinical development. This approach is both time-consuming and costly. Furthermore, PK-PD targets for any novel antibacterial agent cannot be derived from studies with experimental animals. Therefore, alternative strategies have to be identified to prove the principle that a novel antibacterial agent is active under clinically relevant conditions. This review summarizes evidence that the quantitative analysis of shifts in the viable counts of pathogens in infected patients or the evaluation of the PD effect of an investigational agent on indicator organisms of the human resident microflora or colonizers of healthy volunteers, if paralleled with PK monitoring of serum and the target site, provides an alternative to a classical proof-of-principle study in the course of a phase II study program.

show abstract

Comparative In Vitro Activities of Ciprofloxacin, Gemifloxacin, Grepafloxacin, Moxifloxacin, Ofloxacin, Sparfloxacin, Trovafloxacin, and Other Antimicrobial Agents against Bloodstream Isolates of Gram-Positive Cocci

Cited by 49 publications

References 7 publications

Topoisomerase Targeting with and Resistance to Gemifloxacin in Staphylococcus aureus

Topoisomerase Targeting with and Resistance to Gemifloxacin in Staphylococcus aureus

Simultaneous determination of gemifloxacin and diuretics in bulk, pharmaceutical dosage forms and human serum by RP-HPLC

Alternative Strategies for Proof-of-Principle Studies of Antibacterial Agents

Contact Info

Product

Resources

About