Mutant prevention concentration of ciprofloxacin and enrofloxacin against Escherichia coli, Salmonella Typhimurium and Pseudomonas aeruginosa

Pasquali, Frédérique; Manfreda, Gerardo

doi:10.1016/j.vetmic.2006.08.018

Cited by 54 publications

(46 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Failure to attain these ratios has been linked to an increase in bacterial resistance and lack of clinical efficacy (20). Synthesis of a solvate of enrofloxacin (enrofloxacin hydrochloride-dihydrate; enro-C) (13) with improved pharmacokinetics has been advanced as means to obtain improved PK/PD ratios (14,15) and, ideally, to achieve theoretical mutant-preventive concentrations (C MAX ≥ 16 MIC) (21). Enro-C exhibits different physicochemical properties from the parent compound, mainly water solubility (13) and pharmacokinetics, as has been so far shown in broilers (15).…”

Section: Discussionmentioning

confidence: 99%

Serum pharmacokinetics and tissue concentrations of a newrecrystallized enrofloxacin hydrochloride-dihydrate in hamsters

Carrascosa¹,

Peã'a²,

Gutiérrez³

et al. 2015

Turk J Vet Anim Sci

View full text Add to dashboard Cite

Pharmacokinetics (PK), pharmacodynamics (PD), and PK/PD ratios of a new solvate of enrofloxacin (enrofloxacin hydrochloride-dihydrate; enro-C), were studied in hamsters. Enrofloxacin from Baytril® 5% (enro R) served as the reference preparation. Two groups of 60 Syrian golden hamsters were intramuscularly injected individually with 10 mg/kg of enro R or with enro-C. Tissue and serum samples were obtained for 72 h; enrofloxacin concentrations were determined by HPLC with UV detection. Ninety percent minimum inhibitory concentrations (MIC 90 ) were determined for strains of methicillin-resistant Staphylococcus aureus, Leptospira interrogans, and Escherichia coli. All PK variables were statistically different between groups (P < 0.01). C MAX of enrofloxacin for enro-C was 17.3 µg/mL and it was 2.6 µg/mL for enro R . AUC was considerably higher for enro-C (459.2 µg/mL h vs. 19.9 µg/mL h). There were no statistically significant differences in MIC 90 values between enro R and enro-C. Tissue concentrations of enro-C in all cases were higher and remained above the MIC for longer periods than those of enro R . Relevant PK/PD ratios for enrofloxacin (AUC/MIC ≥ 125 and C MAX > MIC = 10-12) are consequently superior for enro-C. Given the outstanding PK/PD ratios of enro-C, this new moiety is proposed as a possible solution when high tissue concentrations of enrofloxacin are necessary.

show abstract

Section: Discussionmentioning

confidence: 99%

Serum pharmacokinetics and tissue concentrations of a newrecrystallized enrofloxacin hydrochloride-dihydrate in hamsters

Carrascosa¹,

Peã'a²,

Gutiérrez³

et al. 2015

Turk J Vet Anim Sci

View full text Add to dashboard Cite

show abstract

“…Several studies have assessed the antibacterial activity of veterinary fluoroquinolones, as well as their ability to select for resistance (Wetzstein, 2005;Boothe et al, 2006;Grobbel et al, 2007;Pasquali & Manfreda, 2007), by determining the MIC and MPC, which are static in vitro parameters. In practice, however, a pharmacodynamic effect in vivo is rather the result of a dynamic exposure of the infective agent to the unbound drug fraction at the relevant effect site and, therefore, a static condition in an in vitro setting can hardly reflect a dynamic situation in a target organ under in vivo conditions (Mueller et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, the MICs of both drugs against resistant strains and representative single-step mutants of E. coli were tested in the presence and absence of an efflux-pump inhibitor (EPI, 20 mg ml 21 ), Phe-Arg-b-naphthylamide (PAN; Sigma), according to a previously described method (Pasquali & Manfreda, 2007). Furthermore, for these strains, the MICs of two other fluoroquinolones commonly used in small animals, difloxacin and orbifloxacin (with or without EPI), as well as other classes of antibacterial agents, including chloramphenicol, erythromycin, gentamicin and tetracycline, were tested as described above.…”

mentioning

confidence: 99%

Mutant-prevention concentration and mechanism of resistance in clinical isolates and enrofloxacin/marbofloxacin-selected mutants of Escherichia coli of canine origin

Gebru

Choi

Lee

et al. 2011

Journal of Medical Microbiology

View full text Add to dashboard Cite

The antibacterial activity and selection of resistant bacteria, along with mechanisms of fluoroquinolone resistance, were investigated by integrating the static [MIC or mutant-prevention concentration (MPC)] and in vitro dynamic model approaches using Escherichia coli isolates from diseased dogs. Using the dynamic models, selected E. coli strains and enrofloxacin and marbofloxacin at a range of simulated area under concentration-time curve over a 24 h interval (AUC 24 h )/MIC ratios were investigated. Our results indicated increasing losses in susceptibility of E. coli upon continuous exposure to enrofloxacin and marbofloxacin in vitro. This effect was transferable to other fluoroquinolones, as well as to structurally unrelated drugs. Our results also confirmed an AUC 24 h /MIC (AUC 24 h /MPC)-dependent antibacterial activity and selection of resistant E. coli mutants, in which maximum losses in fluoroquinolone susceptibility occurred at simulated AUC 24 h /MIC ratios of 40-60. AUC 24 h /MPC ratios of 39 (enrofloxacin) and 32 (marbofloxacin) were considered protective against the selection of resistant mutants of E. coli. Integrating our MIC and MPC data with published pharmacokinetic information in dogs revealed a better effect of the conventional dosing regimen of marbofloxacin than that of enrofloxacin in restricting the selection of resistant mutants of E. coli. Target mutations, especially at codon 83 (serine to leucine) of gyrA, and overexpression of efflux pumps contributed to resistance development in both clinically resistant and in vitro-selected mutants of E. coli. We also report here a previously undescribed mutation at codon 116 of parC in two laboratory-derived resistant mutants of E. coli. Additional studies would determine the exact role of this mutation in fluoroquinolone susceptibility, as well as establish the importance of our findings in the clinical setting.

show abstract

“…A literature search was done to compare our findings with those of other studies, particularly with regard to fluoroquinolones, as the initial study on PA␤N on P. aeruginosa (21) saw an 8-fold increase in susceptibility to fluoroquinolone and levofloxacin. Other studies show that the effect of PA␤N is dependent on strain and antibiotic (4,29,33) for both E. coli and P. aeruginosa and that the fold increase in susceptibility varies from 1 to 8. Pasquali and Manfreda (29) also show that E. coli strain ATCC 25922 had MICs of 0.016 to Ͻ0.06 g/ml in the absence and presence of 80 g/ml PA␤N.…”

mentioning

confidence: 98%

Yersinia pestisacrAB-tolCin Antibiotic Resistance and Virulence

Lister¹,

Raftery²,

Mecsas³

et al. 2012

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The efflux pump AcrAB is important in the antibiotic resistance and virulence of several pathogenic bacteria. We report that deletion of the Yersinia pestis AcrAB-TolC homolog leads to increased susceptibility to diverse substrates, including, though unlike in Escherichia coli, the aminoglycosides. Neither is the Y. pestis pump affected by the efflux pump inhibitor phenylalanine-arginine beta-naphthylamide. In mouse plague models, pump deletion does not have a significant effect on tissue colonization. Increased activity of efflux pumps is a major route to decreased susceptibility (8,15,21,22,39,41) in many bacteria. An important pump in active efflux is 35). TolC is located in the outer membrane and is linked to the inner membrane AcrB through AcrA, thus forming a channel from the cytoplasm to the extracellular space (25). AcrAB-TolC has an extremely broad substrate range but favors lipophilic substrates (25). Efflux pumps are also involved in the pathogenicity of several bacteria, including Pseudomonas aeruginosa, Salmonella enterica serovar Typhimurium, Vibrio cholerae, Francisella tularensis, Klebsiella pneumoniae, and the plant pathogen Erwinia amylovora (3, 27, 30); although not fully understood, the pumps could affect virulence through removal of antibacterial molecules such as bile (25), mammalian steroid hormones (7), and antimicrobial peptides (34, 37, 40) and therefore would aid survival in the host.To explore the function of the AcrAB-TolC pump in susceptibility of Yersinia pestis to antibiotics and virulence, deletion and complemented strains were engineered using splicing by overlap extension, as described previously (11,19), in the attenuated Y. pestis strain KIM 1001 pgm (18), a gift from John Goguen (University of Massachusetts Medical School). Sites of genetic manipulation were verified by sequencing. Growth studies showed no difference in the doubling times of the engineered strains compared with that of the wild-type (WT) strain (data not shown).Drug susceptibility studies were carried out using Etests (AB Biodisk) against antibiotics from different classes, including antibiotics favored in plague treatment and prophylaxis (streptomycin, gentamicin, tetracycline, chloramphenicol, ciprofloxacin, and trimethoprim-sulfamethoxazole) (9). Figure 1 shows the average MIC (from at least three experiments) against selected antibiotics chosen to represent different antibiotic classes. Statistical analysis was performed using one-way analysis of variance (ANOVA) with Tukey's posttest. Deletion of acrAB increased susceptibility to all the antibiotics by 50 to 92%. tolC deletion increased susceptibility to the aminoglycosides by 52 to 66%, but not to the other drugs (9 to 23% increase in susceptibility), compared to the levels for the acrAB strain ( Fig. 1; Table 1). Resistance was restored when strains were complemented with ectopically expressed acrAB or tolC (Table 1). The reason for the variation in the MICs for chloramphenicol between the two tolC strains is uncertain, but as it is only a 2-fold diff...

show abstract

Mutant prevention concentration of ciprofloxacin and enrofloxacin against Escherichia coli, Salmonella Typhimurium and Pseudomonas aeruginosa

Cited by 54 publications

References 21 publications

Serum pharmacokinetics and tissue concentrations of a newrecrystallized enrofloxacin hydrochloride-dihydrate in hamsters

Serum pharmacokinetics and tissue concentrations of a newrecrystallized enrofloxacin hydrochloride-dihydrate in hamsters

Mutant-prevention concentration and mechanism of resistance in clinical isolates and enrofloxacin/marbofloxacin-selected mutants of Escherichia coli of canine origin

Yersinia pestisacrAB-tolCin Antibiotic Resistance and Virulence

Contact Info

Product

Resources

About