Presence Of Moxifloxacin Research Articles

Highly sensitive electrochemical sensing of moxifloxacin based on molecularly imprinted and Au nanoparticle functionalized PEDOT composites

The misuse of antibiotics and continuous antimicrobial resistance is one of the critical challenges facing society today. It is therefore crucial for food safety and environmental protection to develop an analytical technique for the selective detection of trace antibiotics. In this paper, worm-like Au/Poly(3,4-ethylenedioxythiophene) (Au/PEDOT) composites were designed and imprinted with polypyrrole (Ppy) in the presence of moxifloxacin, and molecularly imprinted sensors (MIP/Au/PEDOT/GCE) were prepared for the ultrasensitive detection of moxifloxacin (MOX). It was found that the Au/PEDOT worm-like structure provided a large surface area, increased the number of molecularly imprinted recognition sites, and improved electrochemical sensitivity. The molecularly imprinted sensor has a linear detection range of 0.004–20 μM, a lower detection limit of 1.109 nM, good interference immunity and stability. In addition, the sensor demonstrated good recoveries for the detection of MOX in real samples, indicating the potential of the sensor to be suitable for food and drug safety testing. This work offers a new strategic solution for the accurate quantitative detection of MOX.

Mechanistic and biophysical insight into the inhibitory and disaggregase role of antibiotic moxifloxacin on human lysozyme amyloid formation

Lysozyme amyloidosis is a systemic non-neuropathic disease caused by the accumulation of amyloids of mutant lysozyme. Presently, therapeutic interventions targeting lysozyme amyloidosis, remain elusive with only therapy available for lysozyme amyloidosis being supportive management. In this work, we examined the effects of moxifloxacin, a synthetic fluoroquinolone antibiotic on the amyloid formation of human lysozyme. The ability of moxifloxacin to interfere with lysozyme amyloid aggregation was examined using various biophysical methods like Rayleigh light scattering, Thioflavin T fluorescence assay, transmission electron microscopy and docking method. The reduction in scattering and ThT fluorescence along with extended lag phase in presence of moxifloxacin, suggest that the antibiotic inhibits and impedes the lysozyme fibrillation in concentration dependent manner. From ANS experiment, we deduce that moxifloxacin is able to decrease the hydrophobicity of the protein molecule thereby preventing aggregation. Our CD and DLS results show that moxifloxacin stabilizes the protein in its native monomeric structure, thus also showing retention of lytic activity upto 69% and inhibition of cytotoxicity at highest concentration of moxifloxacin. The molecular docking showed that moxifloxacin forms a stable complex of −7.6 kcal/mol binding energy and binds to the aggregation prone region of lysozyme thereby stabilising it and preventing aggregation. Moxifloxacin also showed disaggregase potential by disrupting fibrils and decreasing the β-sheet content of the fibrils. Our current study, thus highlight the anti-amyloid and disaggregase property of an antibiotic moxifloxacin and hence sheds light on the future of antibiotics against protein aggregation, a hallmark event in many neurodegenerative diseases.

Emerging Enterococcus isolates in postoperative endophthalmitis by selection pressure of fluoroquinolones: an 11-year multicenter and experimental study

ABSTRACT Postoperative endophthalmitis (PE) is the devastating complication that frequently results in vision loss. Recently, enterococcus have emerged as a major cause of PE in several countries and resulted in poor visual outcome. However, the reason remains elusive. We investigate whether selection pressure of fluoroquinolone exerts effects on microorganism profiles isolated from PE. Medical records of patients who were diagnosed with PE at eight resident training institutions between January 2004 and December 2015 were reviewed. The most common isolate was Enterococcus faecalis (28.0%), followed by Staphylococcus epidermidis (18.6%) and other coagulase negative Staphylococci (7.6%). However, the rates of E. faecalis isolated from conjunctival microbes were 6.2% (16/257) and their resistance to fluoroquinolones was higher than those of S. epidermidis. In vitro and in vivo co-culture models of E. faecalis and S. epidermidis were established for survival assays after administration of fourth-generation fluoroquinolone. In in vitro co-culture model, the survival assay of E. faecalis and S. epidermidis against the treatment of moxifloxacin showed that E. faecalis survived significantly better than S. epidermidis in the presence of moxifloxacin 1 µg/mL and more. In in vivo co-culture model, E. faecalis survived significantly better than S. epidermidis after topical treatment of moxifloxacin (5 mg/mL). E. faecalis has been the most common causative strain of PE in Korea. We suggest that the increase of E. faecalis in PE could be associated with the selection pressure of fourth-generation fluoroquinolone. Summary: Enterococcus spp. have emerged as a leading causative strain of postoperative endophthalmitis in 11-year clinical data. We suggest that the increase of Enterococcus spp. is associated with the selection pressure of fourth-generation fluoroquinolone.

Moxifloxacin-loaded acrylic intraocular lenses: In vitro and in vivo performance

To assess the possibility of using acrylic intraocular lenses (IOLs) to ensure controlled and sustained release of moxifloxacin, an antibiotic commonly used for endophthalmitis prophylaxis after cataract surgery. Academic, industrial, and clinical partners from Portugal, Belgium, Iceland, and the United States. Experimental study. The physical properties of IOLs loaded with moxifloxacin by soaking were characterized. Invitro drug-release studies were performed under hydrodynamic conditions similar to those of the eye, and the activity of the released drug was tested. Invitro cytotoxicity was evaluated, and the invivo efficacy of the devices was assessed through rabbit experiments in which the effects of topical moxifloxacin drops (control) and moxifloxacin-loaded IOLs were compared. The presence of moxifloxacin in the IOLs had little effect on the evaluated physical properties and did not induce cytotoxicity. Invitro drug release experiments showed that the IOLs provided controlled release of moxifloxacin for approximately 2weeks. The drug remained active against the tested microorganisms during that period. Moxifloxacin-loaded IOLs and the control treatment induced similar invivo behavior in terms of inflammatory reactions, capsular bag opacification scores, and uveal and capsule biocompatibility. The drug concentration in the aqueous humor after 1week was similar in both groups; however, the concentration with the loaded IOLs was less variable. The moxifloxacin-loaded IOLs released the drug in a controlled manner, providing therapeutic levels.

December consultation #6

To assess the possibility of using acrylic intraocular lenses (IOLs) to ensure controlled and sustained release of moxifloxacin, an antibiotic commonly used for endophthalmitis prophylaxis after cataract surgery.Academic, industrial, and clinical partners from Portugal, Belgium, Iceland, and the United States.Experimental study.The physical properties of IOLs loaded with moxifloxacin by soaking were characterized. In vitro drug-release studies were performed under hydrodynamic conditions similar to those of the eye, and the activity of the released drug was tested. In vitro cytotoxicity was evaluated, and the in vivo efficacy of the devices was assessed through rabbit experiments in which the effects of topical moxifloxacin drops (control) and moxifloxacin-loaded IOLs were compared.The presence of moxifloxacin in the IOLs had little effect on the evaluated physical properties and did not induce cytotoxicity. In vitro drug release experiments showed that the IOLs provided controlled release of moxifloxacin for approximately 2 weeks. The drug remained active against the tested microorganisms during that period. Moxifloxacin-loaded IOLs and the control treatment induced similar in vivo behavior in terms of inflammatory reactions, capsular bag opacification scores, and uveal and capsule biocompatibility. The drug concentration in the aqueous humor after 1 week was similar in both groups; however, the concentration with the loaded IOLs was less variable.The moxifloxacin-loaded IOLs released the drug in a controlled manner, providing therapeutic levels.

Controlled release of moxifloxacin from intraocular lenses modified by Ar plasma-assisted grafting with AMPS or SBMA: An in vitro study

Intraocular lenses (IOLs) present an alternative for extended, local drug delivery in the prevention of post-operative acute endophthalmitis. In the present work, we modified the surface of a hydrophilic acrylic material, used for manufacturing of IOLs, through plasma-assisted grafting copolymerization of 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), with the aim of achieving a controlled and effective drug release. The material was loaded with moxifloxacin (MFX), a commonly used antibiotic for endophthalmitis prevention. The characterization of the modified material showed that relevant properties, like swelling capacity, wettability, refractive index and transmittance, were not affected by the surface modification. Concerning the drug release profiles, the most promising result was obtained when AMPS grafting was done in the presence of MFX. This modification led to a higher amount of drug being released for a longer period of time, which is a requirement for the prevention of endophthalmitis. The material was found to be non-cytotoxic for rabbit corneal endothelial cells. In a second step, prototype IOLs were modified with AMPS and loaded with MFX as previously and, after sterilization and storage (30days), they were tested under dynamic conditions, in a microfluidic cell with volume and renovation rate similar to the eye aqueous humour. MFX solutions collected in this assay were tested against Staphylococcus aureus and Staphylococcus epidermidis and the released antibiotic proved to be effective against both bacteria until the 12th day of release.

Possible interaction of quinolone antibiotics with peptide transporter 1 in oral absorption of peptide-mimetic drugs.

The study investigated whether quinolone antibiotics inhibit the PEPT1-mediated uptake of its substrates. Among the quinolones examined, lomefloxacin, moxifloxacin (MFLX) and purlifloxacin significantly inhibited the uptake of PEPT1 substrate phenylalanine-Ψ(CN-S)-alanine (Phe-Ψ-Ala) in HeLa/PEPT1 cells to 31.6 ± 1.3%, 27.6 ± 2.9%, 36.8 ± 2.2% and 32.6 ± 1.4%, respectively. Further examination showed that MFLX was an uncompetitive inhibitor, with an IC50 value of 4.29 ± 1.29 mm. In addition, MFLX significantly decreased the cephalexin and valacyclovir uptake in HeLa/PEPT1 cells. In an in vivo study in rats, the maximum plasma concentration (C(max)) of orally administered Phe-Ψ-Ala was significantly decreased in the presence of MFLX (171 ± 1 ng/ml) compared with that in its absence (244 ± 9 ng/ml). The area under the concentration-time curve (AUC) of orally administered Phe-Ψ-Ala in the presence of MFLX (338 ± 50 ng/ml · h) tended to decrease compared with that in its absence (399 ± 75 ng/ml · h). The oral bioavailability of Phe-Ψ-Ala in the presence and absence of MFLX was 41.7 ± 6.2% and 49.2 ± 9.2%, respectively. The results indicate that administration of quinolone antibiotics concomitantly with PEPT1 substrate drugs may potentially result in drug-drug interaction.

In vitro moxifloxacin drug interaction with chemotherapeutics: Implications for retinoblastoma management

Retinoblastoma (RB) is a common malignant intraocular tumor primarily affecting children. Multidrug resistance (MDR) proteins (P-gp and MRPs) mediated chemoresistance have been considered as a major cause of treatment failure in treatment of RB. Ocular cells have shown good tolerability against moxifloxacin (MFX). Hence, the aim of present study was to investigate the effect of moxifloxacin on the functionality of MDR proteins. Furthermore, we have also examined an interaction of MFX with anticancer agents (Topotecan, etoposide and vinblastine) for RB treatment. For interaction of MFX with efflux transporter, model cell lines transfected with the efflux transporters (MDCK-MDR1 and MDCK-MRP2) were used to perform uptake and bi-directional transport experiments. Modulation of anticancer induced cell cytotoxicity, pro-inflammatory cytokines (IL-6 and IL-8) release and caspase-3 enzyme activity in presence of MFX was also evaluated. Result indicates that MFX is a substrate of both MDR1 and MRP2 efflux transporters. Furthermore elevation of anticancer uptake and bi-directional transport, reduction in IC50 cytotoxic value and modulation of antiproliferative and cytokines release in presence of MFX by anticancer agents was observed. Our results demonstrate that MFX may not only modulate the permeability of anticancer agents at efflux sites but it may also potentiate antiproliferative activity of anticancer agents in retinoblastoma cells. This study may be further extended to explore in vivo outcome of this finding.

Chemiluminescence determination of moxifloxacin in pharmaceutical and biological samples based on its enhancing effect of the luminol–ferricyanide system using a microfluidic chip

A sensitive determination of a synthetic fluoroquinolone antibacterial agent, moxifloxacin (MOX), by an enhanced chemiluminescence (CL) method using a microfluidic chip is described. The microfluidic chip was fabricated by a soft-lithographic procedure using polydimethyl siloxane (PDMS). The fabricated PDMS microfluidic chip had three-inlet microchannels for introducing the sample, chemiluminescent reagent and oxidant, and a 500 µm wide, 250 µm deep and 82 mm long microchannel. An enhanced CL system, luminol-ferricyanide, was adopted to analyze the MOX concentration in a sample solution. CL light was emitted continuously after mixing luminol and ferricyanide in the presence of MOX on the PDMS microfluidic chip. The amount of MOX in the luminol-ferricyanide system influenced the intensity of the CL light. The linear range of MOX concentration was 0.14-55.0 ng/mL with a correlation coefficient of 0.9992. The limit of detection (LOD) and limit of quantification (LOQ) were 0.06 and 0.2 ng/mL respectively. The presented method afforded good reproducibility, with a relative standard deviation (RSD) of 1.05% for 10 ng/mL of MOX, and has been successfully applied for the determination of MOX in pharmaceutical and biological samples.

Susceptibility of hamsters to infection by historic and epidemic BI Clostridium difficile strains during daily administration of three fluoroquinolones

Background The recent epidemic of Clostridium difficile infection (CDI) has been attributed largely to the REA strain group BI (aka NAP1/027). Current isolates of the BI group differ from historic non-epidemic BI strains in that they have developed resistance to the newer fluoroquinolone (FQ), moxifloxacin. The acquisition of moxifloxacin resistance has been associated with the rise in frequency of CDI caused by these isolates. In order to explore the effect of FQ resistance on CDI we compared colonization and mortality in hamsters challenged with a historic (BI1 – susceptible to moxifloxacin) and a recent epidemic (BI17 – resistant to moxifloxacin) BI strain of CD during continuous administration of 3 different FQs. Methods Groups of 6 hamsters were treated with a 5 day course of ciprofloxacin, levofloxacin, or moxifloxacin given orally once per day. Each hamster was then challenged with 1 × 10 4 CFU of either BI1 or BI17 on day 3 or day 5. Colonization and time to death were recorded. Results Colonization efficiency (CE) following moxifloxacin (92%) was significantly greater than following levofloxacin (50%, p < 0.01) or ciprofloxacin (42%, p < 0.01) for both strains combined. The CE of BI17 was higher than BI1 for ciprofloxacin (67% vs 17%, p = 0.04) and levofloxacin (83% vs 17%, p < 0.01), but not moxifloxacin (100% and 83%, p = 0.48) administration. BI17 also showed a shorter time from inoculation to death than BI1 following moxifloxacin administration (1.8 days vs 3.9 days, p < 0.01). Moxifloxacin shortened the time from inoculation to death compared to ciprofloxacin in hamsters challenged with BI17 (1.8 days vs 4.0 days, p < 0.01) but not levofloxacin (1.8 days vs 2.0 days, p = NS). Conclusions For the epidemic BI17 strain, ciprofloxacin, levofloxacin and moxifloxacin have similar colonization rates, suggesting that the acquisition of high-level FQ resistance increases colonization rates in association with any FQ. Historic strain BI1 which does not carry high-level FQ resistance colonized efficiently only in the presence of moxifloxacin, possibly explaining lower rates of CDI historically prior to the widespread clinical use of moxifloxacin (and gatifloxacin). Current high rates and severity of CDI from 2000 to 2010 may in part be associated with the acquisition of high-level FQ resistance in BI strains and higher patient exposure rates of all FQs, especially moxifloxacin.

Moxifloxacin enhances etoposide-induced cytotoxic, apoptotic and anti-topoisomerase II effects in a human colon carcinoma cell line

Etoposide (VP-16) is a topoisomerase-II (topo II) inhibitor chemotherapeutic agent. Studies have shown that a combination of VP-16 with other drugs demonstrates better clinical responses. The aim of this study was to investigate the effects of moxifloxacin (MXF) and VP-16 on cellular topo II activity in drug-treated cells and evaluate the influence of MXF on the mode of action of VP-16, on proliferation and apoptosis of HT-29 cells. Decatenation assay, band depletion and Western blot analysis, cytotoxic assay (MTT), flow cytometric studies (cell cycle and survivin expression), apoptosis (DAPI-sulforhodamine staining and caspase 3 activity) and IL-8 and VEGF secretion were determined. MXF or VP-16 slightly affected cellular topo II activity in nuclear extracts derived from drug-treated cells while the combination enhanced inhibitory activity and the reduction in band depletion of topo II. VP-16 induced cell cycle arrest at G2/M and the appearance of the subG1 peak which was increased by the addition of MXF. Apoptosis studies (DAPI staining and caspase 3 activity) showed a marked increase in the presence of MXF and VP-16 compared to VP-16 alone. VP-16 induced the release of IL-8, and addition of MXF reduced enhanced release and the spontaneous release of VEGF from the cells. In conclusion, the results suggest that the enhancement in the reduction of topo II activity by the combined MXF/VP-16 treatments was probably due to the increase in the level of the DNA-enzyme cleavable complexes formed by both drugs. The unique combination of MXF/VP-16 may have clinical benefits and a cytotoxic drug 'sparing effect' and should be further studied in vivo.

Differential pulse polarographic determination of Co(II) using moxifloxacine

The polarographic reduction of Co(II) in the presence of moxifloxacin (1-cyclopropyl-7-[(S,S)-2.8-diazabicyclo[4.3.0]non-8-yl]-6-fluoro-8-methoxy-1.4-dihydro-4-oxo-3-quinolinecarboxylic acid) gives rise to an additional adsorption peak corresponding to the reduction of Co(II)-moxifloxacin complex on the mercury drop electrode at −1.17 V. This new peak is applicable to Co(II) determination with the linearity proportional to the Co(II) concentration in the range of 4.93 × 10−7−6.90 × 10−5 M and can be attributed to an adsorption-controlled process with an irreversible reduction. Without using moxifloxacin, the polarographic determination of 2.50 × 10−6 M Co(II) is impossible under the given conditions due to very poor sensitivity at −1.38 V. The proposed method showed good precision and accuracy with a relative standard deviation of 3.01% and relative error of +6.40% for the determination of 2.50 × 10−6 M Co(II) next to 5.0 × 10−6 M of Zn(II), Ni(II), and Cd(II). The accuracy of the method was also checked by the determination of Co(II) spiked with tap water and certified sea water, and the percentage recoveries were 97.5 and 96.7%, respectively (n = 4 at 95% confidence interval).

Relative Potential for Selection of Quinolone-Resistance- Determining-Region Mutations in Streptococcus pneumoniae by Gemifloxacin, Gatifloxacin and Moxifloxacin

Serial passage of a clinical isolate of Streptococcus pneumoniae, in the presence of moxifloxacin, gatifloxacin or gemifloxacin, gave rise to resistant isolates. Non-susceptibility as defined by Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) breakpoints arose on Days 10, 11, and 12 with gatifloxacin, gemifloxacin, and moxifloxacin respectively. Moxifloxacin and gatifloxacin selected for a single step quinolone-resistant-determining-region (QRDR) mutation in DNA gyrase (GyrA) on Day 4 and 7 respectively, whereas gemifloxacin selected simultaneously for multi-step mutations in gyrase and topoisomerase IV (ParC) on Day 17 and activated a non-reserpine inhibited efflux mechanism by Day 4. As found in clinical isolates, mutations included Ser-81-Phe and Glu-85-Lys in GyrA and Ser-79- Phe or Asp-83-Tyr in ParC. At high MICs, moxifloxacin showed a previously unreported 4 amino-acid deletion in GyrB as well as a more unusual substitution Ser-79-Leu/Ile in ParC. Gemifloxacin showed a 2- to 16-fold greater activity than moxifloxacin or gatifloxacin against strains with two or more QRDR mutations, however, its potency did not translate to nonsusceptibility and gemifloxacin MIC values were either at or well above the CLSI nonsusceptible breakpoint concentration.