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Medicines (Basel, Switzerland) May 2023Fluoroquinolones (FQNs) are related to several central nervous system side effects. This review aims to evaluate the clinical-epidemiological profile, pathophysiological... (Review)
Review
BACKGROUND
Fluoroquinolones (FQNs) are related to several central nervous system side effects. This review aims to evaluate the clinical-epidemiological profile, pathophysiological mechanisms, and management of FQNs-associated movement disorders (MDs).
METHODS
Two reviewers identified and assessed relevant reports in six databases without language restriction between 1988 and 2022.
RESULTS
A total of 45 reports containing 51 cases who developed MDs secondary to FQNs were reported. The MDs included 25 myoclonus, 13 dyskinesias, 7 dystonias, 2 cerebellar syndromes, 1 ataxia, 1 tic, and 2 undefined cases. The FQNs reported were ciprofloxacin, ofloxacin, gatifloxacin, moxifloxacin, levofloxacin, gemifloxacin, and pefloxacin. The mean and median age were 64.54 (SD: 15.45) and 67 years (range: 25-87 years). The predominant sex was male (54.16%). The mean and median time of MD onset were 6.02 (SD: 10.87) and 3 days (range: 1-68 days). The mean and median recovery time after MD treatment was 5.71 (SD: 9.01) and 3 days (range: 1-56 days). A complete recovery was achieved within one week of drug withdrawal in 80.95% of the patients. Overall, 95.83% of the individuals fully recovered after management.
CONCLUSIONS
Future cases need to describe the long-term follow-up of the individuals. Additionally, FQN-induced myoclonus should include electrodiagnostic studies.
PubMed: 37367728
DOI: 10.3390/medicines10060033 -
Lipids in Health and Disease Feb 2015To investigate whether amoxillin and pefloxacin perturb lipid metabolism.
BACKGROUND
To investigate whether amoxillin and pefloxacin perturb lipid metabolism.
METHODS
Rats were treated with therapeutic doses of each antibiotic for 5 and 10 days respectively. Twenty four hours after the last antibiotic treatment and 5 days after antibiotic withdrawal, blood and other tissues (liver, kidney, brain, heart and spleen) were removed from the animals after an overnight fast and analysed for their lipid contents.
RESULTS
Both antibiotics produced various degrees of compartment-specific dyslipidemia in the animals. While plasma and erythrocyte dyslipidemia was characterised by up-regulation of the concentrations of the major lipids (cholesterol, triglycerides, phospholipids and free fatty acids), hepatic and renal dyslipidemia was characterised by cholesterogenesis and phospholipidosis. Splenic dyslipidemia was characterised by cholesterogenesis and decreased phospholipid levels. Cardiac and brain cholesterol contents were not affected by the antibiotics. A transient phospholipidosis was observed in the brain whereas cardiac phospholipids decreased significantly. Lipoprotein abnormalities were reflected as down-regulation of HDL cholesterol. Furthermore, the two antibiotics increased the activity of hepatic HMG-CoA reductase. Although erythrocyte phospholipidosis was resolved 5 days after withdrawing the antibiotics, dyslipidemia observed in other compartments was still not reversible.
CONCLUSION
Our findings suggest that induction of cholesterogenesis and phospholipidosis might represent additional adverse effects of amoxillin and pefloxacin.
Topics: Acyl Coenzyme A; Amoxicillin; Animals; Anti-Bacterial Agents; Brain Chemistry; Cholesterol; Erythrocytes; Kidney; Liver; Lung; Male; Myocardium; Pefloxacin; Phospholipids; Rats; Spleen
PubMed: 25879817
DOI: 10.1186/s12944-015-0011-8 -
Colloids and Surfaces. B, Biointerfaces Sep 2022By integrating the fluorescence of quantum dots (QDs) and Mn-pefloxacin mesylate (Mn-pefloxacin), a new type of dual-band fluorescence biosensor for high-efficiency and...
By integrating the fluorescence of quantum dots (QDs) and Mn-pefloxacin mesylate (Mn-pefloxacin), a new type of dual-band fluorescence biosensor for high-efficiency and sensitive determination of double-stranded DNA (dsDNA) is developed. The biosensor is based on the fluorescence "OFF-ON" mode of both QDs and QDs-Mn-pefloxacin. The Mn-pefloxacin complex can quench the QDs fluorescence via photoinduced electron transfer (PET), and its fluorescence is also quenched. Due to the specificity and strong binding affinity of dsDNA for the Mn-pefloxacin complex, it can break the low fluorescent QDs-Mn-pefloxacin and restore the fluorescence of QDs and Mn-pefloxacin complex in their respective bands. Therefore, the dual-band fluorescence quantitative detection of dsDNA by QDs-Mn-pefloxacin can be achieved, while bovine serum albumin, single-stranded DNA, and bio-related ions do not yield similar results. Furthermore, the possible reaction mechanisms are systematically discussed. The detection limits (3δ/K) of herring sperm (hs) DNA in the fluorescence recovery bands of QDs and Mn-pefloxacin complex are 0.0142 and 0.0465 μg/mL, respectively. The developed biosensor was used for dsDNA detection in synthetic samples, and desirable results are obtained.
Topics: Biosensing Techniques; DNA; Fluorescence; Humans; Male; Pefloxacin; Quantum Dots; Semen; Spectrometry, Fluorescence
PubMed: 35753193
DOI: 10.1016/j.colsurfb.2022.112649 -
Chemistry & Biodiversity Sep 2023Twelve new heteroleptic nickel(II) and copper(II) complexes of the type [M(L )(Pfx) ] (1-12), where L =2-benzylidenehydrazinecarbothioamide (L ),...
Theoretical, in Vitro Antiproliferative, and in Silico Molecular Docking and Pharmacokinetics Studies of Heteroleptic Nickel(II) and Copper(II) Complexes of Thiosemicarbazone-Based Ligands and Pefloxacin.
Twelve new heteroleptic nickel(II) and copper(II) complexes of the type [M(L )(Pfx) ] (1-12), where L =2-benzylidenehydrazinecarbothioamide (L ), 2-benzylidene-N-methylhydrazinecarbothioamide (L ), 2-benzylidene-N-phenylhydrazinecarbothioamide (L ), 2-(4-methylbenzylidene)hydrazinecarbothioamide (L ), 2-(4-methylbenzylidene)-N-methylhydrazinecarbothioamide (L ) and 2-(4-methylbenzylidene)-N-phenylhydrazinecarbothioamide (L ), Pfx=pefloxacin and M=Ni(II) or Cu(II) have been synthesised, and their structures were confirmed by different spectral techniques. The spectral data and density functional theory (DFT) calculations supported the bonding of pefloxacin drug molecule via one of the carboxylate oxygen atoms and the pyridone oxygen atom, and the thiosemicarbazone ligand via the imine nitrogen and the thione sulfur atoms with the metal(II) ion, forming distorted octahedral geometry. In vitro antiproliferative activity of the synthesized complexes was evaluated against three human breast cancer (T47D, estrogen negative (MDA-MB-231) and estrogen positive (MCF-7)) as well as non-tumorigenic human breast epithelial (MCF-10a) cell lines, which showed the higher activity for the copper(II) complexes. The interaction of the synthesized complexes with an oncogenic protein H-ras (121 p) was explored by in silico molecular docking studies. Further, in silico pharmacokinetics and ADMET parameters were also analysed to predict the drug-likeness as well as non-toxic and non-carcinogenic behavior, and safe oral administration of the complexes.
Topics: Humans; Copper; Nickel; Molecular Docking Simulation; Pefloxacin; Thiosemicarbazones; Ligands; Coordination Complexes; Estrogens; Oxygen
PubMed: 37528701
DOI: 10.1002/cbdv.202300702 -
Journal of Laboratory Physicians Dec 2020Typhoid fever, caused by and , is a generalized infection with case fatality of about 10%. The symptoms may be severe, with life threatening sequelae of infection in...
Typhoid fever, caused by and , is a generalized infection with case fatality of about 10%. The symptoms may be severe, with life threatening sequelae of infection in a proportion of cases. Antimicrobial agents are the mainstay of therapy in enteric fever so as to prevent the complications associated with severe illness and mortality in the patients. Fluoroquinolones (e.g., ciprofloxacin) are very effective against completely susceptible bacteria. However, their efficacy is doubtful once any resistance is detected. Pefloxacin testing has ultimately helped in the accurate identification of quinolone susceptibility for a better therapeutic success rate. In the present study we have tried to evaluate the quinolone susceptibility in isolates based on minimum inhibitory concentration (MIC) determination. The method used in the study is quinolone susceptibility in isolates based on MIC determination. isolates show intermediate susceptibility to ciprofloxacin using disk diffusion. Both ciprofloxacin and pefloxacin MIC evaluation has been done to corroborate the results with pefloxacin disk diffusion testing. There was a positive correlation between the susceptibility to ciprofloxacin and pefloxacin. However, the isolates with intermediate susceptibility had variations in terms of susceptibility to pefloxacin. MIC values for pefloxacin and our findings suggested that pefloxacin susceptible on disk diffusion as per Clinical and Laboratory Standards Institute guidelines showed lower values for MIC using Pefloxacin HICOMB test and pefloxacin resistant isolates showed higher MIC values.
PubMed: 33390675
DOI: 10.1055/s-0040-1721163 -
Frontiers in Veterinary Science 2017The pharmacokinetics of pefloxacin after single 10 mg/kg BW intravenous (IV) and oral doses were studied in healthy broiler chickens. For 24 h, serial blood samples...
The pharmacokinetics of pefloxacin after single 10 mg/kg BW intravenous (IV) and oral doses were studied in healthy broiler chickens. For 24 h, serial blood samples were obtained after IV and oral administration. Concentrations of pefloxacin and its major metabolite -demethyl pefloxacin (norfloxacin) were measured by use of high-performance liquid chromatography. The plasma concentrations-time data were found to fit a two-compartment open model. For pefloxacin, the elimination half-life () was 8.44 ± 0.48 and 13.18 ± 0.82 h after IV and oral administration, respectively. After single oral dose, pefloxacin was rapidly absorbed with an absorption half-life () and of 0.87 ± 0.07 and 2.01 ± 0.12 h, respectively. Maximum plasma concentration () was 4.02 ± 0.31 µg/mL. Oral bioavailability of pefloxacin was found to be 70 ± 2%. Pefloxacin was converted to -demethyl pefloxacin (norfloxacin). This metabolite represented 5% of the parent drug plasma concentrations. The maximal plasma concentration () of -demethyl pefloxacin (norfloxacin) was calculated as 0.19 ± 0.01 mg/mL. The of -demethyl pefloxacin after oral pefloxacin administration was 10.93 ± 0.80 h. The results indicate that an oral dose of 10 mg pefloxacin/kg BW, every 24 h, should be effective in treatment of the most systemic infections in poultry.
PubMed: 28596959
DOI: 10.3389/fvets.2017.00077 -
ACS Chemical Neuroscience Jun 2022Quinolone antibiotics disrupt bacterial DNA synthesis by interacting with DNA gyrase and topoisomerase IV. However, in addition, they have been shown to act as...
Quinolone antibiotics disrupt bacterial DNA synthesis by interacting with DNA gyrase and topoisomerase IV. However, in addition, they have been shown to act as inhibitors of pentameric ligand-gated ion channels such as GABA receptors and the α7 nicotinic acetylcholine receptor (nAChR). In the present study, we have examined the effects of quinolone antibiotics on the human α4β2 nAChR, an important subtype that is widely expressed in the central nervous system. A key feature of α4β2 nAChRs is their ability to coassemble into two distinct stoichiometries, (α4)(β2) and (α4)(β2), which results in differing affinities for acetylcholine. The effects of nine quinolone antibiotics were examined on both stoichiometries of the α4β2 receptor by two-electrode voltage-clamp recording. All compounds exhibited significant inhibition of α4β2 nAChRs. However, all of the fluoroquinolone antibiotics examined (ciprofloxacin, enoxacin, enrofloxacin, difloxacin, norfloxacin, pefloxacin, and sparfloxacin) were significantly more potent inhibitors of (α4)(β2) nAChRs than of (α4)(β2) nAChRs. This stoichiometry-selective effect was most pronounced with pefloxacin, which inhibited (α4)(β2) nAChRs with an IC of 26.4 ± 3.4 μM but displayed no significant inhibition of (α4)(β2) nAChRs. In contrast, two nonfluorinated quinolone antibiotics (cinoxacin and oxolinic acid) exhibited no selectivity in their inhibition of the two stoichiometries of α4β2. Computational docking studies suggest that pefloxacin interacts selectively with an allosteric transmembrane site at the β2(+)/β2(-) subunit interface, which is consistent with its selective inhibition of (α4)(β2). These findings concerning the antagonist effects of fluoroquinolones provide further evidence that differences in the subunit stoichiometry of heteromeric nAChRs can result in substantial differences in pharmacological properties.
Topics: Anti-Bacterial Agents; Fluoroquinolones; Humans; Nicotinic Antagonists; Oocytes; Pefloxacin; Receptors, Nicotinic
PubMed: 35657695
DOI: 10.1021/acschemneuro.2c00200 -
Pharmaceutics Jul 2019Quinolone antibiotics present an attractive oral treatment option in patients with cystic fibrosis (CF). Prior studies have reported comparable clearances and volumes of...
Quinolone antibiotics present an attractive oral treatment option in patients with cystic fibrosis (CF). Prior studies have reported comparable clearances and volumes of distribution in patients with CF and healthy volunteers for primarily renally cleared quinolones. We aimed to provide the first pharmacokinetic comparison for pefloxacin as a predominantly nonrenally cleared quinolone and its two metabolites between both subject groups. Eight patients with CF (fat-free mass [FFM]: 36.3 ± 6.9 kg, average ± SD) and ten healthy volunteers (FFM: 51.7 ± 9.9 kg) received 400 mg pefloxacin as a 30 min intravenous infusion and orally in a randomized, two-way crossover study. All plasma and urine data were simultaneously modelled. Bioavailability was complete in both subject groups. Pefloxacin excretion into urine was approximately 74% higher in patients with CF compared to that in healthy volunteers, whereas the urinary excretion of metabolites was only slightly higher in patients with CF. After accounting for body size and composition via allometric scaling by FFM, pharmacokinetic parameter estimates in patients with CF divided by those in healthy volunteers were 0.912 for total clearance, 0.861 for nonrenal clearance, 1.53 for renal clearance, and 0.916 for volume of distribution. Nonrenal clearance accounted for approximately 90% of total pefloxacin clearance. Overall, bioavailability and disposition were comparable between both subject groups.
PubMed: 31295857
DOI: 10.3390/pharmaceutics11070323 -
The Journal of Infection Apr 2023The World Health Organization (WHO) recommends multidrug therapy (MDT) with rifampicin, dapsone, and clofazimine for treating leprosy, which is based on very low-quality... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The World Health Organization (WHO) recommends multidrug therapy (MDT) with rifampicin, dapsone, and clofazimine for treating leprosy, which is based on very low-quality evidence. Here, we performed a network meta-analysis (NMA) to produce quantitative evidence to strengthen current WHO recommendations.
METHOD
All studies were obtained from Embase and PubMed from the date of establishment to October 9, 2021. Data were synthesized with frequentist random-effects network meta-analyses. Outcomes were assessed using odds ratios (ORs), 95% confidence intervals (95% CIs), and P score.
RESULTS
Sixty controlled clinical trials and 9256 patients were included. MDT was effective (range of OR: 1.06-1255584.25) for treating leprosy and multibacillary leprosy. Six treatments (Range of OR: 1.199-4.50) were more effective than MDT. Clofazimine (P score=0.9141) and dapsone+rifampicin (P score=0.8785) were effective for treating type 2 leprosy reaction. There were no significant differences in the safety of any of the tested drug regimens.
CONCLUSIONS
The WHO MDT is effective for treating leprosy and multibacillary leprosy, but it may not be effective enough. Pefloxacin and ofloxacin may be good adjunct drugs for increasing MDT efficacy. Clofazimine and dapsone+rifampicin can be used in the treatment of a type 2 leprosy reaction. Single-drug regimens are not efficient enough to treat leprosy, multibacillary leprosy, or a type 2 leprosy reaction.
AVAILABILITY OF DATA AND MATERIALS
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
Topics: Humans; Leprostatic Agents; Rifampin; Clofazimine; Network Meta-Analysis; Drug Therapy, Combination; Leprosy; Dapsone; Leprosy, Multibacillary
PubMed: 36796681
DOI: 10.1016/j.jinf.2023.02.019 -
Genes Jun 2023This study is designed to investigate for the antibiotic resistance genes (ARGs) and integrons from healthy as well as diarrhoeic/diseased animals/birds' faecal...
This study is designed to investigate for the antibiotic resistance genes (ARGs) and integrons from healthy as well as diarrhoeic/diseased animals/birds' faecal samples. A total of eight samples were selected for the study; from each animal, two samples were taken, one from healthy animals/birds and one from diarrhoeic/diseased animals/birds. Antibiotic sensitivity testing (AST) and whole genome sequencing (WGS) was performed for selected isolates. The isolates showed resistance to moxifloxacin, followed by erythromycin, ciprofloxacin, pefloxacin, tetracycline, levofloxacin, ampicillin, amoxicillin, and sulfadiazine (4/8, 50.00% each). The isolates were 100% sensitive to amikacin, followed by chloramphenicol, cefixime, cefoperazone, and cephalothin. A total of 47 ARGs from 12 different antibiotic classes were detected among the eight isolates by WGS. The different classes of antibiotics included aminoglycoside, sulphonamide, tetracycline, trimethoprim, quinolone, fosfomycin, phenicol, macrolide, colistin, fosmidomycin, and multidrug efflux. The class 1 integrons were detected in 6/8 (75.00%) isolates with 14 different gene cassettes.
Topics: Animals; Anti-Bacterial Agents; Escherichia coli; Integrons; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Whole Genome Sequencing; Tetracyclines
PubMed: 37372392
DOI: 10.3390/genes14061212