Review

Authors: Jamir Pitton Rissardo, Ana Letícia Fornari Caprara

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

Authors: Solomon O Rotimi, David A Ojo, Olusola A Talabi...

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

Authors: Jürgen B Bulitta, Yuanyuan Jiao, Cornelia B Landersdorfer...

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

Authors: A Chaibdraa, M S Medjellekh, A Saouli...

Le Pseudomonasest un agent pathogène à l'origine d'infections nosocomiales graves dans les centres des brûlés. Son opportunisme et sa virulence en font une préoccupation majeure. Ce travail se propose d'évaluer la place de cette bactérie dans l'écologie bactérienne locale et d'en apprécier la sensibilité aux antibiotiques. Cette étude rétrospective préliminaire porte sur la période de juin 2003 à décembre 2005. Elle intéresse l'ensemble des prélèvements bactériologiques ayant pu être réalisés au centre des brûlés d'Annaba. L'effectif est de 633 micro-organismes isolés dont 128 Pseudomonas (20,2%): 127 aeruginosa (99,2%), 1 fluorescens (0,8%); distribution selon le site de prélèvement: écouvillon (87,5%), prélèvement trachéobronchique (4,6%), hémoculture (3,1%), cathéters (1,6%), urine (1,6%) et sonde urinaire (1,6%). Le pyocyanique se situe après le staphylocoque pour les prélèvements précoces et repasse en tête après un séjour supérieur à une semaine, où 89% des pyocyaniques sont identifiés. Il est en première position dans les pneumopathies sous ventilation assistée invasive. Il se classe troisième dans les hémocultures et les cultures de cathéters. Dans les infections urinaires il est devancé par Candida et la flore périnéale. Les 128 antibiogrammes regroupent 314 réponses sensibles. La sensibilité à plus de deux antibiotiques est de 68%, à deux antibiotiques 24% et à un antibiotique 8%. Seules quatre molécules restent actives: ciprofloxacine > péfloxacine > pipéracilline > ceftazidime. Une résistance absolue est retrouvée pour trois Pseudomonas (2,4%). Le pronostic sévère des infections nosocomiales à pyocyanique et les risques d'options thérapeutiques très limitées font toute leur gravité, d'où l'intérêt de respecter des règles strictes de prescription des antibiotiques et des mesures de prévention.

PubMed: 21991140
DOI: No ID Found

Authors: Varsha Gupta, Kritika Pal, Alisha Bhagat...

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

Authors: Victoria R Sanders, Aaron Sweeney, Maya Topf...

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

Comparative Study

Authors: Ercan Olcay, Ozan Beytemur, Ferda Kaleagasioglu...

Four fluoroquinolones (pefloxacin, norfloxacin, ofloxacin and ciprofloxacin) were compared according to their biomechanical and histopathological effects on rat Achilles tendon. Wistar rats were divided into one untreated control and four treatment groups in parallel. Pefloxacin mesylate dihydrate (40 mg/kg), norfloxacin (40 mg/kg), ofloxacin (20 mg/kg) and ciprofloxacin (50 mg/kg) were administered by gavage twice daily for three consecutive weeks. 6 weeks after treatment, the test animals were euthanised and Achilles tendon specimens were collected. A computer monitored tensile testing machine was utilised for biomechanical testing. The mean elastic modulus of the control group was significantly higher than that of the norfloxacin and pefloxacin groups (p<0.05 and p<0.01, respectively). The mean yield force (YF) of the control group was significantly higher than those of ciprofloxacin, norfloxacin and pefloxacin groups (p<0.001, p<0.05 and p<0.01, respectively). The mean ultimate tensile force (UTF) of the control group was significantly higher than of the ciprofloxacin, norfloxacin, and pefloxacin groups (p<0.001, p<0.05 and p<0.01, respectively). Hyaline degeneration and fibre disarrangement were observed in the tendons of the ciprofloxacin, pefloxacin, and ofloxacin treated-groups, whereas myxomatous degeneration was observed only in the ciprofloxacin and pefloxacin groups. In conclusion, these findings in our rat model reveal significant deterioration of biomechanical parameters following fluoroquinolone exposure, and indicate significantly higher biomechanical toxicity for ciprofloxacin and pefloxacin.

Topics: Achilles Tendon; Administration, Oral; Animals; Anti-Bacterial Agents; Ciprofloxacin; Elastic Modulus; Elasticity; Fluoroquinolones; Male; Norfloxacin; Ofloxacin; Pefloxacin; Rats; Rats, Wistar; Tensile Strength

PubMed: 21628961
DOI: 10.2131/jts.36.339

Authors: R J Fass, V L Helsel

MICs of pefloxacin and nine antistaphylococcal drugs were determined for 200 isolates of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, and Staphylococcus saprophyticus. All the strains were susceptible to pefloxacin, vancomycin, and rifampin. Oxacillin-resistant strains were uniformly resistant to cephalothin and were more likely to be resistant to gentamicin, erythromycin, clindamycin, doxycycline, and trimethoprim-sulfamethoxazole than were oxacillin-susceptible strains. Time-kill studies with 23 strains of S. aureus, S. epidermidis, and S. haemolyticus indicated that the relative order of bactericidal activities was gentamicin greater than or equal to pefloxacin greater than oxacillin greater than vancomycin greater than rifampin. Pefloxacin combined with oxacillin or vancomycin killed staphylococci more rapidly than oxacillin or vancomycin alone but less rapidly than pefloxacin alone. Gentamicin combined with oxacillin, vancomycin, or pefloxacin resulted in the most rapid killing of gentamicin-susceptible strains. Rifampin combined with oxacillin, vancomycin, or pefloxacin reduced the bactericidal activities of those drugs, but rifampin resistance was not observed as it was with rifampin alone. Pefloxacin is a potentially useful antistaphylococcal agent.

Topics: Anti-Bacterial Agents; Microbial Sensitivity Tests; Norfloxacin; Pefloxacin; Staphylococcus

PubMed: 3481244
DOI: 10.1128/AAC.31.10.1457

Authors: Lei Sha, Xiaoyan Tang, Dengyong Liu...

Lomefloxacin (LOM) and pefloxacin (PEF) are synthetic antibiotics that have been used in the treatment of infectious diseases in both human and animals. In the People's Republic of China, the use of LOM and PEF in livestock has been prohibited because of the concern that the residues of these drugs may pose a risk to public health. Despite this prohibition, these drugs are still being used in the poultry industry illegally, and so far there has been no systematic study of the persistence of LOM and PEF residues in chickens. In this study, laying hens were treated with a daily dose (10 mg/kg of body weight) of LOM or PEF for five consecutive days, and the drug residues in various tissues and eggs were determined over a 15-day period after the last drug administration. The highest LOM and PEF residual concentrations were found in the tissues 4 h after the last drug administration, and concentrations gradually decreased over time. Plasma had the lowest and liver had the highest residual concentrations throughout the 15-day study period. At the end of the 15 days, 3.64 ± 0.74 μg/kg LOM and 1.78 ± 0.28 μg/kg PEF were detected in the liver, with slightly lower residual concentrations in the kidney. No LOM or PEF residue was detected in the ovarian follicle, plasma, and muscle at the end of the 15 days. In eggs, the depletion rate of LOM was slower than that of PEF. LOM and PEF residues were detected in whole eggs for up to 10 and 8 days, respectively, after drug administration ceased. These findings suggest that the liver and, to a lesser extent, the kidney may be the sites where LOM or PEF residues would persist. This information can be a reliable reference for governmental agencies with respect to the screening of LOM and PEF residues in food products derived from laying hens.

Topics: Animals; Anti-Bacterial Agents; Chickens; China; Drug Residues; Eggs; Female; Fluoroquinolones; Organ Specificity; Pefloxacin

PubMed: 29637810
DOI: 10.4315/0362-028X.JFP-17-422

Authors: T H Tsai

1. In vivo microdialysis with HPLC was used to investigate the pharmacokinetics of pefloxacin and its interaction with cyclosporin A. Microdialysis probes were inserted into the jugular vein/right atrium, the striatum and the bile duct of male Sprague-Dawley rats. Biological fluid sampling thereby allowed the simultaneous determination of pefloxacin levels in blood, brain and bile. 2. Following pefloxacin administration, the brain-to-blood coefficient of distribution was 0.036. This was calculated by dividing the area under the concentration curve (AUC) of pefloxacin in brain by its AUC in blood (k=AUC(brain)/AUC(blood)). 3. When the P-glycoprotein cyclosporin A (10 mg kg(-1)) was co-administered with pefloxacin (10 mg kg(-1)), the AUC and the mean residence time in rat blood did not differ significantly (P>0.05). Similarly, the pharmacokinetics of pefloxacin in rat brain was not affected by the presence of cyclosporin A. 4. The AUC of unbound pefloxacin in bile was significantly greater than that in blood. The disposition of pefloxacin in rat bile shows a slow elimination phase following a peak concentration 30 min after pefloxacin administration (10 mg kg(-1), i.v.). The bile-to-blood coefficient of distribution (k=AUC(bile)/AUC(blood)) was 1.53. 5. The results indicated that pefloxacin was able to penetrate the blood-brain barrier and that the concentration in bile was greater than that in the blood, suggesting active biliary excretion of pefloxacin. Current data obtained from rats show no significant impact of cyclosporin A on the pharmacokinetics of pefloxacin in rat blood and brain when administered by concomitant i.v. bolus.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Animals; Anti-Infective Agents; Bile Ducts; Brain; Cyclosporine; Drug Interactions; Enzyme Inhibitors; Injections, Intravenous; Male; Microdialysis; Pefloxacin; Rats; Rats, Sprague-Dawley

PubMed: 11250882
DOI: 10.1038/sj.bjp.0703927