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Recent drug safety concerns described fluoroquinolone (FQ)-induced serious musculoskeletal reactions. The objective of this study was to characterize reports with FQ-associated disabling musculoskeletal disorders, from VigiBase. The analysis included all FQ-induced musculoskeletal and connective tissue disorders adverse drug reaction (ADR) reports (up to July-2019), (disabling/incapacitating, or recovered/resolved with sequelae or fatal). We described aspects like reporter, suspected FQs, ADRs, associated corticosteroid therapy. We also looked into the disproportionality data in terms of proportional reporting ratio (PRR) and information component (IC) values. A total of 5355 reports with 13,563 ADRs and 5558 FQs were reported. The majority of reports were for patients aged 18-64 (62.67%), and the female gender prevailed (61.76%). Consumers reported almost half (45.99%), with a peak in reporting rates in 2017. Top reported ADRs were arthralgia (16.34%), tendonitis (11.04%), pain in extremity (9.98%), tendon pain (7.63%), and myalgia (7.17%). Top suspected FQs were levofloxacin (50.04%), ciprofloxacin (38.41%), moxifloxacin (5.16%), ofloxacin (3.17%) and norfloxacin (1.01%). For these, FQs-ADR association was supported by the disproportionality analysis. Corticosteroids were associated with about 7% of tendon related reports. The results augment the existing data on FQs safety concerns, specifically their potential effect on the musculoskeletal system., (© 2021. The Author(s).)

A nanohybrid formulation of silver‑titanium dioxide nanoparticles/poly(lactic acid) (Ag-TiO 2 /PLA) was designed for Norfloxacin/Tenoxicam (NOR/TENO) targeted delivery to maximize the bioavailability and minimize the side effects of the drugs. Ag-TiO 2 nanoparticles were prepared via Stober method. NOR, TENO and a mixture of NOR/TENO (NT) were loaded onto Ag-TiO 2 nanoparticles and coated by PLA via solution casting. The physical interaction between the drugs and carrier was confirmed by Fourier-transform infrared (FTIR) analysis. X-ray diffraction (XRD) demonstrated that Ag-TiO 2 consists of a cubic phase of Ag with two phases of TiO 2 (anatase and brookite). Ag nanoparticle fine spots coated with TiO 2 were collected to form spheres averaging at 100 nm in size. In-vitro release behavior of drugs was studied at different pH (5.4, 7.4) and the release of drug from NT/Ag-TiO 2 /PLA was faster at pH 7.4. Gram-positive and Gram-negative bacteria were used to investigate antibacterial properties of the nanohybrid. Cytotoxicity of the nanohybrid using an MTT assay was studied against different tumor and normal cell lines. It was found that NT/Ag-TiO 2 /PLA has an excellent cytotoxic effect against various bacterial cells and tumor cell lines. In addition, antioxidant properties of the nanohybrids were tested using ABTS method and the nanohybrid showed moderate antioxidant activity., (Copyright © 2021. Published by Elsevier B.V.)

The nasal drug application has drawn much attention as the strategy for the delivery route of many drug modalities such as the poorly absorbed drugs, peptides, nucleic acid, and central nervous system drugs. The absorption of drug after intranasal (IN) application depends on the nasal residence time of applied drug, affected by mucociliary clearance (MC). MC is a decisive factor in the nasal absorption of drug. We describe the establishment of in vitro evaluation system of nasal MC via the moving velocity of a marker particle on nasal mucosa, and the development of the pharmacokinetic model to which in vitro parameters on nasal MC was incorporated to enable the prediction of drug absorption after IN application. Moreover, the pharmacokinetics of norfloxacin after IN application was investigated using MC-modified rats pretreated with MC modulators. Nasal absorption fluctuated due to changes in the nasal residence time of drug in response to changes in MC. The prediction system enables quantitative evaluation of changes in drug absorption associated with MC fluctuations. In addition, for a precise prediction system for drug absorption after IN application from the drug absorption model, the relationships between in vitro drug permeability through Calu-3 layers, in vivo transnasal permeation of drug and in vivo bioavailability after IN application were evaluated. The significant correlations between these parameters were obtained, suggesting that transnasal permeability and drug absorption after IN application can be predicted from in vitro membrane permeability.

Applying nanotechnology to deliver drug could result in several benefits such as prolong duration of action, enhancement in overall bioavailability, targeting to specific site, low initial loading dose require, systemic stability enhancement etc. Halloysite is one of those clay minerals showing maximum effectiveness when consider as a nano drug carriers for different kind applications. Here, we have used norfloxacin as the model drug for loading into halloysite nanotube (HNT) for its anti-bacterial activity. Norfloxacin was loaded into halloysites by vacuum operation and sonication. The nanotubes were evaluated using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), optical microscopy, water absorption studies, cytotoxicity studies, antimicrobial studies and in vitro diffusion studies. SEM, FT-IR and XRD analysis data showed that the norfloxacin was successfully loaded into nanotubes. TEM analysis confirmed loading of norfloxacin in halloysites' lumen. The halloysite/chitosan nanocomposites were prepared by solvent casting and freeze-drying method. SEM analysis revealed compact and rugged surface of nanocomposites due to existing norfloxacin loaded halloysite. FTIR and XRD confirmed formation of nanocomposite. The nanocomposites showed good antimicrobial effect and good biocompatibility in cytotoxicity study. The in-vitro release studies revealed that halloysite/chitosan nanocomposites were able to sustain the drug release. Also, the nanocomposites were stable in various humidity conditions. Therefore, all the outcomes suggest that the prepared nanocomposites can provide enhanced therapeutic benefits and they can be very potential nano vehicle for sustaining drug delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All the figures are original. If any idea is adopted, we have done proper referencing. We have acknowledged all the authors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The gut microbiota plays a key role in the maintenance of human health and mediates the beneficial effects of natural products including polyphenols. Previous studies have demonstrated that the polyphenol-rich Pandanus tectorius fruit extract (PTF) was effective in ameliorating high-fat diet (HFD)-induced hyperlipidaemia, and polyphenols can significantly change the structure of the gut microbiota., Purpose: In this study, we assessed whether the modulation of the gut microbiota plays a key role in the PTF-induced anti-hyperlipidaemic effects., Methods: Male C57BL/6 J mice were induced with hyperlipidaemia by consuming a high-fat diet (HFD) for 4 weeks. Then, the mice were orally administered PTF, antibiotics (ampicillin+ norfloxacin), PTF+antibiotics or vehicle for another 6 weeks. Body weights and 24-h food intake were assessed weekly. At the end of the experiment, fresh stools were collected for 16S RNA pyrosequencing, and blood and liver and fat tissue were collected for pharmacological analysis., Results: PTF was effective in ameliorating high-fat diet (HFD)-induced hyperlipidaemia and significantly changed the structure of the gut microbiota. However, the anti-hyperlipidaemic effect of PTF was not influenced by the co-treatment with antibiotics (ampicillin+norfloxacin). A microbiological analysis of the gut microbiotas revealed that PTF selectively enhanced the relative abundance of Lactobacillus and decreased the relative abundance of Bacteroides and Alistipes. A correlation analysis between biochemical indexes and individual taxon showed that Lactobacillus was negatively associated with serum lipids and glucose while Bacteroides and Alistipes were positively associated with serum lipids and glucose. The modulatory effect of PTF on Lactobacillus, Bacteroides and Alistipes was not disturbed by the administration of antibiotics., Conclusion: These results demonstrated that the polyphenol-rich PTF as a unique gut microbiota modulating agent and highlighted the richness of Lactobacillus and the decreased abundance of Bacteroides and Alistipes as an effective indicator of the therapeutic effect of medicinal foods on hyperlipidaemia., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: Fixed drug eruption is a clinical entity occurring at the same site each time the drug is administered. They are usually found on lips, genitalia, abdomen, and legs but can occur at any location. The eruptions usually occur within hours of administration of the drug and resolves spontaneously. Most common drugs causing them include antimicrobials. Fluroquinolones especially norfloxacin is commonly used in the treatment of gastrointestinal infections. Cutaneous adverse drug reactions are very rare with norfloxacin., Case Report: In this case report, a young female, soon after taking Nofloxacin tablet, developed a blister with erythema and itching after self treatment for urinary tract infection. It got cured after stopping the drug and taking treatment from a dermatologist. It resolved as a hyper-pigmented scar. She experienced a similar episode of drug eruption on the same site when she again self medicated herself with Norfloxacin for diarrhoea. This time the reaction occurred within few hours and resolved with hyperpigmentation after medication. She was advised not to indulge in self-treatment in future. Suspecting association between the drug and the rash was confirmed and a diagnosis of Norfloxacin induced fixed drug eruption was made., Conclusion: Causality assessment by Naranjo's algorithm revealed a definite relationship between the cutaneous adverse drug reaction and the offending drug., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The global abuse and misuse of antibiotics in the treatment and prevention of bacterial infections has resulted in the ubiquitous existence of these drugs in aquatic environments, which causes frequent antimicrobial resistance and pollution in ecosystems. However, the chronic effects of antimicrobial agents on aquatic animal growth and health have not been fully evaluated. In the present study, three typical antibiotics (tetracycline, erythromycin, and norfloxacin) were administered orally to juvenile sea cucumbers Apostichopus japonicus for 45 days, to mimic the long-term use of antibiotics. As a result, tetracycline and erythromycin promoted the growth and digestive activity of lipase, pepsin, and trypsin, but norfloxacin did not show significant prompting effect on digestive activity and even retarded the weight gain of the sea cucumbers. The mortality was higher in antibiotic treated groups between the 2nd and 4th days after challenge with Vibrio splendidus. At the same time, lower immune-related parameters were found in antibiotic feeding juveniles, suggesting that the use of antibiotics might weaken the immune defense system of sea cucumbers. This study revealed that antibiotic administration could facilitate the growth of sea cucumbers to varying degrees yet coupled with high risks of impaired immune function and compromised disease resistance., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Burkholderia cenocepacia is an opportunistic Gram-negative bacterium that causes serious respiratory infections in patients with cystic fibrosis. Recently, we discovered that B. cenocepacia produces the extracellular bacterial lipocalin protein BcnA upon exposure to sublethal concentrations of bactericidal antibiotics. BcnA captures a range of antibiotics outside bacterial cells, providing a global extracellular mechanism of antimicrobial resistance. In this study, we investigated water-soluble and liposoluble forms of vitamin E as inhibitors of antibiotic binding by BcnA. Our results demonstrate that in vitro , both vitamin E forms bind strongly to BcnA and contribute to reduce the MICs of norfloxacin (a fluoroquinolone) and ceftazidime (a β-lactam), both of them used as model molecules representing two different chemical classes of antibiotics. Expression of BcnA was required for the adjuvant effect of vitamin E. These results were replicated in vivo using the Galleria mellonella larva infection model whereby vitamin E treatment, in combination with norfloxacin, significantly increased larva survival upon infection in a BcnA-dependent manner. Together, our data suggest that vitamin E can be used to increase killing by bactericidal antibiotics through interference with lipocalin binding. IMPORTANCE Bacteria exposed to stress mediated by sublethal antibiotic concentrations respond by adaptive mechanisms leading to an overall increase of antibiotic resistance. One of these mechanisms involves the release of bacterial proteins called lipocalins, which have the ability to sequester antibiotics in the extracellular space before they reach bacterial cells. We speculated that interfering with lipocalin-mediated antibiotic binding could enhance the efficacy of antibiotics to kill bacteria. In this work, we report that when combined with bactericidal antibiotics, vitamin E contributes to enhance bacterial killing both in vitro and in vivo. This adjuvant effect of vitamin E requires the presence of BcnA, a bacterial lipocalin produced by the cystic fibrosis pathogen Burkholderia cenocepacia Since most bacteria produce lipocalins like BcnA, we propose that our findings could be translated into making novel antibiotic adjuvants to potentiate bacterial killing by existing antibiotics., (Copyright © 2018 Naguib and Valvano.)

Background & Aims: There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis., Methods: We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy. The study was performed at 18 clinical sites in France from April 2010 through November 2014. Patients were randomly assigned to groups given 400 mg norfloxacin (n = 144) or placebo (n = 147) once daily for 6 months. Patients were evaluated monthly for the first 6 months and at 9 months and 12 months thereafter. The primary outcome was 6-month mortality, estimated by the Kaplan-Meier method, censoring spontaneous bacterial peritonitis, liver transplantation, or loss during follow-up., Results: The Kaplan-Meier estimate for 6-month mortality was 14.8% for patients receiving norfloxacin and 19.7% for patients receiving placebo (P = .21). In competing risk analysis that took liver transplantation into account, the cumulative incidence of death at 6 months was significantly lower in the norfloxacin group than in the placebo group (subdistribution hazard ratio, 0.59; 95% confidence interval, 0.35-0.99). The subdistribution hazard ratio for death at 6 months with norfloxacin vs placebo was 0.35 (95% confidence interval, 0.13-0.93) in patients with ascites fluid protein concentrations <15 g/L and 1.39 (95% confidence interval, 0.42-4.57) in patients with ascites fluid protein concentrations ≥15 g/L. Norfloxacin significantly decreased the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria., Conclusions: In a randomized controlled trial of patients with advanced cirrhosis without recent fluoroquinolone therapy, norfloxacin did not reduce 6-month mortality, estimated by the Kaplan-Meier method. Norfloxacin, however, appears to increase survival of patients with low ascites fluid protein concentrations. ClinicalTrials.gov ID: NCT01037959., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Nasal drug delivery has attracted significant attention as an alternative route to deliver drugs having poor bioavailability. Large-molecule drugs, such as peptides and central nervous system drugs, would benefit from intranasal delivery. Drug absorption after intranasal application depends on the nasal retention of the drug, which is determined by the nasal mucociliary clearance. Mucociliary clearance (MC) is an important determinant of the rate and extent of nasal drug absorption. The aim of the present study was to clarify the effect of the changes in MC on in vivo drug absorption after nasal application, and to justify the pharmacokinetic model to which the MC parameter was introduced, to enable prediction of bioavailability after intranasal administration. The pharmacokinetics of norfloxacin (NFX) after intranasal administration were evaluated following the modification of nasal MC by pretreatment with the MC inhibitors propranolol and atropine and the MC enhancers terbutaline and acetylcholine chloride. From the relationship between nasal MC and bioavailability after nasal application, prediction of drug absorption was attempted on the basis of our pharmacokinetic model. Propranolol and atropine enhanced the bioavailability of NFX by 90 and 40%, respectively, while the bioavailability decreased by 30% following terbutaline and 40% following acetylcholine chloride. As a result of changes in the MC function, nasal drug absorption was changed depending on the nasal residence time of the drug. On the basis of our pharmacokinetic model, the nasal drug absorption can be precisely predicted, even when the MC is changed. This prediction system allows the quantitative evaluation of changes in drug absorption due to changes in nasal MC and is expected to contribute greatly to the development of nasal formulations.

Aim: Binary and ternary complexes with hydroxypropyl-β-cyclodextrin (HPβCD), using glutamic acid (GA), proline or lysine as the third component, were developed to increase the solubility and the dissolution rate of norfloxacin (NOR)., Methods/results: Complexation was evaluated by phase solubility studies, obtaining the highest NOR solubility with GA and HPβCD. Thermal analysis suggested that different kinds of interactions occur among NOR, HPβCD and each amino acid, and when the systems were prepared by kneading or by means of freeze-drying technique. Dissolution studies, performed on simulated gastric fluid and subsequent simulated intestinal fluid, showed the highest rate of NOR from NOR-HPβCD-GA., Conclusion: NOR:HPβCD:GA was the best approach for improving the bioavailability of NOR.

Nanosponges are a novel class of hyperbranched cyclodextrin-based nanostructures that exhibits remarkable potential as a drug host system for the improvement in biopharmaceutical properties. This work aims the development of cyclodextrin-based nanosponge of norfloxacin to improve its physicochemical characteristics. β-cyclodextrin was used as base and diphenyl carbonate as crosslinker agent at different proportions to produce nanosponges that were evaluated by in vitro and in vivo techniques. The proportion cyclodextrin:crosslinker 1:2 M/M was chosen due to its higher encapsulation efficiency (80%), revealing an average diameter size of 40 nm with zeta potential of -19 mV. Norfloxacin-loaded nanosponges exhibited higher passage of norfloxacin in comparison to norfloxacin drug alone by Ussing chamber method. The nanosponge formulation also revealed a mucoadhesive property that could increase norfloxacin absorption thus improving its antibiotic activity in an in vivo sepsis model. Therefore, nanosponges may be suitable carrier of norfloxacin to maximize and facilitate oral absorption., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: For the prevention of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites, norfloxacin 400 mg per day is recommended as a standard regimen. This study aims to investigate whether ciprofloxacin once weekly administration is not inferior to norfloxacin once daily administration for the prevention of SBP., Methods: This is an investigator-initiated open-label randomized controlled trial conducted at seven tertiary hospitals in South Korea. Liver cirrhosis patients with ascites were screened, and enrolled in this randomized controlled trial if ascitic protein ≤1.5 g/dL or the presence of history of SBP. Ascitic polymorphonucleated cell count needed to be <250/mm 3 . Patients were randomly assigned into norfloxacin daily or ciprofloxacin weekly group, and followed-up for 12 months. Primary endpoint was the prevention of SBP., Results: One hundred twenty-four patients met enrollment criteria and were assigned into each group by 1:1 ratio (62:62). Seven patients in the norfloxacin group and five patients in the ciprofloxacin group were lost to follow-up. SBP developed in four patients (4/55) and in three patients (3/57) in each group, respectively (7.3% vs. 5.3%, P = 0.712). The transplant-free survival rates at 1 year were comparable between the groups (72.7% vs. 73.7%, P = 0.970). Incidence of infectious complication, hepatorenal syndrome, hepatic encephalopathy, and variceal bleeding rates were not significantly different (all P = ns). The factors related to survival were models representing underlying liver function., Conclusion: Once weekly ciprofloxacin was as effective as daily norfloxacin for the prevention of SBP in cirrhotic patients with ascites.

Staphylococcus aureus is among the microorganisms more frequently associated with subclinical bovine mastitis. S. aureus may produce several virulence factors. This study aimed at determining the frequency of virulence factors such as enterotoxins, toxic shock syndrome toxin 1, and ica adhesion genes. In addition, we assessed antimicrobial drug resistance in S. aureus isolated from clinical and subclinical cases of mastitis. A total of 88 cows with clinical or subclinical mastitis were sampled, resulting in 38 S. aureus isolates, from which 25 (65.78%) carried toxin genes, including seb, sec, sed, tst, and icaD adhesion gene. These S. aureus isolates belong to 21 ribotypes and three S. aureus strains belonged to the same ribotype producing ica adhesion gene. Approximately 90% of S. aureus strains obtained in our study demonstrated multiple resistance to different antimicrobial agents. The most efficacious antimicrobial agents against the isolates were gentamicin, amoxicillin, and norfloxacin. Gentamicin was the most efficacious agent inhibiting 78.95% of the S. aureus isolates. The least efficacious were penicillin, streptomycin, and ampicillin. Our results can help in understanding the relationship between virulence factors and subclinical mastitis caused by S. aureus. Further research about diversity of S. aureus isolates and genes responsible for the pathogenicity of subclinical mastitis is essential.

Currently, accumulating evidence is challenging subtherapeutic therapy. Low-dose Norfloxacin (Nor) has been reported to suppress the immune response and worsen leptospirosis. In this study, we investigated the influence of low-dose Nor (0.03 μg/ml, 0.06 μg/ml, 0.125 μg/ml) on leptospiral gene expression and analyzed the immunomodulatory effects of low-dose Nor-treated leptospires in J774A.1 cells. To study the expression profiles of low-dose Nor-treated leptospires, we chose LipL71/LipL21 as reference genes determined by the geNorm applet in this experiment. The results showed that low-dose Nor up-regulated the expression of FlaB and inhibited the expression of 16S rRNA, LipL32, LipL41, Loa22, KdpA, and KdpB compared with the untreated leptospires. These results indicated that low-dose Nor could regulate leptospiral gene expression. Using RT-PCR, the gene expression of IL-1β and TNF-α in J774A.1 cells was detected. Nor-treated leptospires induced higher expression levels of both IL-1β and TNF-α. However, when analyzed by ELISA, the release of mature IL-1β was reduced compared with that observed in cells induced with no Nor-treated leptospires, although the TNF-α protein level showed no significant change. Our study indicated that the gene expression of leptospires could be modulated by low-dose Nor, which induced less IL-1β release in J774A.1 cells., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: The increasing emergence of resistant bacteria imposed an urgent request to discover novel antibacterial agents. This work was to develop naphthalimide nitroimidazoles as potentially antibacterial agents. Results/methodology: Compound 9e showed the strong antibacterial activity (minimal inhibitory concentration = 0.013 μmol/ml) against resistant Acinetobacter baumannii (A. baumannii) with rapid killing effect and no obvious triggering of the development of resistance. Its combination use with chloromycin, norfloxacin or clinafloxacin improved the antibacterial potency. It could not only effectively permeate membrane of resistant A. baumannii bacteria, but also intercalate into resistant A. baumannii DNA to form 9e-DNA complex. The interaction with bacterial DNA gyrase B was driven by hydrogen bonds., Conclusion: Compound 9e should be a potentially multitargeting antibacterial agent against resistant A. baumannii.

The disposition kinetics of norfloxacin, after intravenous, intramuscular and subcutaneous administration was determined in rabbits at a single dose of 10 mg/kg. Six New Zealand white rabbits of both sexes were treated with aqueous solution of norfloxacin (2%). A cross-over design was used in three phases (2 × 2 × 2), with two washout periods of 15 days. Plasma samples were collected up to 72 hr after treatment, snap-frozen at -45°C and analysed for norfloxacin concentrations using high-performance liquid chromatography. The terminal half-life for i.v., i.m. and s.c. routes was 3.18, 4.90 and 4.16 hr, respectively. Clearance value after i.v. dosing was 0.80 L/h·kg. After i.m. administration, the absolute bioavailability was (mean ± SD) 108.25 ± 12.98% and the C max was 3.68 mg/L. After s.c. administration, the absolute bioavailability was (mean ± SD) 84.08 ± 10.36% and the C max was 4.28 mg/L. As general adverse reactions were not observed in any rabbit and favourable pharmacokinetics were found, norfloxacin at 10 mg/kg after i.m. and s.c. dose could be effective in rabbits against micro-organisms with MIC ≤0.14 or 0.11 μg/mL, respectively., (© 2017 John Wiley & Sons Ltd.)

The present study was designed to investigate the solubility and penetrability of norfloxacin after the topical application of developed lipid-polymer hybrid nanoparticle (LPN) formulation. The core shell of the LPNs formulation was composed of poly (lactic-co-glycolic acid) that is highly lipophilic in nature, thus control the release of drug. The developed formulations were characterised for size, shape (transmission electron microscopy [TEM], scanning electron microscopy [SEM], and atomic force microscopy), entrapment efficiency, Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA). Moreover, in vitro skin permeation studies were performed to determine release profile of the drug. Norfloxacin loaded nanoparticles retained there antimicrobial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa. Stability study was suggested that the suitable storage condition should be at 4 ± 2 °C/60 ± 5% RH for the LPNs. Therefore, these nanoparticles showed a safe and effective long-lasting approach for long treatment of bacterial infections due to burn.

Antibiotics play an important role in the treatment of leptospirosis. Many antibiotics at appropriate concentrations improved the survival rate and alleviated tissue injury, while, when dosing strategies fall below subtherapeutic levels, worse therapeutic effects are seen. In the present study, we investigated the efficacy of low-dose norfloxacin (10, 20 and 30 mg/kg) and ciprofloxacin (1, 2 and 5 mg/kg) against leptospirosis in a hamster model using Leptospira interrogans serovar Icterohaemorrhagiae. The histopathology and bacterial loads of target organs (liver, kidney and lung) were also studied by treatment with norfloxacin at the dose of 10 mg/kg in this model. Using RT-PCR, the expression of inflammatory factor IL-1β and TNF-α was analyzed by comparing the norfloxacin and untreated group. All untreated animals, serving as a negative control, displayed 50% survival rate, while hamsters treated with norfloxacin at the dose of 10 and 20 mg/kg and ciprofloxacin at the dose of 1 and 2 mg/kg showed a lower survival rate than the untreated group. Furthermore, norfloxacin at the dose of 10 mg/kg increased bacterial loads and aggravated tissue injury of target organs. The delayed induction of IL-1β and TNF-α was found in tissues of norfloxacin group. Our study indicates an increased risk associated with low-dose norfloxacin and ciprofloxacin in leptospirosis., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

For nasal drug absorption, powder formulations can be expected to provide many advantages. The first aim of this study was to examine drug absorption following nasal administration of powder formulations in rats. Pharmaceutical excipients are typically added to most powder formulations. The second aim was to investigate the change in nasal drug absorption of powder formulations in the presence of sodium carboxymethyl cellulose (CMC-Na). Model drugs used were norfloxacin (NFX), warfarin (WF), and piroxicam (PXC). The absorption from bulk powders is different from that of solutions. The absorption of PXC and WF from powder formulations was enhanced compared to those of the other solutions, while that of NFX, which has a low solubility, was decreased, suggesting that the nasal absorption of many drugs, except poorly soluble drugs, is enhanced when they are administered as powder formulations. CMC-Na enhanced the absorption of NFX and PXC. The presence of CMC-Na slightly decreased the absorption of WF. In vitro transepithelial transport from the powder formulation was not affected by the presence of CMC-Na. Furthermore, the nasal retention of the powder formulation was significantly increased in the presence of CMC-Na. In conclusion, the nasal absorption of many drugs, except those that are poorly soluble, can be increased by administering them as a powder formulation and the nasal absorption of the formulation is enhanced further in the presence of CMC-Na.

Aims: To describe prescribing for women with suspected urinary tract infections, including suspected uncomplicated cystitis, in New Zealand., Methods: Randomly selected community pharmacies participated in the study. Women attending the pharmacy in a 2-week period in 2012 for prescribed or non-prescription treatment of symptoms suggesting a urinary tract infection, or prophylaxis of a urinary tract infection, were invited to self-complete a questionnaire. Analysis focused on prescribing for women with symptoms of cystitis without complicating features., Results: Valid questionnaires arising from a prescription treatment were received from 789 patients from 139 pharmacies. Questionnaire data indicated that 17% of women had symptoms of cystitis without complicating features. Most prescribing was for a first-line agent, trimethoprim (59%) or nitrofurantoin (14%), but norfloxacin was also common (21%). Women with self-reported antibiotic use for suspected cystitis in the past 6 months were more likely to be prescribed norfloxacin than those with no such use. Many prescriptions were for a dose or duration outside those recommended in New Zealand guidelines., Conclusions: While use of first-line agents is generally high, norfloxacin use could be reduced further. There is scope to understand clinical practice that deviates from guideline use regarding dose and duration.

Although it is well known that microbial populations can respond adaptively to challenges from antibiotics, empirical difficulties in distinguishing the roles of de novo mutation and natural selection have left several issues unresolved. Here, we explore the mutational properties of Escherichia coli exposed to long-term sublethal levels of the antibiotic norfloxacin, using a mutation accumulation design combined with whole-genome sequencing of replicate lines. The genome-wide mutation rate significantly increases with norfloxacin concentration. This response is associated with enhanced expression of error-prone DNA polymerases and may also involve indirect effects of norfloxacin on DNA mismatch and oxidative-damage repair. Moreover, we find that acquisition of antibiotic resistance can be enhanced solely by accelerated mutagenesis, i.e., without direct involvement of selection. Our results suggest that antibiotics may generally enhance the mutation rates of target cells, thereby accelerating the rate of adaptation not only to the antibiotic itself but to additional challenges faced by invasive pathogens.

Background and Aim: Primary prevention of spontaneous bacterial peritonitis (SBP) is an important strategy to reduce morbidity and mortality in cirrhotic patients with ascites. Efficacy and safety of alternating rifaximin and norfloxacin as primary prophylaxis is questionable., Methods: Three hundred thirty-four cirrhotic patients with high SAAG (≥1.1) ascites, protein level in ascitic fluid less than 1.5 g/dL with advanced liver disease (Child-Pugh score >9 points with serum bilirubin level >3 mg/dL) or renal impairment (serum creatinine level >1.2 mg/dL, blood urea nitrogen level >25 mg/dL, or serum sodium level <130 mEq/L) were included in an open-label, randomized study aimed at comparing alternating use of norfloxacin and rifaximin vs. norfloxacin or rifaximin alone as primary prophylaxis for SBP. Both intention-to-treat and per-protocol efficacy analyses were done after 6 months of treatment by assessment of ascitic fluid neutrophil count. Safety analysis was done for all intention-to-treat populations., Results: Alternating norfloxacin and rifaximin showed superior prophylaxis by intention-to-treat (74.7 vs. 56.4% vs. 68.3%, p < 0.048). Pairwise analysis showed that alternating regimen had lower probability to develop SBP when compared to a norfloxacin-based regimen in intention-to-treat (p = 0.016) and per protocol analysis (p = 0.039). There was no difference among the studied groups regarding the incidence and severity of adverse events reported., Conclusions: Alternating norfloxacin- and rifaximin-based primary prophylaxis for SBP showed higher efficacy with the same safety profile when compared with monotherapy of norfloxacin.

Biomaterial scaffolds are versatile tools as drug carrier for treatment of wounds. A series of norfloxacin-loaded scaffolds were synthesized for treatment of wounds by combining collagen with two different types of chitosan using freeze-drying technique. Subsequently, scaffolds were screened in terms of morphology, water absorption and retention capacity, biodegradation, ex-vivo bioadhesive strength, in-vitro drug release biological compatibility, X-ray diffractometry, differential scanning calorimetry as well as in-vivo evaluation. The results indicate that the scaffold mechanical strength is dependent on the type of used chitosan. The prepared scaffolds contained interconnected porous architecture. The scaffolds had high water uptake and retention capacity with extended biodegradation rate. Scaffolds prepared with chitosan HCl showed superior bioadhesive strength compared to those prepared with low molecular weight chitosan. All scaffolds showed almost 100% drug release within 24h. As identified by the terahertz pulsed imaging measurements, there is single scaffold area with the same concentration. After 28 days of wound dressing with selected norfoloxacin-loaded or unloaded collagen/chitosan scaffolds in Albino rats, it was found that the tissue regeneration time was fast compared to non-treated wounds. Furthermore, the drug-loaded scaffolds showed normal structure of an intact epidermal layer as well as the underlying dermis as revealed by histopathological studies. The obtained results suggest that the investigated norfloxacin-loaded collagen/chitosan scaffold is a potential candidate for skin regeneration application., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The use of norfloxacin either as primary or secondary prophylaxis of bacterial infections in advanced cirrhosis has improved patient's survival. This may be explained not only due to a significant decrease in the number of infections, but also because of a direct immunomodulatory effect. Selective intestinal decontamination with norfloxacin reduces translocation of either viable bacteria or bacteria-driven products from the intestinal lumen. In addition, norfloxacin directly modulates the systemic inflammatory response. The pro-inflammatory cytokine profile secreted by neutrophils from these patients shows a close, significant, and inverse correlation with serum norfloxacin levels. Similar effects have been described with other quinolones in different clinical conditions. Although the underlying mechanisms are not well defined for most of the antibiotics, the pathways triggered for norfloxacin to induce such immunomodulatory effects involve the down-regulation of pro-inflammatory inducible nitric oxide synthase, cyclooxygenase-2, and NF-κB and the up-regulation of heme-oxygenase 1 and IL-10 expression. The knowledge of these immunomodulatory effects, additional to their bactericidal role, improves our comprehension of the interaction between antibiotics and the cellular host response and offer new possibilities for the development of new therapeutic strategies to manage and prevent bacterial infections in cirrhosis.

Comparative pharmacokinetics of norfloxacin nicotinate (NFXNT) was investigated in common carp (Cyprinus carpio) and crucian carp (Carassius auratus) after a single oral dose of 10 mg/kg body weight (b.w.). Analyses of plasma samples were performed using ultra-performance liquid chromatography (UPLC) with fluorescence detection. After oral dose, plasma concentration-time curves of common carp and crucian carp were best described by a two-compartment open model with first-order absorption. The pharmacokinetic parameters of common carp were similar to those of crucian carp. The distribution half-life (t1/2α ), elimination half-life (t1/2β ), peak concentration (Cmax ), time-to-peak concentration (Tmax ), and area under the concentration-time curve (AUC) of common carp were 1.58 h, 26.33 h, 6069.79 μg/L, 1.08 h, and 103072.36 h·μg/L, respectively, and those corresponding to crucian carp were 1.36 h, 26.55 h, 9586.06 μg/L, 0.84 h, and 126604.4 h·μg/L, respectively. These studies demonstrated that 10 mg NFXNT/kg body weight in common carp and crucian carp following oral dose presented good pharmacokinetic characteristics., (© 2014 John Wiley & Sons Ltd.)

The aim of this study was to investigate the relationship between the administration of chitosan (CTS), expression of permeability glycoprotein (P-gp), and the metabolism of norfloxacin (NOR) in Grass Carp Ctenopharyngodon idella. Fish were administrated with a single dose of either NOR, CTS, 1:5 NOR-CTS or 1:10 NOR-CTS. The P-gp expression was analyzed by immunohistochemistry and real time-PCR. The concentration of NOR was determined using HPLC. The mRNA and protein expression of P-gp in the fish intestine was significantly enhanced following a single dosage of 40 mg/kg NOR, and peak expression occurred at 3 h after drug administration (P < 0.05). A single dosage of both 1:5 NOR-CTS and 1:10 NOR-CTS reduced the intestinal P-gp expression to levels significantly lower than that from NOR alone (P < 0.05), but significantly higher than that from the control (P < 0.05). Interestingly, CTS alone also led to a slight decrease in P-gp expression. In addition, pharmacokinetic assays revealed a marked increase in area under the curve (AUC) of NOR with 1:5 and 1:10 NOR-CTS, by approximately 1.5-fold and threefold, respectively. Finally, the relative bioavailability of NOR after a single oral dosage of 1:5 and 1:10 NOR-CTS was enhanced to 148.02% and 304.98%, respectively. In this study, we demonstrated that the transmembrane glycoprotein P-gp regulates NOR metabolism in the intestine of Grass Carp, suggesting that NOR may be a direct substrate of P-gp. More importantly, we showed that CTS can inhibit P-gp expression in a dose-dependent manner and improve the relative bioavailability of NOR in this species.

Background/aims: This study aimed to evaluate the efficacy and the immunomodulatory effect of rifaximin as another promising prophylactic therapy against spontaneous bacterial peritonitis (SBP) in cirrhotics., Materials and Methods: Seventy cirrhotic patients with ascites were included in the study. Patients were divided into two groups in a randomized single-blind fashion. Group one (n=40) received rifaximin and group two (n=30) received norfloxacin (control group). The treatment duration was 6 months. Serum levels of tumor necrosis factor alpha (TNF-α), interleukin-6 ( IL-6), and interleukin-10 (IL-10) were the primary inflammatory markers of the study to evaluate the effect of the medications used., Results: Three months after treatment, five cases on norfloxacin therapy showed SBP, whereas all cases on rifaxmine therapy were free from SBP. In addition, there was no significant difference between patients on rifaximin and norfloxacin therapy with respect to TNF-α, IL-6, and IL-10 serum levels (p>0.05). Furthermore, patients on both rifaximin and norfloxacin therapies showed a statistically significant decrease in TNF-α and IL-6 serum levels compared with their baseline levels (p=0.000 and p=0.000, respectively). In contrast, serum IL-10 showed a statistically significant increase in both groups in comparison with its baseline level (p>0.00). Six-month after treatment, patients on rifaximin therapy showed more effective remission from SBP than those on norfloxacin therapy., Conclusion: In conclusion, the use of rifaximin not only prevents bacterial translocation but also modulates the immune response of the inflammatory and the anti-inflammatory cytokines in SBP patients. However, the efficacy and the immunomodulatory effect of rifaximin in the prophylaxis of SBP in cirrhotics needs further prospective large-scale, double-blind studies.

Objective: The aim was to optimize norfloxacin niosomes for enhanced antibacterial activity and reduced bacterial resistance., Methods: Pseudomonas aeruginosa, a biofilm forming bacterium, was used as the test organism. Different norfloxacin niosomes were evaluated in vitro and in vivo, respectively, for antibacterial activity compared with aqueous drug solution. The influence of norfloxacin niosomes on biofilm formation was investigated. The interaction of niosomes with bacterial cells was also monitored using the scanning electron microscopy (SEM)., Results: The efficacy of niosomes depended on their composition. Standard niosomes of Span 60 and cholesterol were similar to drug solution. Incorporation of Tween 80, oleic acid (OA), OA/propylene glycol or lecithin produced fluid niosomes which reduced the MIC and inhibited biofilm formation compared with drug solution. Incorporation of a positively charged agent into fluid niosomes enhanced the antibacterial activity and reduced biofilm formation significantly. SEM showed evidence of vesicle adsorption to the bacteria with possible adhesion or fusion with the cell membrane. The in vivo skin model confirmed the in vitro results with optimum niosomes being more efficient than drug solution., Conclusion: Niosomes are promising for enhanced antibacterial activity and reduced resistance to antibiotics. The later can be achieved by inhibition of biofilm formation.

Bacterial resistance to antibiotics has become an increasing threat, requiring not only the development of new targets in drug discovery, but more importantly, a better understanding of cellular response. In the current study, three closely related Escherichia coli strains, a wild type (MG1655) and an isogenic pair derived from the wild type (DPB635 and DPB636) are studied following exposure to sub lethal concentrations of antibiotic (norfloxacin) over time. In particular, genotype similarities between the three strains were assessed based on the lipid regulation response (e.g. presence/absence and up/down regulation). Lipid identification was performed using direct surface probe analysis (matrix-assisted laser desorption/ionization, MALDI), coupled to high-resolution mass spectrometry (Fourier transform ion cyclotron resonance mass spectrometry, FT-ICR MS) followed by statistical analysis of variability and reproducibility across batches using internal standards. Inspection of the lipid profile showed that for the MG1655, DPB635 and DPB636 E. coli strains, a similar distribution of the altered lipids was observed after exposure to norfloxacin antibiotic (e.g. fatty acids and glycerol phospholipids are up and down regulated, respectively). Additionally, variations in the lipid distribution resemble the extent to which each strain can combat the antibiotic exposure. That is, the topA66 topoisomerase I mutation of DPB636 translates into diminished response related to antibiotic sensitivity when compared to MG1655 and the DPB635 strains., (Copyright © 2015 John Wiley & Sons, Ltd.)

Objective: To prospectively compare norfloxacin (N) with trimethoprim-sulfamethoxazole (T-S) in preventing infection in cirrhotic patients., Methods: Cirrhotic patients at high risk of spontaneous bacterial peritonitis (SBP) were recruited and assigned N (400 mg daily) or T-S (160/800 mg daily). Patients were followed up for 12 months. The primary end-point was the incidence of infection. Secondary end-points included the incidence of SBP, bacteremia, extraperitoneal infection requiring antibiotic treatment, liver transplantation, death, side effects and rate of resistance to N or T-S., Results: A total of 80 patients with a mean age of 53.0 ± 9.3 years were prescribed N (n = 40) or T-S (n = 40). Child-Pugh status, model for end-stage liver disease and risk factors for SBP were similar between the groups. There were 10 episodes of infections in the N group and 9 in the T-S group (P = 0.79). Two patients each in the N and T-S group developed SBP (P = 0.60). There was a difference in the rate of transplantation favoring N (P = 0.03) but not death. The number of adverse events for N (n = 7) and T-S (n = 10) were similar (P = 0.59), with T-S being associated with an increased risk of developing a definite or probable adverse event compared to N (22.5% vs 0%, P = 0.01)., Conclusions: This study failed to demonstrate a difference between N and T-S groups in their effects on preventing infection in patients with liver cirrhosis. T-S can be considered an alternative first-line therapy for infection prophylaxis., (© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

The study is devoted to the preparation of a multi-membrane gel system based on poly(N,N-dimethyl-acrylamide-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5) undecane) copolymer. The complex supra-structure was realized by layer by layer deposition technique, from the gel-core to the periphery by crosslinking poly(N,N-dimethyl-acrylamide-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5) undecane) (P(DMA-co-U)) with N,N'-methylene-bis-acrylamide and using as well β-cyclodextrin with double purpose as compound for constructing further the edge of the interfacial supramolecular assemblies and to improve the host-guest complexation of further bioactive compounds. Basic copolymer has dual thermo- and pH sensitive character. The multi-membrane 'onion-like' gel system was tested as matrix for embedding Norfloxacin. Hematologic, biochemical, immunologic studies used to determine the biocompatibility of multi-membrane gel structures loaded with drug that directly contact living tissue provided a reasonable assessment of safety as implants. Histopathologic exams did not reveal any disturbances of the normal liver architecture in animals with multi-membrane gel system containing Norfloxacin compared to control group with sterile cotton pellets implant. Good biocompatibility for the implants based on multi-membrane gel structures loaded with drug were achieved from the in vivo tests these suggesting that biomaterials may be suitable for in vivo use as a local drug delivery system., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objectives: This study intended to describe the development of two novel, biocompatible and potential surface hydroxylated quaternary ammonium chloride based poly(propylene imine) (PPI) dendrimers for effective delivery of the drug Norfloxacin (NFN)., Methods: The synthetic pathway involved the hydroxylation and methylation of generation 2 and 3 PPI dendrimers and thus produced surface hydroxylated and internally quaternised PPI dendrimers viz., QPPI-OH (G2) and QPPI-OH (G3), respectively. The potential of these dendrimers were examined as drug carrier for NFN, by carrying out solubility, in vitro release, cytotoxicity and anti-bacterial studies., Results: It was observed that the QPPI-OH (G2)/QPPI-OH (G3) dendrimers have excellent solubilising potential/drug loading abilities of NFN in aqueous medium and can also sustain delivery of NFN. The effective complexation of NFN with QPPI-OH (G2) and QPPI-OH (G3) increased the solubility of NFN and thus elevates the NFN drug from Class 4 to Class 3 (according to BCS). These dendrimers increase the biocompatibility and increase the tolerance concentration during drug-dendrimer formulations. Anti-bacterial studies showed that the efficacy of the drug was increased in the presence of dendrimer carriers., Conclusions: These results indicate that the QPPI-OH (G2) and QPPI-OH (G3) dendrimers might be considered as potential biocompatible drug carriers of fluoroquinolines under suitable conditions.

A multi-walled carbon nano tube (MWCNT) modified pyrolytic graphite (MPG) electrode is prepared and applied to detect norfloxacin (NFX) based on its electrochemical reduction. The experimental parameters affecting the NFX determination were optimized in terms of MWCNT amount, pH, reaction time, and square wave frequency. The dynamic range for the NFX analysis ranged between 1.2 and 1000µM with a detection limit of 40.6±3.3nM. The effect of NFX on the catabolism of caffeine has been studied by determining its concentration in the urine samples after the prolonged administration of NFX using the MPG electrode. The results show that the catabolism of caffeine is inhibited by ~65% after five days of NFX administration, consequently the caffeine concentration in the urine sample is increased, which is reflected in terms of ~2.5 times increase in the peak current of caffeine. The determinations of NFX and caffeine were selective and the method was successfully applied in biological fluids and pharmaceutical tablets for the test compound analysis. In future this method can be useful for the selective determination of NFX and studying its effect on caffeine catabolism., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background & Objectives: Several chemical compounds isolated from natural sources have antibacterial activity and some enhance the antibacterial activity of antibiotics reversing the natural resistance of bacteria to certain antibiotics. In this study, the hexane and methanol extract of Cordia verbenaceae were assessed for antibacterial activity alone and combinated with norfloxacin against the Staphylococcus aureus strain SA1199B., Methods: The minimum inhibitory concentration (MIC) of extracts was assayed using microdilution assay and the modulatory activity was evaluated using plate diffusion assay., Results: The MIC observed varied between 256 to >1024 μg/ml. However, the antibiotic activity of norfloxacin was enhanced in the presence of subinhibitory concentrations of hexane extract of C. verbenaceae (HECV). INTERPRETATIONS & CONCLUSIONS: Our results indicate that Cordia verbenaceae DC. can be a source of plant derived products with antibiotic modifying activity.

Purpose: To report the effect of repeated corneal swabbing in patients with microsporidial keratoconjunctivitis., Design: Retrospective noncomparative case series., Methods: Sixteen eyes of 14 healthy patients with microsporidial keratoconjunctivitis were diagnosed based on the detection of microsporidia in corneal scrapings using Gram stain, the modified Kinyoun acid-fast stain, or both. Polymerase chain reaction plus gene analysis of the microsporidian 16S ribosomal RNA had been performed in 10 patients who sought treatment between 2010 and 2011. Some of the lesions were scraped for procurement of specimens. The remaining lesions were wiped off gently by cotton swabs. Repeated swabbing was performed if infection persisted or new lesions were observed at follow-up. To prevent secondary bacterial infection, 0.3% norfloxacin or 0.25 % chloramphenicol were prescribed., Results: The mean age was 52.2 years. All patients had the characteristic disseminated, punctate, slightly elevated, white epithelial lesions. The denser white lesions could be removed easily after gentle swabbing, and most epithelium remained intact. The 10 cases with positive polymerase chain reaction results were all identified to be Vittaforma corneae. The mean number of corneal swabbing was 3.3, and the mean disease resolution time was 6.6 days. No patients had recurrence or loss of visual acuity at last follow-up., Conclusions: Repeated swabbing effectively can eradicate corneal epithelial microsporidial lesions in approximately 1 week. It is easy to perform, less painful, and more acceptable for the patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Cataracts treatment usually involves the extraction of the opaque crystalline lens and its replacement by an intraocular lens (IOL). A serious complication is the occurrence of endophthalmitis, a post-surgery infection mainly caused by Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa. IOLs having the ability to load and to release norfloxacin in a controlled way and at efficient therapeutic levels may help to overcome these issues. In this work, acrylic hydrogels combining 2-hydroxyethyl methacrylate (HEMA) and 2-butoxyethyl methacrylate (BEM) at various ratios were prepared to attain biocompatible networks that can be foldable even in the dry state and thus insertable through minor ocular incision, and that load therapeutic amounts of norfloxacin. Acrylamide (AAm) and methacrylic acid (MAAc) were also incorporated as functional comonomers in small proportions. Water sorption, contact angle, protein adsorption, and optical properties of the networks were characterized. BEM notably decreased the T(g) of the networks, but also the loading by immersion in aqueous solution (presoaking). Then, a scCO(2)-based impregnation/deposition (SSI) method was implemented to improve the uptake of the drug. Loading capacities were discussed in terms of the comonomers composition and the employed method and operational conditions. The networks prepared with HEMA/BEM 20:80 vol/vol and processed with supercritical fluids combine adequate mechanical properties, biocompatibility and norfloxacin loading/release, and seem to be suitable for developing norfloxacin-eluting IOLs., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A comparative study has evaluated the effect of fluoroquinolones and beta-lactams on clinical and biochemical manifestations of chronic pyelonephritis (CPN). 108 patients aged from 18 to 59 years (mean age - 40.26 +/- 10.09 years) with secondary CPN against dysmetabolic nephropathy and nephrolithiasis in a phase of active inflammation were observed. The majority of patients were women - 89 (82.4%). CPN was diagnosed in accordance with the N.A. Lopatkin and V.E. Rodoman clinical classification (1974) based on results of complete clinical and laboratory, radiologic and ultrasound examinations. Special methods of investigation included determination of the activity of lipid peroxidation, antioxidant system and the structural parameters of the cell membrane ofpolymorphonuclear leukocytes (PMN). Pain, dysuria, and intoxication syndrome were arrested in all patients after 14 days of therapy. The high efficacy was reported for patients treated with sparfloxacin. A similar trend was observed in the dynamics of intoxication syndrome regression. In addition, there was a significant reduction of lipid peroxidation products and an increase of alpha-tocopherol in the PMN membranes; the content of phospholipids significantly increased and cholesterol level declined during the treatment. The results showed that use of fluoroquinolones and the B-lactams in the treatment of patients with CPN against the nephrolithiasis leads to a significant relief of clinical symptoms of the disease, as well as to restoration the structural and functional state of PMN membranes. The most distinct and early clinical-laboratory effect was obtained against the background of use of fluoroquinolone sparfloxacin.

Present study was designed to establish in-vitro and in-vivo correlation (IVIVC) of two immediate release tablet formulations of 400mg Norfloxacin [Drug A as test and Drug B as reference]. Dissolution study was conducted in 0.1 N HCl using USP apparatus II. In-vivo evaluation was carried out in 18 healthy humans according to a single dose, two-sequence, and cross-over randomized with a wash-out period of one week. After dosing, serial blood samples were collected for a period of 10 hours. Plasma harvested from blood, was analyzed for norfloxacin by a sensitive, reproducible and accurate HPLC method. Various pharmacokinetic parameters were determined from plasma concentrations for both the formulations. Non-significant difference was found for test/reference ratio of these parameters and the value of F was found to be 0.99 which is in good agreement with the limits given in FDA and WHO guidelines for such parameters. Difference factor (f(1)), similarity factor (f(2)) and level A IVIVC were evaluated showing that drug A is bioequivalent to drug B.

Purpose: To develop a simple, novel polymeric drug-delivery device for prevention of postoperative bacterial infection after cataract surgery in the developing world., Methods: A poly(2-hydroxyethyl-methacrylate) (pHEMA) hydrogel was developed to achieve sustained release characteristics of antibiotics. The in vitro antibiotic release kinetics and efficacy of antibiotic function were tested using a silicone biofilm model. In vivo feasibility was investigated using a rabbit model. The control group of rabbits underwent standard cataract surgery with intraocular lens (IOL) implant and postoperative topical antibiotic and steroid. The experimental group received the polymeric device inserted with standard three-piece IOL at the time of surgery and received only topical steroids postoperatively. In vivo intraocular antibiotic levels and outcomes after cataract surgery were evaluated., Results: The in vitro studies demonstrate the antibiotic release kinetics can be controlled by optimization of the surface coating. The in vivo results showed sustained sufficient antibiotic concentration (above minimum inhibitory concentration for most common bacteria related to endophthalmitis) for >4 weeks. There was minimum toxicity observed in vivo. The device was effective in treating induced intraocular infection after cataract surgery., Conclusions: The initial findings of the polymeric drug-delivery device demonstrate the feasibility delivering sufficient antibiotic in the anterior chamber for the immediate postoperative period in a rabbit model. The device is simple to produce and may help alleviate the potential postsurgical infections in the developing nations.

Few new drugs are available against methicillin-resistant Staphylococcus aureus (MRSA), because MRSA has the ability to acquire resistance to most antibiotics, which consequently increases the cost of medication. The objective of this study is to evaluate the potentiation of sanguinarine (SN) with selected antibiotics (ampicillin [AC], oxacillin [OX], norfloxacin [NR], ciprofloxacin [CP], and vancomycin [VC]) against MRSA. Minimum inhibitory concentration was determined by using the broth microdilution method and the synergistic effect of AC, OX, NR, CP, and VC in combination with SN was examined by the checkerboard dilution test. The results of the checkerboard test suggested that all combinations exhibited some synergy, partial synergy, or additivity. None of the combinations showed an antagonism effect. The combination of SN plus CP exhibited maximum synergistic effect in 11/13 strains, followed by SN plus NR in 9/13 strains, and AC and OX in 7/13 strains each. The combination of SN with VC, however, mostly showed partial synergy in 11/13 strains. The time-kill assay showed that SN in combination with other antibiotics reduced the bacterial count by 10(2)-10(3) colony forming units after 4 h and to less than the lowest detectable limit after 24 h. Although in vivo synergy and clinical efficacy of SN cannot be predicted, it can be concluded that SN has the potential to restore the effectiveness of the selected antibiotics, and it can be considered in an alternative MRSA treatment.

This work aims to develop norfloxacin-solid lipid nanoparticles (NFX-SLN) as an oral delivery formulation. Hot homogenization and ultrasonic technique was employed to prepare NFX-SLN using stearic acid as lipid matrix and polyvinyl alcohol as surfactant. The physicochemical characteristics of SLN were investigated by optical microscope scanning electron microscopy and photon correlation spectroscopy. Antibacterial experiments of NFX-SLN were carried out by broth dilution technique. Pharmacokinetics was studied after oral administration in male Sprague-Dawley rats. The results showed that NFX-SLN was spherical and the SLN of the optimized formulation had diameters 301 ± 16.64 nm, polydispersity index 0.15 ± 0.04, zeta potential -30.8 ± 0.69 mv, loading capacity 8.58 ± 0.21% and encapsulation efficiency 92.35 ± 2.24% with good stability at 4 °C. The NFX-SLN had sustained release effect and sustained bactericidal activity. Cytotoxicity studies in cell culture demonstrated that the nanoparticles were not toxic. NFX-SLN resulted in significantly higher plasma drug concentration than native NFX. The SLN increased the relative bioavailability of NFX by 12 folds, prolonged the plasma drug level above the average minimum inhibition concentration from 14 to 168 h. These studies demonstrate that NFX-SLN could be a promising oral formulation for enhanced bioavailability and pharmacological activities.

Biomaterial-centred bacterial infections present common and challenging complications with medical implants like ureteral stent which provide substratum for the biofilm formation. Hence the purpose of this study is to make antibacterial stent surface with biodegradable polymer (tocopherol acetate) and anti-infective agents (norfloxacin and metronidazole) using a modified dip-coating procedure. This is done by impregnating the stent pieces in the anti-infective solution (a mixture of norfloxacin-metronidazole and polymer) for uniform surface coating (drug-carrier-coated stents). After coating, agar diffusion test was performed as qualitative test to find out the sensitivity of coated stents against the clinical isolates, Staphylococcus epidermidis and Escherichia coli. Quantitative test was measured by calculating the numbers of adhered bacteria on coated and uncoated stents by incubating the stent pieces in artificial urine. Difference in the number of viable bacteria adhered on the surface of coated and uncoated stents were statistically calculated using chi square test with p < 0.05 considered significant. The stent colonising ability of Staphylococcus epidermidis and Escherichia coli in a controlled environment chamber was determined using two-challenge dose of the isolates by in vitro challenge test. In qualitative test, the zone of inhibition around the coated stents showed sensitivity against the clinical isolates. In quantitative test, the number of adhered bacteria on the surface of coated stents was reduced to a significant level (p < 0.05). The polymer, tocopherol acetate is highly biodegradable in nature. Due to its degrading ability in body tissues, it releases the anti-infective drugs at a constant and sustained rate.

The aim of this research was to design and study norfloxacin (NFX) release in floating conditions from compressed hydrophilic matrices of hydroxypropylmethylcellulose (HPMC) or poly(ethylene oxide) (PEO). Module assembling technology for drug delivery system manufacturing was used. Two differently cylindrical base curved matrix/modules, identified as female and male, were assembled in void configuration by friction interlocking their concave bases obtaining a floating release system. Drug release and floatation behavior of this assembly was investigated. Due to the higher surface area exposed to the release medium, faster release was observed for individual modules compared to their assembled configuration, independently on the polymer used and concentration. The release curves analyzed using the Korsmeyer exponential equation and Peppas & Sahlin binomial equation showed that the drug release was controlled both by drug diffusion and polymer relaxation or erosion mechanisms. However, convective transport was predominant with PEO and at low content of polymers. NFX release from PEO polymeric matrix was more erosion dependent than HPMC. The assembled systems were able to float in vitro for up to 240min, indicating that this drug delivery system of norfloxacin could provide gastro-retentive site-specific release for increasing norfloxacin bioavailability., (Copyright © 2010. Published by Elsevier B.V.)

Background & Aims: The hepatopulmonary syndrome occurs in up to one-third of patients with cirrhosis. Animal models of this disease suggest that endotoxemia might cause nitric oxide-mediated vascular dilatation that can be inhibited by the antibiotic norfloxacin. We sought to test this hypothesis in humans., Methods: We conducted a pilot randomized, controlled crossover trial of norfloxacin 400 mg twice daily for 4 weeks with a 4-week washout period to assess the feasibility of a larger trial. The primary clinical end point was change in alveolar-arterial oxygen gradient (AaDO₂)., Results: Recruitment was challenging, and change in AaDO₂ was highly variable. We recruited 9 adults (1 woman; age, 60 ± 9 years; AaDO₂, 50 ± 22 mm Hg). AaDO₂ decreased by 0.8 ± 4.8 and 3.4 ± 12.4 mm Hg while on norfloxacin and placebo, respectively (P = .59)., Conclusions: Recruitment difficulties and variability of the primary outcome measure suggest the need for a multicenter clinical research network for future therapeutic trials in this disease. There was no major effect of norfloxacin on gas exchange in patients with hepatopulmonary syndrome., (Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Efficacy and tolerance of furamag and norbactin were compared in a prospective controlled trial with participation of 82 females aged 18-60 years with acute uncomplicated cystitis. All the women were divided into two groups. Group 1 (n=42) received norbactin (norfloxacin) in a dose 400 mg twice a day for 7 days. Group 2 (n=40) was given furamag in a dose 50 mg 3 times a day for 10 days. The results were evaluated 2 weeks after the treatment. The comparison of the treatment results showed that a new nitrofuranic drug furamag has significantly higher clinical and bacteriological efficacy: acute cystitis was cured in 95% patients, eradication of the infective agent occurred in 96.4% patients, tolerance was good in 97.5% patients. Sensitivity of the agents causing acute cystitis to nitrofurans reached 98.2% while to norbactin--only 86%.

Intraocular lens implantation after opacified natural lens removal is the primary treatment for cataracts in developed countries. Cataract surgery is generally considered safe, but entails significant risks in countries where sophisticated sterile operating theaters are not widely available. Post-operative infection (endophthalmitis) is a potential blinding complication. Infection often results from bacterial colonization of the new lens implant and subsequent antibiotic-tolerant biofilm formation. To combat this risk, we developed a polymeric hydrogel system that can deliver effective levels of antibiotic over an extended period of time within the globe of the eye. Norfloxacin antibiotic was loaded into cross-linked poly(2-hydroxyethyl methacrylate) (pHEMA) gels, which were subsequently surface-modified with octadecyl isocyanate to produce a hydrophobic rate-limiting barrier controlling norfloxacin release. Octadecyl surface modification was characterized using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). A 15-min modification leads to a uniform surface coating and near zero order release of norfloxacin from the matrix. Norfloxacin released from coated pHEMA kills Staphylococcus epidermidis in suspension and on a simulated medical implant surface. With these data, we demonstrate a new and effective system for sustained drug release from a hydrogel matrix with specific application for intraocular lens surgery.