Design and evaluation of ocular hydrogel containing combination of ofloxacin and dexamethasone for the treatment of conjunctivitis

Abstract Conjunctivitis is an inflammation of the conjunctiva, which covers the white part of the eyeball. It can be caused by allergies, bacterial or viral infection. In situ hydrogels are three-dimensional hydrophilic cross-linked network of polymers. In situ hydrogel provided better therapeutic index when compared to conventional treatment. The present work describes the formulation and evaluation of ofloxacin and dexamethasone based on the concept of pH triggered in situ gelation. Carbopol 934p was used as the gelling agent in combination with HPMC, as a viscosity-enhancing agent, benzalkonium chloride as preservative, sodium chloride as tonicity adjusting agent. The prepared formulations were liquid at the low pH and underwent rapid transition into viscous gel at the pH of the tear fluid. Formulations were evaluated for various rheological, in vitro and in vivo release characteristics. Infrared spectroscopy studies showed that there were no interactions between the drug and polymers. Viscosity of the prepared hydrogels lies in the optimum range and drug was released up to 85 % as the end of 13 h. The prepared in situ hydrogel was sterile, non-irritant to the eye. The present study indicated that it is possible to develop safe and physiologically effective in situ hydrogel which is patient compliant.

Urrets-Zavalia Syndrome Following Trabeculectomy

PURPOSE: We report a case of Urrets-Zavalia syndrome with a fixed dilated pupil after an uneventful trabeculectomy.CASE SUMMARY: Trabeculectomy was performed on a 51-year-old male who had a history of recurrent uveitis in the left eye, with uncontrolled intraocular pressure despite maximally-tolerated medial therapy. There was no unexpected event during surgery. Topical 1% atropine was used for only 2 days after surgery. In the early postoperative period, 1% prednisolone and 0.3% ofloxacin were given four times a day, then gradually reduced. One month later, only 1% prednisolone was given once a day. Intraocular pressure in his left eye was well controlled from 8–14 mmHg after surgery. One month after surgery, the pupils remained dilated. There was no reaction to topical 2% pilocarpine and no relative afferent pupillary defect or posterior synechia.CONCLUSIONS: Our case, although rare, suggests that Urrets-Zavalia syndrome should be considered in patients with well-controlled intraocular pressure after uneventful trabeculectomy.

Preparation and characterization of novel, mucoadhesive ofloxacin nanoparticles for ocular drug delivery

The efficacy of conventional ocular formulations is limited by poor corneal retention and permeation, resulting in low ocular bioavailability. Mucoadhesive chitosan (CS)/ tripolyphosphatesodium (TPP) and chitosan (CS)/ tripolyphosphatesodium (TPP)-alginate (ALG) nanoparticles were investigated for the prolonged topical ophthalmic delivery of ofloxacin. A modified ionotropic gelation method was used to produce ofloxacin-loaded nanoreservoir systems. The ofloxacin-loaded CS/TPP and CS/TPP-ALG nanoparticles were characterized for particle size, morphology, zeta potential, encapsulation efficiency, subsequent release and corneal penetration study. The designed nanoparticles have a particle size from 113.8 nm to 509 nm and zeta potential from 16.2 mV to 40.3 mV and encapsulation efficiency values ranging from 19.7% to 33.1%. Nanoparticles revealed a release during the first hours, followed by a more gradual drug release. The ofloxacin-loading CS/TPP or CS/TPP-ALG NPs developed are pronounced penetration enhancing effect as compared to OFX solution (5-6.5 times). Thus, these nanoparticles have a strong potential for ocular drug delivery.

Predictors of mortality in multidrug-resistant tuberculosis patients from Brazilian reference centers, 2005 to 2012

ABSTRACT Objectives To determine the main predictors of death in multidrug-resistant (MDRTB) patients from Brazil. Design Retrospective cohort study, a survival analysis of patients treated between 2005 and 2012. Results Of 3802 individuals included in study, 64.7% were men, mean age was 39 (1-93) years, and 70.3% had bilateral pulmonary disease. Prevalence of human immunodeficiency virus (HIV) was 8.3%. There were 479 (12.6%) deaths. Median survival time was 1452 days (4 years). Factors associated with increased risk of death were age greater than or equal to 60 years (hazard rate [HR] = 1.6, confidence interval [CI] = 1.15-2.2), HIV co-infection (HR = 1.46; CI = 1.05-1.96), XDR resistance pattern (HR = 1.74, CI = 1.05-2.9), beginning of treatment after failure (HR = 1.72, CI = 1.27-2.32), drug abuse (HR = 1.64, CI = 1.22-2.2), resistance to ethambutol (HR = 1.30, CI = 1.06-1.6) or streptomycin (HR = 1.24, CI = 1.01-1.51). Mainly protective factors were presence of only pulmonary disease (HR = 0.57, CI = 0.35-0.92), moxifloxacin use (HR = 0.44, CI = 0.25-0.80), and levofloxacin use (HR = 0.75; CI = 0.60-0.94). Conclusion A more comprehensive approach is needed to manage MDRTB, addressing early diagnostic, improving adhesion, and comorbidities, mainly HIV infection and drug abuse. The latest generation quinolones have an important effect in improving survival in MDRTB.

Resistência de Neisseria gonorrhoeae a antimicrobianos na prática clínica: como está o Brasil? / Antimicrobials resistance of Neisseria gonorrhoeae in clinical practice: where Brazil stands?

Estima-se que um milhão de infecções sexualmente transmissíveis (IST) sejam adquiridas por dia no mundo, segundo a Organização Mundial da Saúde. Elas podem ser causadas por diversos micro-organismos pelo contato sexual. Embora tratáveis, as infecções, como a clamidiana, sífilis, tricomoníase e gonorreia, são responsáveis por 350 milhões de novos casos de IST anualmente no mundo. A gonorreia é a segunda IST bacteriana mais prevalente no planeta e tem chamado atenção nos últimos anos em decorrência da baixa eficácia em seu tratamento. O agente etiológico é a Neisseria gonorrhoeae. Na maioria das mulheres, a infecção por esse micro-organismo é assintomática, dificultando ainda mais seu diagnóstico e tratamento e, portanto, aumentando o risco de desenvolvimento de suas complicações associadas. Mesmo quando diagnosticada, essa infecção está sujeita a um alto índice de insucesso terapêutico que se deve, principalmente, à grande plasticidade genética da N. gonorrhoeae para aquisição de genes cromossômicos ou plasmidiais de resistência. O aumento da resistência desse micro-organismo a antimicrobianos comumente utilizados no tratamento, como penicilina, tetraciclina e ciprofloxacina, tem sido relatado em diversos países. No Brasil, poucos estudos estão disponíveis, mas em alguns estados já foram relatadas linhagens resistentes à ciprofloxacina. Dessa forma, deve-se ressaltar a importância de novos estudos que visem descrever o perfil da resistência da N. gonorrhoeae a antimicrobianos. Tais achados certamente nortearão a implementação de sistemas de vigilância epidemiológica no país visto que, até o momento, as infecções por N. gonorrhoeae sequer estão incluídas na lista nacional de doenças e agravos de notificação compulsória.(AU)

According to the World Health Organization, approximately one million sexually transmitted infections (STI) are acquired daily in the world. These infections can be caused by several microorganisms via contact. The treatable STI, such as chlamydia, syphilis, trichomoniasis and gonorrhea, account for 350 million new cases of STI each year worldwide. Gonorrhoea is caused by Neisseria gonorrhoeae and is the second most common bacterial STI in the world. It has drawn more attention in the last years due to the low efficacy in its treatment. Most women with this infection are asymptomatic, which makes its diagnosis and treatment troublesome increasing the risk for its associated complications. Even when diagnosed, this infection is subject to a high rate of therapeutic failure mainly due to the great genetic plasticity of N. gonorrhoeae for the acquisition of chromosomal or resistance plasmid enes. Increased resistance of this microorganism to antimicrobials commonly used in treatment such as penicillin, tetracycline and ciprofloxacin has been reported in several countries. In Brazil, few studies are available, but in some states strains resistant to ciprofloxacin were alreadyreported. The refore, it is important to highlight the importance of new studies aimed at describing the resistance profile of N. gonorrhoeae to antimicrobials in Brazil context. These findings will certainly guide the implementation of epidemiological surveillance systems in the country, since until now N. gonorrhoeae infections do not figure into the national list of compulsorily notifiable diseases.(AU)

Utilização de lente de contato escleral na abordagem terapêutica da úlcera neurotrófica corneana / Use of scleral contact lens in the therapeutic approach of corneal neurotrophic ulcer

Resumo Neste artigo descrevemos como conduzimos com sucesso um caso de úlcera neurotrófica não responsivo à terapia convencional com o uso de lente de contato escleral e as vantagens desta terapêutica.

Abstract In this paper we describe how we successfully conducted a case of neurotrophic ulcer not responsive to conventional therapy using scleral contact lens and the advantages of this therapy.

Adverse drug reaction monitoring during antimicrobial therapy for septicemia patients at a university hospital in New Delhi

BACKGROUND/AIMS: Adverse drug reaction (ADR) is an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product. The present study was conducted in order to monitor the frequency and severity of ADR during antimicrobial therapy of septicemia. METHODS: A prospective, observational, and noncomparative study was conducted over a period of 6 months on patients of septicemia admitted at a university hospital. Naranjo algorithm scale was used for causality assessment. Severity assessment was done by Hartwig severity scale. RESULTS: ADRs in selected hospitalized patients of septicemia was found to be in 26.5% of the study population. During the study period, 12 ADRs were confirmed occurring in 9, out of 34 admitted patients. Pediatric patients experienced maximum ADRs, 44.4%. Females experienced a significantly higher incidence of ADRs, 66.7%. According to Naranjo’s probability scale, 8.3% of ADRs were found to be definite, 58.3% as probable, and 33.3% as possible. A higher proportion of these ADRs, 66.7% were preventable in nature. Severity assessment showed that more than half of ADRs were moderate. Teicoplanin was found to be the commonest antimicrobial agent associated with ADRs, followed by gemifloxacin and ofloxacin. CONCLUSIONS: The incidence and severity of ADRs observed in the present study was substantially high indicating the need of extra vigilant during the antimicrobial therapy of septicemia.

Concurrent Use of Sulfonylureas and Antimicrobials of the Elderly in Korea: A Potential Risk of Hypoglycemia

BACKGROUND: Previous studies have noted that the simultaneous use of sulfonylureas and antimicrobials, which is common, could increase the risk of hypoglycemia. In particular, an age of 65 years or older is a known risk factor for sulfonylurea-related hypoglycemia in hospitalized patients. Therefore, we performed this study to determine the potential risk of hypoglycemia from the concurrent use of antimicrobials and sulfonylureas. METHODS: We performed a cross-sectional study on the National Health Insurance Service-National Sample Cohort from 2013. The eligibility criteria included patients of 65 years of age or older taking a sulfonylurea with 25 different antimicrobials. Different risk ratings of severity in drug-drug interactions (potential DDIs), level X, D, or C in Lexi-Interact™online, and contraindicated, major, or moderate severity level in Micromedex® were included. SAS version 9.4 was used for data analysis. RESULTS: A total of 6,006 elderly patients with 25,613 prescriptions were included. The largest age group was 70 to 74 (32.7%), and 39.7% of patients were men. The mean number of prescriptions was 4.3 per patient. The most frequently used antimicrobials were levofloxacin (6,583, 25.7%), ofloxacin (6,549, 25.6%), fluconazole (4,678, 18.0%), and ciprofloxacin (2,551, 9.8%). Among sulfonylureas, glimepiride was prescribed most frequently, followed by gliclazide, glibenclamide, and glipizide. CONCLUSION: Of the antimicrobials with a high potential of hypoglycemia, levofloxacin, ofloxacin, fluconazole, and ciprofloxacin were used frequently. Thus, the monitoring of clinically relevant interactions is required for patients concurrently administered sulfonylureas and antimicrobials.

Determining Genotypic Drug Resistance by Ion Semiconductor Sequencing With the Ion AmpliSeq™ TB Panel in Multidrug-Resistant Mycobacterium tuberculosis Isolates

BACKGROUND: We examined the feasibility of a full-length gene analysis for the drug resistance-related genes inhA, katG, rpoB, pncA, rpsL, embB, eis, and gyrA using ion semiconductor next-generation sequencing (NGS) and compared the results with those obtained from conventional phenotypic drug susceptibility testing (DST) in multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates. METHODS: We extracted genomic DNA from 30 pure MDR-TB isolates with antibiotic susceptibility profiles confirmed by phenotypic DST for isoniazid (INH), rifampin (RIF), ethambutol (EMB), pyrazinamide (PZA), amikacin (AMK), kanamycin (KM), streptomycin (SM), and fluoroquinolones (FQs) including ofloxacin, moxifloxacin, and levofloxacin. Enriched ion spheres were loaded onto Ion PI Chip v3, with 30 samples on a chip per sequencing run, and Ion Torrent sequencing was conducted using the Ion AmpliSeq TB panel (Life Technologies, USA). RESULTS: The genotypic DST results revealed good agreement with the phenotypic DST results for EMB (Kappa 0.8), PZA (0.734), SM (0.769), and FQ (0.783). Agreements for INH, RIF, and AMK+KM were not estimated because all isolates were phenotypically resistant to INH and RIF, and all isolates were phenotypically and genotypically susceptible to AMK+KM. Moreover, 17 novel variants were identified: six (p.Gly169Ser, p.Ala256Thr, p.Ser383Pro, p.Gln439Arg, p.Tyr597Cys, p.Thr625Ala) in katG, one (p.Tyr113Phe) in inhA, five (p.Val170Phe, p.Thr400Ala, p.Met434Val, p.Glu812Gly, p.Phe971Leu) in rpoB, two (p.Tyr319Asp and p.His1002Arg) in embB, and three (p.Cys14Gly, p.Asp63Ala, p.Gly162Ser) in pncA. CONCLUSIONS: Ion semiconductor NGS could detect reported and novel amino acid changes in full coding regions of eight drug resistance-related genes. However, genotypic DST should be complemented and validated by phenotypic DSTs.

Antibacterial and Pharmacological Evaluation of Fluoroquinolones: A Chemoinformatics Approach

Fluoroquinolone (FQ) antibiotics are an important class of synthetic antibacterial agents. These are the most extensively used drugs for treating bacterial infections in the field of both human and veterinary medicine. Herein, the antibacterial and pharmacological properties of four fluoroquinolones: lomefloxacin, norfloxacin, ciprofloxacin, and ofloxacin have been studied. The objective of this study was to analyze the antibacterial characteristics of the different fluoroquinolones. Also, the pharmacological properties of the compounds including the Lipinski rule of five, absorption, distribution, metabolism, and excretion, LD50, drug likeliness, and toxicity were evaluated. We found that among all four FQ molecules, ofloxacin showed the highest antibacterial activity through in silico assays with a strong interaction (−38.52 kJ/mol) with the antibacterial target protein (topoisomerase-II DNA gyrase enzyme). The pharmacological and pharmacokinetic analysis also showed that the compounds ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin have good pharmacological properties. Notably, ofloxacin was found to possess an IGC50 (concentration needed to inhibit 50% growth) value of 0.286 μg/L against the Tetrahymena pyriformis protozoa. It also tested negative for the Ames toxicity test, showing its non-carcinogenic character.

Periocular Allergic Contact Dermatitis Associated with the Use of Ofloxacin Ophthalmic Ointment: A Case Report / 대한피부과학회지

Allergic contact dermatitis is an inflammatory condition associated with periorbital erythema, edema, and pruritus. The periorbital skin is relatively thin compared with the skin over other facial areas; therefore, it is vulnerable to allergen penetration and may show a variety of cutaneous manifestations. Recently, vision enhancement surgery is a widely performed procedure, and the prevalence of senile cataract and glaucoma is increasing. The prevalence of periocular allergic contact dermatitis is increasing secondary to the growing use of topical ophthalmic medications. Several studies in Korea have reported periocular allergic contact dermatitis secondary to the use of topical ophthalmic medications including latanoprost (Latano®), fluorometholone (Tolon®), polymyxin B (Terramycin®), atropine sulfate (Atropine®), neomycin sulfate (Cambison®), and befunolol hydrochloride (Bentos®), among others. However, ofloxacin (Effexin®)-induced allergic contact dermatitis has not been reported in the domestic and/or foreign literature. We report a case of periocular allergic contact dermatitis secondary to the use of ofloxacin ophthalmic ointment.

Síntesis de nanopartículas de ácido poliláctico cargadas con antibióticos y su actividad antibacteriana contra Escherichia coli O157:H7 y Staphylococcus aureus resistente a meticilina / Synthesis of antibiotic loaded polylactic acid nanoparticles and their antibacterial activity against Escherichia coli O157:H7 and methicillin-resistant Staphylococcus aureus

Resumen Introducción: Las nanopartículas poliméricas constituyen una herramienta nanotecnológica que podría ayudar a combatir los microorganismos patógenos que han desarrollado resistencia a los antibióticos convencionales. Objetivo: Sintetizar nanopartículas de ácido poliláctico cargadas con ofloxacina y vancomicina, y determinar su actividad antibacteriana frente a Escherichia coli O157:H7 y Staphylococcus aureus resistente a la meticilina (SARM). Materiales y métodos: Las nanopartículas de ácido poliláctico cargadas con ofloxacina y vancomicina se sintetizaron utilizando el método de emulsión y evaporación de solvente. Se caracterizaron mediante dispersión de luz en modo dinámico, electroforesis Doppler con láser y microscopía electrónica de barrido (S-TEM). Se evaluó la actividad antibacteriana in vitro de las nanopartículas de ácido poliláctico con ofloxacina contra E. coli O157:H7 y nanopartículas de ácido poliláctico con vancomicina contra SARM, mediante el método de microdilución en caldo. Resultados: Se obtuvieron nanopartículas poliméricas con tamaños inferiores a 379 nm y carga superficial positiva de hasta 21 mV. Las nanopartículas cargadas con ofloxacina presentaron una concentración inhibitoria mínima (CIM50) de 0,001 μg/ml frente a E. coli O157:H7, valor 40 veces menor que la concentración de antibiótico libre necesaria para lograr el mismo efecto (CIM50=0,04 μg/ml). Para SARM, las nanopartículas mejoraron la potencia farmacológica in vitro de la vancomicina al exhibir una MIC50 de 0,005 μg/ml, comparada con la de 0,5 μg/ml del antibiótico libre. Conclusiones: Se mejoró el efecto antibacteriano de la ofloxacina y la vancomicina incorporadas en la matriz polimérica de ácido poliláctico. Las nanopartículas poliméricas constituirían una alternativa para el control de cepas bacterianas de interés en salud pública.

Abstract Introduction: Polymeric nanoparticles are promising nanotechnology tools to fight pathogenic bacteria resistant to conventional antibiotics. Objective: To synthesize polylactic acid nanoparticles loaded with ofloxacin and vancomycin, and to determine their antibacterial activity against Escherichia coli O157:H7 and methicillin-resistant Staphylococcus aureus (MRSA). Materials and methods: We synthesized ofloxacin or vancomycin loaded polylactic acid nanoparticles by the emulsification-solvent evaporation method, and characterized them by dynamic light scattering, laser Doppler electrophoresis and scanning electron microscopy. We evaluated in vitro antibacterial activity of ofloxacin- and vancomycin-loaded polylactic acid nanoparticles against E. coli O157:H7 and MRSA using the broth microdilution method. Results: Ofloxacin- and vancomycin-loaded polylactic acid nanoparticles registered a positive surface charge density of 21 mV and an average size lower than 379 nm. In vitro minimum inhibitory concentration (MIC50) of ofloxacin-polylactic acid nanoparticles was 0,001 μg/ml against E. coli O157:H7, i.e., 40 times lower than the free ofloxacin (MIC50: 0.04 μg/ml), indicating enhanced antibacterial activity while the in vitro MIC50 of vancomycin-polylactic acid nanoparticles was 0,005 μg/ml against MRSA, i.e., 100 times lower than that of free vancomycin (MIC50: 0.5 μg/ml). Conclusion: Polylactic acid nanoparticles loaded with ofloxacin and vancomycin showed a higher antibacterial activity. Polymeric nanoparticles are a possible alternative for drug design against pathogenic bacterial strains of public health interest.

Usefulness of In Vivo and In Vitro Diagnostic Tests in the Diagnosis of Hypersensitivity Reactions to Quinolones and in the Evaluation of Cross-Reactivity: A Comprehensive Study Including the Latest Quinolone Gemifloxacin

PURPOSE: Reports evaluating diagnosis and cross reactivity of quinolone hypersensitivity have revealed contradictory results. Furthermore, there are no reports investigating the cross-reactivity between gemifloxacin (GFX) and the others. We aimed to detect the usefulness of diagnostic tests of hypersensitivity reactions to quinolones and to evaluate the cross reactivity between different quinolones including the latest quinolone GFX. METHODS: We studied 54 patients (mean age 42.31±10.39 years; 47 female) with 57 hypersensitivity reactions due to different quinolones and 10 nonatopic quinolone tolerable control subjects. A detailed clinical history, skin test (ST), and single-blind placebo-controlled drug provocation test (SBPCDPT), as well as basophil activation test (BAT) and lymphocyte transformation test (LTT) were performed with the culprit and alternative quinolones including ciprofloxacin (CFX), moxifloxacin (MFX), levofloxacin (LFX), ofloxacin (OFX), and GFX. RESULTS: The majority (75.9%) of the patients reported immediate type reactions to various quinolones. The most common culprit drug was CFX (52.6%) and the most common reaction type was urticaria (26.3%). A quarter of the patients (24.1%) reacted to SBPCDPTs, although their STs were negative; while false ST positivity was 3.5% and ST/SBPCDPTs concordance was only 1.8%. Both BAT and LTT were not found useful in quinolone hypersensitivity. Cross-reactivity was primarily observed between LFX and OFX (50.0%), whereas it was the least between MFX and the others, and in GFX hypersensitive patients the degree of cross-reactivity to the other quinolones was 16.7%. CONCLUSIONS: These results suggest that STs, BAT, and LTT are not supportive in the diagnosis of a hypersensitivity reaction to quinolone as well as in the prediction of cross-reactivity. Drug provocation tests (DPTs) are necessary to identify both culprit and alternative quinolones.

High Dose Ofloxacin-induced Bimodal Hallucinations in a 4 Years Old Child

Ofloxacin is a commonly used quinolone antibiotic both in adults as well as children. It is generally safe and well tolerated. Rarely, neurological and psychiatric adverse reactions are reported to occur with ofloxacin. We report a case of a child who developed delirium after ofloxacin treatment, that resolved after medication discontinuation and treatment with low dose olanzapine.

Low Levels of Extensively Drug-resistant Tuberculosis among Multidrug Resistant Tuberculosis Isolates and Their Relationship to Risk Factors: Surveillance in Tehran, Iran; 2006 to 2014

OBJECTIVES: Extensively drug-resistant tuberculosis (XDR-TB) is more expensive and difficult to treat than multidrug-resistant tuberculosis (MDR-TB), and outcomes for patients are much worse; therefore, it is important that clinicians understand the magnitude and distribution of XDR-TB. We conducted a retrospective study to compare the estimated incidence of and risk factors for M/XDR-TB with those of susceptible TB controls. METHODS: Sputum culture and drug susceptibility testing (DST) were performed in patients with known or suspected TB. Strains that were identified as MDR were subjected to DST for second-line drugs using the proportion method. RESULTS: Among 1,442 TB patients (mean age, 46.48 ± 21.24 years) who were culture-positive for Mycobacterium tuberculosis, 1,126 (78.1%) yielded isolates that were resistant to at least one first-line drug; there were 33 isolates (2.3%) of MDR-TB, of which three (0.2%) were classified as XDR-TB. Ofloxacin resistance was found in 10 (0.7%) isolates. Women were 15% more likely than men to yield M/XDR-TB isolates, but this difference was not significant. In a multivariate analysis comparing susceptible TB with X/MDR-TB, only one variable—the number of previous treatment regimens—was associated with MDR (odds ratio, 1.06; 95% confidence interval, 1.14–21.2). CONCLUSION: The burden of M/XDR-TB cases is not sizeable in Iran. Nonetheless, strategies must be implemented to identify and cure patients with pre-XDR-TB before they develop XDR-TB. Our results provide a greater understanding of the evolution and spread of M/XDR-TB in an environment where drug-resistant TB has a low incidence.

Penetration of 0. 3% ciprofloxacin, 0. 3% ofloxacin, and 0. 5% moxifloxacin into the cornea and aqueous humor of enucleated human eyes

We aimed to quantify the penetration of ciprofloxacin, ofloxacin, and moxifloxacin into the cornea and aqueous humor of cadaver eyes. A total of 60 enucleated eyes, not eligible for corneal transplantation, were divided into three groups and immersed in commercial solutions of 0.3% ciprofloxacin, 0.3% ofloxacin, or 0.5% moxifloxacin for 10 min. Whole corneas and samples of aqueous humor were then harvested and frozen, and drug concentrations analyzed by liquid chromatography tandem mass spectrometry. The mean corneal concentration of moxifloxacin was twice as high as ofloxacin, and the latter was twice as high as ciprofloxacin. The mean concentration of moxifloxacin in the aqueous humor was four times higher than the other antibiotics, and the mean concentrations of ciprofloxacin and ofloxacin were statistically similar. The amount of drug that penetrated the anterior chamber after a 10-min immersion was far below the safe limit of endothelial toxicity of each preparation. Moxifloxacin demonstrated far superior penetration into the cornea and anterior chamber of cadaver eyes compared to ciprofloxacin and ofloxacin. One should not expect endothelial toxicity with the commercial eye drops of ciprofloxacin, ofloxacin, and moxifloxacin that reach the anterior chamber through the cornea.

Quinolone susceptibility and genetic characterization of Salmonella enterica subsp. enterica isolated from pet turtles / 한국실험동물학회지

Turtle-borne Salmonella enterica owns significance as a leading cause in human salmonellosis. The current study aimed to determine the quinolone susceptibility and the genetic characteristics of 21 strains of S. enterica subsp. enterica isolated from pet turtles. Susceptibility of four antimicrobials including nalidixic acid, ciprofloxacin, ofloxacin, and levofloxacin was examined in disk diffusion and MIC tests where the majority of the isolates were susceptible to all tested quinolones. In genetic characterization, none of the isolates were positive for qnr or aac(6')-Ib genes and no any target site mutations could be detected in gyrA, gyrB, and parC quinolone resistance determining regions (QRDR). In addition, neighbor-joining phylogenetic tree derived using gyrA gene sequences exhibited two distinct clads comprising; first, current study isolates, and second, quinolone-resistant isolates of human and animal origin. All results suggest that studied strains of S. enterica subsp. enterica isolated from pet turtles are susceptible to quinolones and genetically more conserved with regards to gyrA gene region.

Current Status of Fluoroquinolone Use for Treatment of Tuberculosis in a Tertiary Care Hospital in Korea / 결핵및호흡기질환

BACKGROUND: Fluoroquinolones are considered important substitutes for the treatment of tuberculosis. This study investigates the current status of fluoroquinolone for the treatment of tuberculosis. METHODS: In 2009, a retrospective analysis was performed at one tertiary referral center for 953 patients diagnosed with tuberculosis. RESULTS: A total of 226 patients (23.6%), who received fluoroquinolone at any time during treatment for tuberculosis, were enrolled in this study. The most common reasons for fluoroquinolone use were adverse events due to other anti-tuberculosis drugs (52.7%), drug resistance (23.5%), and underlying diseases (16.8%). Moxifloxacin (54.0%, 122/226) was the most commonly administered fluoroquinolone, followed by levofloxacin (36.3%, 82/226) and ofloxacin (9.7%, 22/226). The frequency of total adverse events from fluoroquinolone-containing anti-tuberculosis medication was 22.6%, whereas fluoroquinolone-related adverse events were estimated to be 2.2% (5/226). The most common fluoroquinolone-related adverse events were gastrointestinal problems (3.5%, 8/226). There were no significant differences in the treatment success rate between the fluoroquinolone and fluoroquinolone-naïve groups (78.3% vs. 78.4%, respectively). CONCLUSION: At our institution, fluoroquinolones are commonly used for the treatment of both multidrug-resistant tuberculosis and susceptible tuberculosis, especially as a substitute for adverse event-related drugs. Considering the low adverse event rates and the comparable treatment success rates, fluoroquinolones seem to be an invaluable drug for the treatment of tuberculosis.

Development and evaluation of bilayer tablets of combination of antibiotics for the treatment of sexually transmitted disease

ABSTRACT The present research work was envisaged to develop bilayer tablets to improve therapeutic efficacy of antibiotic combination for the treatment of sexually transmitted diseases. The combination of two antibiotics i.e. cefixime trihydrate and ofloxacin were used for the preparation of bilayer tablets which act against genito-urinary infections. The formulations comprise of cefixime trihydrate as immediate release layer formulated using different superdisintegrants and ofloxacin as extended release layer containing HPMC K100M. Evaluation of bilayer tablets were performed for the immediate release cefixime layer and sustain release ofloxacin layer with optimization of excipients. The immediate release layer of cefixime showed complete release within 30 min and ofloxacin release was extended up to 24 hours. The similarity factor value of ofloxacin sustained release layer was found to be 87.01 for initial and 80.35 after 3 months stability when compared with marketed reference product. The present study revealed that cefixime trihydrate and ofloxacin bilayer tablets were successfully developed for the use against sexually transmitted infections.