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This study explores the utilization of adsorption and advanced oxidation processes for the degradation of ofloxacin (OFL) and ciprofloxacin (CIP) using a green functionalized carbon nanotube (MWCNT-OH/COOH-E) as adsorbent and catalyst material. The stability and catalytic activity of the solid material were proved by FT-IR and TG/DTG, which also helped to elucidate the reaction mechanisms. In adsorption kinetic studies, both antibiotics showed similar behavior, with an equilibrium at 30 min and 60% removal. The adsorption kinetic data of both antibiotics were well described by the pseudo-first-order (PFO) model. Different advanced oxidation processes (AOPs) were used, and the photolytic degradation was not satisfactory, whereas heterogeneous photocatalysis showed high degradation (⁓ 70%), both processes with 30 min of reaction. Nevertheless, ozonation and catalytic ozonation have resulted in the highest efficiencies, 90%, and 70%, respectively, after 30-min reaction. For AOP data modeling, the first-order model better described CIP and OFL in photocatalytic and ozonation process. Intermediates were detected by MS-MS analysis, such as P313, P330, and P277 for ciprofloxacin and P391 and P332 for ofloxacin. The toxicity test demonstrated that a lower acute toxicity was observed for the photocatalysis method samples, with only 3.1 and 1.5 TU for CIP and OFL, respectively, thus being a promising method for its degradation, due to its lower risk of inducing the proliferation of bacterial resistance in an aquatic environment. Ultimately, the analysis of MWCNT reusability showed good performance for 2 cycles and regeneration of MWCNT with ozone confirmed its effectiveness up to 3 cycles.

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This paper investigated the uptake of CIP and OFL in single and multicomponent adsorptive systems using modified carbon nanotubes (CNTs) as adsorbent material. The characterization analyses of the pre- and post-process material by XPS, TG/DTG, FT-IR, SEM/EDS, and XRD helped in the elucidation of the mechanisms, indicating greater involvement of n-n and π -π interactions. In the kinetic studies, the simple systems with CIP and OFL were similar, both showed equilibrium time around 20/30 min and increased adsorptive capacity with increasing initial drug concentration. In the multicomponent system, different fractions of CIP and OFL were tested and the time to reach equilibrium also varied between 20 and 30 min. In general, the adsorption capacity of CIP is slightly lower than that of OFL under the conditions tested. The selectivity analysis of the system showed that the selectivity's of the two drugs are identical in equimolar fractions. The mathematical modeling of the kinetic data indicated that in monocomponent systems, the model of pseudo-second order (PSO) adequately described both CIP and OFL kinetics. Furthermore, with the implementation of Artificial Neural Networks (ANN), it was possible to obtain a more assertive prediction of the behavior of single and binary systems.

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Removal of emerging contaminants, such as antibiotics, from wastewater by adsorption is a simple, low-cost, and high-performance process; however, regeneration and reuse of the exhausted adsorbent are necessary to make the process economically viable. This study aimed to investigate the possibility of electrochemical-based regeneration of clay-type materials. For this, the calcined Verde-lodo (CVL) clay was saturated with the antibiotics ofloxacin (OFL) and ciprofloxacin (CIP) in one-component systems by an adsorption process and then subjected to photo-assisted electrochemical oxidation (0.45 A, 0.05 mol/L NaCl, UV-254 nm, and 60 min), which promotes both pollutant degradation and adsorbent regeneration. The external surface of the CVL clay was investigated by X-ray photoelectron spectroscopy before and after the adsorption process. The influence of regeneration time was evaluated for the CVL clay/OFL and CVL clay/CIP systems, and the results demonstrate high regeneration efficiencies after 1 h of photo-assisted electrochemical oxidation. Clay stability during regeneration was investigated by four successive cycles in different aqueous matrices (ultrapure water, synthetic urine, and river water). The results indicated that the CVL clay is relatively stable under the photo-assisted electrochemical regeneration process. Furthermore, CVL clay was able to remove antibiotics even in the presence of natural interfering agents. The hybrid adsorption/oxidation process applied here demonstrated the electrochemical-based regeneration potential of CVL clay for the treatment of emerging contaminants, since it can be operated quickly (1h of treatment) and with lower consumption of energy (3.93 kWh kg-1) than the traditional method of thermal regeneration (10 kWh kg-1).

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There are several techniques for the removal of pharmaceuticals (drugs) from wastewater; however, strengths and weaknesses have been observed in their elimination processes that limit their applicability. Therefore, we aimed to evaluate the best techniques for the removal of pharmaceuticals from municipal and hospital wastewater. For this, a non-experimental, descriptive, qualitative-quantitative design was used, corresponding to a systematic review without meta-analysis. Based on established inclusion and exclusion criteria, 31 open-access articles were selected from the Scopus, ProQuest, EBSCOhost, and ScienceDirect databases. The results showed that high concentrations of analgesics such as naproxen (1.37 mg/L) and antibiotics such as norfloxacin (0.561 mg/L) are frequently found in wastewater and that techniques such as reverse osmosis, ozonation, and activated sludge have the best removal efficiency, achieving values of 99%. It was concluded that reverse osmosis is one of the most efficient techniques for eliminating ofloxacin, sulfamethoxazole, carbamazepine, and diclofenac from municipal wastewater, with removal rates ranging from 96 to 99.9%, while for hospital wastewater the activated sludge technique proved to be efficient, eliminating analgesics and antibiotics in the range of 41-99%.

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A new electrode was prepared based on functionalized graphene and gold nanoparticles dispersed in a chitosan film. Such an electrochemical sensor determines ofloxacin in the presence of dopamine, paracetamol, and caffeine. Characterization (morphological and electrochemical) was done using scanning electron microscopy, electrochemical impedance spectroscopy, and cyclic voltammetry. The sensor design improved the analytical signal, the electrochemical activity, and the electron transfer rate. Ofloxacin was determined by square-wave voltammetry, with a linear concentration range of 0.10-4.9 µmol L-1 (r = 0.999, LOD = 12 nmol L-1). The proposed sensor showed good repeatability and selectivity and was applied successfully to the determination of ofloxacin in pharmaceutical formulations, synthetic urine, and water river samples. The proposed method proved to be excellent; therefore, it is an alternative method for the determination of ofloxacin.

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INTRODUCTION: Traumatic large tympanic membrane perforations usually fail to heal and require longer healing times. Few studies have compared the healing and hearing outcomes between gelatin sponge patching and ofloxacin otic solution. OBJECTIVES: To compare the healing outcomes of large traumatic tympanic membrane perforations treated with gelatin sponge, ofloxacin otic solution, and spontaneous healing. METHODS: Traumatic tympanic membrane perforations >50% of the entire eardrum were randomly divided into three groups: ofloxacin otic solution, gelatin sponge patch and spontaneous healing groups. The healing outcome and hearing gain were compared between the three groups at 6 months. RESULTS: A total of 136 patients with large traumatic tympanic membrane perforations were included in analyses. The closure rates were 97.6% (40/41), 87.2% (41/47), and 79.2% (38/48) in the ofloxacin otic solution, gelatin sponge patch, and spontaneous healing groups, respectively (p=0.041). The mean times to closure were 13.12±4.61, 16.47±6.24, and 49.51±18.22 days in these groups, respectively (p<0.001). CONCLUSIONS: Gelatin sponge patch and ofloxacin otic solution may serve as effective and inexpensive treatment strategies for traumatic large tympanic membrane perforations. However, ofloxacin otic solution must be self-applied daily to keep the perforation edge moist, while gelatin sponge patching requires periodic removal and re-patching.

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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.

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The search for new antibacterial agents has become urgent due to the exponential growth of bacterial resistance to antibiotics. Nitrogen-containing heterocycles such as 1,8-naphthyridine derivatives have been shown to have excellent antimicrobial properties. Therefore, the purpose of this study was to evaluate the antibacterial and antibiotic-modulating activities of 1,8-naphthyridine derivatives against multi-resistant bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the following compounds: 7-acetamido-1,8-naphthyridin-4(1H)-one and 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide. The antibiotic-modulating activity was analyzed using subinhibitory concentrations (MIC/8) of these compounds in combination with norfloxacin, ofloxacin, and lomefloxacin. Multi-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were used in both tests. Although the compounds had no direct antibacterial activity (MIC ≥ 1.024 µg/mL), they could decrease the MIC of these fluoroquinolones, indicating synergism was obtained from the association of the compounds. These results suggest the existence of a structure-activity relationship in this group of compounds with regard to the modulation of antibiotic activity. Therefore, we conclude that 1,8-naphthyridine derivatives potentiate the activity of fluoroquinolone antibiotics against multi-resistant bacterial strains, and thereby interesting candidates for the development of drugs against bacterial infections caused by multidrug resistant strains.

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Although multidrug therapy is considered an effective treatment for leprosy, antimicrobial resistance is a serious concern. We performed a systematic review of studies on the diagnostic accuracy and screening of tests for antimicrobial resistance in leprosy. This review was registered in PROSPERO (CRD42020177958). In April 2020, we searched for studies in the PubMed, EMBASE, Web of Science, Scopus, Scielo, and LILACS databases. A random effects regression model was used for the meta-analysis. We included 129 studies. Molecular tests for dapsone resistance had a sensitivity of 78.8% (95% confidence interval [CI] = 65.6−87.9) and a specificity of 97.0% (95% CI = 94.0−98.6). Molecular tests for rifampicin resistance had a sensitivity and specificity of 88.7% (95% CI = 80.0−93.9) and 97.3% (95% CI = 94.3−98.8), respectively. Molecular tests for ofloxacin resistance had a sensitivity and specificity of 80.9% (95% CI = 60.1−92.3) and 96.1% (95% CI = 90.2−98.5), respectively. In recent decades, no increase in the resistance proportion was detected. However, the growing number of resistant cases is still a clinical concern(AU).

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A hanseníase é uma doença infectocontagiosa crônica causada pelo Mycobacterium leprae (M. leprae). Manifesta-se, principalmente, por lesões de pele com alteração de sensibilidade térmica, dolorosa e tátil, decorrentes da predileção de seu agente etiológico por células cutâneas e nervosas periféricas. No mundo, em 2018, foram reportados à Organização Mundial da Saúde (OMS), 208.619 casos novos; desses, 28.660 foram notificados no Brasil, sendo o segundo país com maior número detectado. Acredita-se que a transmissão e infecção ocorram através de secreções provenientes das vias aéreas superiores, pelo contato íntimo e prolongado de indivíduo suscetível com paciente multibacilar sem tratamento, por meio da inalação dos bacilos. O tratamento preconizado pela OMS consiste na associação de três medicamentos ­ dapsona (DDS), rifampicina (RFP) e clofazimina (CLO) ­ com o objetivo de atuar na prevenção da seleção de cepas mutantes do M. leprae resistentes a uma ou mais drogas utilizadas. A ofloxacina (OFLO) é usada como esquema alternativo ao tratamento padrão, associando-se a RFP e CLO, sendo útil nos casos de resistência medicamentosa ou intolerância a uma das drogas. O bacilo não se reproduz em meios de cultura artificiais ou celulares ­ obstáculo para o avanço em estudos do patógeno. Em 1960, Charles Shepard, demonstrou pela primeira vez a multiplicação do M. leprae em coxim plantar de camundongo imunocompetente, técnica considerada marco na pesquisa do bacilo, propiciando a verificação de sua viabilidade e uma possível resistência às drogas utilizadas no tratamento da doença. O presente estudo teve como objetivo validar o método fenotípico, por meio da inoculação do bacilo em coxim plantar posterior de camundongos imunocompetentes da linhagem BALB/c (técnica de Shepard), para detecção de sensibilidade à CLO e OFLO. Os animais foram inoculados com suspensão de bacilos obtidos de camundongos nude mouse atímicos previamente infectados com a cepa Thai53, que possui perfil genético de sensibilidade às drogas, e divididos em grupo controle (não tratado), RFP (10mg/kg), CLO (50mg/kg) e OFLO (150mg/kg). Após cinco meses de inoculação e tratamento, os animais foram eutanasiados, e os coxins excisados para contagem do número de bacilos e análise histopatológica. No grupo controle, o número de bacilos recuperados foi maior que 1,0x105 /coxim, compatível com multiplicação bacilar; a análise histopatológica evidenciou infiltrado inflamatório intenso com bacilos agrupados ou em globias, íntegros e bem corados. Nos grupos tratados, não foi observada evidência de multiplicação bacilar, mostrando sensibilidade às drogas testadas; a análise histopatológica evidenciou infiltrado inflamatório discreto a moderado com ausência de bacilos. A técnica de Shepard é considerada padrão ouro para a multiplicação do bacilo, sendo fundamental para validar a identificação de novos alvos de mutação em genes determinantes da ação das drogas anti-hansênicas. Os resultados gerados no presente estudo terão grande impacto, principalmente para compreender a falha terapêutica em pacientes com recidiva que não apresentaram perfil de resistência pelos mecanismos moleculares até o momento descritos para a doença.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae). It is mainly manifested by skin lesions with changes in thermal, sensory and tactile sensitivity resulting from the predilection of its etiologic agent by skin and peripheral nerve cells. The World Health Organization (WHO) reported 208,619 new cases in 2018 worldwide; among these, 28,660 were reported in Brazil, the second country with the highest number detected. It is believed that transmission and infection occur by inhaling bacilli through the upper airways, while in close and prolonged contact of a susceptible individual with an untreated multibacillary patient. The treatment recommended by the WHO consists of the combination of three drugs -dapsone (DDS), rifampicin (RFP) and clofazimine (CLO) - in order to prevent the selection of mutant M. leprae strains resistant to one or more drugs. Ofloxacin (OFLO) is used as an alternative regimen to standard treatment, in association with RFP and CLO, being useful in cases of drug resistance or intolerance to one of the drugs. The bacillus does not reproduce in artificial or cellular culture media - an obstacle to progress in studies of the pathogen. In 1960, Charles Shepard, demonstrated for the first time the multiplication of M. leprae in an immunocompetent mouse footpad, a technique considered a landmark in the bacillus research, enabling the verification of its viability and a possible resistance to drugs used in the treatment of the disease. The present study aimed to validate the phenotypic method, by inoculating the bacillus in the hind footpads of immunocompetent BALB/c mice strain (Shepard's technique), to detect sensitivity to CLO and OFLO. The animals were inoculated with a suspension of bacilli obtained from athymic nude mouse previously infected with the Thai-53 strain, a sensitive strain. Mice were divided into a control (untreated), RFP (10mg / kg), CLO (50mg / kg) and OFLO (150mg / kg) groups. After five months of inoculation and treatment, the animals were euthanized and the foopads excised for enumeration of bacilli and histopathological analysis. In the control group, the number of bacilli recovered was greater than 1.0x105 /footpad, compatible with bacillary multiplication; histopathological analysis showed an intense inflammatory infiltrate with well stained grouped bacilli and globi. In the treated groups, there was no evidence of bacillary multiplication, showing sensitivity to the drugs tested; histopathological analysis showed mild to moderate inflammatory infiltrate with no bacilli. The Shepard technique is considered the gold standard for bacillus multiplication, being essential to validate the identification of new mutation targets in genes that determine anti-leprosy drugs activity. The results generated in the present study will have a great impact, mainly to understand the therapeutic failure in patients with recurrence who did not present a resistance profile using molecular mechanisms described so far for the disease.

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