Efetividade e segurança do regime de tratamento contendo gemifloxacino no tratamento de primeira linha para Helicobacter pylori / Efficacy and safety of gemifloxacin containing treatment regimen in first-line treatment of helicobacter pylori

ABSTRACT Background: After eradication of Helicobacter pylori (H. pylori) chronic gastritis will resolve, complications due to H. pylori infection and recurrence of infection will be prevented. Objective: To determine efficacy and safety of gemifloxacin containing treatment regimen in first line treatment of H. pylori with comparison to bismuth containing quadruple therapy. Methods: This retrospective study was conducted in a tertiary care university hospital between January 2018 and January 2021 with 410 participants who were diagnosed to have H. pylori infection with biopsies obtained during upper gastrointestinal system endoscopy. Patients were distributed into two groups according to their first-line treatment regimens. First group patients were treated with amoxicillin, gemifloxacin and pantoprazole and second group patients were treated with amoxicillin, metronidazole, bismuth subcitrate and pantoprazole for seven days. Results: Intention to treat and per protocol ratios for gemifloxacin containing regimen were 90.0% and 91.2%, while quadruple treatment has these ratios as 91.7% and 93.8% respectively. Treatment success rate in both regimens were similar. But adverse effects were lower and patient compliance were better in patients who had gemifloxacin containing treatment (P<0.001). Conclusion: Gemifloxacin containing treatment regimen is as effective as bismuth containing quadruple treatment regimen for H. pylori infection and patient compliance is better in this group. Gemifloxacin containing treatment regimens may be novel and effective alternatives for eradication of H. pylori infection.

RESUMO Contexto: Após a erradicação do Helicobacter pylori (HP), a gastrite crônica será resolvida, as complicações devido à infecção por HP e a recorrência da infecção serão prevenidas. Objetivo: Determinar a eficácia e segurança do regime de tratamento contendo gemifloxacino no tratamento de primeira linha do HP, em comparação com a terapia quádrupla contendo bismuto. Métodos: Este estudo prospectivo foi conduzido em um hospital universitário de atendimento terciário entre janeiro de 2018 e janeiro de 2021, com 410 participantes diagnosticados com infecção por HP, obtidos por meio de biópsias durante a endoscopia do sistema gastrointestinal superior. Os pacientes foram divididos em dois grupos de acordo com seus regimes de tratamento de primeira linha. Os pacientes do primeiro grupo foram tratados com amoxicilina, gemifloxacino e pantoprazol, e os pacientes do segundo grupo foram tratados com amoxicilina, metronidazol, subcitrato de bismuto e pantoprazol por 7 dias. Resultados: As taxas de intenção de tratar e por protocolo para o regime contendo gemifloxacino foram de 90,0% e 91,2%, enquanto o tratamento quádruplo apresentou essas taxas como 91,7% e 93,8%, respectivamente. A taxa de sucesso do tratamento em ambos os regimes foi similar. No entanto, os efeitos adversos foram menores e a adesão dos pacientes foi melhor nos que receberam o tratamento contendo gemifloxacino (P<0,001). Conclusão: O regime de tratamento contendo gemifloxacino é tão eficaz quanto o regime de tratamento quádruplo contendo bismuto para a infecção por HP, e a adesão dos pacientes é melhor neste grupo. Os regimes de tratamento contendo gemifloxacino podem ser alternativas novas e eficazes para a erradicação da infecção por HP.

Monitoring fluoroquinolone resistance among ESBL-positive and ESBL-negative Escherichia coli strains isolated from urinary tract infections: An alert for empirical treatment

ABSTRACT Background: Bacterial resistance to extended-spectrum beta-lactamases (ESBL) is present worldwide. Empirical antibiotic therapy is often needed, and the use of fluoroquinolones, such as ciprofloxacin and norfloxacin, is common. This study aimed to analyze the urine cultures from 2,680 outpatients in January 2019, 2020, 2021, and 2022, with bacterial counts above 100,000 CFU/mL in which Escherichia coli was the etiological agent. Methods: We monitored the resistance of ESBL-positive and ESBL-negative strains to ciprofloxacin and norfloxacin and evaluated resistance rates. Results: Significantly higher fluoroquinolone resistance rates were observed among ESBL-positive strains in all years studied. Furthermore, a significant increase in the rate of fluoroquinolone resistance was observed between 2021 and 2022 in ESBL-positive and -negative strains, as well as from 2020 to 2021 among the ESBL-positive strains. Conclusions: The data obtained in the present study showed a tendency towards an increase in fluoroquinolone resistance among ESBL-positive and -negative E. coli strains isolated from urine cultures in Brazil. Since empirical antibiotic therapy with fluoroquinolones is commonly used to treat diverse types of infections, such as community-acquired urinary tract infections, this work highlights the need for continuous monitoring of fluoroquinolone resistance among E. coli strains circulating in the community, which can mitigate the frequency of therapeutic failures and development of widespread multidrug-resistant strains.

Glycogen synthase kinase-3 (GSK-3) a magic enzyme: it's role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review / Glicogênio sintase quinase-3 (GSK-3), uma enzima mágica: seu papel no diabetes mellitus e na homeostase da glicose: interações com fluoroquinolonas. Uma mini-revisão

Abstract Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer's disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.

Resumo O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis ​​pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.

Glycogen synthase kinase-3 (GSK-3) a magic enzyme: it’s role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review / Glicogênio sintase quinase-3 (GSK-3), uma enzima mágica: seu papel no diabetes mellitus e na homeostase da glicose: interações com fluoroquinolonas. Uma mini-revisão

Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer’s disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.

O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.

Glycogen synthase kinase-3 (GSK-3) a magic enzyme: its role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review

Abstract Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimers disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.

Resumo O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.

Isolation of Fluoroquinolones Resistant Salmonella spp. from Stool Samples of Patients Attending General Hospital Minna and Ibrahim Badamasi Babangida Specialist Hospital, Minna, Nigeria

Typhoid fever continues to be a major health problem despite the use of antibiotics and the development of newer antibacterial drugs. This study aim was to isolate fluoroquinolones resistant Salmonella spp from stool samples of informed and consenting patient attending General Hospital and Ibrahim Badamasi Babangida Specialist Hospital in Minna Niger State Nigeria. A total 450 stool samples were collected from the Hospital. The results showed that 69 (30.4%) of the sample collected were positive for Salmonella species. On the basis of age children within the age range of 0-10 recorded the highest prevalence of 22.7% followed by age range 51-60 having the prevalence of 19.4%, age range >60 had the prevalence of 16.7% and age range 21-30 and 11-20 had a similar prevalence of (10.1% and 10.3% respectively) while age range 31-40 had the least prevalence of 7.8%. There were 69 isolates of Salmonella species Identified, 65(94.2%) were Resistant to the antibiotics used. The highest resistance was shown to Pefloxacin 62 (89.9%) and the lowest was shown to Ciprofloxacin 27 (39.1%). Salmonella species exhibited 52 antibiotic resistant patterns for the ten antibiotics tested with multiple antibiotic resistance index (MARI) ranging from 0.3-1.0. Molecular analysis was carried out on 5 representative isolates to identify their strains. Polymerase chain reaction (PCR) assay showed the identified Salmonella strains were Salmonella enterica subsp. arizonae strain ATCC 13314, Salmonella enterica subsp. enterica serovar Typhi strain 2018K-0756, Salmonella bongori strain SL18, Salmonella bongori strain GH3Rp and Salmonella enterica subsp. arizonae strain ATCC 13314, they all showed resistance to fluoroquinolones.

Effective extraction of fluoroquinolones from water using facile modified plant fibers / 药物分析学报

In this study,ecofriendly and economic carboxy-terminated plant fibers(PFs)were used as adsorbents for the effective in-syringe solid phase extraction(IS-SPE)of fluoroquinolone(FQ)residues from water.Based on the thermal esterification and etherification reaction of cellulose hydroxy with citric acid(CA)and sodium chloroacetate in aqueous solutions,carboxy groups grafted onto cotton,cattail,and corncob fibers were fabricated.Compared with carboxy-terminated corncob and cotton,CA-modified cattail with more carboxy groups showed excellent adsorption capacity for FQs.The modified cattail fibers were reproducible and reusable with relative standard deviations of 3.2％-4.2％within 10 cycles of adsorption-desorption.A good extraction efficiency of 71.3％-80.9％was achieved after optimizing the extraction condition.Based on carboxylated cattail,IS-SPE coupled with ultra-performance liquid chromatography with a photodiode array detector was conducted to analyze FQs in environmental water samples.High sensitivity with limit of detections of 0.08-0.25 μg/L and good accuracy with recoveries of 83.8％—111.7％were obtained.Overall,the simple and environment-friendly modified waste PFs have potential appli-cations in the effective extraction and detection of FQs in natural waters.

Nanocristais de besifloxacino para o tratamento de conjuntivite bacteriana: preparação, caracterização físico-química e toxicidade / Besifloxacin nanocrystals for treating bacterial conjunctivitis: preparation, physicochemical characterization, and toxicity

A conjuntivite bacteriana tem significante impacto na Saúde Pública. Essa infecção representa mais de um terço das doenças oculares relatadas em âmbito global. É uma doença altamente contagiosa causada por variedade de bactérias aeróbias e anaeróbias. Diferentes antibióticos empregados no tratamento dessa doença têm apresentado elevada incidência de resistência bacteriana. Dentre os antibióticos de última geração, destaca-se o besifloxacino, antibiótico de quarta geração da classe das fluoroquinolonas, indicado exclusivamente para uso oftálmico tópico. Entretanto, esse fármaco possui baixa solubilidade em água, diminuindo sua biodisponibilidade. Tendo em vista superar esse desafio, foi proposta abordagem nanotecnológica para o desenvolvimento de nanocristais desse fármaco. A preparação de nanocristais de besifloxacino empregando moagem via úmida em escala reduzida foi promissora empregando tensoativo Povacoat®. O Diâmetro hidrodinâmico médio (DHM) da partícula foi de aproximadamente 550 nm, com índice de polidispersão (IP) menor que 0,2. Esse resultado permitiu aumentar a solubilidade de saturação em aproximadamente duas vezes em relação a matéria-prima, possibilitando aumentar a velocidade de dissolução desse fármaco e melhorar sua biodisponibilidade e segurança. Além disso, foi validado o método para quantificação do besifloxacino por CLAE, apresentando especificidade, linearidade no intervalo de 20 a 80µg/mL (r= 0,9996), precisão por repetibilidade (DPR= 1,20%, 0,84% e 0,39%), precisão intermediária (DPR= 0,94%) e exatidão 99,03%. Estudo de estabilidade acelerado (90 dias) na condição 40°C±2°C/75%UR±5%UR e estudo de estabilidade de acompanhamento (150 dias) na condição: 25°C ± 2°C / 60% UR ± 5% UR evidenciaram a estabilidade do teor no período avaliado. Ainda, a nanossuspensão de besifloxacino 0,6% m/m (nanocristais) na dose máxima (500 mg/kg) e o estabilizante Povacoat® (750 mg/kg) não apresentaram toxicidade em larvas de G. mellonella. A concentração inibitória mínima (CIM) para a formulação inovadora foi de 0,0960 µg/mL e 1,60 µg/mL frente a Staphylococcus aureus e Pseudomonas aeruginosa, respectivamente, confirmando eficácia in vitro

Bacterial conjunctivitis greatly impacts the population's health, presenting more than a third of eye diseases reported worldwide. It is an infection caused by various aerobic and anaerobic bacteria and is highly contagious. Therefore, it presents a high incidence of bacterial resistance to the antibiotics commonly used for treatment. Among the most recent antibiotics, besifloxacin is a fourth-generation fluoroquinolone antibiotic indicated exclusively for topical ophthalmic use. Due to its importance in treating bacterial conjunctivitis and its low solubility in the water, a nanotechnological approach was proposed to develop besifloxacin nanocrystals. The preparation of besifloxacin nanocrystals using small-scale wet milling was promising using Povacoat® surfactant. The particle's average hydrodynamic diameter (DHM) was approximately 550 nm, with a polydispersity index (IP) of less than 0.2. This result increased the saturation solubility approximately two times concerning the raw material, making it possible to increase the dissolution rate of this drug and improve its bioavailability and safety. In addition, the method for quantification of besifloxacin by HPLC was validated, presenting specificity, linearity in the range of 20 to 80µg/mL (r= 0.9996), precision by repeatability (DPR= 1.20%, 0.84% and 0.39%), intermediate precision (DPR= 0.94%) and accuracy 99.03%. Accelerated stability study (90 days) at 40°C±2°C/75%RH±5%RH condition and follow-up stability study (150 days) at 25°C ± 2°C / 60% RH ± condition 5% RH showed the stability of content in the evaluated period. Furthermore, the 0.6% besifloxacin nanosuspension (nanocrystals) at the maximum dose (500 mg/kg) and the Povacoat® stabilizer (750 mg/kg) did not show toxicity in G. mellonella larvae. The minimum inhibitory concentration (MIC) to innovative formulation was 0.0960 µg/mL and e 1.60 µg/mL against Staphylococcus aureus and Pseudomonas aeruginosa, respectively, confirming in vitro efficacy

Resistencia de Mycobacterium tuberculosis a quinolonas y fármacos inyectables en el departamento del Atlántico, 2013-2016 / Resistance of Mycobacterium tuberculosis to quinolone and injectable drugs in Atlántico department, 2013-2016

Introducción: En el departamento del Atlántico los estudios de resistencia del Mycobacterium tuberculosis se han limitado a drogas de segunda línea. Objetivo: Determinar prevalencia de resistencia a amikacina, kanamicina, capreomicina y ofloxacina en casos de tuberculosis resistente a isoniacida, rifampicina o a ambas drogas, en el periodo 2013 a 2016 en el departamento del Atlántico. Métodos: Estudio transversal de 194 aislamientos resistentes a isoniacida, rifampicina o ambas, por metodología Genotype MTBDR plus versión 2, enviados al Instituto Nacional de Salud en el periodo 2013 al 2016 para ser confirmados y procesados para drogas de segunda línea. La proporción de resistencia, se hizo según variables sociodemográficas, clínica y de vigilancia en salud pública. Resultados: Las comorbilidades frecuentes encontradas fueron desnutrición con el 18,56 por ciento, seguido de infección concomitante VIH-tuberculosis con el 13,40 por ciento. La ofloxacina en casos no tratados obtuvo la mayor resistencia global con el 1,50 por ciento (IC 95 por ciento 0,18-5,33). En los que fueron previamente tratados la resistencia global a capreomicina fue del 8,10 por ciento (IC 95 por ciento 2,7-17,8). En los resistentes a rifampicina, un caso fue extensivamente resistente y dos casos resistentes en los multidrogorresistente. Conclusiones: Se encontró baja resistencia a fluoroquinolonas y fármacos inyectables en pacientes no tratados resistentes a isoniacida, rifampicina o ambas, que muestra que todavía no constituye un problema mayor en el departamento del Atlántico. Se debe complementar su seguimiento con buen manejo tanto físico como psicológico y un equipo de salud fortalecido que actúe prontamente y ayude a la adherencia del paciente a los tratamientos(AU)

Introduction: In Atlántico department, resistance studies of Mycobacterium tuberculosis have been limited to second-line drugs. Objective: Determine prevalence of resistance to amikacin, kanamycin, capreomycin and ofloxacin in cases of tuberculosis resistant to isoniazid, rifampicin or both, in the period 2013 to 2016 in Atlántico department. Methods: Cross-sectional study of 194 isolations resistant to isoniazid, rifampicin or both, by Genotype MTBDR plus version 2 methodology, that were sent to the National Institute of Health from 2013 to 2016 to be confirmed and processed for second-line drugs. The resistance ratio was made according to sociodemographic, clinical and public health surveillance variables. Results: The common comorbilities found were malnutrition with 18.56 percent, followed by concomitant HIV-tuberculosis infection with 13.40 percent. Ofloxacin in non-treated cases achieved the highest overall resistance with 1.50 percent (95 percent CI 0.18-5.33). In those previously treated, global resistance to capreomycin was 8.10 percent (95 percent CI 2.7-17.8). In the ones resistant to rifampicin, one case was extensively resistant and two cases were resistant in multi-drugs resistant. Conclusions: Low resistance to fluoroquinolones and injectable drugs was found in non-treated patients who were resistant to isoniazid, rifampicin or both, showing that it is not yet a major problem in Atlántico department. Its follow-up should be complemented with good physical and psychological management and a strengthened health team that acts promptly and helps the patient adherence to treatments(AU)

Laboratory-based surveillance of Shigella spp. from human clinical cases in Colombia, 1997-2018 / Vigilancia por el laboratorio de Shigella spp. aislada de casos clínicos humanos en Colombia, 1997-2018

Abstract | Introduction: Shigellosis is endemic in low-and middle-income countries, causing approximately 125 million episodes of diarrhea and leading to approximately 160.000 deaths annually one-third of which is associated with children. Objective: To describe the characteristics and antimicrobial resistance profiles of Shigella species recovered in Colombia from 1997 to 2018. Materials and methods: We received isolates from laboratories in 29 Colombian departments. We serotyped with specific antiserum and determined antimicrobial resistance and minimal inhibitory concentrations for ten antibiotics with Kirby-Bauer tests following the Clinical and Laboratory Standards Institute recommendations. Results: We analyzed 5,251 isolates of Shigella spp., most of them obtained from stools (96.4%); 2,511 (47.8%) were from children under five years of age. The two most common species were S. sonnei (55.1%) and S. fbxneri (41.7%). The highest resistance rate was that of tetracycline (88.1%) followed by trimethoprim-sulfamethoxazole (79.3%) and ampicillin (65.5%); 50.8% of isolates were resistant to chloramphenicol, 43.6% to amoxicillin/clavulanic acid, and less than 1% to cefotaxime, ceftazidime, gentamicin, and ciprofloxacin. In S. sonnei, the most common resistance profile corresponded to trimethoprim-sulfamethoxazole (92%) whereas in S. fbxneri the most common antibiotic profiles were multidrug resistance. Conclusions. In Colombia, children under five years are affected by all Shigella species. These findings should guide funders and public health officials to make evidence-based decisions for protection and prevention measures. The antimicrobial resistance characteristics found in this study underline the importance of combating the dissemination of the most frequently isolated species, S. sonnei and S. ftexneri.

Resumen | Introducción. La shigelosis es endémica en los países de ingresos bajos y medios y ocasiona aproximadamente 125 millones de episodios de diarrea y 160.000 muertes al año, un tercio de los cuales se presenta en niños. Objetivo. Describir las características y los perfiles de resistencia antimicrobiana en aislamientos de Shigella spp. recuperados en Colombia entre 1997 y 2018. Materiales y métodos. Los aislamientos provenían de laboratorios en 29 departamentos de Colombia. La serotipificación se hizo con antisueros específicos de Shigella spp. y, la determinación de los perfiles de resistencia y la concentración inhibitoria mínima de diez antibióticos, por Kirby-Bauer. Resultados. Se estudiaron 5.251 aislamientos de Shigella spp. obtenidos de materia fecal (96,4 %); el 47,8 % de ellos correspondía a niños menores de cinco años. Las especies más frecuentes fueron S. sonnei (55,1 %) y S. ftexneri (41,7 %). Se presentó resistencia a tetraciclina (88,1 %), trimetoprim-sulfametoxasol (79,3 %), ampicilina (65,5 %), cloranfenicol (50,8 %) y amoxicilina-acido clavulánico (43,6 %). La resistencia no superó el 1 % contra cefotaxime, ceftazidima, gentamicina y ciprofloxacina. Para S. sonnei, el perfil de resistencia más frecuente correspondió a trimetoprim-sulfametoxasol, en contraste con S. ftexneri, cuyos perfiles fueron todos multirresistentes. Conclusiones. Los niños menores de cinco años se vieron afectados por todas las especies de Shigella spp., aspecto que los legisladores en salud pública deben considerar a la hora de tomar decisiones en torno a las medidas de prevención y protección frente a esta enfermedad. Las características de resistencia antimicrobiana de los aislamientos de Shigella spp. en Colombia ponen de manifiesto la importancia de combatir la diseminación de las dos especies más frecuentes en casos clínicos, S. sonnei y S. ftexneri.

Clinical outcomes and molecular characterization of drug-resistant tuberculosis in pre- and extensively drug-resistant disease based on line probe assays

ABSTRACT Multidrug-resistant tuberculosis (MDR-TB) represents a significant impact in transmission, outcome, and health costs. The World Health Organization recommends implementation of rapid diagnostic methods for multidrug-resistance detection. This study was performed to evaluate the frequency of pre- and extensively drug resistant tuberculosis (pre-XDR-TB and XDR-TB) among MDR-TB patients, the pattern of resistance mutations for fluoroquinolones and the clinical outcome. Adult patients followed at a Brazilian regional reference center for TB, from January 2013 to June 2019 were included. Stored Mycobacterium tuberculosis (Mtb) cultures were recovered, the DNA was extracted, and the susceptibility test was performed using the line probe assay for second line antimycobacterial drugs, Genotype MTBDRsl version 2.0 (Hain Lifescience, CmbH, Germany). Among 33 MDR-TB included patients, we diagnosed XDR-TB or pre-XDR in five (15%) cases. Of these, mutations related to fluoroquinolones resistance were observed in four Mtb isolates, including one who had no phenotypic resistance profile. In two other patients with phenotypic resistance to ofloxacin, genotypic resistance was not found. Case fatality rate was 60% in pre/XDR-TB group, compared to 3.6% in the remaining of patients. This study observed few cases of pre-XDR and XDR-TB among a MDR-TB cohort. Phenotypic and genotypic assays presented good agreement. Clinical outcome was more favorable for patients with susceptibility to fluoroquinolones and injectable drugs.

Perfiles de resistencia a fluoroquinolonas en cocos Gram positivos de importancia clínica / Fluoroquinolone's resistance profiles in Gram-positive cocci of clinical importance

Para evaluar la resistencia a fluoroquinolonas en aislamientos clínicos de cocos grampositivos se revisaron los resultados de los cultivos procesados en el Centro de Referencia Bacteriológica del Servicio Autónomo Hospital Universitario de Maracaibo, durante el periodo enero 2011-diciembre 2015. Los datos fueron analizados mediante el software WHONETTM, (versión 5,6) y el IBM® SPSS® Statistics para Windows, (versión 25). Se encontró una frecuencia de 29,70% para los cocos grampositivos (9.292 cepas), correspondiendo el 76,18% de los aislamientos al género Staphylococcus (7.072); 15,30% a Enterococcus (1.422) y 8,59% a Streptococcus (798). Para Staphylococcus, la resistencia fue mayor en cepas resistentes a meticilina. Las tasas de resistencia más elevadas se detectaron en los enterococos, especialmente en Enterococcus faecium resistente a vancomicina. No se detectó resistencia a fluoroquinolonas en las cepas de Enterococcus faecalis resistentes a vancomicina. Los estreptococos, incluyendo Streptococcus pneumoniae, se mostraron, mayormente, sensibles a las fluoroquinolonas. La mayoría de las cepas de estafilococos y enterococos; presentó, resistencia cruzada a todas las fluoroquinolonas probadas. La distribución de la resistencia a las fluoroquinolonas por año de estudio en cada género bacteriano fue diferente. La resistencia a las fluoroquinolonas muestra una tendencia creciente en los tres géneros de cocos grampositivos evaluados

To evaluate the resistance to fluoroquinolones in clinical isolates of Gram-positive cocci records of processed culture al the Bacteriological Reference Center of the Autonomous Service University Hospital of Maracaibo during the period January 2011-December 2015, were reviewed. The data was analyzed using WHONETTM software (version 5.6) and IBM® SPSS® Statistics for Windows (version 25). A frequency of 29.70% was found for Gram-positive cocci (9,292 strains), with 76.18% of isolates corresponding to the genus Staphylococcus (7,072); 15.30% to Enterococcus (1422) and 8.59% to Streptococcus (798). For Staphylococcus, resistance was higher in methicillin-resistant strains. The highest resistance rates were detected in enterococci, especially vancomycin-resistant Enterococcus faecium. No resistance to fluoroquinolones was detected in vancomycin-resistant Enterococcus faecalis strains. Streptococci, including Streptococcus pneumoniae, were mostly sensitive to fluoroquinolones. Most strains of staphylococci and enterococci; presented cross resistance to all tested fluoroquinolones. The distribution of resistance to fluoroquinolones per year of study in each bacterial genus was different. Resistance to fluoroquinolones shows an increasing trend in the three genera of Gram-positive cocci evaluated

Characterization and distribution of viridans group streptococci isolated from infectious endophthalmitis and keratitis / Caracterização e distribuição de estreptococos do grupo viridans isolados de endoftalmite infecciosa e ceratite

ABSTRACT Purpose: The aims of this study were to characterize alpha-hemolytic streptococci among isolates from cases of infectious endophthalmitis and keratitis and to determine their distributions. Methods: The sample included 27 and 35 nonduplicated isolates of alpha-hemolytic streptococci recovered from patients with infectious endophthalmitis (2002-2013) and keratitis (2008-2013), respectively. Isolates were identified by the optochin susceptibility and bile solubility tests, using a biochemical identification system. The minimum inhibitory concentration was determined by the broth microdilution method. Molecular identification was performed by analyses of three constitutive genes and the complementary multilocus sequence. The molecular epidemiology of Streptococcus pneumoniae was investigated using multilocus sequence typing, and the presence of the capsular polysaccharide-encoding gene was assessed using conventional polymerase chain reaction. Outcomes were evaluated using the patients' medical records. Results: Phenotypic tests differentiated S. pneumoniae from other alpha-hemolytic streptococci, consistent with later molecular identifications. Streptococcus oralis was significantly prevalent among the endophthalmitis isolates, as was S. pneumoniae in the keratitis isolates. High levels of susceptibility to antibiotics were observed, including vancomycin, cephalosporins, and fluoroquinolones. High genetic variability was detected among the 19 S. pneumoniae strains, with 15 predicted to be encapsulated. The medical records of patients with infectious endophthalmitis were reviewed (n=15/27; 56%), and final visual acuity was assessed in 12 cases (44%). Many patients progressed to a final visual acuity state of "no light perception" (6/12; 50%), "light perception" (3/12; 25%), or "hand motion" (1/12; 8%). The medical records of patients with infectious keratitis were also reviewed (n=24/35; 69%), and final visual acuity was assessed in 18 cases (51%). Similarly, most patients progressed to a final visual acuity state of "no light perception" (6/18; 33%), "light perception" (1/18; 6%), or "hand motion" (6/18; 33%). Overall, the majority of patients progressed to a final visual acuity state of "no light perception" (12/30), "light perception" (4/30), or "hand motion" (7/30). Conclusions: The distribution of alpha-hemolytic streptococci in ocular infections suggested the presence of a species-specific tissue tropism. The prognoses of patients with ocular streptococcal infections were highly unfavorable, and antibiotic resistance did not contribute to the unfavorable clinical progressions and poor outcomes.

RESUMO Objetivo: O objetivo deste estudo foi caracterizar os estreptococos alfa-hemolíticos isolados de endoftalmite infecciosa e ceratite e determinar sua distribuição. Métodos: A amostra incluiu 27 e 35 isolados não-duplicados de estreptococos alfa-hemolíticos recuperados de pacientes com endoftalmite infecciosa (2002-2013) e ceratite (2008-2013), respectivamente. Os isolados foram identificados pelos testes de suscetibilidade à optoquina e bile solubilidade, utilizando um sistema de identificação bioquímica. A concentração inibitória mínima foi determinada pelo método de microdiluição em caldo. A identificação molecular foi realizada pela análise de três genes constitutivos e análise complementar de sequências multilocus. A epidemiologia molecular do Streptococcus pneumoniae foi investigada por tipagem de sequência multilocus, e a presença do gene codificador do polissacarídeo capsular foi avaliada por reação em cadeia da polymerase convencional. Os resultados foram avaliados utilizando os prontuários médicos dos pacientes. Resultados: Os testes fenotípicos diferenciaram S. pneumoniae dos outros estreptococos alpha-hemolíticos, consistentes com identificações moleculares posteriores. S. oralis foi significativamente prevalente entre os isolados de endoftalmite, assim como S. pneumoniae nos isolados de ceratite. Foram observados altos níveis de suscetibilidade a antibióticos, incluindo vancomicina, cefalosporinas e fluoroquinolonas. Alta variabilidade genética foi detectada entre as 19 cepas de S. pneumoniae, com 15 previstas para serem encapsuladas. Os prontuários médicos dos pacientes com endoftalmite infecciosa foram revisados (n=15/27; 56%), e a acuidade visual final foi avaliada em 12 casos (44%). Muitos pacientes evoluiram para um estado final de acuidade visual de "sem percepção luminosa" (6/12; 50%), "percepção luminosa" (3/12; 25%) ou "movimentos de mãos" (1/12; 8%). Também foram revisados os prontuários médicos dos pacientes com ceratite infecciosa (n=24/35; 69%), e a acuidade visual final foi avaliada em 18 casos (51%). Da mesma foram, a maioria dos pacientes evoluiu para um estado final de acuidade visual de "sem percepção luminosa" (6/18; 33%), "percepção luminosa" (1/18; 6%) ou "movimentos de mãos" (6/18; 33%). No geral, a maioria dos pacientes evoluiu para um estado final de acuidade visual de "sem percepção luminosa" (12/30), "percepção luminosa" (4/30) ou "movimentos de mãos" (7/30). Conclusões: A distribuição de estreptococos alfa-hemolíticos nas infecções oculares sugeriu a presença de um tropismo de tecido específico da espécie. Os prognósticos dos pacientes com infeções oculares por estreptococos foram altamente desfavoráveis e a resistência a antibióticos contribuiu não para as progressões clínicas des­favoráveis e os maus resultados.

Frequency of Chromosomally Encoded gyrA and parC Genetic Determinants of Fluoroquinolone Resistance in A. baumannii

Fluoroquinolones are administered as routine drugs of choice for treating complicated urinary tract infections caused by multidrug resistant Acinetobacter baumannii strains. It is now a world-wide issue that gyr and par induced quinolone resistance as one of the major drug resistance mechanisms. This investigation is thus aimed to assess the prevalence of quinolone resistance and to characterize the gyrA and parC producing strains of A. baumannii. Genomic DNA from 50 fluoroquinolone resistant A. baumannii were screened for gyrA and parC by PCR for the genetic relatedness with fluoroquinolone resistance, with sequencing of the representative strains. All the strains were positive for gyrA(100%) and 82% (n=41)for parC. Presence of parC was observed in 56.09% (n=23) ciprofloxacin resistant A. baumannii with 43.90% (n=18) in levofloxacin resistant A baumannii. The findings of the present study showed the prevalence of fluoroquinolone resistance among A. baumannii in urinary tract infections and the frequency of gyrA and parC in inducing the resistance

Quinolones resistance in Salmonella spp. isolated from broilers and chickens carcasses under federal inspection / Resistência à quinolonas em Salmonella spp. isoladas de frangos vivos e carcaças sob inspeção federal

We analyzed 77 Salmonella spp. strains, from which 20 were isolated from broilers (cloacal swabs) and 57 from chickens from slaughterhouses under federal inspection. The following serotypes were identified: Salmonella Saint Paul (29), Salmonella Heidelberg (27), Salmonella Anatum (9), Salmonella Cerro (5), Salmonella Senftenberg (5), Salmonella enterica (O: 4,5) (1) and Salmonella enterica (O: 9.12) (1). Fifteen strains (19.5%) were resistant to enrofloxacin, six (7.8%) to ciprofloxacin, and 26 (33.8%) to nalidixic acid in the Disk Diffusion Test. The fifteen enrofloxacin resistant strains were selected for the PCR to detect the genes gyrA, gyrB, parC, and parE, and genetic sequencing to identify mutations in these genes. Five strains (33.3%) had point mutations in the gyrA gene, and one (6.7%) presented a point mutation in the parC gene. None of the 15 strains had mutations in the gyrB and parE genes, and none had more than one mutation in the gyrA gene or the other genes. The presence of point mutations in the strains studied corroborates with the phenotypic resistance observed to nalidixic acid. However, it did not explain the resistance to fluoroquinolones found in the 15 strains. Other mechanisms may be related to the fluoroquinolones resistance, highlighting the need for additional mutation screening.(AU)

Foram analisadas neste estudo 77 estirpes de Salmonella spp., 20 isoladas de frangos vivos (suabes de cloaca) e 57 isoladas de carcaças, provenientes de abatedouros frigoríficos sob Inspeção Federal. Foram identificados os seguintes sorotipos: Salmonella Saint Paul (29), Salmonella Heidelberg (27), Salmonella Anatum (9), Salmonella Cerro (5), Salmonella Senftenberg (5), Salmonella enterica (O: 4,5) (1) e Salmonella enterica (O: 9,12) (1). Do total de estirpes estudadas, 15 (19,5%) se mostraram resistentes à enrofloxacina, seis (7,8%) à ciprofloxacina e 26 (33,8%) ao ácido nalidíxico no Teste de Difusão em Disco. Foram selecionadas as 15 estirpes resistentes à enrofloxacina para a realização da PCR para detecção dos genes gyrA, gyrB, parC e parEe para sequenciamento genético do produto da PCR para identificação de mutações nesses genes. Cinco estirpes (33,3%) apresentaram mutações pontuais no gene gyrA e uma (6,7%) apresentou mutação pontual no gene parC. Nenhuma das 15 estirpes apresentou mutações nos genes gyrB e parE e nenhuma apresentou mais de uma mutação no gene gyrA ou nos outros genes. A existência apenas de mutações pontuais em alguns genes das estirpes analisadas está de acordo com a resistência fenotípica observada ao ácido nalidíxico, mas não explica a resistência às fluoroquinolonas encontrada nas 15 estirpes. Outros mecanismos de resistência podem estar relacionados à resistência encontrada às fluoroquinolonas e estudos adicionais são necessários para investigar sua presença.(AU)

Prescripción e indicaciones de uso de fluoroquinolonas en un grupo de pacientes ambulatorios de Colombia / Prescription and indications for the use of fluoroquinolones in a group of outpatients in Colombia

Introducción. Existen evidencias sobre el uso indiscriminado de antibióticos en el tratamiento de diversas enfermedades. Objetivo. Determinar los patrones de prescripción y de indicaciones de uso de las fluoroquinolonas en un grupo de pacientes ambulatorios en Colombia. Materiales y métodos. Se llevó a cabo un estudio descriptivo farmacoepidemiológico del tipo de prescripción e indicaciones de uso a partir de una base de datos poblacionales que incluía pacientes con prescripciones ambulatorias de fluoroquinolonas entre mayo y octubre de 2018. Se recabó la información sobre las variables sociodemográficas, farmacológicas y clínicas (diagnóstico según la Clasificación Internacional de Enfermedades, versión 10) y se estableció la proporción del uso de fluoroquinolonas en indicaciones aprobadas y no aprobadas por las agencias reguladoras. Resultados. Se identificaron 23.373 pacientes que habían recibido fluoroquinolonas; su edad media era de 47,9 ± 18,1 años y 15.767 eran mujeres (67,5 %). La ciprofloxacina fue el medicamento más prescrito (n=19.328; 82,7 %), seguida de la norfloxacina (n=3.076; 13,2 %), la levofloxacina (n=573; 2,5 %) y la moxifloxacina (n=394; 1,7 %). Las principales indicaciones fueron la infección de las vías urinarias en sitio no especificado (n=10.777; 46,1 %), la diarrea y la gastroenteritis de presunto origen infeccioso (n=3.077, 13,2 %) y la cistitis aguda (n=956; 4,2 %). El 76 % (n=17.759) de las prescripciones correspondía a indicaciones aprobadas y el resto a usos no aprobados, como la rinofaringits o las infecciones de tejidos blandos. El ser hombre (odds ratio, OR=1,26; IC95%: 1,18-1,34) y tener menos de 35 años (OR=1,92; IC95%:1,48-1,50) se asociaron con una mayor probabilidad de uso de fluoroquinolonas en indicaciones no aprobadas. Conclusión. Las fluoroquinolonas, en particular la ciprofloxacina, se están prescribiendo especialmente a mujeres con infecciones de las vías urinarias, pero hasta la cuarta parte de los pacientes las recibieron para usos no aprobados por las agencias reguladoras.

Introduction: There is evidence of the indiscriminate use of antibiotics for different pathologies. Objective: To determine the prescription patterns and indications for the use of fluoroquinolones in a group of outpatients in Colombia. Materials and methods: We conducted a descriptive pharmaco-epidemiological study on prescription-indication using a population database where patients with outpatient fluoroquinolone prescriptions were included from May to October, 2018. We obtained the information on sociodemographic, pharmacological, and clinical variables, as well as on the diagnosis according to the International Classification of Diseases, version 10, and we established if the use was approved by the regulatory agencies or if it was off-label. Results: A total of 23,373 patients were identified who were using fluoroquinolones; their mean age was 47.9 ± 18.1 years and women predominated (n=15,767, 67.5%). Ciprofloxacin was the medication most commonly prescribed (n=19,328, 82.7%), followed by norfloxacin (n=3076, 13.2%), levofloxacin (n=573, 2.5%), and moxifloxacin (n=394; 1.7%). The main indications were urinary tract infection in unspecified site (n=10,777, 46.1%), diarrhea and gastroenteritis of presumed infectious origin (n=3077, 13.2%), and acute cystitis (n=956; 4.2%). The prescriptions followed approved indications in 76% (n=17,759) of cases while the rest were used off-label or without indication for nasopharyngitis or soft-tissue infections, for example. Being male (OR=1.26, 95%CI:1.18-1.34) and under 35 years of age (OR=1.92, 95%CI:1.48-1.50) were associated with a greater probability of using fluoroquinolones in unapproved indications. Conclusions: Fluoroquinolones, particularly ciprofloxacin, are being prescribed especially to women with urinary tract infections, but up to a quarter of the patients received them for unapproved indications by regulatory agencies.

Treatment Outcomes after Discontinuation of Ethambutol due to Adverse Events in Mycobacterium avium Complex Lung Disease

BACKGROUND: Long-term administration of ethambutol (EMB) for Mycobacterium avium complex lung disease (MAC-LD) sometimes leads to permanent discontinuation of EMB due to various adverse events. This study aimed to investigate treatment outcomes after discontinuation of EMB.METHODS: Among patients diagnosed with MAC-LD between January 2001 and December 2014, 508 patients whose treatment was initiated with standard regimen until May 2018 were enrolled at a tertiary referral center in Korea. Of these 508 patients, 60 (11.8%) discontinued EMB due to various adverse effects. Among these 60 patients, treatment outcomes were analyzed for 44 patients by comparing their outcomes with those of matched subjects who received the standard treatment regimen without EMB discontinuation.RESULTS: The mean age of the 60 patients who discontinued EMB was 64.4 years. Ocular toxicity was the most common cause of discontinuation of EMB (75.0%, 45/60). The mean duration of EMB administration before its discontinuation was 7.0 ± 4.6 months. The treatment failure rate of the 44 patients with EMB discontinuation analyzed for treatment outcome was 29.6%, which was higher than that of the matched patients who received the standard regimen (18.3%), although the difference was not significant (P = 0.095). Of these 44 patients, EMB was substituted with later-generation fluoroquinolone in 23 patients, and the treatment failure rate of these 23 patients was significantly higher than that of the matched patients who received the standard regimen (39.1% vs. 19.3%, P = 0.045).CONCLUSION: These findings suggest that treatment outcomes are unsatisfactory in patients with MAC-LD who discontinue EMB owing to adverse events. Notably, there was a statistically significant high failure rate in patients who were prescribed fluoroquinolone to replace EMB.

Validation of an analytical method by high-performance liquid chromatography and microbiological assay, biological safety and in silico toxicity for danofloxacin

Danofloxacin is a veterinary fluoroquinolone used to treat respiratory and gastrointestinal diseases of birds, pigs and cattle. The literature reviewed shows some analytical methods to quantify this fluoroquinolone, but microbiological and biological safety studies are limited. The analytical methods were validated by the Official Codes. The LC-DAD method was developed and validated using an RP-18 column, mobile phase containing a mixture of 0.3% triethylamine (pH 3.0) and acetonitrile (85:15, v/v). The microbiological assay was performed by agar diffusion method (3 x 3) and Staphylococcus epidermidis as a microorganism test. Forced degradation studies were performed in both methods. The minimum inhibitory concentration (MIC) was performed by test microdilution and toxicity studies were evaluated using in silico study, cell proliferation, cell viability test, micronuclei and comet assay. LC and a microbiological assay proved linear, accurate, precise, and robust to quantify danofloxacin, but only the LC method showed selectivity to quantify the drug in the presence of its degradation products. These results demonstrate that the LC method is suitable for stability studies of danofloxacin, but a microbiological assay cannot be used to quantify the drug due to the biological activity of the photoproducts. Ex-vivo cytotoxicity and theoretical and experimental genotoxicity were also observed.

Fluoroquinolones At The Back Foot : A Study On Fluoroquinolone Resistance In Enterococcus Species Isolated From Urinary Specimens In A Tertiary Care Hospital In Kolkata, India

OBJECTIVE: The study aims to detect the resistance pattern of fluoroquinolones (ciprofloxacin & levofloxacin) in Urinary Tract Infection (UTI) caused by Enterococcus species. MATERIALS AND METHOD: 77 isolates of Enterococcus species from the urine samples of clinically suspected cases of UTI were studied. Identification and antimicrobial susceptibility testing was performed by conventional as well as automated methods. RESULT: Enterococcus faecalis (53.25%) was the commonest. Most of the isolates were resistant to both levofloxacin (83.12%) and ciprofloxacin (85.71%). • CONCLUSION: Resistance to fluoroquinolones is of concern as it serves as an excellent oral choice of drug. So, the inclusion of this group of drug in the treatment regime should be reconsidered and effective strategies developed to contain the same.

Dna Topoisomerases: A Review On Their Functionalaspects In Cell Division

DNA is double helical macromolecule which carries all the genetic information and it is usually found enveloped inside a nucleus. The DNA helix relaxes and supercoils itself frequently in order to derive information from the genes during processes like transcription, condensation, replication and recombination, which require mutable or immutable alterations to cause the separation of the two DNA strands. Due to problems caused by the helical structure of DNA, these topoisomerase enzymes perform the required DNA uncoiling. Their role in cell cycle is also significant as their mutation leads to failure of anaphase separation (1, 2). In the present review, the important roles of DNA topoisomerases and their inevitable role in cell growth and cell cycle are discussed viz. how they function in cell proliferation and what are the results when different inhibitors are added to the cells, affecting cell cycle at various checkpoints .