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.

Phenotypic and molecular characterization of fluoroquinolone resistant Pseudomonas aeruginosa isolates in Palestine / Caracterização fenotípica e molecular de isolados de Pseudomonas aeruginosa resistentes a fluoroquinolonas na Palestina

Fluoroquinolones are important antimicrobial agents for the treatment of Pseudomonas infections. A total of 11 isolates of P. aeruginosa were collected from different clinical samples from different medical centers in the North West Bank-Palestine during 2017. In this study, resistance to fluoroquinolones and secretions of ß-lactamases were detected by phenotypic methods, while presence of ß-lactamase gene sequences and other virulence factors were detected by PCR technique. PCR product for gyrA, parC and parE genes were sequenced for further analyses. The phylogenetic analyses, population diversity indices and haplotypes determination were conducted using computer programs MEGA version 6, DnaSP 5.1001 and median-joining algorithm in the program Network 5, respectively. Results of this study showed that the MIC for ciprofloxacin and norfloxacin had a range of 32-256 µg/ml. In addition, all isolates carried either exoT or exoT and exoY genes, different ß-lactamase genes and 82% of these isolates harbored class 1 integrons. Analyses of the gyrA, parC and parE sequences were found to be polymorphic, had high haplotype diversity (0.945-0.982), low nucleotide diversity (0.01225-0.02001) and number of haplotypes were 9 for each gyrA and parE genes and 10 haplotypes for parC gene. The founder haplotypes being Hap-1 (18%), Hap-2 (27.3%) and Hap-6 (9.1%) for gyrA, parC and parE genes, respectively. Two of ParE haplotypes were detected as indel haplotypes. The Median-joining- (MJ) networks constructed from haplotypes of these genes showed a star-like expansion. The neutrality tests (Tajima's D test and Fu's Fs test) for these genes showed negative values. Palestinian fluoroquinolone resistant P. aeruginosa strains showed high MIC level for fluoroquinolones, ß-lactamase producers, carried type III secretion exotoxin-encoding genes, most of them had integrase I gene and had high level of mutations in QRDR regions in gyrA, parC and parE genes. All these factors may play an important role in the invasiveness of these strains and make them difficult to treat. Isolation of these strains from different medical centers, indicate the need for a strict application of infection control measures in Medical centers in the North West Bank-Palestine that aim to reduce expense and damage caused by P. aeruginosa infections. Molecular analyses showed that Palestinian fluoroquinolone resistant P. aeruginosa haplotypes are not genetically differentiated; however, more mutations may exist in these strains.

Fluoroquinolonas são agentes antimicrobianos importantes para o tratamento de infecções por Pseudomonas. Um total de 11 bacilos isolados de P. aeruginosa foram coletados de diferentes amostras clínicas provenientes de diferentes centros médicos na Cisjordânia-Palestina durante o ano de 2017. Neste estudo, resistência a fluoroquinolonas e secreções de ß-lactamases foram detectadas por métodos fenotípicos, enquanto a presença de sequências do gene ß-lactamase e outros fatores de virulência foram detectados pela técnica de PCR (Proteína C-reativa). O produto de PCR para os genes gyrA, parC e parE foram sequenciados para análises posteriores. As análises filogenéticas, os índices de diversidade populacional e a determinação de haplótipos foram realizados utilizando os softwares MEGA versão 6, DnaSP 5.1001 e o algoritmo de junção de mediana do programa Network 5, respectivamente. Os resultados deste estudo mostraram que a MIC para ciprofloxacina e norfloxacina tinha um intervalo de 32-256 µg/ml. Além disso, todos os bacilos isolados carregavam genes exoT ou exoT e exoY, genes de ß-lactamase diferentes e 82% desses isolados continham integrons de classe 1. As análises das sequências gyrA, parC e parE foram consideradas polimórficas, com alta diversidade de haplótipos (0,945-0,982), baixa diversidade de nucleotídeos (0,01225-0,02001) e o número de haplótipos foi de 9 para cada gene de gyrA e parE e 10 haplótipos para o gene parC. Os haplótipos fundadores são Hap-1 (18%), Hap-2 (27,3%) e Hap-6 (9,1%) para os genes gyrA, parC e parE, respectivamente. Dois dos haplótipos parE foram detectados como haplótipos InDel. As redes Median-joining (MJ) construídas a partir de haplótipos desses genes mostraram uma expansão semelhante à de uma estrela. Os testes de neutralidade (teste D de Tajima e teste Fs de Fu) para esses genes apresentaram valores negativos. As cepas palestinas de P. aeruginosa resistentes a fluoroquinolonas mostraram alto nível de MIC para fluoroquinolonas, produtores de ß-lactamase, genes codificadores de exotoxina de secreção tipo III, a maioria deles tinha o gene integrase I e tinha alto nível de mutações nas regiões QRDR nos genes gyrA, parC e parE. Todos esses fatores podem desempenhar um papel importante na invasão dessas cepas e torná-las difíceis de tratar. O isolamento dessas cepas em diferentes centros médicos, indica a necessidade de uma aplicação estrita de medidas de controle de infecção em centros médicos da Cisjordânia-Palestina que visam reduzir despesas e danos causados por infecções por P. aeruginosa. As análises moleculares mostraram que os haplótipos de P. aeruginosa resistentes à fluoroquinolona palestina não são geneticamente diferenciados; no entanto, mais mutações podem existir nessas cepas.

Phenotypic and molecular characterization of fluoroquinolone resistant Pseudomonas aeruginosa isolates in Palestine / Caracterização fenotípica e molecular de isolados de Pseudomonas aeruginosa resistentes a fluoroquinolonas na Palestina

Fluoroquinolones are important antimicrobial agents for the treatment of Pseudomonas infections. A total of 11 isolates of P. aeruginosa were collected from different clinical samples from different medical centers in the North West Bank-Palestine during 2017. In this study, resistance to fluoroquinolones and secretions of β-lactamases were detected by phenotypic methods, while presence of β-lactamase gene sequences and other virulence factors were detected by PCR technique. PCR product for gyrA, parC and parE genes were sequenced for further analyses. The phylogenetic analyses, population diversity indices and haplotypes determination were conducted using computer programs MEGA version 6, DnaSP 5.1001 and median-joining algorithm in the program Network 5, respectively. Results of this study showed that the MIC for ciprofloxacin and norfloxacin had a range of 32-256 µg/ml. In addition, all isolates carried either exoT or exoT and exoY genes, different β-lactamase genes and 82% of these isolates harbored class 1 integrons. Analyses of the gyrA, parC and parE sequences were found to be polymorphic, had high haplotype diversity (0.945-0.982), low nucleotide diversity (0.01225-0.02001) and number of haplotypes were 9 for each gyrA and parE genes and 10 haplotypes for parC gene. The founder haplotypes being Hap-1 (18%), Hap-2 (27.3%) and Hap-6 (9.1%) for gyrA, parC and parE genes, respectively. Two of ParE haplotypes were detected as indel haplotypes. The Median-joining- (MJ) networks constructed from haplotypes of these genes showed a star-like expansion. The neutrality tests (Tajima’s D test and Fu’s Fs test) for these genes showed negative values. Palestinian fluoroquinolone resistant P. aeruginosa strains showed high MIC level for fluoroquinolones, β-lactamase producers, carried type III secretion exotoxin-encoding genes, most of them [...].

Fluoroquinolonas são agentes antimicrobianos importantes para o tratamento de infecções por Pseudomonas. Um total de 11 bacilos isolados de P. aeruginosa foram coletados de diferentes amostras clínicas provenientes de diferentes centros médicos na Cisjordânia-Palestina durante o ano de 2017. Neste estudo, resistência a fluoroquinolonas e secreções de β-lactamases foram detectadas por métodos fenotípicos, enquanto a presença de sequências do gene β-lactamase e outros fatores de virulência foram detectados pela técnica de PCR (Proteína C-reativa). O produto de PCR para os genes gyrA, parC e parE foram sequenciados para análises posteriores. As análises filogenéticas, os índices de diversidade populacional e a determinação de haplótipos foram realizados utilizando os softwares MEGA versão 6, DnaSP 5.1001 e o algoritmo de junção de mediana do programa Network 5, respectivamente. Os resultados deste estudo mostraram que a MIC para ciprofloxacina e norfloxacina tinha um intervalo de 32-256 µg/ml. Além disso, todos os bacilos isolados carregavam genes exoT ou exoT e exoY, genes de β-lactamase diferentes e 82% desses isolados continham integrons de classe 1. As análises das sequências gyrA, parC e parE foram consideradas polimórficas, com alta diversidade de haplótipos (0,945-0,982), baixa diversidade de nucleotídeos (0,01225-0,02001) e o número de haplótipos foi de 9 para cada gene de gyrA e parE e 10 haplótipos para o gene parC. Os haplótipos fundadores são Hap-1 (18%), Hap-2 (27,3%) e Hap-6 (9,1%) para os genes gyrA, parC e parE, respectivamente. Dois dos haplótipos parE foram detectados como haplótipos InDel. As redes Median-joining (MJ) construídas a partir de haplótipos desses genes mostraram uma expansão semelhante à de uma estrela. Os testes de neutralidade (teste D de Tajima e teste Fs de Fu) para esses genes apresentaram valores negativos. As cepas palestinas de P. aeruginosa resistentes a fluoroquinolonas mostraram alto nível de MIC para [...].

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.

Mycobacterium leprae: aspectos da resistência aos fármacos na poliquimioterapia / Drug resistance in multidrug therapy for Mycobacterium leprae

Introdução: O diagnóstico da hanseníase possui números significativos que causam preocupação à saúde pública. Os casos de resistência medicamentosa nessa doença se iniciaram em meados dos anos 60 e diante do problema, a Organização Mundial da Saúde instituiu em 1981 a poliquimioterapia, associação dos antibióticos rifampicina, dapsona e clofazimina, tratamento atual de escolha. A resistência aos fármacos na hanseníase é reportada pela literatura, desvelando um obstáculo à sua eliminação. Apresentamos nessa revisão os principais aspectos da resistência medicamentosa no tratamento para hanseníase e seus impactos. Metodologia: Revisão sistemática sobre os aspectos da resistência medicamentosa utilizando a pesquisa exploratória como metodologia de abordagem. Foram pesquisados os termos resistência medicamentosa, hanseníase, recidiva, alterações genéticas e os operadores booleanos "and" e "or" na busca. Resultados e discussão: A dificuldade de tomar a medicação corretamente foi um dos principais fatores que acarretaram resistência do bacilo Mycobacterium leprae aos fármacos. Homens de países norte e sul-americanos e asiáticos foram os mais atingidos por episódios de resistência. A resistência medicamentosa é uma das principais causas de recidivas em hanseníase. O principal fármaco causador de resistência medicamentosa descrito nos trabalhos foi a dapsona (46,6%) e a maioria das alterações genéticas encontradas estão no gene rpoB; 23,2% dos registros relatados foram de resistência secundária aos fármacos e, também, sete casos de resistência múltipla a esses medicamentos. Conclusão: Os principais aspectos da resistência medicamentosa na hanseníase são os equívocos ao ingerir os medicamentos e as alterações genéticas na bactéria. Os impactos causados estão na dificuldade de refazer o tratamento, a possibilidade de nova transmissão e o aparecimento de sintomas mais graves.

Introduction: The diagnosis of leprosy has significant numbers causing public health concern. Reports of drug resistance in this disease begun in the mid-1960s and due to this problem, the World Health Organization instituted a multidrug therapy with rifampicin, dapsone, and clofazimine antibiotic association in 1981, which is currently the first-choice treatment for leprosy. Cases of drug resistance have been reported in literature, revealing an obstacle to the eradication of the disease. This paper has the purpose of presenting the key aspects and impacts of drug resistance in the treatment for leprosy. Methods: Systematic review of the drug resistance aspects using exploratory research as an approach methodology. The authors searched the terms drug resistance, leprosy, recurrence, genetic alterations, and the Boolean operators "and" and "or" between them. Results and discussion: The difficulty in taking the medication correctly was one of the key factors that led to drug resistance for Mycobacterium leprae. Men from North and South American, as well as from Asian countries, were the most affected by episodes of resistance. Drug resistance is one of the main causes of leprosy recurrences. Dapsone was the most frequently identified drug resistance in the studies (46.6%), while most of the genetic alterations were found in the rpoB gene; 23.2% of the cases were from secondary resistance episodes, and seven cases of multiple resistance were reported. Conclusion: The misconceptions when taking the treatment and the Mycobacterium leprae genetic alterations have been described as the key aspects of drugs resistance in leprosy and the impacts caused are the difficulty in redoing the treatment, the possibility of new transmission, and the appearance of more severe symptoms.

Enterobacterales productores de betalactamasas de espectro extendido portadores del gen mcr-1 en Lima, Perú / Extended-spectrum beta-lactamase-producing enterobacterales carrying the mcr-1 gene in Lima, Peru

RESUMEN Se analizó la presencia del gen mcr-1 en 165 enterobacterales productores de betalactamasas de espectro extendido (EP-BLEE) recuperados en 2017 de sangre (40), orina (57), secreciones respiratorias bajas (12) e hisopados rectales (56) de pacientes hospitalizados en el Instituto Nacional de Enfermedades Neoplásicas (Perú). La identificación y la susceptibilidad antimicrobiana se determinaron por el sistema automatizado Phoenix M50; la resistencia a colistina por Colistin Agar-Spot (CAS); la detección de mrc-1 por el método fenotípico de predifusión de colistina e inhibición con EDTA (CPD-E) y por reacción en cadena de la polimerasa (PCR, por sus siglas en inglés). De los 165 EP-BLEE 25 fueron positivos para mcr-1 por el método CPD-E y se confirmó por PCR. Por el método CAS, 20/165 fueron resistentes a colistina. Además, mostraron resistencia a las fluoroquinolonas y a la gentamicina, y permanecieron sensibles a la amikacina; dos aislamientos presentaron metalocarbapenemasas. La obtención de datos sobre la resistencia a antimicrobianos considerados de última línea (colistina) es crucial para establecer medidas para su control.

ABSTRACT We analyzed the presence of the mcr-1 gene in 165 extended-spectrum beta-lactamase-producing enterobacterales (ESBL-PE) obtained during 2017, from blood (40), urine (57), lower respiratory secretions (12) and rectal swabs (56) of patients hospitalized in the Instituto Nacional de Enfermedades Neoplásicas (Peru). Antimicrobial identification and susceptibility were determined by the Phoenix M50 automated system; colistin resistance by Colistin Agar-Spot (CAS); mrc-1 detection by colistin pre-diffusion and inhibition with EDTA test (CPD-E) and by polymerase chain reaction (PCR). We found that from the 165 ESBL-PE, 25 were positive for mcr-1 by the CPD-E method and confirmed by PCR. Colistin resistance was found in 20/165 by using the CAS method. Additionally, they showed resistance to fluoroquinolones and gentamicin, while remaining sensitive to amikacin; two isolates presented metallo-carbapenemases. Obtaining data on resistance to last-line antimicrobials (colistin) is crucial to establish measures for its control.

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.

Informe diário de evidências COVID-19: busca realizada em 16 e 18 de maio de 2020 / COVID-19 daily evidence report: search conducted on May 16 and 18, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 22 artigos e 10 protocolos.

Artralgia inducida por levofloxacina: Reporte de un caso / Levofloxacin induced arthralgia: a case report

Mujer quien inició tratamiento de rescate de segunda línea para Helicobacter pylori con levofloxacina un gramo cada 12 horas, amoxicilina 500 mg cada 8 horas y lansoprazol 40 mg cada 24 horas. Al quinto día de tratamiento manifestó mialgias generalizadas seguido por artralgias y limitación del movimiento en rodillas y codos. Al séptimo día, sin mejora, la paciente suspende la medicación y presenta resolución completa de los síntomas una semana después. No hubo secuelas, ni complicaciones, ni re-exposición al medicamento. El caso fue clasificado como probable, con un puntaje de siete en la escala de Naranjo. Este caso nos recuerda que la administración de fluoroquinolonas puede asociarse con artralgias y artropatía reversible aguda, y debería ser la primera sospecha diagnóstica en pacientes sin comorbilidad.

Woman who initiated second-line rescue therapy for Helicobacter pylori with levofloxacin one gram every 12 hours, amoxicillin 500 mg every 8 hours and lansoprazole 40 mg every 24 hours. On the fifth day of treatment, she manifested generalized myalgia followed by bilateral knee and elbow arthralgia with limitation of movements. On the seventh day, without improvement, the patient discontinues the medication and achieve complete resolution of the symptoms one week later. There were no sequelae, no complications, no re-exposure to the drug. The case was classified as probable attaining a score of seven under the Naranjo's scale. This case reminds us that administration of fluoroquinolones may be associated with arthralgia and acute reversible arthropathy and should be the first diagnostic suspicion in patients without comorbidity.

Cambios en las prescripciones y el consumo de antimicrobianos, luego de la implementación de recomendaciones de uso: experiencia en un hospital universitario / Changes in prescriptions and antibiotic consumption after the implementation of recommendations for use: experience in a university hospital

Resumen Introduccion: Actualmente cerca de la mitad de las prescripciones de antimicrobianos son inadecuadas, lo que aumenta la resistencia bacteriana. Tanto cefalosporinas como fluoroquinolonas se asocian con este fenomeno: aumento de bacterias productoras de β-lactamasas e infecciones por Clostridioides difficile, por lo que las agencias reguladoras buscan racionalizar su uso. Objetivo: Evaluar el efecto de recomendaciones para el uso adecuado de antimicrobianos en la proporcion de prescripciones inadecuadas de ceftriaxona y fluoroquinolonas. Metodologia: Se desarrollo un estudio de antes y despues, prospectivo e intervencional, que comparo la calidad y la cantidad de uso de ceftriaxona y fluoroquinolonas antes y despues de la implementacion de recomendaciones de uso para tratamientos de enfermedades infecciosas adquiridas en la comunidad. Los parametros medidos fueron: proporcion de prescripciones inadecuadas y DDD. Los datos se analizaron por medio del test de χ2, correccion de Fisher y test de Student. Resultados: Se evaluaron 206 pacientes, observandose una disminucion de 35% en las prescripciones inadecuadas, una reduccion del consumo de ceftriaxona y levofloxacina y un aumento significativo de la utilizacion de ampicilina/sulbactam. Conclusiones: La implementacion de recomendaciones de uso basadas en evidencia cientifica y susceptibilidad local, permitieron disminuir la proporcion de prescripciones inadecuadas y reducir el consumo de ceftriaxona y fluoroquinolonas.

Background: Nowadays about half of antibiotic prescriptions are inadequate, increasing bacterial resistance. Both cephalosporins and fluoroquinolones are associated with this phenomenon: increase of β-lactamase producing bacteria and Clostridioides difficile infections, which is why regulatory agencies seek to rationalize their use. Aim: To evaluate the effect of use recommendations on the proportion of inadequate prescriptions of ceftriaxone and fluoroquinolones. Methods: A prospective and interventional study was developed, comparing the quality and quantity of use of ceftriaxone and fluoroquinolones before and after the implementation of use recommendations for treatments of infectious diseases acquired at the community. The outcomes were: proportion of inadequate prescriptions and defined daily dose (DDD). Data were analyzed using the Chi-square test, Fisher's correction and Student's test. Results: A total of 206 patients were evaluated, a 35% decrease in inadequate prescriptions, a decline in the consumption of ceftriaxone and levofloxacin, and a significant increase in the use of ampicillin/ sulbactam was observed. Conclusions: The implementation of use recommendations based on scientific evidence and local susceptibility allowed to reduce the proportion of inadequate prescriptions and to reduce de consumption of ceftriaxone and fluoroquinolones.

Role of moxifloxacin-dexamethasone in cardiac histomorphometric findings among Wistar rats from infected mothers

Abstract Purpose: To investigate cardiac changes in young rats, whose mothers underwent autogenic fecal peritonitis, during organogenesis phase and to evaluate the role of intravenous administration of moxifloxacin and dexamethasone in preventing infection-related cardiac changes. Methods: A prospective histomorphometric study was performed on 29 hearts of Wistar four-month old rats. Animals were divided into three groups: Negative Control Group (NCG) included 9 subjects from healthy mothers; Positive Control Group (PCG) included 10 subjects from mothers with fecal peritonitis (intra-abdominal injection of 10% autogenic fecal suspension in the gestational period) and did not receive any treatment; and Intervention Group (IG), with 10 animals whose infected mothers received moxifloxacin and dexamethasone treatment 24 hours after induction of fecal peritonitis. Results: Nuclear count was higher in the IG group as compared to PCG (p = 0.0016) and in NCG as compared to PCG (p = 0.0380). There was no significant difference in nuclear counts between NCG and IG. Conclusion: Induced autogenic fecal peritonitis in pregnant Wistar rats determined myocardial changes in young rats that could be avoided by the early administration of intravenous moxifloxacin and dexamethasone.

Indicaciones y perfil de seguridad de las fluoroquinolonas en el tratamiento de la tuberculosis en un hospital general de la Ciudad Autónoma de Buenos Aires / Indications and safety profile of fluoroquinolones in the treatment of tuberculosis in a general hospital of the Autonomous City of Buenos Aires

Introducción: Con frecuencia las fluoroquinolonas integran los esquemas de tratamiento de tuberculosis, tanto en aquellos con enfermedad multirresistente (parte esencial de la prescripción), como también en individuos con tuberculosis sensible e intolerancia a drogas de primera línea. Objetivos: Evaluar cuáles fueron las indicaciones para incluir fluoroquinolonas en el tratamiento antituberculosis y describir los eventos adversos relacionados con su utilización. Materiales y Métodos: Se realizó un análisis retrospectivo de pacientes que iniciaron tratamiento para tuberculosis entre el 1 de enero de 2014 y el 31 de diciembre de 2016. Definimos evento adverso como aquella condición que derivó en la suspensión de un medicamento o la necesidad de utilizar drogas específicas para su manejo. Se utilizó la prueba de c2 para las comparaciones entre grupos. Resultados: Entre los 267 pacientes que iniciaron tratamiento en el período descripto, recibieron fluoroquinolonas 24 individuos (11 hombres) representando el 9% del total; 19 se trataron con moxifloxacina 400 mg/día y el resto con levofloxacina 750 mg/día. Comparando los grupos con fluoroquinolonas vs. sin fluoroquinolonas, no hubo diferencias significativas en el porcentaje de participantes de sexo masculino (46 vs. 58%), edad (34.7 ± 12 vs. 35.1 ± 15 años), afectación pulmonar (58 vs. 68%) y proporción de abandonos (26 vs. 21%). Hubo una mayor proporción de argentinos en el grupo con fluoroquinolonas vs. sin fluoroquinolonas (71 vs. 44%, p = 0.012) y de individuos VIH positivos (46 vs. 8.6%, p < 0.05). Se indicaron fluoroquinolonas en reemplazo de rifampicina en 9 pacientes (37.5%) debido a la interacción de ésta con antirretrovirales, en 9 (37.5%) por intolerancia y en 5 (21%) por resistencia a anti TB de primera línea, en 1 por el antecedente de cirrosis (en lugar de pirazinamida). El tiempo de tratamiento con fluoroquinolonas fue de 203 ± 158 días (rango 30-660) sin observarse eventos adversos relacionados con su uso. Conclusión: En el grupo examinado el uso de fluoroquinolonas no se asoció a eventos adversos, siendo las indicaciones más frecuentes en estos pacientes las interacciones medicamentosas en pacientes VIH positivos y la intolerancia a las drogas de primera línea.

Introduction: The floroquinolones are frequently used in the treatment regimes for tuberculosis (TB) in both those with multidrug-resistant TB (MDR-TB), where it forms an essential part of the regimen, as well as intolerance to first-line drugs in the TB sensitive. Objectives: To evaluate the indications to include floroquinolones in TB treatment and to describe the adverse events associated with its use. Materials and Methods: A retrospective analysis of the patients who began treatment for TB between 1 January 2014 and 31 December 2016 was performed. We define adverse event as that condition that results in the suspension of a medicine or the need to use specific drugs for its management. Group characteristics were comparing by using c2 test. Results: Among the 267 patients who began treatment in the period described, 24 (11 men) received fluoroquinolones representing 9% of the total: 19 moxifloxacin 400 mg/day and the rest levofloxacin 750 mg/day. Comparing the groups with fluoroquinolones vs. without fluoroquinolones, there were no significant differences in the percentage of men (46 vs. 58%), age (34.7 ± 12 vs. 35.1 ± 15 years), pulmonary involvement (58 vs. 68%), and proportion of dropouts (26 vs. 21%). There was a higher proportion of Argentines in the group with fluoroquinolones vs. without fluoroquinolones (71 vs. 44%, p = 0,012) and HIV-positive (46 vs. 8.6%, p < 0.05). Fluoroquinolones were indicated in replacement of rifampicin in 9 patients (37.5%) due to the interaction with antiretroviral drugs, in 9 (37.5%) by intolerance and in 5 (21%) for resistance to first-line anti-TB drugs, in 1 by the history of cirrhosis (instead of pyrazinamide). The time of treatment with fluoroquinolones was 203 ± 158 days (range 30-660) with no observed adverse events related to its use. Conclusion: The use of fluoroquinolones was not associated with adverse events in the group of patients studied, drug interactions in HIV positive patients and the intolerance to first-line drugs were the most frequent indications in the studied group.

Indications and safety profile of fluoroquinolones in the treatment of tuberculosis in a general hospital of the Autonomous City of Buenos Aires

Introduction: Fluoroquinolones are frequently used in treatment regimes for tuberculosis both in cases of multidrug-resistant tuberculosis, where they are an essential part of the regime, and also in cases of drug-sensitive tuberculosis with intolerance to first-line drugs. Objectives: To evaluate indications to include fluoroquinolones in the anti-tuberculosis treatment and to describe the adverse events associated with their use. Materials and Methods: A retrospective analysis of the patients who began treatment for tuberculosis between January 1, 2014 and December 31, 2016 was performed. We defined an adverse event as the condition that resulted in the suspension of a drug or the need to use specific drugs for its management. Group characteristics were compared by using the c2 test. Results: Of the 267 patients who began treatment in said period, 24 (11 men) received fluoroquinolones, representing 9% of the total population; 19 were treated with 400 mg/day of moxifloxacin and the rest with 750 mg/day of levofloxacin. In the comparison of the groups receiving fluoroquinolones versus the ones without fluoroquinolones, there were no significant differences in the percentage of male participants (46 vs. 58%), age (34.7 ± 12 vs. 35.1 ± 15 years), pulmonary involvement (58 vs. 68%) and withdrawal rate (26 vs. 21%). There was a higher proportion of Argentinians (71 vs. 44%, p = 0.012) and of HIV-positive individuals (46 vs. 8.6%) p < 0.05) in the group with fluoroquinolones vs. the group without fluoroquinolones. Fluoroquinolones were indicated in replacement of rifampicin in 9 patients (37.5%) due to its interaction with antiretroviral drugs, in 9 patients (37.5%) due to intolerance, and in 5 patients (21%) due to resistance to first-line anti-tuberculosis drugs. In one individual, fluoroquinolones were indicated instead of pyrazinamide due to history of cirrhosis. The time of treatment with fluoroquinolones was 203 ± 158 days (range 30-660) with no observed adverse events related to their use. Conclusion: In the group under study, the use of fluoroquinolones was not associated with adverse events. The most frequent indications in these patients were drug interactions in HIV-positive patients and intolerance to first-line drugs.

Disglucemia asociada a fluoroquinolonas: una revisión estructurada / Hypo or hyperglycemia associated with fluoroquinolone use

Fluoroquinolone type antimicrobials can cause hypo or hyperglycemia in certain patients. We performed a structured review about this side effect, searching articles published in English or Spanish with full text access in PubMed/Medline. The following MESH terms were used: Hypoglycemia, Hyperglycemia, Quinolones, Ciprofloxacin, Levofloxacin, Moxifloxacin. Additionally, we evaluated the clinical relevance of potential drug interactions, based on the probability of occurrence and the severity of the interaction effect. We obtained 42 publications about the issue; 22 references were selected, where the severity of the interaction in patients with risk factors was evaluated. Patients receiving antidiabetic medications and with risk factors such as advanced age and renal failure may be more likely to have a severe hypoglycemia. In these patients, this drug interaction should be considered clinically relevant since its risk is high or very high.

Intracameral moxifloxacin after cataract surgery: a prospective study / Moxifloxacino intracameral após cirurgia da catarata: estudo prospectivo

ABSTRACT Objective: To study the safety parameters associated with intracameral moxifloxacin application five weeks after cataract surgery. Methods: The study was a prospective case series set in a private hospital in Recife, Pernambuco, Brazil. A consecutive sample of 1,016 cataract surgeries was evaluated. The inclusion criteria were patients with indications for cataract surgery, a minimum of 55 years of age, and no history of allergy to quinolones. Patients were prepared for surgery using a 5% povidone solution diluted as a topical antiseptic agent. The operative technique was phacoemulsification with intraocular lens implantation. A 0.3-mL syringe was partially filled with moxifloxacin and 150 µg/0.03 mL of moxifloxacin was administered through the surgical incision at the end of the surgery. Postoperatively, patients were prescribed: (1) 0.5% moxifloxacin eyedrops 5 times daily for 1 week, and (2) 1% prednisolone acetate eyedrops 5 times daily for 1 week, followed by 4 times daily for 1 week and, subsequently, 2 times daily for 3 weeks. The outcomes were incidence of acute endophthalmitis, mean changes from baseline to 5 postoperative weeks in corneal endothelial cell density, corrected distance visual acuity and intraocular pressure. Results: The mean age was 67 ± 5 years, and 56.2% of the patients were female. There were no cases of endophthalmitis. The mean preoperative corrected distance visual acuity was 58 letters ± 10 (SD), and the mean postoperative corrected distance visual acuity was 80 letters ± 4 (SD). The mean change in corneal endothelial cell density was 249 cells/mm (-10.3%). There was almost no difference in intraocular pressure. No study-related adverse events were observed. Conclusion: The results suggest moxifloxacin is a safe option for intracameral use after cataract surgery.

RESUMO Objetivo: Estudar alguns parâmetros de segurança da moxifloxacino intracameral nas cinco semanas após a cirurgia de catarata. Métodos: O estudo foi uma série de casos prospectivos. O cenário era um hospital privado em Recife, Pernambuco, Brasil. Foi considerada uma amostra consecutiva de 1.016 cirurgias de catarata. Os critérios de inclusão foram pacientes com indicação para cirurgia de catarata, com pelo menos 55 anos de idade e sem história de alergia a quinolonas. Os pacientes foram preparados para cirurgia usando uma solução de povidona a 5% diluída como agente anti-séptico tópico. A técnica operatória foi a facoemulsificação com implante de lente intraocular. Uma seringa de 0,3 mL foi parcialmente preenchida com moxifloxacino. Os pacientes receberam 150 µg/0,03 mL de moxifloxacino através da incisão cirúrgica no final da cirurgia. No pós-operatório, os pacientes foram prescritos: (1) moxifloxacino 0,5% 5 vezes ao dia durante 1 semana e (2) colírio de acetato de prednisolona a 1% 5 vezes ao dia durante 1 semana, seguido de 4 vezes ao dia durante 1 semana e, posteriormente, 2 vezes diariamente por 3 semanas. Os desfechos foram a incidência de endoftalmite aguda, variações entre os valores basais e os na 5ª semana pós-operatória referente à densidade celular endotelial corneana, acuidade visual corrigida para longe e pressão intraocular. Resultados: A média da idade foi de 67 ± 5 anos, e 56,2% dos pacientes eram do sexo feminino. Não houve casos de endoftalmite. A acuidade visual corrigida para longe préoperatório médio foi de 58 letras ± 10 (SD), e a acuidade visual corrigida para longe pósoperatório médio foi de 80 letras ± 4 (SD). A alteração média na densidade celular endotelial corneana foi de 249 células/mm (10,3%). Não houve diferença na pressão intraocular. Não foram observados eventos adversos relacionados ao estudo. Conclusão: Os resultados sugerem que o moxifloxacino é uma opção segura para o uso intracameral após a cirurgia de catarata.

Application of statistical process control for spotting compliance to good pharmaceutical practice

ABSTRACT For the release of pharmaceutical products into the drug market; most of the pharmaceutical companies depend on acceptance criteria - that are set internally, regulatory and/or pharmacopeially. However, statistical process control monitoring is underestimated in most quality control in cases; although it is important not only for process stability and efficiency assessment but also for compliance with all appropriate pharmaceutical practices such as good manufacturing practice and good laboratory practice, known collectively as GXP. The current work aims to investigate two tablet inspection characteristics monitored during in-process control viz. tablet average weight and hardness. Both properties were assessed during the compression phase of the tablet and before the coating stage. Data gathering was performed by the Quality Assurance Team and processed by Commercial Statistical Software packages. Screening of collected results of 31 batches of an antibacterial tablet - based on Fluoroquinolone -showed that all the tested lots met the release specifications, although the process mean has been unstable which could be strongly evident in the variable control chart. Accordingly, the two inspected processes were not in the state of control and require strong actions to correct for the non-compliance to GXP. What is not controlled cannot be predicted in the future and thus the capability analysis would be of no value except to show the process capability retrospectively only. Setting the rules for the application of Statistical Process Control (SPC) should be mandated by Regulatory Agencies.