Resistencia a los antimicrobianos en Chile y el paradigma de Una Salud: manejando los riesgos para la salud pública humana y animal resultante del uso de antimicrobianos en la acuicultura del salmón y en medicina / Antimicrobial resistance in Chile and The One Health paradigm: dealing with threats to human and veterinary health resulting from antimicrobial use in salmon aquaculture and the clinic

El aumento de la resistencia bacteriana múltiple a antimicrobianos es considerado una gran amenaza para la salud pública mundial y como generador de una importante crisis en el funcionamiento de los sistemas de salud. Esta crisis es discutida diariamente por los gobiernos y los parlamentos, las instituciones globales de salud, fundaciones benéficas y de científicos y de profesionales de la salud y también de consumidores de productos animales. En todos los países del orbe se ha identificado al uso de antimicrobianos en la crianza industrial de animales como un importante determinante en la selección de esta resistencia. Aprovechando la oportunidad que se ha planteado en Chile con el diseño del Plan Nacional Contra la Resistencia a los Antimicrobianos, hemos creído importante revisitar y actualizar sumariamente nuestros estudios sobre el uso de antimicrobianos en la acuicultura del salmón y de su potencial impacto en el ambiente y la salud humana y animal. Estos estudios indican que 95% de tres grupos de antimicrobianos importados al país, que incluyen tetraciclinas, fenicoles y quinolonas, son usados en medicina veterinaria y mayormente en la acuicultura del salmón. Nuestros estudios indican que el excesivo uso de estos antimicrobianos genera la presencia de residuos de antimicrobianos en el ambiente marino hasta 8 km de los sitios de acuicultura, los que seleccionan a bacterias con resistencia múltiple en dicho ambiente, ya que ellas contienen variados genes de resistencia a estos antimicrobianos. Estos genes de resistencia están contenidos en elementos genéticos móviles incluyendo plásmidos e integrones, los que son trasmitidos a otras bacterias permitiendo su potencial diseminación epidémica entre poblaciones bacterianas. Bacterias del ambiente marino contienen genes idénticos a los genes de resistencia a quinolonas e integrones similares a los de patógenos humanos, sugiriendo comunicación genética entre estas bacterias de diversos ambientes. Alrededor de los recintos de acuicultura, este uso exagerado de antimicrobianos contamina con ellos también a peces silvestres para consumo humano y potencialmente selecciona BRA en su carne y en los productos de acuicultura. El consumo de estos productos selecciona bacterias resistentes en el microbioma humano y facilita también el intercambio genético entre bacterias del ambiente acuático y la microbiota comensal y patógena humana. El pasaje de antimicrobianos al ambiente marino disminuye la diversidad en él, y potencialmente podría facilitar la aparición de florecimientos de algas nocivas, la infección de peces por patógenos piscícolas resistentes los antimicrobianos y la aparición de patógenos zoonóticos resistentes, incluyendo a Vibrio parahaemolyticus. Estos hallazgos sugieren que la prevención de infecciones en peces y la disminución del uso de antimicrobianos en su crianza, será en Chile un factor determinante en la prevención de infecciones humanas y animales con resistencia múltiple a los antimicrobianos, de acuerdo con el paradigma moderno e integral de Una Salud.

The emergence and dissemination of antimicrobial-resistant bacteria (ARB) is currently seen as one of the major threats to human and animal public health. Veterinary use of antimicrobials in both developing and developed countries is many-fold greater than their use in human medicine and is an important determinant in selection of ARB. In light of the recently outlined National Plan Against Antimicrobial Resistance in Chile, our findings on antimicrobial use in salmon aquaculture and their impact on the environment and human health are highly relevant. Ninety-five percent of tetracyclines, phenicols and quinolones imported into Chile between 1998 and 2015 were for veterinary use, mostly in salmon aquaculture. Excessive use of antimicrobials at aquaculture sites was associated with antimicrobial residues in marine sediments 8 km distant and the presence of resistant marine bacteria harboring easily transmissible resistance genes, in mobile genetic elements, to these same antimicrobials. Moreover, quinolone and integron resistance genes in human pathogens isolated from patients in coastal regions adjacent to aquaculture sites were identical to genes isolated from regional marine bacteria, consistent with genetic communication between bacteria in these different environments. Passage of antimicrobials into the marine environment can potentially diminish environmental diversity, contaminate wild fish for human consumption, and facilitate the appearance of harmful algal blooms and resistant zoonotic and human pathogens. Our findings suggest that changes in aquaculture in Chile that prevent fish infections and decrease antimicrobial usage will prove a determining factor in preventing human and animal infections with multiply-resistant ARB in accord with the modern paradigm of One Health.

Meta-analysis on the efficacy and tolerability of the augmentation of antidepressants with atypical antipsychotics in patients with major depressive disorder

We assessed the efficacy and tolerability of the augmentation of antidepressants (ATDs) with atypical antipsychotics (AAPs) to treat patients with major depressive disorder. A retrograde study to identify relevant patient data included databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects. Data from 17 trials, involving 3807 participants, were identified. The remission rate (RR) and overall response rate (ORR) of adjunctive treatment with AAPs were significantly higher than placebo treatment: RR=1.90 (95%CI=1.61-2.23, z=7.74, P<0.00001) and ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001). We found that the short-term (4 weeks) treatment [ORR=1.70 (95%CI=0.98-2.95, Z=1.89, P=0.06)] was significantly different from the long-term (6-12 weeks) treatment [ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001)]. No significant difference in ORR was observed between groups with or without sedative drugs. The discontinuation rate due to adverse effects was higher for adjunctive treatment with AAPs: ORR=3.32 (95%CI=2.35-4.70, z=6.78, P<0.00001). These results demonstrate that the augmentation of ATDs with AAPs (olanzapine, quetiapine, aripiprazole, and risperidone) was more effective than a placebo in improving response and remission rates, although associated with a higher discontinuation rate due to adverse effects.

Proposta sobre uso de dados de receitas de antimicrobianos retidas: a experiência EUREQA / A proposal for using data from antimicrobial prescriptions: the EUREQA experience

A presente nota pesquisa demonstra que o uso das informações de receituário ou prescrição médica tem fundamental valor para a compreensão das correlações da dinâmica da resistência bacteriana comunitária. Além disso, a análise dos dados gerada pode ajudar a estabelecer medidas e políticas de saúde pública mais adequadas para o controle e a otimização do consumo de antimicrobianos. Para isso, o artigo usa como base o modelo lógico desenvolvido pelo Projeto EUREQA voltado para aquisição, classificação, interpretação e análise das informações relacionadas à prescrição dos antimicrobianos de uso oral.

This study demonstrates that the use of information from medical prescriptions is essential for understanding the dynamics of community bacterial resistance. The resulting analysis can also influence and help establish more adequate public health policies on the control and optimization of antimicrobial use. The article demonstrates the use of a logical model developed by the EUREQA project for acquisition, classification, interpretation, and analysis of data from prescriptions for oral antimicrobial use.

Controversias sobre el uso de fluoroquinolonas en los niños / Debate over the use of fluoroquinolones in children

En ciertas especies de animales inmaduros se ha documentado que las quinolonas generan el desarrollo de una artropatía secundaria a alteración del cartílago de crecimiento

[Investigation of the preventive effect of glucosamine, chondroitin alone and in combination on cartilage insult caused by quinolone in juvenile rats]

Osteoarthritis is considered the most common joint disease in the world, especially among the aged population. But it may affect the kids as a secondary type when kids were administered some groups of drugs such as quinolones which cause cartilage deformations and predispose to secondary type of osteoarthritis. This study aims to investigate the protective effect of glucosamine and chondroitin alone and in combination in the treatment of arthritis in Juvenile Rats. This study was applied on 5 groups of juvenile wistar rats, which divided as: normal group, control group, the group of GA, group of CS, the group of combination between GA+CS. At the end of the study all of rats were killed, then measurement of maximum extension of the right knee were performed, also histological and functional analysis of the articular cartilage of the knee were performed. Control group showed the degenerative changes as compared to the normal group, which is improved into the groups of GA, CS, which distinguished from the combination group. This study shows that GA and CS have protective effect able to opposite the destructive effect of quinolone on immature cartilages

Monitoramento de eventos adversos em ambiente hospitalar: relato de farmacovigilância, São Paulo / Monitoring of adverse events in hospitals: report of pharmacovigilance, São Paulo

Introdução: O percentual de internações hospitalares devido às reações adversas (RA) a medicamentos em alguns países é cerca de 10% (OPAS/OMS) e acarreta gastos adicionais para o sistema de saúde. Objetivo: Determinar medicamentos mais envolvidos em RA e as RA mais comuns. Métodos: Realizou-se um monitoramento descritivo de RA em hospital privado de São Paulo, de 2004 a 2008, em 197 leitos, totalizando 100 notificações. Dados descritos em frequência (n de RA relatadas). Resultados: Os medicamentos mais envolvidos em RA foram:cefalosporinas (13%) e quinolonas (12%). As RAs foram: rash cutâneo (20%), prurido (13%), hiperemia (12%), náusea (10%), tremores (9%), placas eritematosas (6%), etc. Observou-se que 61% dos indivíduos com RA são do sexo feminino. Conclusão: Sugere-se uma atitude positiva em farmacovigilância, para que a notificação se torne rotina. Verificou-se que houve crescimento das notificações. Pacientes do sexo feminino apresentaram mais RA e os antibióticos foram os medicamentos com maior RA.

Introduction: According to PAHO/WHO, the hospital admissions? due to adverse drug reactions (ADR) in some countries is around 10%, resulting in additional costs for health system. Objective: To determine which drugs are involved in adverse drug reactions and the most common reactions. Methods: We conducted a descriptive monitoring of ADR in a private hospital in São Paulo (Brazil), from 2004 to 2008, in 197 beds, totaling 100 notifications. Data described in frequency (n ADR reported). Results: The drugs most commonly involved in ADR were cephalosporins (13%) and quinolones (12%). The adverse reactions were rash (20%), pruritus (13%), redness (12%), nausea (10%), tremors (9%), erythematous plaques (6%), etc. We observed that 61% of individuals with ADR are female. Conclusion: Achieve the development of positive attitude towards pharmacovigilance among healthcare professionals to ADR becomes accepted and understood. There was an increase in notifications, antibiotics are involved in ADR and female have more ADR.

Efficacy and safety of atypical antipsychotic drugs (quetiapine, risperidone, aripiprazole and paliperidone) compared with placebo or typical antipsychotic drugs for treating refractory schizophrenia: overview of systematic reviews / Eficácia e segurança dos antipsicóticos atípicos (quetiapina, risperidona, aripiprazol, paliperidona) em comparação com um placebo ou medicamentos antipsicóticos típicos no tratamento da esquizofrenia refratária: overview de revisão sistemática

CONTEXT AND OBJECTIVE: According to some cohort studies, the prevalence of refractory schizophrenia (RS) is 20-40 percent. Our aim was to evaluate the effectiveness and safety of aripiprazole, paliperidone, quetiapine and risperidone for treating RS. METHODS: This was a critical appraisal of Cochrane reviews published in the Cochrane Library, supplemented with reference to more recent randomized controlled trials (RCTs) on RS. The following databases were searched: Medical Literature Analysis and Retrieval System Online (Medline) (1966-2009), Controlled Trials of the Cochrane Collaboration (2009, Issue 2), Embase (Excerpta Medica) (1980-2009), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) (1982-2009). There was no language restriction. Randomized controlled trials, systematic reviews and meta-analyses evaluating atypical antipsychotics for treating RS were included. RESULTS: Seven Cochrane systematic reviews and 10 additional RCTs were included in this review. The data generally showed minor differences between the atypical antipsychotics evaluated and typical antipsychotics, regarding improvement in disease symptoms, despite better adherence to treatment with atypical antipsychotics. Risperidone was specifically evaluated in patients with RS in one of the systematic reviews included, with favorable outcomes, but without definitive superiority compared with other drugs of proven efficacy, like amisulpride, clozapine and olanzapine. CONCLUSIONS: The findings underscore the difficulty in treating these patients, with high dropout rates and treatment patterns of modest improvement in assessments of effectiveness. Atypical antipsychotics have advantages over typical antipsychotics mainly through their better safety profile, which leads to better adherence to treatment. A combination of antipsychotics may also be an option for some refractory patients.

CONTEXTO E OBJETIVO: De acordo com alguns estudos de coorte, a prevalência da esquizofrenia refratária (ER) está entre 20-40 por cento. Nosso objetivo foi avaliar a efetividade e segurança de aripiprazol, paliperidona, quetiapina e risperidona no tratamento da esquizofrenia refratária. MÉTODOS: Avaliação crítica das revisões Cochrane publicadas na Biblioteca Cochrane e complementação com referências de ensaios clínicos randomizados (ECRs) mais atualizados sobre ER. As seguintes bases de dados foram pesquisadas: Medline (Medical Literature Analysis and Retrieval System Online) (1966-2009), Ensaios Controlados da Colaboração Cochrane (2009, edição 2), Embase (Excerpta Database) (1980-2009), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) (1982-2009). Não houve restrição a idiomas. Ensaios clínicos randomizados, revisões sistemáticas e metanálises que avaliaram antipsicóticos atípicos no tratamento da esquizofrenia refratária foram incluídos. RESULTADOS: Sete revisões sistemáticas Cochrane e 10 ECRs complementares foram incluídos nessa revisão. No geral os dados demonstram pequenas diferenças entre os antipsicóticos atípicos avaliados e os típicos na melhora dos sintomas da doença, apesar da melhor adesão ao tratamento com os atípicos. A risperidona foi avaliada especificamente em pacientes com esquizofrenia refratária em uma das revisões sistemáticas incluídas, a qual demonstrou desfechos favoráveis, porém não definitivos quando comparada a drogas também com eficácia comprovada como amisulprida, clozapina e olanzapina. CONCLUSÕES: Os dados reforçam a dificuldade de tratar esses pacientes, com elevadas taxas de desistência do tratamento e padrões de melhora modestos nas avaliações de eficácia. Os antipsicóticos atípicos têm vantagens sobre os típicos principalmente pelo melhor perfil de segurança, o que leva a melhor adesão ao tratamento. A associação de antipsicóticos também pode ser uma opção em alguns pacientes refratários ao tratamento.

O uso de antipsicóticos em pacientes com diagnóstico de demência / The use of antipsychotics in patients with dementia

OBJETIVO: Revisar sistematicamente as evidências que sustentam o uso de antipsicóticos no tratamento dos sintomas comportamentais e psicológicos em pacientes com demência, assim como rever as controvérsias e desvantagens dessa prescrição, tendo em vista, por um lado, a elevada prevalência destas manifestações no curso clínico das demências e, por outro, a maior susceptibilidade do idoso aos eventos adversos desses medicamentos. MÉTODO: Revisão sistemática da literatura sobre o uso de antipsicóticos típicos e atípicos em pacientes portadores de síndromes demenciais. As bases de dados usadas para este fim foram o PubMed/Medline, Embase e SciELO. A busca por trabalhos se limitou aos anos de 1986 a 2007, selecionando-se ensaios clínicos randomizados e metanálises da literatura. RESULTADOS: Há evidências a partir de ensaios randomizados, duplamente encobertos, controlados por placebo, de que os antipsicóticos típicos e atípicos são eficazes no tratamento dos sintomas comportamentais que ocorrem nas síndromes demenciais, especialmente os quadros psicóticos e alterações do comportamento motor. Entretanto, o uso destas medicações está associado a eventos adversos importantes. Embora os antipsicóticos atípicos estejam menos associados aos efeitos colaterais extrapiramidais, comuns entre os neurolépticos de primeira geração, podem aumentar a incidência de eventos cerebrovasculares e do risco de morte, sobretudo em pacientes vulneráveis. CONCLUSÃO: Os antipsicóticos devem ser usados com cautela nos pacientes com demência, buscando otimizar o regime de dosagem e duração do tratamento, e avaliando-se individualmente a relação risco-benefício.

OBJECTIVE: The objective of the present study is to systematically review the supporting evidence for the use of antipsychotics in the treatment of behavioral and psychological symptoms in patients with dementia, as well as the controversies and limitations of this prescription. We discuss the available evidence in the light of the high prevalence of behavioral and psychological symptoms of dementia in this population, along with the greater susceptibility of elderly patients to adverse events. METHOD: Systematic literature review of the use of typical and atypical antipsychotics in patients with dementia was carried out in the databases PubMed/Medline, Embase and SciELO. The search was limited to clinical trials and meta-analysis of the literature published from 1986 to 2007. RESULTS: Evidence drawn from randomized, double-blind, placebo controlled trials support the use of both typical and atypical antipsychotics in the treatment of behavioral symptoms of dementia, especially psychotic symptoms and abnormal psychomotor activity. Nevertheless, the use of these drugs in demented patients is not devoid of important adverse events. Although the induction of extrapiramidal symptoms is not as frequent or severe with atypical antipsychotics as it is with first-generation neuroleptics, the former drugs may particularly increase the risk of cerebrovascular events and death. CONCLUSION: Although effective, antipsychotic drugs must be prescribed cautiously in patients with dementia. Dose regimens, duration of treatment and a cautious assessment of risk-benefit must be established for each patient.

Fluoroquinolonas respiratorias como antibiótico de primera línea en neumonía adquirida en la comunidad, posición en contra / Respiratory fluoroquinolones as first-line antibiotic in community acquired pneumonia, position against

Las fluoroquinolonas respiratorias, son efectivas contra la mayoría de los posibles patógenos de neumonía adquirida en la comunidad (NAC), tienen biodisponibilidad adecuada y baja toxicidad. Podrían ser consideradas una opción de primera línea para la NAC. Ciprofloxacina muestra tasas bajas de resistencia a S. pneumoniae, pero un aumento creciente de resistencia para enterobacterias. Existe aumento de la resistencia a quinolonas del neumococo en varios países, en Hong Kong llegó al 13.3 %. En Argentina la resistencia a levofloxacina fue 2% en 2004. Preocupa la coexistencia de resistencia de S. pneumoniae a penicilina y macrólidos. En pacientes que necesitan internación por su gravedad, se puede usar fluoroquinolonas como tratamiento alternativo. Las quinolonas son activas ®in vitro¼ contra Myobacterium tuberculosis, el uso de estos antibióticos con sospecha de NAC que en realidad padecen tuberculosis se asocia a retraso en el diagnóstico y creciente resistencia a fluoroquinolonas. No hay evidencias las quinolonas como primera opción en el paciente ambulatorio con NAC, produzca mejores resultados que losBeta-lactámicos. Esa indicación ocasionaría un aumento importante en el consumo de esas drogas, lo que traería como consecuencia, un aumento de la resistencia del neumococo y otros gérmenes sin una clara ventaja terapéutica.

The newer fluoroquinolones are active against most of the potencial pathogens of community acquired pneumonia (CAP), and have high bioavailability and low toxicity. They could be considered a first line option for CAP. Ciprofloxacin presents low resistance rates for S.pneumoniae, but an increasing incidence of resistance among enterobacteriaceae.Quinolones’ resistance is growing, in Hong Kong achieved 13.3%. In Argentina resistance to levofloxacin was 2% in 2004. The coexistence of S. pneumoniae resistant to penicillinand macrolides is worrisome. Fluoroquinolones could be an alternative for those CAP patients that need to be admitted because of their severity of illness. Quinolones are active ®invitro¼ against Myobacterium tuberculosis, the use of these antibiotics for CAP suspicion in patients with tuberculosis has been associated with a delay in the therapy and worseningof resistance to fluoroquinolones. There are not evidences supporting that the use of these antibiotics as the first line of therapy in the outpatient with CAP produces better results than beta-lactams. The indiscriminate use may produce a significant increase in the use of quinolones and as a consequence to an increase of resistance of pneumococcus and other microorganisms, without a clear advantage.

Effect of flumequine on the growth, residual measurements and chromosomal aberrations in tilapia fish

Flumequine [Flu] is a powerful antibacterial agents used against bacterial infections in fish farming because of their high potency against Gram-negative bacteria. The present work aimed to study the effect of different doses of flumequine [0, 6, 8, 10, 12 mg during 90 days and 12 mg therapeutic dose for 5 days] on growth performance, feed utilization, body composition, chromosomal aberrations and determination of flumequine residues in tissues of the tilapia fish. The results revealed that the dose of 10 mg/kg body weight/ day caused significant increase in final body weight, body length, weight gain, specific growth rate and feed intake. Moreover, it improved feed conversion ratio with the same dose whereas the other doses caused non-significant change in feed conversion ratio compared with control group. Also, he best protein efficiency ratio [1.95] was recorded by fish fed the diet with 10 mg/kg body weight/day]. Results of proximate analysis of whole fish body showed that, the fish with dose 10 mg/kg body weight/day gained the highest percentage of protein and the lowest percentage of moisture, fat and ash. Determination of flumequine residues in muscle of fish at the end of the experiment after three month showed negative results. Flumequine at dose of 10 mg/kg body weight/ day caused the lowest percentage in total chromosomal aberrations compared with the other doses that caused the highest percentage of total chromosomal aberration. In conclusion, this study recommended the addition of flumequine to fish diets at a dose of 10 mg/kg body weight/ day as prophylactic dose in order to increase growth performance, feed utilization and decrease mortality of Nile tilapia

Tratamiento de la gonorrea en adolescentes y adultos / Gonorrhea treatment in adolescents and adults

La gonorrea continúa siendo una enfermedad frecuente. En Chile 70 porciento de las cepas de neisseria gonorrhoeae son resistentes a penicilina y mantienen 100 porciento de sensibilidad a cefalosporinas de tercera generación y ciprofloxacina. Se revisan los esquemas terapéuticos propuestos para las infecciones gonocóccicas uretrales, cervicales, rectales, faríngeas, conjuntivales, forma diseminada, endocarditis y meningitis. Además se comentan las exigencias del tratamiento en la mujer embarazada, en pacientes infectados por virus de inmunodeficiencia humana, en casos de coexistencia con chlamydia trachomatis y en pacientes alérgicos a b lactámicos

Quinolonas y terapia antimicrobiana / Quinolones and anti-microbian therapy

Se revisan las características químicas y el mecanismo de acción de las quinolonas y se hace hincapié en las fluoroquinolonas. Se comentan los aspectos más importantes en relación con su actividad in vitro, así como sus características farmacológicas más importantes. Se señalan las indicaciones más frecuentes y se especifican en algunos casos las dosis y las vías de administración. Se reseñan los efectos adversos más comunes y se hace una breve revisión de algunas de las nuevas quinolonas en fase de experimentación

Novos antimicrobianos utilizados por via oral na prática pediátrica / New antibiotics for oral use in children

Os autores descrevem e analisam os novos antibióticos empregados na prática pediátrica à luz da experiência da Equipe do Hospital Universitário da USP. Concluem pela utilização limitada destes antimicrobianos em situaçòes clínicas específicas (au)