ABSTRACT
RESUMO O alarmante aumento na taxa de resistência aos antibióticos põe em check à eficácia da terapia antibacteriana futura. Em contrapartida, as indústrias farmacêuticas negligenciam os investimentos em pesquisa e desenvolvimento de novos fármacos antimicrobianos em virtude de questões financeiras, legais e farmacológicas. Assim sendo, o reposicionamento de agentes disponíveis clinicamente torna-se uma promissora ferramenta para tentar driblar o desinteresse das indústrias. O fármaco antipsicótico clorpromazina (CPZ) destaca-se por possuir uma ampla faixa de atividade antibacteriana, a qual cobre desde patógenos Gram-positivos e Gram-negativos, até as mico-bactérias. A atividade antibacteriana é independente do perfil de susceptibilidade do microrganismo, sendo ela mantida mesmo em cepas altamente resistentes aos antibióticos. Alguns estudos mostram que mesmo nas concentrações clinicamente disponíveis no plasma (entre 0,1-0,5 (g/mL), a CPZ é capaz de matar Staphylococcus aureus e Mycobacterium tuberculosis dentro dos macrófagos. Em adição, estudos clínicos têm revelado os benefícios do uso da CPZ na terapia de suporte para pacientes com infecções em curso. Em conclusão, a CPZ pode eventualmente ser direcionada ao arsenal terapêutico antimicrobiano, especialmente no manejo das infecções causadas por microrganismos intracelulares com fenótipo multirresistente.
SUMMARY The substantial increase in the antibiotic resistance brings on an alarm to the future of the antibiotic therapy. However, the pharmaceutical industry has been neglecting its investments in new drug research and development, mainly because of the pharmacologic, financial and legal factors. Therefore, the drug repositioning of clinic available agents become a promising tool to bypass the lack of interest of the pharmaceutical industry. A drug used to treat psychoses, the Chlorpromazine (CPZ), stands out as a large spectrum antibiotic, which covers Gram-positive and Gram -negative bacteria, and also mycobacteria. Its antibacterial activity is not related to microorganism susceptibility profile, and it could be maintained even on strains highly resistant to the conventional antibiotics. Studies point out that even on serum concentrations clinically available, the CPZ can eliminate Staphylococcus aureus and Mycobacterium tuberculosis inside of macrophages. In addition, clinical trials have revealed its benefits on support therapy for patients suffering from active infections. As a result, the CPZ could be used as an optional antibiotic therapy, especially in case of infections due to intracellular microorganisms with multidrug resistance phenotype.
ABSTRACT
Staphylococcus aureus (S. aureus) es actualmente el agente etiológico más frecuente en infecciones de piel y tejidos blandos. El S. aureus meticilino resistente (SAMR) aislado en infecciones de pacientes de la comunidad ha ido aumentando, constituyéndose en un problema de salud pública a nivel mundial. En Paraguay existen pocos registros sobre la meticilino resistencia y factores de virulencia a nivel comunitario, por lo que se realizó este estudio observacional descriptivo para determinar la frecuencia de SAMR y del factor de virulencia leucocidina de Panton Valentine (PVL-Panton Valentine leukocidin), así como el perfil de resistencia antimicrobiana acompañante a la meticilino resistencia en S. aureus aisladosde infecciones de piel y partes blandas de pacientes ambulatorios de dos laboratorios de Asunción, Paraguay, entre octubre de 2012 a febrero de 2014. La identificación bacteriana se realizó mediante técnicas microbiológicas convencionales y la susceptibilidad antimicrobiana por la prueba de difusión en disco. Elgen mecA y luk-PV fueron detectados por la técnica de PCR. De los 70 aislados de S. aureus estudiados, el 54,3% (38/70) fue SAMR tanto por método fenotípico como molecular. La frecuenciade PVL fue de 15,7% (11/70), siendo mayor en los SAMR (21%; 8/38) que en los SAMS (9,4%; 3/32). El 2,6% de los SAMR presentó resistencia a ciprofloxacina, no se observó multiresistencia en ningún aislado. Se encontró alta frecuencia de SAMR comparado con reportes previos en Paraguay. Se requiere fortalecer estrategias de vigilancia, prevención y control de la resistencia bacteriana en ambientes hospitalarios y de la comunidad.
Staphylococcus aureus (S. aureus) is currently the most common etiologic agentof skin and soft tissue infections. The isolation of methicillin-resistant S. aureus(MRSA) from infections of patients in the community has increased, becoming a public health problem worldwide. In Paraguay, there are few records aboutmethicillin resistance and virulence factors at community level. Therefore, this descriptive observational study was performed to determine the frequency of MRSA and factor virulence of Panton-Valentine leukocidin (PVL) as well as the antimicrobial resistance profile accompanying methicillin resistance in S. aureusisolated from skin and soft tissue infections in ambulatory patients from two laboratories of Asuncion, Paraguay from October, 2012 to February, 2014. The bacterial identification was performed using conventional microbiological techniques and the antimicrobial susceptibility was determined by disk diffusion. The mecA andluk-PV genes were detected by PCR technique. Out of the 70 S. aureus isolates studied, 54.3% (38/70) was SAMR by phenotypic and molecular methods. PVL frequency was 15.7% (11/70) being higher in MRSA (21%; 8/38) than in the SAMS (9.4%; 3/32), 2.6% of the MRSA was resistant to ciprofloxacin and multidrug resistance was not observed in any isolates. A high frequency of MRSA was found compared with previous reports in Paraguay. It is required to strengthen surveillance, prevention and control of bacterial resistance strategies in hospital and community environments.