RESUMO
ABSTRACT The use of drugs in fixed-dose combination (FDC) is now recommended by the World Health Organization (WHO) due to the emergence of multidrug-resistant strains of Mycobacterium tuberculosis. FDC uses different drugs against tuberculosis (TB) in a single tablet for phase-intensive therapeutic intervention. This therapy aims to optimize treatment, to prevent inappropriate use of drugs, and to prevent the emergence of new resistant strains. This study aims to evaluate the susceptibility of clinical isolates of M. tuberculosis against rifampicin, isoniazid, ethambutol, and pyrazinamide. The antimicrobials were tested separately and in associations according to FDC. This was used for broth microdilution method, which was compared to the proportions method previously considered as the gold standard. In antimicrobials testing alone, several strains were resistant to one, two, or three drugs. However, when applied to association of drugs in FDC, there was no antimicrobial resistance. The results strengthen the FDC's concept, which aims to unite the four anti-TB drugs to combat bacterial resistance.
Assuntos
Pirazinamida/administração & dosagem , Rifampina/administração & dosagem , Etambutol/administração & dosagem , Isoniazida/administração & dosagem , Anti-Infecciosos/análise , Mycobacterium tuberculosis , Mycobacterium tuberculosis/classificação , Preparações Farmacêuticas , Testes de Sensibilidade a Antimicrobianos por Disco-DifusãoRESUMO
Rapidly growing mycobacteria (RGM) are opportunistic pathogens found in the environment. When in biofilms, mycobacteria is highly resistant to antibacterial treatments. The purpose of this study is to evaluate the antibiofilm activity of antimicrobials commonly used in therapy against mycobacteria. The antimicrobial susceptibility of Mycobacterium abscessus, Mycobacterium fortuitum and Mycobacterium massiliense was determined in planktonic and sessile populations. The antimicrobials amikacin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole were tested. For each drug, it was evaluated the susceptibility of the pathogen, the ability to inhibit biofilm formation and the resistance of biofilms to antimicrobial activity. Results showed although, the antimicrobials tested are used as an alternative therapy for RGM, M. abscessus proved to be resistant to clarithromycin, beside that, M. massiliense showed a resistant profile to clarithromycin and sulfamethoxazole. Moreover, the inhibition of biofilm formation and its destruction have not been fully met. Considering that the biofilms are a known form of bacterial resistance, the failure of alternatives to inhibit or destroy biofilms can trigger the recurrence of infections. In RGM, besides causing treatment failures, biofilms are a factor of pathogenic risk, since these microorganisms are found in environmental sources and can cause infections easily.
Assuntos
Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Micobactérias não Tuberculosas/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana , Violeta Genciana/análise , Testes de Sensibilidade Microbiana , Micobactérias não Tuberculosas/fisiologia , Espectrofotometria , Coloração e RotulagemRESUMO
Mycobacteriosis is a type of infection caused by rapidly growing mycobacteria (RGM), which can vary from localized illness, such as skin disease, to disseminated disease. Amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole are antimicrobial drugs chosen to treat such illnesses; however, not all patients obtain the cure. The reason why the treatment does not work for those patients is related to the fact that some clinical strains present resistance to the existing antimicrobial drugs; thereby, the research of new therapeutic approaches is extremely relevant. The coordination of antimicrobial drugs to metals is a promising alternative in the development of effective compounds against resistant microorganisms. Sulfonamides complexed with Au, Cd, Ag, Cu, and Hg have shown excellent activity against a variety of microorganisms. Considering the importance of fighting against infections associated with RGM, the objective of this study is to evaluate the antimycobacterial activity of metal complexes of sulfonamides against RGM. Complexed sulfonamides activity were individually tested and in association with trimethoprim. The minimum inhibitory concentration (MIC) and time-kill curve of compounds against the standard strains of RGM [Mycobacterium abscessus (ATCC 19977), Mycobacterium fortuitum (ATCC 6841) and Mycobacterium massiliense (ATCC 48898)] was determined. The interaction of sulfonamides with trimethoprim was defined by inhibitory concentration index fractional for each association. The results showed that sulfonamides complexed whit metals have outstanding antimicrobial activity when compared to free sulfamethoxazole, bactericidal activity and synergistic effect when combined with trimethoprim.
Assuntos
Antibacterianos/farmacologia , Complexos de Coordenação/farmacologia , Metais Pesados/farmacologia , Mycobacterium/efeitos dos fármacos , Mycobacterium/crescimento & desenvolvimento , Sulfonamidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Metais Pesados/química , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Sulfonamidas/químicaRESUMO
This study evaluated the prevalence of nontuberculous mycobacterium (NTM) in relation to the total number of cases of mycobacterial infections detected in patients admitted at the University Hospital of Santa Maria from 2008 to 2010. From the positive samples for the genus Mycobacterium, 67% belonged to the Mycobacterium tuberculosis complex (MTBC) and 33% of them were classified as NTM. This investigation aims to contribute to the epidemiology of mycobacterioses, inasmuch as patients infected by NTM require distinctive treatment and monitoring in comparison with those infected by MTBC.
Foi avaliada a prevalência de micobactérias não tuberculosas (MNT) em relação ao total de casos de micobacterioses identificadas em pacientes do Hospital Universitário de Santa Maria, entre os anos de 2008 e 2010. Entre as amostras positivas para o gênero Mycobacterium, 67% eram do complexo Mycobacterium tuberculosis (CMTB) e 33% foram classificadas como MNT. Este estudo procura contribuir com a epidemiologia das micobacterioses, uma vez que os pacientes infectados por MNT necessitam de tratamento e acompanhamento diferenciado dos infectados pelo CMTB.