Synergistic effect of sertraline and disulfiram against multidrug resistant bacteria as a new alternative to drug repositioning

The repositioning of approved drugs is atopic of interest for the academy and the pharmaceutical industry. The synergistic combination of these drugs can be successful in the treatment of infections caused by resistant bacteria. This study aimed to assess the in vitro synergistic antibacterial activity of sertraline and disulfiram and their interaction with ciprofloxacin and sulfamethoxazole/trimethoprim. We determined the minimum inhibitory concentration, the minimum bactericidal concentration and the fractional inhibitory concentration index. Eighteen bacterial strains were used, being nine American Type Culture Collection reference strains and nine multidrug resistant clinical isolates. Synergy was detected between sertraline and disulfiram against a strain of Staphylococcus aureusATCC 25923 and a clinical isolate of S. aureus. When associated to sulfamethoxazole/trimethoprim and ciprofloxacin, sertraline and disulfiram showed eight synergistic events, which occurred against three different standard strains and two multidrug resistant clinical isolates. When the minimum bactericidal concentration was determined, the bactericidal activity of sertraline was enhanced with disulfiram. Our results suggest that these drugs, widely used to treat depression and chronic alcoholism, have antibacterial potential individually, in association, and combined with antimicrobials, what makes their repositioning a promising therapeutic alternative for the effective treatment of infections caused by multidrug resistant bacteria.

Prevalência e perfil de sensibilidade de bactérias isoladas da urina de gestantes atendidas no serviço de obstetrícia de um hospital terciário / Prevalence and susceptibility profile of bacteria isolated from urine of pregnant women seen at the department of obstetrics of a tertiary hospital

OBJETIVOS: Avaliar a prevalência e o perfil de sensibilidade aos antimicrobianos de bactérias isoladas de uroculturas de gestantes atendidas no ambulatório do Serviço de Obstetrícia do Hospital Universitário de Santa Maria, Brasil. MÉTODOS: Foi realizado um estudo retrospectivo dos laudos emitidos pelo Laboratório de Análises Clínicas do Hospital Universitário de Santa Maria. Foram incluídas no estudo todas as uroculturas positivas de gestantes atendidas no ambulatório do Serviço de Obstetrícia deste hospital, no período de janeiro a dezembro de 2014. Os testes de identificação dos micro-organismos isolados e os perfis de sensibilidade frente aos antimicrobianos foram efetuados por meio de um sistema automatizado. RESULTADOS: No período do estudo foram identificadas neste laboratório 423 uroculturas positivas provenientes de gestantes. A bactéria Gram negativa Escherichia coli foi a mais prevalente (46,50% das culturas positivas). A segunda bactéria mais frequente foi a Gram positiva Staphylococcus saprophyticus (6,2%). O fungo Candida spp. foi isolado de 94 (21,8%) amostras de urina. Nitrofurantoína e amoxicilina/ácido clavulânico foram os antimicrobianos com menor taxa de resistência por parte de E. coli (91,33% e 90,77% de sensibilidade, respectivamente). Já frente às bactérias Gram positivas prevalentes, ampicilina foi a que mostrou maior sensibilidade. CONCLUSÕES: O perfil de suscetibilidade apresentado neste estudo indica que a escolha para o tratamento da ITU na gestação pode recair em nitrofurantoína e/ou amoxicilina/ácido clavulânico para as bactérias Gram negativas. Tendo em vista a prevalência encontrada, esses antimicrobianos podem ser iniciados empiricamente antes do resultado da urocultura, nos casos de ITU sintomática. Este estudo ratifica, entretanto, a importância da realização da urocultura entre os exames pré-natais e sua repetição no terceiro trimestre da gravidez, tendo em vista a variedade de micro-organismos identificados e os diferentes perfis de sensibilidade aos antimicrobianos testados.

AIMS: To evaluate the prevalence of bacteria in urine cultures of pregnant women seen at the outpatient clinic of the Department of Obstetrics at the University Hospital of Santa Maria, Brazil, and to determine the antibiotic sensitivity profile of these bacteria. METHODS: The reports issued by the Laboratory of Clinical Analysis of the University Hospital of Santa Maria were retrospectively analyzed. All positive urine cultures of pregnant women seen at the Department of Obstetrics from January to December 2014 were included in the study. The tests for the identification of bacterial isolates and their sensitivity profiles were assessed by an automated system. RESULTS: A total of 423 positive urine cultures were detected in the pregnant women. Gram-negative Escherichia coli was the most prevalent microorganism (46.50%). Gram-positive Staphylococcus saprophyticus was the second most prevalent bacterium (6.2%). Candida spp. was isolated from 94 (21.8%) urine samples. Nitrofurantoin and amoxicillin/clavulanic acid showed the lowest antimicrobial resistance against E. coli (91.33% and 90.77%, respectively). Ampicillin had the highest sensitivity among prevalent Gram-positive bacteria. CONCLUSIONS: The sensitivity profile found in this study allows us to suggest nitrofurantoin and/or amoxicillin/clavulanic acid for the treatment of urinary tract infection caused by Gram-negative bacteria during pregnancy. Given the prevalence rates detected in this study, these antimicrobials can be initiated empirically before the urine culture results are known, in the cases of symptomatic urinary tract infection. This study underscores the importance of urine culture in the prenatal period and in the third trimester because of the different microorganisms identified and the different sensitivity to the antimicrobials tested.

Evaluation of constitutive and inducible resistance to clindamycin in clinical samples of Staphylococcus aureus from a tertiary hospital

Introduction Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have become common in hospitals and the community environment, and this wide resistance has limited patient treatment. Clindamycin (CL) represents an important alternative therapy for infections caused by S. aureus. Antimicrobial susceptibility testing using standard methods may not detect inducible CL resistance. This study was performed to detect the phenotypes of resistance to macrolides-lincosamides-streptogramin B (MLSB) antibiotics, including CL, in clinical samples of S. aureus from patients at a tertiary hospital in Santa Maria, State of Rio Grande do Sul, Brazil. Methods One hundred and forty clinical isolates were submitted to the disk diffusion induction test (D-test) with an erythromycin (ER) disk positioned at a distance of 20mm from a CL disk. The results were interpreted according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI). Results In this study, 29 (20.7%) of the 140 S. aureus samples were resistant to methicillin (MRSA), and 111 (79.3%) were susceptible to methicillin (MSSA). The constitutive resistance phenotype (cMLSB) was observed in 20 (14.3%) MRSA samples and in 5 (3.6%) MSSA samples, whereas the inducible resistance phenotype (iMLSB) was observed in 3 (2.1%) MRSA samples and in 8 (5.8%) MSSA samples. Conclusions The D-test is essential for detecting the iMLSB phenotype because the early identification of this phenotype allows clinicians to choose an appropriate treatment for patients. Furthermore, this test is simple, easy to perform and inexpensive. .