Abstract
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.
Highlights
The indiscriminate use of antimicrobials in clinical therapy has triggered the emergence of multidrug resistant bacteria (MDR) (Dos Santos, La Rocca, Hörner, 2016), what represents a serious problem for public health worldwide since the therapeutic alternatives for treatments have become limited (Franco, Menezes, Cabral, 2015)
MDR bacteria are microorganisms resistant to different classes of antimicrobials tested in microbiological control tests.The use of these isolates for clinical research was approved by the Research Ethics Committee of Universidade Federal de Santa Maria (UFSM) under the protocol number: 38850614.4.0000.5346
Sertraline and disulfiram showed a synergistic effect against Staphylococcus aureus American Type Culture Collection (ATCC) 25923 and the isolate S. aureus MDR (1) (MIC = 4 μg mL‐1; fractional inhibitory concentration index (FICI)=0 5)
Summary
The indiscriminate use of antimicrobials in clinical therapy has triggered the emergence of multidrug resistant bacteria (MDR) (Dos Santos, La Rocca, Hörner, 2016), what represents a serious problem for public health worldwide since the therapeutic alternatives for treatments have become limited (Franco, Menezes, Cabral, 2015). there is an increasing need for active compounds against MDR bacteria, research for new drugs has not evolved in line with the demand, and alternative measures are necessary for the control of infectious diseases (Grillo etal., 2014). The indiscriminate use of antimicrobials in clinical therapy has triggered the emergence of multidrug resistant bacteria (MDR) (Dos Santos, La Rocca, Hörner, 2016), what represents a serious problem for public health worldwide since the therapeutic alternatives for treatments have become limited (Franco, Menezes, Cabral, 2015). Ashburn and Thor (2004) defined drug repositioning as the process of finding a new indication for a drug which has already been approved. This method has proved to be the preferred alternative strategy for the fast-moving discovery of drugs, since it is relatively cheaper and represents a minimum risk to patients due to the availability of previous pharmacological, safety and toxicological data (Mehndiratta et al, 2016).
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