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Vol. 22. Num. 3.May - June 2018
Pages 159-256
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Vol. 22. Num. 3.May - June 2018
Pages 159-256
Letter to the editor
DOI: 10.1016/j.bjid.2018.05.007
Open Access
Drug repositioning, a new alternative in infectious diseases
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Marissa Bolson Serafina, Rosmari Hörnera,b,
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rosmari.ufsm@gmail.com

Corresponding author.
a Universidade Federal de Santa Maria, Programa de Pós-graduacão em Ciências Farmacêuticas, Santa Maria,RS, Brazil
b UniversidadeSanta Maria, Departamento de Análises Clínicas e Toxicológicas, Santa Maria, RS, Brazil
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Table 1. Studies of repositioning non-antibiotic drugs with antibiotic effect.
Dear Editor:
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There has been a significant decrease in the number of approved antibiotics in the last two decades, and in parallel, a steady increase of multidrug resistant bacteria (MDR) has been occurring. Thus, MDR have become a global issue of public health, and with this threat, the challenge to develop new antibiotics has emerged in all areas: governmental, scientific, and the private pharmacological industry.1 In this sense, drug repositioning has arisen as an alternative approach for the faster identification of drugs that are effective against infectious diseases.2

The expressions “Drug repositioning” and “drug repurposing” was first described by Ashburn and Thor (2004)3 in their paper “Drug repositioning: identifying and developing new uses for existing drugs”. According to the authors, this is the process to find new uses for clinically approved drugs, and this is also known as redirecting and reprofiling.

Several studies have signalled that drug repositioning has advantages compared to the traditional way of seeking for active substances,2,4–7 since pharmacological, toxicological and bioavailability data, among others, are already available. Thus, less time is spent in their development, leading to a significant reduction in costs, and it proves to be a preferred and advantageous alternative strategy to discover drugs more quickly.4 Other encouraging data are the success rates for repositioned drugs, which are higher when compared to new drugs, reaching 30% in the last few years. Also, together with the positive aspects of repositioning is its recent approval by the Food and Drug Administration (FDA).8

Comparing repurposing and use off-label, there is a similarity between these practices: a new indication of the drug, other than the usual one. However, the use outside the label goes beyond this, since it may include different age groups, dosage or route of administration. Although this is considered a legal and common application, it is often performed in the absence of adequate scientific data, and may expose patients to unrestricted and ineffective experimentation of drugs with unknown health risks.9

In Table 1, we present a summary of the repositioning of drugs for antibacterial treatment: examples of studies that investigate the antimicrobial activities of several pharmacological classes, including psychotropics, local anaesthetics, tranquilizers, cardiovascular drugs, antihistamines, anti-inflammatories, being these called “non-antibiotic drugs”.10–14

Table 1.

Studies of repositioning non-antibiotic drugs with antibiotic effect.

Drug  Original indication  New indicationReference 
AAS  Non-steroidal Anti-inflammatory  MRSAChan et al., 201710 
Amitriptiline  AntidepressantStaphylococcus spp.
Enterococcus faecalis
Micrococcus luteus
Bacillus spp.
Shigella spp.
Salmonella spp.
Vibrio cholerae
Vibrio parahaemolyticus
Escherichia coli
Klebsiella pneumonia
Pseudomonas spp.
Proteus spp.
Citrobacter spp.
Providencia spp.
Enterobacter cloacae
Hafnia spp.
Lactobacillus sporogenes
Micrococcus flavus
Vibrio cholerae 
Mandal et al., 201011

Muthukumar and Janakiraman, 201422 
Auranofin  RheumatoidarthritisMRSA  Harbut et al., 201523 
Chlorpromazine  Anti-psychoticCorynebacterium urealyticum
Escherichia coli
Klebsiella pneumoniae
Citrobacter freundii
Morganella morganii
Acinetobacter baumannii
Haemophilus influenzae
Moraxella catarrhalis
Campylobacter jejuni
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus pyogenes
Streptococcus agalactiae
Enterococcus faecalis
Clostridium perfringens
Clostridium difficile
Bacreroides fragilis
Prevotella spp.
Brucella spp. 
Munoz-Bellido, Munoz-Criado and García-Rodríguez, 199612

Munoz-Bellido, Munoz-Criado and García-Rodríguez, 200013 
Clofazime  TuberculosisMycobacterium leprae  Naylorand Schonfeld, 201424 
Clomipramine  AntidepressantSerratia marcescens
Morganella morganii
Acinetobacter baumannii
Haemophilus influenza
Campylobacter jejuni
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus pyogenes
Streptococcus agalactiae
Enterococcus faecalis
Clostridium perfringens
Clostridium difficile
Bacteroides fragilis
Prevotella spp.
Brucella spp. 
Munoz-Bellido, Munoz-Criado and García-Rodríguez, 200013 
Disulfiram  AlcoholismMRSA
Pseudomonas aeruginosa 
Phillips et al., 199125
Velasco-García et al., 200626 
Ebselen  NeuroprotectorMRSA
VRSA
Streptococcus spp.
Enterococcus spp. 
Thangamani, Younis e Seleem 20156,7 
Escitalopram  AntidepressantKlebsiella pneumoniae
Proteus mirabilis
Enterobactor cloacae
Staphylococcus aureus Pseudomonas aeruginosa 
Akilandeswari, Ruckmani and Ranjith, 201327 
Fluoxetine  AntidepressantCorynebacterium urealyticum
Haemophilus influenzae
Moraxella catarrhales
Campylobacter jejuni 
Munoz-Bellido, Munoz-Criado and García-Rodríguez, 199612
Munoz-Bellido, Munoz-Criado and García-Rodríguez, 200013 
Ibuprofen  Non-steroidalAnti-inflammatoryMRSA  Chan et al., 201710 
Iproniazid  AntidepressantMycobacterium tuberculosis  López-Muñoz and Alamo, 200928 
Loperamide  DiarrhoeaSalmonella enterica  Ejim et al., 201116 
Sertraline  AntidepressantCorynebacterium urealyticum
Escherichia coli
Klebsiella pneumoniae
Enterococcus cloacae
Citrobacter freundii
Serratia marcescens
Proteus mirabilis
Proteus vulgaris
Morganella morganii
Acinetobacter baumannii
Haemophilus influenzae
Moraxella catarrhalis
Campylobacter jejuni
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus pyogenes
Streptococcus agalactiae
Enterococcus faecalis
Clostridium perfringens
Clostridium difficile
Bacteroides fragilis
Prevotella spp.
Brucella spp.
Staphylococcus spp.
Micrococcus luteus
Bacillus subtilis
Shigella spp.
Salmonella spp.
Vibrio cholerae
Vibrio parahaemolyticus
Pseudomonas aeruginosa
Providencia spp.
Lactobacillus sporogenes 
Munoz-Bellido, Munoz-Criado and García-Rodríguez, 199612

Munoz-Bellido, Munoz-Criado and García-Rodríguez, 200013

Samanta et al., 201229 
Paroxetine  AntidepressantCorynebacterium urealyticum
Haemophilus influenzae
Moraxella catarrhales
Campylobacter jejuni 
Munoz-Bellido, Munoz-Criado and García-Rodríguez, 199612
Munoz-Bellido, Munoz-Criado and García-Rodríguez, 200013 
Risperidone  Anti-psychoticCorynebacterium urealyticum  Munoz-Bellido, Munoz-Criado and García-Rodríguez, 199612
Munoz-Bellido, Munoz-Criado and García-Rodríguez, 200013 
Simvastatin and Atorvastatin  Cardiovascular diseasesStaphylococcus epidermidis
Staphylococcus aureus
Salmonella spp.
Pseudomonas aeruginosa
Micrococcus luteus
Klebsiella pneumoniae
Escherichia coli
Enterococcus faecalis
Enterobacter hormaechei
Bacillus cereus
Staphylococcus spp.
Staphylococcus coagulase negative
MRSA 
Rampelotto et al., 2018 in press14

Graziano et al., 201530 
Thalidomide  Anti-nauseaMycobacterium leprae  Paravar and Lee, 200831 

MRSA, methicillin-resistant Staphylococcus aureus; VRSA, vancomycin-resistant Staphylococcus aureus; AAS, acetylsalicylic acid.

The treatment of chronic bacterial infections in immunocompromised patients with synergistic drug combinations is well established, and this procedure has been used for several years.15 These synergistic combinations are used because of three main advantages: expansion of the antibiotic spectrum16,17; overcoming resistance18; and decrease of resistance to antibiotics through their careful use.19–21

Since repositioned non-antibiotic drugs have shown antibiotic effects among themselves as well as when used together with antimicrobials, these combinations presently consist of a useful option to overcome the problem of weak activity of individual drugs.2,10,16

Based on the several studies presented, it can be inferred that the repositioning of non-antibiotic drugs with known toxicity profiles represents a promising alternative for the treatment of bacterial infections. Nevertheless, it is a consensus in the global scientific community that it is only the starting point, and additional studies regarding mechanisms of action and in vivo studies, among others, are vital for the safe use of these drugs.

Conflicts of interest

The authors declare no conflicts of interest.

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Copyright © 2018. Sociedade Brasileira de Infectologia
The Brazilian Journal of Infectious Diseases

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