Abstract
There is an urgent need for novel antibiotics as the current antibiotics are losing their value due to increased resistance among clinically important bacteria. Sertraline, an on-marked anti-depressive drug, has been shown to modify bacterial activity in vitro, including increasing the susceptibility of Escherichia coli to antibiotics. The aim of the present study was to investigate if the antimicrobial activity of sertraline could be documented under clinical settings, hereunder if sertraline could potentiate the effect of tetracycline in treatment of an experimentally induced ascending infection in poultry. A total of 40 chickens were divided in four groups of 10 chickens each. All chickens were challenged with 4x103 colony forming units (CFU) of a tetracycline resistant E. coli strain using a surgical infection model, and subsequently treated with either high-dose sertraline, tetracycline, a combination hereof or received no treatment. Seven days post challenge all birds were submitted to necropsy and scored pathologically for lesions. The average lesion scores were significantly higher (P<0.05) in the groups that were treated with high-dose sertraline or high-dose sertraline combined with tetracycline. In conclusion high-dose treatments (four times the maximum therapeutic dose for treating human depression) with sertraline as an adjuvant for treatment of antibiotic resistant E. coli infections exacerbate the pathological outcome of infection in chickens.
Highlights
The progressive incline in antimicrobial resistance of clinical important bacteria has led to an increased focus of so-called non-antibiotics, which may be defined as medical compounds whose primary indication for use is non-infectious diseases, and processes antimicrobial or antimicrobial helper compound effects [1]
Tetracycline is used in humane medicine, the use has decreased in the last decade, likely due to development of better antibiotics and due to a dramatic increase in tetracycline resistant bacteria [17]
In poultry E. coli is the most frequent cause of ascending infections, and accumulating evidence suggest that the clones of E. coli causing ascending infections in poultry are highly similar to clones of E. coli causing urinary tract infections (UTI) in human [23,37]
Summary
The progressive incline in antimicrobial resistance of clinical important bacteria has led to an increased focus of so-called non-antibiotics, which may be defined as medical compounds whose primary indication for use is non-infectious diseases, and processes antimicrobial or antimicrobial helper compound effects [1]. The increase in the prevalence of tetracycline resistance in clinically important bacteria in animals is a major problem as it forces the use of other antibiotics for treatment of infectious disease in livestock production. Substituting tetracycline with other antibiotics primarily used for human infections, e.g. cephalosporines would favour selection of cephalosporin-resistant bacteria, which may be directly or indirectly transferred to humans [19,20]
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