In vitro synergy of sertraline and tetracycline cannot be reproduced in pigs orally challenged with a tetracycline resistant Escherichia coli

Abstract

BackgroundAntimicrobial helper-compounds may reverse antimicrobial resistance. Sertraline, a antidepressant drug, has been suggested as a tetracycline helper-compound. Tetracycline is the preferred antimicrobial for treatment of enteric diseases in pigs. This study is the first to evaluate the potency of sertraline as a tetracycline adjuvant in pigs.MethodsForty-eight nursery pigs were divided into four treatment groups: Tetracycline, sertraline, tetracycline/sertraline or un-medicated control. Fecal and ileal samples were obtained before treatment, 48 h and nine days after five days of treatment, respectively. Colony forming units (CFU) of tetracycline resistant coliforms in each sample (ileal or fecal) and CFU of an orally inoculated tetracycline-resistant strain of Escherichia coli were determined at each sampling point. The microbiome of fecal and ileal and samples was analyzed by sequencing of the 16S V3-V4 region.ResultsThe results did not provide evidence that sertraline in combination with tetracycline has any impact on tetracycline resistant bacteria in either fecal or ileum samples, while in the tetracycline treated group of pigs, an increase in the prevalence of a tetracycline resistant indicator strain of Escherichia coli shortly after ended five-day treatment was observed. The ileal samples obtained shortly after ended treatment showed treatment-associated changes in the composition of the microbiota in the groups of pigs treated with tetracycline (+/−) sertraline. While tetracycline treatment increased the abundance in the reads of E. coli, sertraline/tetracycline treatment led to increased abundances of Streptococcus spp. and decreased abundances of Lactobacillus spp. However, all observed differences (on CFU counts and microbiota composition) between groups shortly after treatment had diminished in less than two weeks after last treatment day.ConclusionsSertraline (+/−) tetracycline treatment did not reduce the long-term level of tetracycline-resistant bacteria in the feces or small intestine contents of piglets compared to the un-medicated control group of pigs. The result of this study reflects the importance of in vivo studies for confirmation of the antimicrobial helper-compound potential of an in vitro active compound.Electronic supplementary materialThe online version of this article (10.1186/s12866-018-1383-5) contains supplementary material, which is available to authorized users.

Repurposing the drug duloxetine for its antibacterial activity against catheter associated urinary tract infections

“…Consequently, the lowest concentration which inhibits the growth of both Escherichia coli and Enterococcus faecalis was determined as 37.5 µg/ml. Our study was correlated with previous report in which sertraline showed antibacterial effect against Escherichia coli in combination with tetracycline [Kromann S et al, 2019]. Our study was supported by previous study wherein a repurposing ebselen (organoselenium compound) showed excellent activity against both methicillin and vancomycin resistant Staphylococcus aureus by inhibiting the protein synthesis and toxin production [Thangamani S et al, 2015].…”

Prediction of Minocycline Activity in the Gut From a Pig Preclinical Model Using a Pharmacokinetic -Pharmacodynamic Approach

“…For minocycline, about 19-35% of the dose could be found unchanged in feces after administration to patients (Macdonald et al, 1973;Jonas and Cunha, 1982). As a consequence of intestinal elimination, tetracyclines given by oral or parenteral route modify the gut microbiota (as demonstrated in vitro in human microbiota and in vivo in pigs) (Wagner et al, 2008;Graesbøll et al, 2017;Keerthisinghe et al, 2019;Kromann et al, 2019) and amplify tetracycline-resistant coliform bacteria (Graesbøll et al, 2017;Kromann et al, 2019). Nonetheless, clinical studies of the effects of therapeutic doses on the patients' microbiota remain relatively scarce (Sullivan et al, 2001;Ley et al, 2006), whereas exploring the link between therapeutic doses and gut exposure to active drug, in terms of time development and magnitude, is essential for understanding the emergence and spread of MDR bacteria inside the gut microbiota.…”