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.
Highlights
Level of tetracycline resistant bacteria in feces before inoculation Two days before treatment start and just prior to inoculation of all pigs in all four groups (Time point T[− 2] the level of fecal tetracycline resistant coliforms in the 48 individual fecal samples ranged from 3.3–7.7 log10 Colony forming units (CFU) per gram of feces (Fig. 1)
None of the fecal samples contained bacteria which could be cultured on the indicator agar plate (MacConkey agar supplemented with tetracycline, ampicillin and rifampicin)
At T[0] the indicator bacteria could be re-isolated in all fecal samples, while for one out of eight pigs the indicator bacteria could not be detected in the ileal samples at this time point
Summary
Sertraline, a antidepressant drug, has been suggested as a tetracycline helper-compound. Tetracycline is the preferred antimicrobial for treatment of enteric diseases in pigs. Some helper-compounds possess antimicrobial activities themselves [7], while others interfere with the resistance mechanism of the bacterial resistance, e.g. by blocking antimicrobial efflux pumps [8]. Sertraline, a selective serotonin reuptake inhibitor (SSRI), is a medical compound normally prescribed for human mental disorders, such as depression and anxiety, and it has been suggested as tetracycline helper-compound by several research groups [9,10,11,12,13]. Sertraline itself do possess antimicrobial activity against a number of Gram-negative bacterial species, the main reason of interest for sertraline as a helper-compound is due to the interference with the tetracycline resistant efflux pump, TetA [10, 13]. While several in vitro results have been published on the antimicrobial helper-drug activities of SSRIs, including sertraline, only very limited literature on the clinical in vivo effect of sertraline’s helper-compound activity exist
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