Treatment with high-dose antidepressants severely exacerbates the pathological outcome of experimental <i>Escherichia coli</i> infections in poultry

<div><p>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 <i>in vitro</i>, including increasing the susceptibility of <i>Escherichia coli</i> 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 <i>E</i>. <i>coli</i> 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 <i>E</i>. <i>coli</i> infections exacerbate the pathological outcome of infection in chickens.</p></div

Minimal inhibitory concentration (MIC) of sertraline and tetracycline alone or combined.

<p>For each combination exposure on sertraline and tetracycline, the fractional inhibitory concentration index (FICI) is stated.</p

Overview of experimental groups.

<p>Each group consisted of 10 commercially brown layers, 45 weeks of age.</p

Colony-forming units (CFU).

<p>CFU per gram salpinx in the different treatment groups. Vertical bars indicate the standard deviation.</p

Weight changes during infection.

<p>Percent weight change seven days after infection compared to before infection per chicken in the different treatment groups.</p