Uropathogenic Escherichia coli (UPEC) infection is a common cause of epididymitis in men. Empirical antibiotic therapy provides a microbiological cure, but 40% of these patients suffer from subsequent subfertility. This may be due to obstructive damage resulting from epididymal inflammation and fibrosis, which is not directly targeted by antibiotic treatment. In previous studies using a murine model of UPEC-induced epididymitis, epididymal damage was found to be reduced in MyD88 null mice deficient in inflammatory signalling.
The current study assessed the effects of antibiotics on epididymal damage in adult mice infected with UPEC administered by retrograde injection via the vas deferens. Three days post-infection, mice were treated with Levofloxacine (0.5 mg/kg, subcutaneously) daily for seven days, or received no antibiotic treatment. Control mice received retrograde injection of saline without bacteria.
Compared with saline-injected controls, the epididymal cauda of UPEC-infected mice was enlarged, with leukocytic infiltrates, granulomas, macroscopic abscesses, and fibrotic adhesions of the organ to surrounding tissues. Epididymal duct cross sections were obscured due to destruction of the epithelium and luminal occlusion. Increased collagen IV immunostaining indicated thickening of the basement membrane, but other markers of fibrosis (α-smooth muscle actin, fibronectin, and collagen I) did not show an overall increase in staining intensity. However, an increase in the distribution of fibronectin and collagen I indicated expansion of the interstitial tissue in the UPEC-infected cauda. The corpus and caput were also affected, but much less severely than the cauda. Crucially, there was no observable reduction in damage in the mice given antibiotics.
These data indicate that epididymal damage occurs despite rapid antibiotic treatment in mice with UPEC-induced epididymitis, supporting the hypothesis that antibiotics on their own are unable to prevent damage and maintain fertility. This suggests that there may be clinical benefits from the concurrent use of anti-inflammatory and/or anti-fibrotic treatments.