Infection by uropathogenic Escherichia coli (UPEC) is a common cause of epididymitis in men. Empirical antibiotic therapy provides bacteriological clearance, but these men often suffer from subsequent subfertility. This may be due to epididymal inflammation and fibrosis leading to obstructive damage, which is not resolved by antibiotics alone. In previous studies using a murine model of UPEC-induced epididymitis, epididymal damage was found to be reduced in mice deficient in inflammatory signalling (MyD88 null).
In the following study, the effects of antibiotics on epididymal damage were investigated 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 had 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. Crucially, there was no observable reduction in damage in mice given antibiotics.
These data indicate that epididymal damage persists despite 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 anti-fibrotic treatments with antibiotics.