Co-trimoxazole and prevention of relapses of PR3-ANCA positive vasculitis with pulmonary involvement

Abstract

BackgroundBacterial and viral respiratory tract infections may trigger relapses in patients with PR3-positive vasculitis. Data have suggested that treatment with co-trimoxazole may be beneficial, because this antibiotic could act by eliminating the offending microbe and thereby stopping the initiating stimulus.Goal and methodsProspective, randomized, placebocontrolled study of the efficacy of co-trimoxazole given 960 mg thrice weekly for 18 months in preventing relapses in patients with Wegener's granulomatosis (WG) in remission, after treatment with cyclophosphamide and prednisolone was conducted. Relapses and infections were assessed with predefined criteria based on clinical, laboratory, serological, microbiological, and histopathological findings. Sixteen patients were assigned to receive co-trimoxazole and 15 to receive placebo.ResultsSeventy five percent of the patients in the co-trimoxazole group remained in remission at 18 months and 55% of those in the placebo group. A proportional hazard regression analysis identified a positive PR3-ANCA test at the start of treatment, chronic nasal crusting, and Staphylococus aureus infection as risk factors for relapse. Furthermore, the analysis identified treatment with co-trimoxazole as an independent factor associated with prolonged diseasefree interval.ConclusionTreatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener's granulomatosis in remission.

Pathogenesis of ANCA-Associated Vasculitis

“…This is much higher than in the general population. S. aureus carriers are at higher risk of relapse of GPA than non-carriers, and treatment with trimethoprim-sulfamethoxazole resulted in significant reduction of relapse rate [76][77][78]. Multiple mechanisms may contribute to the increased risk of relapse conveyed by S. aureus.…”

What is the evidence for prophylactic antibiotic treatment in patients with systemic vasculitides?

“…A second report [48] from the same group also concluded inefficacy of co-trimoxazole prophylaxis for maintaining remission in generalized Wegener's granulomatosis, although the drug could be effective in the initial phase, that is locoregional Wegener's granulomatosis. A more recent controlled study [49] on the prophylactic use of co-trimoxazole (960 mg thrice weekly) in maintaining remission in 31 patients with Wegener's granulomatosis showed a small but significant effect of co-trimoxazole: 75% of patients (n ¼ 16) in the co-trimoxazole group vs. 55% in the placebo group (n ¼ 15) maintained remission during the 18 months' study period. This study also confirmed risk factors for relapse: a positive test for PR3-ANCA at remission, chronic nasal crusting, and carriage of S. aureus.…”

Ocular manifestations of Wegener’s granulomatosis

“…Data have suggested that treatment with cotrimoxazole may be beneficial, because this antibiotic could act by eliminating the offending microbe and thereby stopping the initiating stimulus in these patients. Treatment with cotrimoxazole has been shown to reduce the incidence of relapses in patients with WG/GPA in remission in previous studies [142,143], and should be considered in cases of persistent endonasal activity of WG/GPA, together with S. aureus carriage [144]. Cotrimoxazole was also recommended by both EULAR [128] and the British Society for Rheumatology (BSR) and British Health Professionals in Rheumatology (BPHR) guidelines [145] as prophylaxis against Pneumocystis jerovicii infection in patients with WG/GPA.…”