MP111INCIDENCE AND PREDICTIVE FACTORS OF INFECTIONS, POSITIVE MICROBIOLOGICALCULTURES IN PATIENTS WITH SEVERE ANCA-ASSOCIATED VASCULITIS

Abstract

Introduction and Aims: Infectious morbidity and mortality of ANCA-associated vasculitis (AAV) remained high in the modern era of immunosuppression. Understanding the risk factors associated with infection development is crucial in AAV to increase the life expectancy of these patients. Methods: In this single centre retrospective cohort study we assessed the cumulative incidence of infections, investigated the predictive factors of infections, and evaluated the positive microbiological cultures in patients with severe AAV. Number of infections requiring antibiotic treatment, incidence of infection/patient-year during induction immunosuppression (6 months) and in remission, routine laboratory data, ANCA serology, baseline Charlson comorbidity index (CCI, without age and renal function), leucopenia and steroid diabetes were documented. Infections were categorized as severe (sepsis, endocarditis, meningitis, pneumonia, abscess, pyelonephritis, CAPD-related peritonitis), moderate (upper respiratory tract-, joint-, enteral infections, cellulitis, zoster) and mild (lower urinary tract infections and soor). Results of Student's t-test, Mann-Whitney U test, chi-square and logistic regression analyses are given as mean±SD, median [interquartile range IQ], odds ratio (OR) and 95% confidence interval [CI]. Results: Between 1999-2015 104 patients (age 62±12 years, 39% male) were diagnosed with AAV. Their Birmingham Vasculitis Activity Score (BVAS) was 21.2±5.4, baseline creatinine 560±337 umol/l, 53% of patients needed dialysis at diagnosis, 37% remained dialysis dependent, 26% had relapse. Protocolized therapy consisted IV bolus methylprednisolone (11.4±4.3 mg/kg), continued orally 1 mg/kg and tapered gradually, and monthly IV bolus cyclophosphamide (CYC) (9.63±1.56 mg/kg) six times, and then repeated at months 9 and 12. During the median follow-up of 2.6 years [IQR 5.8], 56% of patients died, and infection was responsible for 33% of the total mortality. Two-hundred and sixty-four infections occurred, of which 120 were severe in 60 patients. Incidence of total and severe infection/patient-year was 3.69±5.0 and 1.76±3.23 during induction immunosuppression, 0.78±2.24 and 0.54±2.20 in remission, respectively. Subgroup analysis of patients with lower and higher incidence rate of total infections than median (0.93 [3.5]) during the entire follow-up showed age of 60±13 and 64±11 years (p=0.044); creatinine 488±322 and 638±340 umol/l (p=0.006); albumin 32.7±5.1 and 29.4±5.2 g/l (p=0.002); CCI 0.6±0.9 and 1.2±1.2 (p=0.009) at diagnosis; leucopenia 0 and 14% during induction (p=0.006), respectively. Severe infections were predicted by baseline creatinine both during induction and maintenance immunosuppression, OR 1.002 [CI 1.000-1.004] and 1.002 [1.000-1.004] respectively, corrected for age, baseline CCI, corticosteroid and CYC dose. Number of positive cultures was 158; Gram negative bacteria were responsible for sepsis in 35%, and for respiratory tract infections in 65% of cases. Conclusions: Advanced renal failure at diagnosis increased the risk of severe infections during induction immunosuppression, also in remission. Infections were more frequent in elderly patients, also in those with more comorbidity at baseline. Preventing, identifying and treating infections are vital to improve the long-term prognosis of patients with AAV.