title: Adverse events and infectious burden, microbes and temporal outline from immunosuppressive therapy in antineutrophil cytoplasmic antibody-associated vasculitis with native renal function.
abstract: BACKGROUND
  Disease control in anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) with immunosuppression is effective but burdened by adverse events, especially infections. The study goal was to evaluate risks and types of infections in patients with AAV.
  
  
  METHODS
  Biopsy-proven AAV patients (diagnosed 1/1991-6/2011) followed in an inception cohort were evaluated for adverse events. Severe infections (requiring intravenous antibiotics, intensive care unit, or causing death) were recorded. Infection number was grouped as none, 1-2 or ≥3. Cox regression was used to estimate hazard ratios with 95% confidence intervals.
  
  
  RESULTS
  A total of 489 patients (median age 59; 47% female, 55% myeloperoxidase-ANCA) were followed for 2.8 years (median). At 1, 2 and 5 years cumulative incidence of infection was 51, 58 and 65% and severe infection was 22, 23 and 26%. Pulmonary and upper respiratory infections were most common (42 and 30% ever experienced each, respectively), highest in the first 3 months. Staphylococcus aureus was most frequently seen among positive cultures (41%, 78 S. aureus/192 total positive cultures), and only one Pneumocystis jiroveci pneumonia (6 weeks into treatment). All-cause death in 12 months was associated with infections (% deaths: 0 infections 3%; 1-2 infections 10%, ≥3 infections 13%, P = 0.002). Controlling for age, sex and kidney function, patients with severe infections were 4.2 times more likely to die within 12 months (95% CI 2.0-8.7; P = 0.001).
  
  
  CONCLUSIONS
  More infections increase the risk of a severe infection which increases risk of all-cause mortality. Respiratory and S. aureus infections are dominant. Targeted prophylactic therapy could decrease morbidity.
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: JulieAnne G
authors: JG
authors: McGregor
authors: Hospital Universitario-UANL Monterrey, Monterrey, Nuevo Leon, Mexico.
authors: Roberto
authors: R
authors: Negrete-Lopez
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Caroline J
authors: CJ
authors: Poulton
authors: Virginia Commonwealth University, Richmond, VA, USA.
authors: Jason M
authors: JM
authors: Kidd
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Suzanne L
authors: SL
authors: Katsanos
authors: University of Colorado, Denver, CO, USA.
authors: Lindsey
authors: L
authors: Goetz
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Yichun
authors: Y
authors: Hu
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Patrick H
authors: PH
authors: Nachman
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Ronald J
authors: RJ
authors: Falk
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Susan L
authors: SL
authors: Hogan
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000150:complications / Q000188:drug therapy*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009657:North Carolina / Q000453:epidemiology; D009195:Peroxidase / Q000276:immunology*; D011379:Prognosis; D013203:Staphylococcal Infections / Q000139:chemically induced / Q000453:epidemiology / Q000382:microbiology* / Q000401:mortality; D013211:Staphylococcus aureus / Q000302:isolation & purification; D015996:Survival Rate
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D007166:Immunosuppressive Agents; D009195:Peroxidase
keywords: ANCA; glomerulonephritis; immunosuppression; outcomes; risk factors