title: Differences between a probable and proven BCG infection following intravesical instillations: 16 years experience in a tertiary care hospital.
abstract: BACKGROUND
  Intravesical instillation of Bacillus Calmette-Guérin (BCG) is an efficient immunotherapy for superficial bladder cancer. BCG infection represents a major yet uncommon adverse event that occurs in 5-10% of the patients treated with BCG instillations, though the pathogenesis of this entity is not clear.
  
  
  METHODS
  We report two cases of patients presented at our institution with BCG infection after instillation: one with microbiological BCG isolate and another without, and review all the medical records of patients instilled with BCG in our institution from 1996 until 2012, comparing patients with probable and proven BCG infection.
  
  
  RESULTS
  During the study period, a total of 786 patients received BCG intravesical instillations. Of them, 31 (4%) patients had to suspend treatment because of adverse events and, specifically, 11 (1.3%) patients had to interrupt treatment because of suspected BCG infection. The incidence of BCG infection during our study period was 0.87 episodes per 1,000 instilled patients/year and 140 cases per 10,000 instilled patients. Of the 11 patients with suspected BCG infection, 7 (64%) had a probable BCG infection, while 4 (36%) patients had a proven BCG infection. All patients with a proven infection had a previous underlying condition, compared to a high proportion of patients with probable infection (57%) that did not present with underlying diseases. Common findings between both groups of patients were abnormal imaging studies and laboratory tests. Regarding treatment, 8 (73%) of the 11 patients with BCG infection received at least two first line drugs active against M. bovis (isoniazid, rifampicin or ethambutol), four patients (36%) received steroids as part of the treatment and curation was obtained in 10 (91%) patients, while 1 patient with a proven infection had a death related to BCG infection.
  
  
  CONCLUSIONS
  We can conclude that BCG infection after intravesical instillations has a low incidence in our institution. Patients with previous underlying conditions seem to have more proven infections. A high proportion of patients do not yield positive microbiological tests; in those cases the diagnosis relies in clinical, radiological and laboratory findings. Treatment for BCG infection should include at least two active drugs against M. bovis and coadjuvant steroid treatment for systemic BCG infections.
authors.affiliation: Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. Electronic address: marcelag.delv@gmail.com.
authors.forename: Marcela
authors.initials: M
authors.lastname: González-Del Vecchio
authors.affiliation: Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Ruíz-Serrano
authors.affiliation: Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Gijón
authors.affiliation: Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Sánchez-Somolinos
authors.affiliation: Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Viviana
authors.initials: V
authors.lastname: de Egea
authors.affiliation: Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain.
authors.forename: Darío
authors.initials: D
authors.lastname: García de Viedma
authors.affiliation: Farmacy Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: María Norberta
authors.initials: MN
authors.lastname: Sánchez Fresneda
authors.affiliation: Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bouza
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use; D001691:Biological Therapy / Q000009:adverse effects* / Q000379:methods*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000302:isolation & purification*; D062606:Tertiary Care Centers; D014376:Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D001749:Urinary Bladder Neoplasms / Q000628:therapy
chemical_list: D000995:Antitubercular Agents
keywords: BCG; Infection; Mycobacterium bovis; Transurethral resection