title: Isoniazid Mono-Resistant Tuberculosis: Impact on Treatment Outcome and Survival of Pulmonary Tuberculosis Patients in Southern Mexico 1995-2010.
abstract: BACKGROUND
  Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated.
  
  
  OBJECTIVE
  To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico.
  
  
  METHODS
  We conducted a prospective cohort study of pulmonary TB patients in Southern Mexico. From 1995 to 2010 patients with acid-fast bacilli or culture proven Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. We included patients who harbored isoniazid mono-resistant (IMR) strains and patients with strains susceptible to isoniazid, rifampicin, ethambutol and streptomycin. All patients were treated following Mexican TB Program guidelines. We performed annual follow-up to ascertain treatment outcome, recurrence, relapse and mortality.
  
  
  RESULTS
  Between 1995 and 2010 1,243 patients with pulmonary TB were recruited; 902/1,243 (72.57%) had drug susceptibility testing; 716 (79.38%) harbored pan-susceptible and 88 (9.75%) IMR strains. Having any contact with a person with TB (adjusted odds ratio (aOR)) 1.85, 95% Confidence interval (CI) 1.15-2.96) and homelessness (adjusted odds ratio (aOR) 2.76, 95% CI 1.08-6.99) were associated with IMR. IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38-45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00-10.84). All the models were adjusted for socio-demographic and clinical variables.
  
  
  CONCLUSIONS
  The results from our study provide evidence that the standardized treatment schedule with first line drugs in new and previously treated cases with pulmonary TB and IMR produces a high frequency of treatment failure and death due to tuberculosis. We recommend re-evaluating the optimal schedule for patients harboring IMR. It is necessary to strengthen scientific research for the evaluation of alternative treatment schedules in similar settings.
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.|Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México.
authors.forename: Renata
authors.initials: R
authors.lastname: Báez-Saldaña
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Delgado-Sánchez
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: Lourdes
authors.initials: L
authors.lastname: García-García
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: Luis Pablo
authors.initials: LP
authors.lastname: Cruz-Hervert
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: Marlene
authors.initials: M
authors.lastname: Montesinos-Castillo
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: Leticia
authors.initials: L
authors.lastname: Ferreyra-Reyes
authors.affiliation: Laboratorio de Microbiología, Instituto Nacional de Ciencias Médicas y de Nutrición Salvador Zubirán, Ciudad de México, México.
authors.forename: Miriam
authors.initials: M
authors.lastname: Bobadilla-Del-Valle
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: Sergio
authors.initials: S
authors.lastname: Canizales-Quintero
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ferreira-Guerrero
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: Norma
authors.initials: N
authors.lastname: Téllez-Vázquez
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Montero-Campos
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.|Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, San Luis Potosí, México.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Yanes-Lane
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: Norma
authors.initials: N
authors.lastname: Mongua-Rodriguez
authors.affiliation: Laboratorio de Microbiología, Instituto Nacional de Ciencias Médicas y de Nutrición Salvador Zubirán, Ciudad de México, México.
authors.forename: Rosa Areli
authors.initials: RA
authors.lastname: Martínez-Gamboa
authors.affiliation: Dirección Médica, Instituto Nacional de Ciencias Médicas y de Nutrición Salvador Zubirán, Ciudad de México. México.
authors.forename: José
authors.initials: J
authors.lastname: Sifuentes-Osornio
authors.affiliation: Laboratorio de Microbiología, Instituto Nacional de Ciencias Médicas y de Nutrición Salvador Zubirán, Ciudad de México, México.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ponce-de-León
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality*
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid