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The rates of isoniazid (INH) and multidrug-resistant (MDR) tuberculosis (TB) among European children vary between 10.4% and 3.5%. Spain is a low endemic country with reported rates of 4.9% of INH resistance and 1.3% of MDR in adults. However, data regarding patterns of TB resistance in children are scarce. Our aim is to determine the incidence and risk factors for pediatric-resistant TB in our setting to help developing age-targeted guidelines.A multicenter, retrospective study including 22 hospitals from Madrid region (EREMITA study group) was performed from January 2005 to June 2010. Medical records from children diagnosed with TB were reviewed for demographic characteristics, clinical presentation and outcomes. Risk factors for INH and MDR TB were identified.Of 396 children diagnosed with TB, 72.4% were born to foreign parents. Microbiologic confirmation by culture (n = 200) or PCR (n = 8) was documented in 208 children (52.5%). Drug susceptibility results were available in 188 children: 9.6% (n = 18) were resistant to INH and 3.1% (n = 6) were MDR. INH resistance was more common in immigrants compared with native families (11.9% vs. 0%; P = 0.013), as was also MDR (4.5% vs. 0%; P = 0.34). Extrapulmonary TB and previous antituberculous treatment were significantly associated with INH and MDR, while immunosuppression was associated only with MDR.The rates of INH and MDR TB were different according to the parents’ origin, with higher rates among children born to foreign parents. Local surveillance of drug-resistant TB is critical to develop appropriate guidelines for treatment.