we performed a cross - sectional study of clinical and demographic factors associated with isoniazid resistance on initial susceptibility testing in patients with tbm by using data from the united states national tuberculosis surveillance system . we examined data on all tb cases reported from january 1 , 1993 , through december 31 , 2005 . patients were included if a clinical diagnosis of meningitis was made , positive cultures for m. tuberculosis were obtained from csf , and results of any initial drug susceptibility testing were recorded . to study factors associated with isoniazid resistance in patients without a treatment history , we excluded patients with a previous diagnosis of tb . we also excluded patients with multidrug - resistant disease on the basis of evidence for differences in the epidemiology of isoniazid - resistant ( rifampin - susceptible ) and multidrug - resistant tb ( 5 ) . differences in characteristics between the isoniazid - resistant and isoniazid - susceptible groups were assessed by using  test and were selected for evaluation in a multivariable logistic regression model if unadjusted analysis demonstrated an association ( p<0.25 ) . an odds ratio ( or ) for the association between a patient characteristic and initial isoniazid resistance multiple imputation was used to account for missing observations and permit complete data methods for analysis , under the assumption that missing data followed a missing - at - random pattern ( 6 ) . likelihood ratio testing was used to compare nested models , and the akaike information criteria were used to compare non - nested models . during 19932005 , a total of 1,649 patients had a diagnosis of tbm , no previous history of tb , positive csf cultures , and initial drug susceptibility testing . of these 1,649 patients , 234 patients ( 14% ) were infected with an isolate resistant to at least 1 first - line agent ( isoniazid , rifampin , ethambutol , pyrazinamide , or streptomycin ) . overall , 133 of 1,649 ( 8% ) patients were infected with an isolate resistant to at least isoniazid . after we excluded 11 patients without susceptibility testing results for isoniazid and 24 patients with multidrug - resistant disease , we compared 109 patients with at least isoniazid - resistant disease with 1,505 patients with isoniazid - susceptible disease . unadjusted associations of clinical and demographic characteristics with initial isoniazid resistance are shown in table 1 . foreign - born patients were more likely than us - born patients to have isoniazid - resistant disease , with an or of 2.53 ( 95% ci 1.663.88 ) . overall , 849 of 1,614 ( 53% ) patients in the primary analysis had a known hiv status , and 765 of 1,614 ( 47% ) patients had unknown hiv status . of the patients with known hiv status , 362 of 849 ( 43% ) were hiv positive , and 487 of 849 were hiv negative ( 57% ) . hiv infection was not associated with initial isoniazid resistance ( or 1.10 , 95% ci 0.621.95 ) . among hiv - positive patients , the association between foreign birth and initial isoniazid resistance was 3.05 ( 95% ci 1.546.06 ) , and among hiv - negative patients it was 1.60 ( 95% ci 0.703.65 ) . * or , odds ratio us - born persons were defined as persons born in the united states , puerto rico , or us outlying area , or born abroad to american parents ; all other persons were defined as foreign - born . california reported only patients matched to the california aids registry from 19932004 as hiv positive ; all other california patients are missing hiv status . based on unadjusted analyses , the multivariable model included age , race , residence in a long - term care facility , and foreign birth . before age was adjusted for , the or for foreign birth and initial isoniazid resistance was 2.53 ( 95% ci 1.663.88 ) , and after adjusting for age , the or was 2.25 ( 95% ci 1.473.43 ) . mexico was the most commonly reported country of origin for foreign - born patients , accounting for 20 of 69 foreign - born patients with isoniazid - resistant disease . countries in asia accounted for 7 of 9 countries with > 2 cases of isoniazid - resistant tbm ( figure ) . * or , odds ratio ; ci , confidence interval . countries of origin for foreign - born persons with tuberculous meningitis , united states , 19932005 . black bar sections indicate isoniazid - resistant and white bar sections isoniazid - sensitive tuberculosis . in this national cohort of patients with tbm , initial isoniazid resistance was more commonly seen in patients born outside the united states . in an earlier study of all forms of isoniazid monoresistant tb in the united states , foreign birth although we excluded patients with a diagnosis of tb , clinicians may have been unaware of a patient s previous episode of tb that was treated before their arrival in the united states . foreign - born patients may also have emigrated from countries with a higher prevalence of isoniazid resistance among newly diagnosed cases . older persons may have been exposed to tb antecedent to the use of isoniazid in treatment regimens , leading to reactivation with a drug - susceptible strain . hiv infection is associated not only with increased risk for progression to active tb , but also an increased risk for extrapulmonary involvement among patients with active cases , including an increased risk for tbm ( 7 ) . however , we did not see an association between hiv and initial isoniazid resistance among persons with known hiv status ( p = 0.73 ) , and the strength of the association between foreign birth and initial isoniazid resistance was not significantly modified by the presence of hiv infection . similar to our findings , a lack of association between hiv and isoniazid resistance was seen in all cases of tb in the united states ( with 13% known hiv positive ) and the united kingdom ( with 5% known hiv positive ) ( 5,8 ) . for all states except california , reporting of hiv status to the national tuberculosis surveillance system increased from 36% in 1993 to 79% in 2008 ( 9 ) . california reported only patients matched to the california aids registry during 19932004 as hiv positive . individual mic levels for isoniazid were unavailable , and reporting does not distinguish between low - level and high - level resistance . although we excluded patients with a history of tb , we were unable to identify patients previously treated for latent tb , which was shown to be associated with isoniazid monoresistance in patients for whom active tb subsequently developed ( 10 ) . in conclusion , foreign - born persons with tbm who seek care in the united states were more likely to be infected with an isoniazid - resistant strain of m. tuberculosis compared with us - born persons , and persons > 64 years of age were less likely to have an isoniazid - resistant infection than were persons 2534 years of age . prospective studies are needed to determine whether individual patient characteristics can guide the selection of tbm therapies and lead to an improvement in clinical outcomes .
to determine patient characteristics associated with isoniazid resistance in cases of tuberculous meningitis , we conducted a cross - sectional study by using data from the us national tuberculosis surveillance system during 19932005 . 
 foreign - born patients were more likely to be infected with an isoniazid - resistant strain .