A total of 1,846 patients were enrolled during the study period. Among these, 605 (32.8%) did not have baseline DST results, either due to a nonviable sample (99.2%) or incomplete resistance data for both isoniazid and rifampin (0.8%). The remaining 1,241 (67.2%) patients constitute the cohort for analysis presented here.

Of these 1,241, 419 (33.8%) had baseline MDR TB, among whom 195 (46.5%) had never been treated for TB and 224 (53.5%) had a history of previous TB treatment. Eight patients had extensively drug-resistant TB; 1 was a medical student, 1 had received prior self-administered treatment, 2 had household contacts (1 was a pediatric patient and the other was an adult), and 4 were identified as suspected category I failures, i.e., failure of first-line treatment for new patients. Of these 8 case-patients, only 1 (who had received self-administered treatment) had completed previous treatment.

Descriptive characteristics of the cohort are shown in Table 2. Compared with patients with drug-susceptible TB, those with MDR TB were younger, more likely to be single, more educated, and less likely to have ever smoked. Clinically, they were less likely to have been tested by using the BACTEC-460 system and more likely to have hemoptysis. MDR TB patients and patients with drug-susceptible TB did not significantly differ with respect to their year of enrollment, gender, and history of TB treatment. Compared with patients with drug-susceptible TB, patients with monoresistant TB were younger and more likely to be single.

The most frequent risk factors prompting referral for DST among patients with new smear-positive TB were being adults with a household contact with known or suspected MDR TB (32.1%), diabetes mellitus (20.0%), and suspected category I failures (19.5%). Among previously treated patients with smear-positive TB, those with multiple (>2) treatments (43.2%), adult household contact (18.6%), default of category I treatment (16.8%), and previously self-administered treatment (14.9%) were most frequently referred for DST. Among all patients with smear-positive TB, a single risk factor was identified in 485 (43.54%) patients, whereas 382 (34.29%), 205 (18.40%), 38 (3.41%), and 4 (0.36%) had 2, 3, 4, and 5 risk factors, respectively (data not shown).

The prevalence of MDR TB in Peru in 2007 among all TB patients, previously treated TB patients, and new TB patients is shown in Table 3 (21). In this national surveillance report, 8.3% of all TB patients, 5.2% of new TB patients, and 24.2% of previously treated TB patients in Peru were estimated to have MDR TB (21). Limiting surveillance data to the 2 districts where our cohort was enrolled, 12.4% of all TB patients, 9.9% of new TB patients, and 24.0% of previously treated TB patients had MDR TB (Ministerio de Salud, unpub. data). In our cohort of 1,241 subjects, 33.8% of all patients, 31.6% of new TB patients, and 35.8% of previously treated TB patients had MDR TB. Because national surveillance was conducted on smear-positive samples only, we compared the proportion of MDR TB among patients with smear-positive results in our cohort to prevalence of MDR TB from regional surveillance estimates. As shown in Tables 4 and 5, our cohort showed higher risk for MDR TB among new TB patients and previously treated TB patients.

When stratifying our cohort by risk group, we found that diabetes mellitus (16.8%), adult (33.5%) or child (53.9%) patients with household contacts with known or suspected MDR TB, and suspected category I failure, i.e., positive smear or culture during the second or third month of category I therapy (66.7%), were associated with significantly higher relative risks of MDR TB among patients with new smear-positive TB, when compared with regional surveillance prevalence estimates. Among the 18 patients with diabetes and new smear-positive MDR TB, 10 (55.6%) had 2 risk factors for MDR TB at the time of enrollment. Of these, 5 (27.8%) had suspected category I failure, 4 (22.2%) were adults with a household contact, and 1 (5.6%) had confirmed category I failure. Breslow-Day tests for homogeneity indicated that the effect of adult household contact on the odds of MDR TB is modified by diabetes (p<0.0001), and that the effect of suspected category I failure on the odds of MDR TB is modified by diabetes (p = 0.0113). One patient with new smear-positive TB was suspected of failing category II treatment (i.e., positive smear or culture during the second or third month of category II therapy); this same patient met the risk group criteria for adult household contact and private or self-administered treatment. Among previously treated patients with smear-positive TB, the following factors were significantly associated with a higher relative risk for MDR TB, compared with regional surveillance prevalence estimates: adult household contact (51.4%), failure of category I treatment (73.3%), early relapse after category I treatment (40.0%), suspected (84.6%) or confirmed (61.1%) failure of category II treatment, and history of >2 previous TB treatments (38.3%).

We describe the proportion of drug resistance among TB patients as detected by using the screening strategy for MDR TB instituted in Lima, Peru, starting in 2005. When these data were compared with nearly concurrent population-based surveillance data, the proportion of MDR TB among new and previously treated TB cases was found to be significantly higher, indicating that screening high-risk patients may be an effective strategy. The proportion of MDR TB detected among patients with new smear-positive TB is comparable to that among previously treated patients with smear-positive TB in the cohort (p = 0.458). In the Peruvian NTP surveillance regional data corresponding to the study area, the prevalence of MDR TB among patients with new smear-positive TB was significantly lower than the prevalence among previously treated patients with smear-positive TB (p<0.001). This finding shows that the strategy implemented in Lima was especially effective in detecting MDR TB among patients with new smear-positive TB.

The risk groups with the highest rates of MDR TB were those with diabetes mellitus, adults or children with household contacts with known or suspected TB, suspected failure of category I or II treatment (i.e., positive smear or culture during the second or third month of therapy), failure or early relapse to category I treatment, failure of category II treatment, and multiple (>2) previous TB treatments. Ample literature supports these findings in a variety of settings (22–25). Screening for drug resistance among these groups is easily implemented and should be strongly considered by national TB programs.

In addition to identifying risk groups with high prevalence of MDR TB, other considerations are pertinent to the design of an optimal programmatic strategy. For example, risk groups with a relatively low prevalence of MDR TB may still merit DST if delays in initiation of MDR TB treatment would have severe consequences (e.g., children or HIV-positive patients) or if the absolute number of MDR TB cases within that risk group is substantial (e.g., patients with diabetes). The relative complexity of implementing certain testing strategies is also a consideration. Compared with alternative testing strategies such as universal testing or testing by geographic region, a strategy that focuses on high-risk patients requires training health care workers to screen each TB patient for numerous risk factors. Therefore, case finding may be variable under routine program conditions.

The findings of this evaluation are subject to several limitations. Although our study personnel would visit local health establishments in a purely observational capacity, the frequent visits by data collectors in the health centers could have sensitized health care workers to follow screening and referral protocols more closely than they would have otherwise. In addition, given the use of phenotypic methods, the drug-resistance status of particular isolates could be determined only for culture-positive samples. Although the yield of positive cultures was high for all methods used (67.4% for indirect conventional DST, 78.5% for direct NRA, and 35.3% for largely paucibacillary or smear-negative samples submitted for BACTEC; data not shown), the contribution to relative risk of MDR TB among those without DST results could not be determined. These results call attention to one of the shortcomings of all phenotypic methods, i.e., a substantial fraction of patients never have positive cultures or DST results to confirm the diagnosis or guide therapy, despite being at high risk for having MDR TB. Nonetheless, the yield of positive cultures in our sample is similar to that obtained by programs that have used the same sputum-processing methods (n-acetyl-l-cysteine and centrifugation, with cultivation on LJ medium). Finally, this evaluation was observational in nature and lacks a concurrent comparison group, such as one that had undergone an alternative screening strategy. On the other hand, this study has key strengths. The programmatic nature of this intervention, an active field presence to capture accurate and complete data on a large cohort, and the fortuitous concurrent surveillance study have allowed us to assess the effects of these programmatic efforts to identify patients with MDR TB.

To date, little research has been conducted on the comparative effectiveness of varied approaches to MDR TB screening and treatment referral. To our knowledge, the only study to show clinical results for performing rapid DST is a retrospective study carried out in California, which showed that using a molecular beacon assay led to earlier diagnosis and treatment initiation for MDR TB (26). An important aspect of program evaluation is feedback of findings to further improve treatment programs. In Peru, the results of this evaluation have been conveyed to the NTP and NRL. The aim of this communication is to describe an intensive evaluation of one of Peru's public health strategies for improving MDR TB control. In other low- to middle-income countries, similar program evaluations should be implemented to clarify national and regional MDR TB epidemiology, identify key risk groups for MDR TB, and inform national strategies to diagnose and treat MDR TB. Ultimately, the effects of these changes on turn-around time, time to culture conversion, cure rates, and costs will determine the comparative success of these strategies.