Dalia Guerra

Comprehensive Treatment of Extensively Drug-Resistant Tuberculosis

BACKGROUND Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru. METHODS A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant. RESULTS Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [+/-SD] number of regimens, 4.2+/-1.9 vs. 3.2+/-1.6; P<0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4+/-1.1 vs. 5.3+/-1.5; P<0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3+/-1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36). CONCLUSIONS Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis.

Surgery for patients with drug-resistant tuberculosis: report of 121 cases receiving community-based treatment in Lima, Peru

Background: While most patients with tuberculosis (TB) can be successfully treated using short-course medical chemotherapy, thoracic surgery is an important adjunctive strategy for many patients with drug-resistant disease. The need for physical, technical and financial resources presents a potential challenge to implementing surgery as a component of treatment for multidrug-resistant TB (MDR-TB) in resource-poor settings. However, a cohort of patients with severe MDR-TB in Lima, Peru underwent surgery as part of their treatment. Methods: 121 patients underwent pulmonary surgery for drug-resistant tuberculosis between May 1999 and January 2004. Surgery was performed by a team of thoracic surgeons under the Ministry of Health. Patient demographic data, clinical characteristics, surgical procedures and surgical outcomes were studied. Results: Most of the patients had failed multiple TB regimens and were resistant to a median of seven drugs. The median time of follow-up after surgery was 33 months. 79.3% of patients were culture-positive before surgery, and sustained culture-negative status among survivors was achieved in 74.8% of patients. 63% of those followed up for at least 6 months after surgery were either cured or probably cured. Postoperative complications, observed in 22.6% of patients, were associated with preoperative haemoptysis, vital capacity <50% and low forced expiratory volume in 1 s. Conclusions: This is one of the largest cohorts with MDR-TB to be treated with surgery, and the first from a resource-poor country. Although surgery is not often considered an option for patients in resource-poor settings, the findings of this study support the argument that adjunctive surgery should be considered an integral component of MDR-TB treatment programmes, even in poor countries such as Peru.

Treatment of Multidrug-Resistant Tuberculosis during Pregnancy: A Report of 7 Cases

Multidrug-resistant tuberculosis (MDR-TB) is a global public health problem affecting women of childbearing age. Little is known, however, about the safety of the drugs used to treat MDR-TB during pregnancy. We describe 7 patients who were treated for MDR-TB during pregnancy. These patients had chronic tuberculosis that had caused extensive parenchymal damage and had high-grade resistance to antituberculous drugs. All patients received individualized antituberculous therapy prior to delivery of healthy term infants. Neither obstetrical complications nor perinatal transmission of MDB-TB was observed. One patient experienced treatment failure, and another abandoned therapy. The other 5 patients are currently cured or in treatment and have culture-negative status. In each of these 7 cases, excellent treatment outcomes were obtained for the women and their children. Under certain circumstances, MDR-TB can be successfully treated during pregnancy.

Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

Rationale A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. Objectives This study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort. Methods This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. Measurements and Main Results In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). Conclusions The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.

Drug-Resistant Tuberculosis and Pregnancy: Treatment Outcomes of 38 Cases in Lima, Peru

BACKGROUND Multidrug-resistant tuberculosis (MDR-TB) disproportionately affects young adults, including women of childbearing age; however, treatment of MDR-TB during pregnancy is still controversial. This study looks at the treatment and pregnancy outcomes in a cohort of women who were treated for MDR-TB during pregnancy during a period of 10 years. METHODS A retrospective case study was performed using a standardized data collection form and data from 3 ranked sources of patient records. All 38 participants were treated during pregnancy with individualized regimens that included second-line TB medications. We examined the frequency of favorable and adverse outcomes with regard to disease and pregnancy. RESULTS After completion of MDR-TB treatment, 61% of the women were cured, 13% had died, 13% had defaulted, 5% remained in treatment, and 5% had experienced treatment failure. Four of the women experienced clinical deterioration of TB during pregnancy. Five of the pregnancies terminated in spontaneous abortions, and 1 child was stillborn. Among the living newborns, 3 were born with low birth weight, 1 was born prematurely, and 1 had fetal distress. CONCLUSIONS The rates of success in treating MDR-TB in our cohort are comparable to those of other MDR-TB treatment programs in Peru. The birth outcomes of our cohort are similar to those among the general Peru population. Therefore, we advocate that a woman should be given the option to continue treatment of MDR-TB rather than terminating pregnancy or discontinuing MDR-TB treatment.

HIV-positive patients treated for multidrug-resistant tuberculosis: clinical outcomes in the HAART era.

SETTING Multidrug-resistant tuberculosis (MDR-TB) and the human immunodeficiency virus (HIV) pose two of the greatest threats to global tuberculosis (TB) control. Given expanding global access to antiretroviral therapy (ART) and second-line TB drugs, more data are needed on experiences treating MDR-TB and HIV co-infection in resource-poor settings. OBJECTIVE To describe the clinical characteristics, management, outcomes, and factors associated with survival among HIV-positive individuals receiving treatment for MDR-TB. DESIGN This was a retrospective case series of 52 HIV-positive individuals receiving treatment for MDR-TB in Lima, Peru. We used Cox proportional hazards regression models to identify risk factors for mortality. RESULTS A total of 31 (57%) of the cohort died on treatment, with the majority of deaths due to MDR-TB. Low baseline weight predicted a three-fold increased rate of death (aHR 3.1, 95%CI 1.5-6.7), while individuals receiving highly active ART experienced a significantly lower rate of death compared to those who were not (aHR 0.4, 95%CI 0.2-0.9). CONCLUSION Early ART is likely a key component of effective MDR-TB management in co-infected individuals.

Time to culture conversion and regimen composition in multidrug-resistant tuberculosis treatment.

Sputum cultures are an important tool in monitoring the response to tuberculosis treatment, especially in multidrug-resistant tuberculosis. There has, however, been little study of the effect of treatment regimen composition on culture conversion. Well-designed clinical trials of new anti-tuberculosis drugs require this information to establish optimized background regimens for comparison. We conducted a retrospective cohort study to assess whether the use of an aggressive multidrug-resistant tuberculosis regimen was associated with more rapid sputum culture conversion. We conducted Cox proportional-hazards analyses to examine the relationship between receipt of an aggressive regimen for the 14 prior consecutive days and sputum culture conversion. Sputum culture conversion was achieved in 519 (87.7%) of the 592 patients studied. Among patients who had sputum culture conversion, the median time to conversion was 59 days (IQR: 31–92). In 480 patients (92.5% of those with conversion), conversion occurred within the first six months of treatment. Exposure to an aggressive regimen was independently associated with sputum culture conversion during the first six months of treatment (HR: 1.36; 95% CI: 1.10, 1.69). Infection with human immunodeficiency virus (HR 3.36; 95% CI: 1.47, 7.72) and receiving less exposure to tuberculosis treatment prior to the individualized multidrug-resistant tuberculosis regimen (HR: 1.58; 95% CI: 1.28, 1.95) were also independently positively associated with conversion. Tachycardia (HR: 0.77; 95% CI: 0.61, 0.98) and respiratory difficulty (HR: 0.78; 95% CI: 0.62, 0.97) were independently associated with a lower rate of conversion. This study is the first demonstrating that the composition of the multidrug-resistant tuberculosis treatment regimen influences the time to culture conversion. These results support the use of an aggressive regimen as the optimized background regimen in trials of new anti-TB drugs.

Scaling up HIV treatment in Peru: applying lessons from DOTS-Plus.

Many countries with financial support for HIV treatment experience delays in scale-up because of bureaucratic, operational, and technical obstacles. The authors describe the Peruvian National HIV Programs response to such challenges. A team of consultants experienced in the scale-up of the Peruvian national program to treat multidrug-resistant tuberculosis worked with the national HIV program to identify and address key factors contributing to slow enrollment of HIV patients into the antiretroviral treatment program. The rate of enrollment into the antiretroviral treatment program increased from 124 patients/month in the first 9 months of the program to 226 patients/month in the last 7 months, an increase of 83%. This strategy achieved 38.5% coverage of the population in need. Effective programmatic expansion of the Peruvian National HIV Program was facilitated by a multidisciplinary collaboration in a systematized effort to overcome barriers to scale-up.