Treatment Outcomes for Adolescents With Multidrug-Resistant Tuberculosis in Lima, Peru.

Treatment outcomes for adolescents with multidrug-resistant tuberculosis are rarely reported and, to date, have been poor. Among 90 adolescents from Lima, Peru, 68 (75.6%) achieved cure or completion of treatment. Unsuccessful treatment was less common in the Peru cohort than previously described in the literature.

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.

Aggressive regimens for multidrug-resistant tuberculosis reduce recurrence.

BACKGROUND: Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatment-related factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy. METHODS: We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis. RESULTS: Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2-53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17-0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17-50.60]; P = .004). CONCLUSIONS: Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease.

Risk factors for in-hospital mortality among children with tuberculosis: the 25-year experience in Peru.

OBJECTIVE: We examined factors associated with in-hospital death among children with tuberculosis (TB). We hypothesized that a negative response to tuberculin skin testing (TST) would predict decreased survival. METHODS: This retrospective cohort comprised 2392 children ages 0 to 14 years hospitalized with TB at a Peruvian referral hospital over the 25-year study period. Detailed chart abstraction captured clinical history including TB contacts, physical examination findings, diagnostic data, treatment regimen, and hospitalization outcome. We used Cox proportional hazards regression analyses to determine risk factors for mortality. RESULTS: Of 2392 children, 2 (0.1%) were known to be HIV-positive, 5 (0.2%) had documented multidrug-resistant TB, and 266 (11%) died. The median time from hospitalization to death was 16 days (interquartile range: 4-44 days). Reaction of <5 mm induration on TST predicted death in a multivariable analysis (hazard ratio [HR]: 3.01; 95% confidence interval [CI]: 2.15-4.21; P < .0001). Younger age, period of admission, alteration of mental status (HR: 3.25; 95% CI: 2.48-4.27; P < .0001), respiratory distress (HR: 1.40; 95% CI: 1.07-1.83; P = .01), peripheral edema (HR: 1.97; 95% CI: 1.42-2.73; P < .0001), and hemoptysis (HR: 0.57; 95% CI: 0.32-1.00; P = .05) were associated with mortality. Treatment regimens that contained rifampicin (HR: 0.47; 95% CI: 0.33-0.68; P < .0001) were associated with improved survival. CONCLUSIONS: Negative reaction to TST is highly predictive of death among children with active TB. In children with clinical and radiographic findings suggestive of TB, a negative TST should not preclude or delay anti-TB therapy.

South-south collaboration in scale-up of HIV care: building human capacity for care.

OBJECTIVES: South-south collaborations in building human resource capacity have been inadequately emphasized globally despite the growing experience among resource-poor countries in scaling up HIV care and the funding to implement programmes. This paper aims to describe one such successful collaboration, in which a model of HIV care was developed in Haiti, adapted and expanded to Lesotho, and allowed the effective scale-up of HIV and other treatment services in a rural African setting. METHODS: Institutional experiences and lessons learned over a 10-year period in Haiti and a 3-year period in Lesotho are discussed. RESULTS: The Haiti-Lesotho collaborative model shows that human resource capacity can be built using creative partnerships and exchanges between developing countries, particularly with financial support from the north. The collaboration allows for the sharing of experiences and solutions through perspectives and experiences that are unique to developing countries. Healthcare workers in Haiti and Lesotho have established meaningful and fruitful cross-country working relationships, job satisfaction and retention has been improved and a sense of solidarity developed. The model of care developed in Haiti was successfully adapted, replicated and implemented in Lesotho. CONCLUSION: South-south collaborations are an important way for countries with established experience managing HIV in resource-poor settings to share their skills in a collaborative fashion with other nations facing similar disease problems and infrastructural challenges. This model for scaling up effective practice should be encouraged and supported by programme funders.

Tratamiento quirúrgico de la tuberculosis pulmonar multidrogo resistente en el Perú: serie de 304 casos / Surgical therapy of multidrug-resistant pulmonary tuberculosis in Peru: report of 304 cases

El tratamiento de la tuberculosis pulmonar (TB) es esencialmente farmacológico, pero debido a la aparición de resistenciaa drogas, el tratamiento se ha dificultado. En ese contexto la cirugía pulmonar es una importante estrategia coadyuvantepara el tratamiento de la tuberculosis multidrogo resistente (TB MDR). Objetivo. Describir las características clínicas,resultados y complicaciones en una serie de 304 pacientes con TB MDR sometidos a terapia quirúrgica. Materiales y métodos. Entre mayo de 1999 y enero del 2007 un total de 336 intervenciones quirúrgicas fueron realizadas en 304 pacientes, pertenecientes al Programa Nacional de Control de la Tuberculosis, los cuales fueron operados por un equipoquirúrgico del Ministerio de salud, en el Hospital Nacional Hipólito Unanue y en un Centro Privado de Lima. Resultados. Lamayoría de casos fueron de sexo masculino (60 por ciento) y el promedio de edad fue 28 años. Los pacientes tuvieron resistencia a una mediana de 5 drogas. Las lesiones cavitarias fueron las más frecuentes (91.8 por ciento) y la lobectomía fue el procedimiento quirúrgico más utilizado (68.4 por ciento). La morbilidad postoperatoria ocurrió en 12,8 por ciento de los casos y la mortalidad post-operatoria fue de 2 por ciento. Los pacientes fueron seguidos hasta 79,3 meses y la curación fue alcanzada en el 77,2 por ciento de los casos. Conclusiones. La cirugía pulmonar coadyuvante es una alternativa efectiva para la curación en pacientes con TB MDR. Esta estrategia debe ser incluida como parte de los programas de tratamiento de la TB MDR.

Treatment for pulmonary tuberculosis (TB) is drug-based but the emergence of drug-resistance has decreased itstherapeutic efficacy. Pulmonary surgery is an important beneficial adjuvant strategy for MDR TB treatment in this context.Objectives. To describe the clinical characteristics results and complications in a series of 304 patients with MDR TBsubmitted to surgical therapy. Material and methods. Between May of 1999 and January of 2007 a total of 336 surgicalinterventions were performed on 304 patients from the National Program of TB Control who, were operated by a surgicalteam of the Ministry of Health in the Hipolito Unanue National Hospital and in a Private Center in Lima. Results. Mostcases were male (60 per cent) and the mean age was 28 years. Patients were resistant to a median of 5 drugs. Cavitarylesions were the most common (91.8 per cent) and lobectomy was the most commonly performed surgical procedure (68.4 per cent). Postoperative morbidity and mortality occurred in 12.8 per cent and 2 per cent respectively. Patients were followed post-operatively for a maximum time of 79.3 months and healing was reached in the 77.2 per cent of cases. Conclusions. Pulmonary adjuvantsurgery on MDR TB patients is an effective alternative for cure. This strategy should be included as part of treatmentprograms for MDR TB.

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.

Long-term follow-up for multidrug-resistant tuberculosis.

Patients treated in Peru for multidrug-resistant tuberculosis (MDR-TB) were followed-up for a median of 67 months. Among 86 patients considered cured after completion of treatment, 97% remain healthy; 1 patient relapsed. Employment increased from 34% before treatment to 71%. We observed favorable long-term outcomes among MDR-TB patients.

Community-based treatment of multidrug-resistant tuberculosis in Lima, Peru: 7 years of experience.

Programs implementing community-based directly observed therapy (DOT) have demonstrated success in the treatment of patients with tuberculosis. However, given complexities in the management and treatment of patients infected with multidrug-resistant tuberculosis (MDR-TB), the utilization of community-based DOT to treat MDR-TB patients has only recently been successfully attempted. We describe the first such program and highlight the crucial components and most critical challenges to creating a successful community-based MDR-TB treatment program.

Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru.

BACKGROUND: Despite the prevalence of multidrug-resistant tuberculosis in nearly all low-income countries surveyed, effective therapy has been deemed too expensive and considered not to be feasible outside referral centers. We evaluated the results of community-based therapy for multidrug-resistant tuberculosis in a poor section of Lima, Peru. METHODS: We describe the first 75 patients to receive ambulatory treatment with individualized regimens for chronic multidrug-resistant tuberculosis in northern Lima. We conducted a retrospective review of the charts of all patients enrolled in the program between August 1, 1996, and February 1, 1999, and identified predictors of poor outcomes. RESULTS: The infecting strains of Mycobacterium tuberculosis were resistant to a median of six drugs. Among the 66 patients who completed four or more months of therapy, 83 percent (55) were probably cured at the completion of treatment. Five of these 66 patients (8 percent) died while receiving therapy. Only one patient continued to have positive cultures after six months of treatment. All patients in whom treatment failed or who died had extensive bilateral pulmonary disease. In a multiple Cox proportional-hazards regression model, the predictors of the time to treatment failure or death were a low hematocrit (hazard ratio, 4.09; 95 percent confidence interval, 1.35 to 12.36) and a low body-mass index (hazard ratio, 3.23; 95 percent confidence interval, 0.90 to 11.53). Inclusion of pyrazinamide and ethambutol in the regimen (when susceptibility was confirmed) was associated with a favorable outcome (hazard ratio for treatment failure or death, 0.30; 95 percent confidence interval, 0.11 to 0.83). CONCLUSIONS: Community-based outpatient treatment of multidrug-resistant tuberculosis can yield high cure rates even in resource-poor settings. Early initiation of appropriate therapy can preserve susceptibility to first-line drugs and improve treatment outcomes.