[Loss to follow-up in patients treated for multidrug-resistant tuberculosis in EcuadorA Perda de seguimento de pacientes tratados para tuberculose multirresistente a medicamentos no Equador]. / Pérdida en el seguimiento de pacientes tratados por tuberculosis resistente a rifampicina o multidrogorresistente en Ecuador.

OBJECTIVE: Determine the incidence of loss to follow-up (LTFU) in patients treated for rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant tuberculosis (RR/MDR-TB), and the factors associated with this discharge status in Ecuador. METHODS: Retrospective cohort study of patients with RR/MDR-TB who followed the World Health Organization's 18-24-month treatment regimen in 2014 and 2015, as reported by the Ministry of Health of Ecuador. The incidence of LTFU was determined, and clinical and epidemiological manifestations of cases discharged as LTFU were compared with those discharged as successfully treated. Survival was analyzed with Cox regression in order to evaluate factors associated with LTFU. RESULTS: Of 328 cases, 270 (82.3%) were analyzed because they had a reported discharge status. Discharge as LTFU accounted for 39.6% of cases, and as successfully treated, 50.4%. The risk factors associated with LTFU were: previous discharge as LTFU in a previous TB episode [hazard ratio (HR): 2.96 (1.53-5.73), P < 0.001]; addiction to alcohol or drugs [HR: 2.82 (1.10-7.23), P = 0.031]; and having an Xpert® diagnosis (TB-RR) [HR: 1.53 (1.0-2.35), P = 0.048]. Of the total LTFU, 43% occurred after nine months of treatment. CONCLUSION: The incidence of LTFU in patients with RR/MDR-TB in Ecuador is above the average for the Region of the Americas. The three identified factors support implementation of shorter regimens and patient-centered care, in line with the End TB Strategy.

OBJETIVO: Determinar o percentual de perda de seguimento de pacientes tratados para tuberculose resistente à rifampicina (TB-RR) ou tuberculose multirresistente a medicamentos (TB-MR) e os fatores associados à interrupção do tratamento no Equador. MÉTODOS: Estudo de coorte retrospectivo de casos de pacientes com TB-RR/TB-MR tratados em 2014 e 2015 com o esquema farmacológico de 18 a 24 meses de duração da Organização Mundial da Saúde (OMS) que foram notificados ao Ministério da Saúde do Equador. Foi determinado o percentual de perda de seguimento e foram comparadas as características clínicas e epidemiológicas dos casos de interrupção do tratamento por perda de seguimento e daqueles com alta por sucesso no tratamento. Uma análise da sobrevida com o modelo de regressão de Cox foi realizada para avaliar os fatores associados à perda de seguimento. RESULTADOS: De 328 casos registrados, 270 (82,3%) foram incluídos na análise por terem tido sua interrupção ou alta notificadas. Houve interrupção por perda de seguimento em 39,6% dos casos e alta por sucesso no tratamento em 50,4%. Os fatores de risco associados à perda de seguimento foram: história de perda de seguimento em tratamento anterior de TB, razão de riscos (hazard ratio, HR) 2,96 (1,53­5,73, P < 0,001); consumo excessivo de álcool ou drogas, HR 2,82 (1,10­7,23, P = 0,031); e diagnóstico de tuberculose pelo teste Xpert® (TB-RR), HR 1,53 (1,0­2,35, P = 0,048). A perda de seguimento ocorreu após nove meses de tratamento em 43% dos casos. CONCLUSÃO: O percentual de perda de seguimento de pacientes com TB-RR/TB-MR no Equador está acima da média da Região das Américas. Os três fatores identificados no estudo reforçam ser necessário implementar esquemas de tratamento mais curtos e prestar atenção centrada no paciente, segundo as recomendações da Estratégia pelo Fim da Tuberculose.

Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB.

No large study has ever evaluated the efficacy, safety and tolerability of meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR- and XDR-TB cases.Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49% versus 6.0%, p<0.0001) and the median (interquartile range (IQR)) number of antibiotic resistances was higher (8 (6-9)versus 5 (4-6)). Patients were treated with a meropenem/clavulanate-containing regimen for a median (IQR) of 85 (49-156) days.No statistically significant differences were observed in the overall MDR-TB cohort and in the subgroups with and without the XDR-TB patients; in particular, sputum smear and culture conversion rates were similar in XDR-TB patients exposed to meropenem/clavulanate-containing regimens (88.0% versus 100.0%, p=1.00 and 88.0% versus 100.0%, p=1.00, respectively). Only six cases reported adverse events attributable to meropenem/clavulanate (four of them then restarting treatment).The nondifferent outcomes and bacteriological conversion rate observed in cases who were more severe than controls might imply that meropenem/clavulanate could be active in treating MDR- and XDR-TB cases.

Comparison of effectiveness and safety of imipenem/clavulanate- versus meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB.

No large study to date has ever evaluated the effectiveness, safety and tolerability of imipenem/clavulanate versus meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to compare the therapeutic contribution of imipenem/clavulanate versus meropenem/clavulanate added to background regimens to treat MDR- and XDR-TB cases.84 patients treated with imipenem/clavulanate-containing regimens showed a similar median number of antibiotic resistances (8 versus 8) but more fluoroquinolone resistance (79.0% versus 48.9%, p<0.0001) and higher XDR-TB prevalence (67.9% versus 49.0%, p=0.01) in comparison with 96 patients exposed to meropenem/clavulanate-containing regimens. Patients were treated with imipenem/clavulanate- and meropenem/clavulanate-containing regimens for a median (interquartile range) of 187 (60-428) versus 85 (49-156) days, respectively.Statistically significant differences were observed on sputum smear and culture conversion rates (79.7% versus 94.8%, p=0.02 and 71.9% versus 94.8%, p<0.0001, respectively) and on success rates (59.7% versus 77.5%, p=0.03). Adverse events to imipenem/clavulanate and meropenem/clavulanate were reported in 5.4% and 6.5% of cases only.Our study suggests that meropenem/clavulanate is more effective than imipenem/clavulanate in treating MDR/XDR-TB patients.

Pérdida en el seguimiento de pacientes tratados por tuberculosis resistente a rifampicina o multidrogorresistente en Ecuador

[RESUMEN]. Objetivo. Determinar la incidencia de pérdida en el seguimiento (PEES) en pacientes tratados por tuberculosis (TB) resistente a rifampicina o multidrogorresistente (TB-RR/MDR) y los factores asociados a esta condición de egreso en Ecuador. Métodos. Estudio de cohorte retrospectivo de pacientes con TB-RR/MDR tratados con el esquema de 18 a 24 meses de la Organización Mundial de la Salud en 2014 y 2015 notificados al Ministerio de Salud del Ecuador. Se determinó la incidencia de PEES y se compararon las características clínicas y epidemiológicas de los casos egresados como PEES versus los egresados como éxito de tratamiento. Se analizó la sobrevida con regresión de Cox para evaluar factores asociados a PEES. Resultados. De 328 casos, 270 (82,3%) fueron analizados porque tuvieron condición de egreso notificada. El egreso como PEES fue 39,6% y el éxito de tratamiento 50,4%. Los factores de riesgo asociados a PEES fueron: antecedente de egreso como PEES en episodio previo de TB, cociente de riesgos instantáneos (HR, por sus siglas en inglés): 2,96 (1,53-5,73), P < 0,001; adicción al alcohol o drogas, HR: 2,82 (1,10-7,23), P = 0,031 y tener diagnóstico por la prueba Xpert® (TB-RR), HR: 1,53 (1,0-2,35), P = 0,048. Del total de PEES, 43% ocurrió después de nueve meses de tratamiento. Conclusión. La incidencia de PEES en pacientes con TB-RR/MDR en Ecuador está por encima del promedio en la Región de las Américas. Los tres factores identificados refuerzan la implementación de regímenes acortados y atención centrada en el paciente, siguiendo la Estrategia Fin a la Tuberculosis.

[ABSTRACT]. Objective. Determine the incidence of loss to follow-up (LTFU) in patients treated for rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant tuberculosis (RR/MDR-TB), and the factors associated with this discharge status in Ecuador. Methods. Retrospective cohort study of patients with RR/MDR-TB who followed the World Health Organization’s 18-24-month treatment regimen in 2014 and 2015, as reported by the Ministry of Health of Ecuador. The incidence of LTFU was determined, and clinical and epidemiological manifestations of cases discharged as LTFU were compared with those discharged as successfully treated. Survival was analyzed with Cox regression in order to evaluate factors associated with LTFU. Results. Of 328 cases, 270 (82.3%) were analyzed because they had a reported discharge status. Discharge as LTFU accounted for 39.6% of cases, and as successfully treated, 50.4%. The risk factors associated with LTFU were: previous discharge as LTFU in a previous TB episode [hazard ratio (HR): 2.96 (1.53-5.73), P < 0.001]; addiction to alcohol or drugs [HR: 2.82 (1.10-7.23), P = 0.031]; and having an Xpert® diagnosis (TBRR) [HR: 1.53 (1.0-2.35), P = 0.048]. Of the total LTFU, 43% occurred after nine months of treatment. Conclusion. The incidence of LTFU in patients with RR/MDR-TB in Ecuador is above the average for the Region of the Americas. The three identified factors support implementation of shorter regimens and patient-centered care, in line with the End TB Strategy.

[RESUMO]. Objetivo. Determinar o percentual de perda de seguimento de pacientes tratados para tuberculose resistente à rifampicina (TB-RR) ou tuberculose multirresistente a medicamentos (TB-MR) e os fatores associados à interrupção do tratamento no Equador. Métodos. Estudo de coorte retrospectivo de casos de pacientes com TB-RR/TB-MR tratados em 2014 e 2015 com o esquema farmacológico de 18 a 24 meses de duração da Organização Mundial da Saúde (OMS) que foram notificados ao Ministério da Saúde do Equador. Foi determinado o percentual de perda de seguimento e foram comparadas as características clínicas e epidemiológicas dos casos de interrupção do tratamento por perda de seguimento e daqueles com alta por sucesso no tratamento. Uma análise da sobrevida com o modelo de regressão de Cox foi realizada para avaliar os fatores associados à perda de seguimento. Resultados. De 328 casos registrados, 270 (82,3%) foram incluídos na análise por terem tido sua interrupção ou alta notificadas. Houve interrupção por perda de seguimento em 39,6% dos casos e alta por sucesso no tratamento em 50,4%. Os fatores de risco associados à perda de seguimento foram: história de perda de seguimento em tratamento anterior de TB, razão de riscos (hazard ratio, HR) 2,96 (1,53–5,73, P < 0,001); consumo excessivo de álcool ou drogas, HR 2,82 (1,10–7,23, P = 0,031); e diagnóstico de tuberculose pelo teste Xpert® (TB-RR), HR 1,53 (1,0–2,35, P = 0,048). A perda de seguimento ocorreu após nove meses de tratamento em 43% dos casos. Conclusão. O percentual de perda de seguimento de pacientes com TB-RR/TB-MR no Equador está acima da média da Região das Américas. Os três fatores identificados no estudo reforçam ser necessário implementar esquemas de tratamento mais curtos e prestar atenção centrada no paciente, segundo as recomendações da Estratégia pelo Fim da Tuberculose.