Treatment outcomes and adverse drug effects of ethambutol, cycloserine, and terizidone for the treatment of multidrug-resistant tuberculosis in South Africa

Treatment outcomes among multidrug-resistant tuberculosis (MDR-TB) patients receiving ethambutol, cycloserine, or terizidone as part of a standardized regimen were compared, determining occurrence of serious adverse drug events (SADEs). Newly diagnosed adult MDR-TB patients were enrolled between 2000 and 2004, receiving a standardized multidrug regimen for 18 to 24 months, including ethambutol, cycloserine, or terizidone. Cycloserine and terizidone were recorded individually. SADEs and factors associated with culture conversion and unfavorable treatment outcomes (default, death, treatment failure) were determined. Of 858 patients, 435 (51%) received ethambutol, 278 (32%) received cycloserine, and 145 (17%) received terizidone. Demographic and baseline clinical data were comparable. Successful treatment occurred in 56%, significantly more in patients receiving cycloserine (60%) and terizidone (62%) than in those receiving ethambutol (52% [P = 0.03]). Defaults rates were 30% in ethambutol patients versus 15% and 11% for cycloserine and terizidone patients, respectively. Terizidone was associated with fewer unfavorable outcomes (adjusted odds ratio [AOR], 0.4; P = 0.008; 95% confidence interval [CI], 0.2 to 0.8). Patients receiving cycloserine were more likely to achieve culture conversion than those receiving ethambutol or terizidone (AOR, 2.2; P = 0.02; 95% CI, 1.12 to 4.38). Failure to convert increased the odds of unfavorable outcomes (AOR, 23.7; P < 0.001; 95% CI, 13 to 44). SADEs were reported in two patients receiving ethambutol, seven patients receiving cycloserine, and three receiving terizidone (P = 0.05). Ethambutol was associated with high culture conversion and default rates. Cycloserine achieved higher culture conversion rates than terizidone. Fewer patients on terizidone experienced SADEs, with lower default rates. The differences that we observed between cycloserine and terizidone require further elucidation.SAMRChttp://aac.asm.orghj2022Medical Microbiolog

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Adherence to Concurrent Tuberculosis Treatment and Antiretroviral Treatment among Co-Infected Persons in South Africa, 2008-2010.

BACKGROUND:Adherence to tuberculosis (TB) treatment and antiretroviral therapy (ART) reduces morbidity and mortality among persons co-infected with TB/HIV. We measured adherence and determined factors associated with non-adherence to concurrent TB treatment and ART among co-infected persons in two provinces in South Africa. METHODS:A convenience sample of 35 clinics providing integrated TB/HIV care was included due to financial and logistic considerations. Retrospective chart reviews were conducted among persons who received concurrent TB treatment and ART and who had a TB treatment outcome recorded during 1 January 2008-31 December 2010. Adherence to concurrent TB and HIV treatment was defined as: (1) taking ≥80% of TB prescribed doses by directly observed therapy (DOT) as noted in the patient card; and (2) taking >90% ART doses as documented in the ART medical record during the concurrent treatment period (period of time when the patient was prescribed both TB treatment and ART). Risk ratios (RRs) and 95% confidence intervals (CIs) were used to identify factors associated with non-adherence. RESULTS:Of the 1,252 persons receiving concurrent treatment, 138 (11.0%) were not adherent. Non-adherent persons were more likely to have extrapulmonary TB (RR: 1.71, 95% CI: 1.12 to 2.60) and had not disclosed their HIV status (RR: 1.96, 95% CI: 1.96 to 3.76). CONCLUSIONS:The majority of persons with TB/HIV were adherent to concurrent treatment. Close monitoring and support of persons with extrapulmonary TB and for persons who have not disclosed their HIV status may further improve adherence to concurrent TB and antiretroviral treatment

Study Population Included in TB/HIV Concurrent Treatment Analysis, 2008–2010.

<p>Study Population Included in TB/HIV Concurrent Treatment Analysis, 2008–2010.</p

Multivariate analysis of the relationship between characteristics of persons receiving concurrent TB/HIV treatment in selected THAT’SIT clinics and non-adherence to concurrent TB and HIV treatment (N = 1252).

<p>TB = tuberculosis, HIV = human immunodeficiency virus.</p

Bivariate relationship between characteristics of persons receiving concurrent TB/HIV treatment in selected THAT’SIT clinics and adherence to treatment (N = 1,252).

<p>BMI = body mass index; TB = tuberculosis; HRZE = isoniazid, rifampin, pyrazinamide, ethambutol; HRZES = isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin; DOT = directly observed therapy; WHO = World Health Organization; HIV = human immunodeficiency virus; ARV = antiretroviral; D4T/3TC/EFV = stavudine, lamivudine, efavirenz; D4T/3TC/NVP = stavudine, lamivudine, nevirapine.</p

Demographic, clinical, and social characteristics of patients receiving concurrent TB/HIV treatment in selected THAT’SIT clinics, South Africa, 2008–2010 (N = 1,252).

<p>BMI = body mass index; TB = tuberculosis; IRZE = isoniazid, rifampin, pyrazinamide, ethambutol; DOT = directly observed therapy; WHO = World Health Organization; HIV = human immunodeficiency virus; ARV = antiretroviral; D4T/3TC/EFV = stavudine, lamivudine, efavirenz; D4T/3TC/NVP = stavudine, lamivudine, nevirapine.</p