Treatment Outcomes in Global Systematic Review and Patient Meta-Analysis of Children with Extensively Drug-Resistant Tuberculosis

Abstract

Extensively drug-resistant tuberculosis (XDR TB) has extremely poor treatment outcomes in adults. Limited data are available for children. We report on clinical manifestations, treatment, and outcomes for 37 children (<15 years of age) with bacteriologically confirmed XDR TB in 11 countries. These patients were managed during 1999-2013. For the 37 children, median age was 11 years, 32 (87%) had pulmonary TB, and 29 had a recorded HIV status; 7 (24%) were infected with HIV. Median treatment duration was 7.0 months for the intensive phase and 12.2 months for the continuation phase. Thirty (81%) children had favorable treatment outcomes. Four (11%) died, 1 (3%) failed treatment, and 2 (5%) did not complete treatment. We found a high proportion of favorable treatment outcomes among children, with mortality rates markedly lower than for adults. Regimens and duration of treatment varied considerably. Evaluation of new regimens in children is required.

Keywords: MDR TB; TB; XDR TB; antimicrobial resistance; bacteria; children; extensively drug-resistant tuberculosis; global systematic review; meta-analysis; mortality; multidrug-resistant TB; outcomes; respiratory infections; treatment outcomes; tuberculosis; tuberculosis and other mycobacteria.

Figure 1

Flow chart for 37 children with confirmed XDR TB and details of TB treatment history, type of TB treatment, and treatment outcome. DR, drug-resistant; DS, drug-susceptible, MDR, multidrug-resistant; TB, tuberculosis; XDR TB, extensively drug-resistant TB.

Figure 2

Mycobacterial drug susceptibility test pattern for children treated for extensively drug-resistant tuberculosis. All children had organisms that were resistant to rifampin and isoniazid. *Includes moxifloxacin, levofloxacin, ofloxacin, or ciprofloxacin. †Includes second-line injectable drugs kanamycin, amikacin, or capreomycin. AMK, amikacin, amikacin; CAP, capreomycin; CIP, ciprofloxacin; CYS, cycloserine; EMB, ethambutol; ETH, ethionamide; KAN, kanamycin; LVX, levofloxacin; MXF, moxifloxacin; OFX, ofloxacin; PAS, para-aminosalicylic acid; PTH, prothionamide; PZA, pyrazinamide; STR, streptomycin; TRZ, terizidone.

Figure 3

Drugs used for treatment of children with extensively drug resistant tuberculosis. *Includes moxifloxacin, levofloxacin, ofloxacin or ciprofloxacin. †Includes second-line injectable drugs kanamycin, amikacin, or capreomycin. AMK, amikacin, AMX, amoxicillin; CAP, capreomycin; CFZ, clofazimine; CIP, ciprofloxacin; CLA, clavulanic acid; CLM, clarithromycin; CYS, cycloserine; EMB, ethambutol; ETH, ethionamide; INH, isoniazid; INN, thioacetazone; KAN, kanamycin; LVX, levofloxacin; LZD, linezolid; MXF, moxifloxacin; OFX, ofloxacin; PAS, para-aminosalicylic acid; PTH, prothionamide; PZA, pyrazinamide; RFB, fifabutin; RIF, rifampin; STR, streptomycin; TRZ, terizidone.

Figure 4

Treatment outcomes for 37 children treated for XDR TB. XDR TB, extensively drug-resistant tuberculosis.