Multidrug-resistant tuberculosis (MDR-TB) treatment in the UK: A study of injectable use and toxicity in practice

Background: Multidrug-resistant tuberculosis (MDR-TB) is an increasing challenge to health services globally. Although new drugs are in development, current guidelines still recommend prolonged use of injectable antimicrobials (usually amikacin, kanamycin or capreomycin). The evidence base to inform treatment and monitoring strategies is very limited. Methods: We conducted a retrospective study of patients initiating injectable antimicrobials for MDR-TB treatment in five UK centres between January 2004 and December 2009. (i) Current treatment and monitoring strategies were reviewed. (ii) The incidence of ototoxicity (defined both clinically and on audiological testing) and factors associated with ototoxicity were investigated using logistic regression. Results: (i) The choice of injectable antimicrobial varied. Of 50 MDR-TB patients, 29/50 (58%) received amikacin, 11/50 (22%) received capreomycin and 10/50 (20%) received streptomycin or a combination; reflecting a difference in policy between centres. Only 21/50 (42%) patients received baseline screening by audiogram within 2 weeks of starting treatment and 16/50 (32%) then had monthly audiograms, with the majority screened more infrequently and 12/50 (24%) receiving no screening. (ii) Of the 50 patients, 14 (28%) experienced ototoxicity, with 9/50 (18%) left with long-term hearing loss. Increased age (P=0.02), use of amikacin (P=0.02) and decreased renal function (P=0.01) were significantly associated with ototoxicity. Conclusions: There is local variation in both the choice of injectable agent and in ototoxicity screening practices. Long-term morbidity from injectable treatment is significant even in this well-resourced setting, and the data suggest capreomycin might be associated with less ototoxicity when compared with amikacin. There is a need for more high-quality clinical data to inform future guidelines for treatment and monitoring.