Drug concentration in lung tissue in multidrug-resistant tuberculosis

Abstract

To the Editor: Multidrug-resistant tuberculosis (MDR-TB) is emerging worldwide, with 3.7% of new cases and 20% of previously treated tuberculosis (TB) cases having MDR-TB. Unfortunately, second-line TB drugs, used for MDR-TB treatment, are less effective than first-line drugs [1]. Sputum culture rather than sputum smear microscopy is recommended to monitor treatment response [1]. Therapeutic drug monitoring (TDM), which may help optimise efficacy and minimise side-effects with the potential to safeguard intestinal absorption of drugs [2], is currently not recommended in World Health Organization (WHO) treatment guidelines [1]. Although TDM yields information on serum drug concentrations, penetration of second-line TB drugs into diseased tissues such as destroyed lung tissue has, to our knowledge, not been addressed in studies [3]. Herein, we report simultaneous blood and tissue concentrations of second-line TB drugs in lung tissue destroyed by MDR-TB. A 13-year-old Somalian, HIV sero-negative female, residing in the Netherlands since 2010, was admitted to our TB Unit (TB Center Beatrixoord, University Medical Center Groningen, Groningen, the Netherlands) in September 2011 with a 3-month history of cough, fever, chest pain and unintentional 14 kg weight loss. TB contacts were denied and she had not received a bacilli Calmette–Guerin vaccination. Apart from almost absent breathe sounds and dullness to percussion over the left lung field her physical examination was normal. Chest radiography showed infiltrates in the left lung, particularly in the left upper lobe. Sputum microscopy revealed acid-fast bacilli, and she was started on TB treatment with isoniazid, rifampicin, pyrazinamide and ethambutol. 2 weeks later, molecular diagnostic tests revealed mutations in both the katG and rpoB genes. MDR-TB was now considered and she was transferred to our hospital (University …