title: 'Z(S)-MDR-TB' versus 'Z(R)-MDR-TB': improving treatment of MDR-TB by identifying pyrazinamide susceptibility.
abstract: Indispensable for shortening treatment of drug-susceptible tuberculosis (TB), pyrazinamide (PZA, Z) is also essential in the treatment of multidrug-resistant (MDR)-TB. While resistance to PZA in MDR-TB is associated with poor treatment outcome, bacillary susceptibility to PZA along with the use of fluoroquinolone (FQ) and second-line injectable drugs (SLIDs) may predict improved treatment success in MDR-TB. Despite a high prevalence of PZA resistance among MDR-TB patients (10%-85%), PZA susceptibility testing is seldom performed because of technical challenges. To improve treatment of MDR-TB, we propose to: (i) classify MDR-TB into PZA-susceptible MDR-TB (Z(S)-MDR-TB) and PZA-resistant MDR-TB (Z(R)-MDR-TB); (ii) use molecular tests such as DNA sequencing (pncA, gyrA, rrs, etc.) to rapidly identify Z(S)-MDR-TB versus Z(R)-MDR-TB and susceptibility profile for FQ and SLID; (iii) refrain from using PZA in Z(R)-MDR-TB; and (iv) explore the feasibility of shortening the treatment duration of Z(S)-MDR-TB with a regimen comprising PZA plus at least two bactericidal agents especially new agents like TMC207 or PA-824 or delamanid which the bacilli are susceptible to, with one or two other agents. These measures may potentially shorten therapy, save costs, and reduce side effects of MDR-TB treatment.
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University , Baltimore, MD 21205, USA ; Department of Infectious Diseases, Huashan Hospital, Fudan University , Shanghai 200040, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tuberculosis and Chest Service, Department of Health , Hong Kong, China.
authors.forename: Kwok
authors.initials: K
authors.lastname: Chiu Chang
authors.affiliation: Tuberculosis and Chest Service, Department of Health , Hong Kong, China.
authors.forename: Chi-Chiu
authors.initials: CC
authors.lastname: Leung
authors.affiliation: Department of Microbiology, Chinese University of Hong Kong , Hong Kong, China.
authors.forename: Wing
authors.initials: W
authors.lastname: Wai Yew
authors.affiliation: Unite de Génétique Mycobactérienne, Institut Pasteur , 28 rue du Dr. Roux 75015 Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.affiliation: Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute at University of Medicine and Dentistry of New Jersey , Newark, NJ 07103, USA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Fallows
authors.affiliation: Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute at University of Medicine and Dentistry of New Jersey , Newark, NJ 07103, USA.
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University , Baltimore, MD 21287, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chaisson
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University , Shanghai 200040, China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Zhang
keywords: MDR-TB; pncA; pyrazinamide; susceptibility testing; therapy; tuberculosis