title: Second-line drug susceptibility breakpoints for Mycobacterium tuberculosis using the MODS assay.
abstract: OBJECTIVE
  To establish breakpoint concentrations for the fluoroquinolones (moxifloxacin [MFX] and ofloxacin [OFX]) and injectable second-line drugs (amikacin [AMK], kanamycin [KM] and capreomycin [CPM]) using the microscopic observation drug susceptibility (MODS) assay.
  
  
  METHODS
  A multinational study conducted between February 2011 and August 2012 in Peru, India, Moldova and South Africa.
  
  
  METHODS
  In the first phase, breakpoints for the fluoroquinolones and injectable second-line drugs (n = 58) were determined. In the second phase, MODS second-line drug susceptibility testing (DST) as an indirect test was compared to MGIT™ DST (n = 89). In the third (n = 30) and fourth (n = 156) phases, we determined the reproducibility and concordance of MODS second-line DST directly from sputum.
  
  
  RESULTS
  Breakpoints for MFX (0.5 μg/ml), OFX (1 μg/ml), AMK (2 μg/ml), KM (5 μg/ml) and CPM (2.5 μg/ml) were determined. In all phases, MODS results were highly concordant with MGIT DST. The few discrepancies suggest that the MODS breakpoint concentrations for some drugs may be too low.
  
  
  CONCLUSIONS
  MODS second-line DST yielded comparable results to MGIT second-line DST, and is thus a promising alternative. Further studies are needed to confirm the accuracy of the drug breakpoints and the reliability of MODS second-line DST as a direct test.
authors.affiliation: Biomedical Sciences, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Medical Research Council Centre for Molecular and Cellular Biology, Stellenbosch University, Cape Town, South Africa.
authors.forename: A P
authors.initials: AP
authors.lastname: Trollip
authors.affiliation: TB Centre and Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: D
authors.initials: D
authors.lastname: Moore
authors.affiliation: Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: J
authors.initials: J
authors.lastname: Coronel
authors.affiliation: Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: L
authors.initials: L
authors.lastname: Caviedes
authors.affiliation: Biomedical Sciences, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Medical Research Council Centre for Molecular and Cellular Biology, Stellenbosch University, Cape Town, South Africa.
authors.forename: S
authors.initials: S
authors.lastname: Klages
authors.affiliation: Biomedical Sciences, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Medical Research Council Centre for Molecular and Cellular Biology, Stellenbosch University, Cape Town, South Africa.
authors.forename: T
authors.initials: T
authors.lastname: Victor
authors.affiliation: Microbiology and Morphology Laboratory, Phthisiopneumology Institute, Chisinau, Moldova.
authors.forename: E
authors.initials: E
authors.lastname: Romancenco
authors.affiliation: Microbiology and Morphology Laboratory, Phthisiopneumology Institute, Chisinau, Moldova.
authors.forename: V
authors.initials: V
authors.lastname: Crudu
authors.affiliation: Department of Microbiology, Parmanand Deepchand Hinduja National Hospital and Medical Research Centre Tertiary Care Hospital, Mumbai, India.
authors.forename: K
authors.initials: K
authors.lastname: Ajbani
authors.affiliation: Department of Microbiology, Parmanand Deepchand Hinduja National Hospital and Medical Research Centre Tertiary Care Hospital, Mumbai, India.
authors.forename: V P
authors.initials: VP
authors.lastname: Vineet
authors.affiliation: Department of Microbiology, Parmanand Deepchand Hinduja National Hospital and Medical Research Centre Tertiary Care Hospital, Mumbai, India.
authors.forename: C
authors.initials: C
authors.lastname: Rodrigues
authors.affiliation: University of California San Diego School of Medicine, La Jolla, California, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Jackson
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: K
authors.initials: K
authors.lastname: Eisenach
authors.affiliation: University of California San Diego School of Medicine, La Jolla, California, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Garfein
authors.affiliation: Division of Global Public Health, University of California San Diego School of Medicine, La Jolla, California, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Rodwell
authors.affiliation: Mycobacteriology and Mycology Section, Microbial Diseases Laboratory, California Department of Public Health, Richmond, California, USA.
authors.forename: E
authors.initials: E
authors.lastname: Desmond
authors.affiliation: University of California San Diego, Veterans' Affairs San Diego Healthcare System, La Jolla, California, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Groessl
authors.affiliation: University of California San Diego Health Services Research Center, UCSD, La Jolla, California, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Ganiats
authors.affiliation: University of California San Diego School of Medicine, La Jolla, California, USA.
authors.forename: A
authors.initials: A
authors.lastname: Catanzaro
mesh_terms: D000583:Amikacin / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002207:Capreomycin / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial; D024841:Fluoroquinolones / Q000627:therapeutic use; D006801:Humans; D007194:India; D007612:Kanamycin / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests / Q000379:methods*; D008853:Microscopy; D008966:Moldova; D000077266:Moxifloxacin; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D015242:Ofloxacin / Q000627:therapeutic use; D010568:Peru; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013019:South Africa; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D002207:Capreomycin; D007612:Kanamycin; D000583:Amikacin; D015242:Ofloxacin; D000077266:Moxifloxacin