title: Minimum inhibitory concentration distributions for Mycobacterium avium complex-towards evidence-based susceptibility breakpoints.
abstract: BACKGROUND
  Patients with clinical infections caused by the Mycobacterium avium complex (MAC) are treated for at least 1 year following sputum conversion with a regimen that suffers from a suboptimal cure rate. The correlation between clinical outcome and drug susceptibility testing breakpoints other than for the macrolides is regarded to be poor. A systematic evaluation of clinical breakpoints for MAC has not been performed so far; thus, the aim of this study was to initiate the process by establishing minimum inhibitory concentration (MIC) distributions.
  
  
  METHODS
  The MICs of the major drugs used in the treatment of MAC infections were determined for 229 clinical MAC isolates in cation-adjusted Mueller-Hinton II broth.
  
  
  RESULTS
  The MIC50and MIC ranges were established and compared to suggested susceptibility breakpoints for clarithromycin (2; 0.064-128mg/l), rifabutin (0.25; ≤0.25-16mg/l), ethambutol (8; 0.5-32mg/l), amikacin (16; 1-128mg/l), moxifloxacin (2; 0.25-16mg/l), linezolid (32; 1-128mg/l), rifampicin (8; 0.125-16mg/l), and trimethoprim-sulfamethoxazole (2/38; 0.125/2-16/304mg/l).
  
  
  CONCLUSIONS
  These results, together with those from available studies, indicate that MICs are high for drugs such as rifabutin, rifampicin, ethambutol, linezolid, and moxifloxacin used against MAC at levels unlikely to be associated with clinical efficacy at current dosing. This may partly explain the poor correlation between susceptibility testing and clinical outcomes for drugs other than clarithromycin.
authors.affiliation: Department of Clinical Microbiology and Infectious Diseases, Kalmar County Hospital, 391 85 Kalmar, Sweden; Department of Clinical and Experimental Medicine (IKE), Division of Medical Microbiology, Linköping University, Linköping, Sweden. Electronic address: tschon@hotmail.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schön
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden; Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Erja
authors.initials: E
authors.lastname: Chryssanthou
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D015269:Mycobacterium avium Complex / Q000187:drug effects* / Q000302:isolation & purification; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents
keywords: Amikacin; Antimicrobial susceptibility breakpoints; Clarithromycin; Epidemiological cut-off value (ECOFF); Rifampicin; Sulfamethoxazole