Minimum inhibitory concentration distributions for Mycobacterium avium complex—towards evidence-based susceptibility breakpoints

Minimum inhibitory concentration distributions for Mycobacterium avium complex—towards evidence-based susceptibility breakpoints

International Journal of Infectious Diseases, January 2017

28069470

Thomas Schön, Erja Chryssanthou

Patients with clinical infections caused by the Mycobacterium avium-complex (MAC) are treated for at least one year following sputum conversion with a regimen suffering from suboptimal cure rates. 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 against MAC has not been performed so far and thus our aim was to initiate this process by establishing minimal inhibitory concentration (MIC) distributions. The MIC against the major drugs used for treatment was determined in 229 clinical MAC isolates in cation-adjusted Mueller-Hinton II broth. The MIC50 and 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; 1-128), rifampicin (8; 0.125-16mg/L) and trimethoprim/sulfamethoxazole (2/38; 0.125/2-16/304mg/L). Our results together with 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 with current dosing. This may partly explain the poor correlation between susceptibility testing and clinical outcome for drugs other than clarithromycin.