Synergistic antimycobacterial activity between ethambutol and the beta-lactam drug cefepime

The activity of cefepime alone and in combination with ethambutol was assessed, using the BACTEC radiometric system, on 33 mycobacterial strains, 14 Mycobacterium avium complex (MAC), 6 isolates of M. malmoense, and 13 multidrug-resistant (MDR) isolates of M. tuberculosis. All tested mycobacteria were resistant to 8 mg/l cefepime. However, at a concentration of 32 mg/l cefepime was active on 7/13 (54%) MDR isolates of M. tuberculosis and 2/6 (33%) M. malmoense strains. All MAC strains were also resistant to this concentration. Synergistic antimycobacterial effects were seen for the combination of cefepime and ethambutol against all isolates of MAC and M. malmoense and on 4/13 (31%) MDR M. tuberculosis isolates. Moreover, this drug combination rendered 17/24 (71%) initially resistant mycobacterial strains susceptible. These promising results suggest that the antimycobacterial activity of combinations of beta-lactam drugs and ethambutol should be studied further.