Evaluation of the post-antibiotic effect of six anti-mycobacterial agents against Mycobacterium avium by the Bactec radiometric method

We compared and evaluated the duration of the post-antibiotic effect (PAE) of six antimycobacterial agents (ethambutol, isoniazid, rifampicin, amikacin, ciprofloxacin and clarithromycin), alone and in combination, against ten strains of Mycobacterium avium. PAE was determined by conventional viable counting and the Bactec growth system, analysed by the T-100 value (the time to produce a cumulative growth index of 100). A 2 h exposure to the drug did not induce significant killing. Thus, comparison of regrowth could be evaluated without the potential need to adjust viable counts. The correlation of duration of PAE between the viable count method and the T-100 Bactec method was excellent (r = 0.94). No significant PAE (< 8 h) was induced using sub-inhibitory drug concentrations or with ethambutol or isoniazid alone. Rifampicin (20-41 h) and amikacin (8-36 h) demonstrated consistent and extended PAEs, white ciprofloxacin (1-15 h) and clarithromycin (2-10 h) displayed variable PAE activities. Different three-drug combinations (all including ethambutol) displayed variable results with a combination of ethambutol, isoniazid and rifampicin being the most effective combination for extending the PAE (greater than or equal to 8 h) which was observed in half the strains tested. It was concluded that the T-100 Bactec method is highly suitable for evaluating PAE against M. avium, producing a definitive result in 5 days.