Background: The mainstays of treatment for pulmonary disease caused by opportunist mycobacteria are rifampicin (R) and ethambutol (E). The role of macrolides, quinolones and immunotherapy with Mycobacterium vaccae is not clear. A trial was undertaken to compare clarithromycin (Clari) and ciprofloxacin (Cipro) as third drugs added to [corrected] 2 years of treatment with R and E for pulmonary disease caused by M avium-intracellulare (MAC), M malmoense and M xenopi (REClari and RECipro). An optional comparison of immunotherapy with M vaccae vs no immunotherapy was also performed.
Methods: Progress was monitored annually during the 2 years of treatment and for 3 years thereafter. If the patient was not improving at 1 year the regimen was supplemented by the addition of the drug not received in the original allocation of treatment.
Results: 371 patients (186 REClari, 185 RECipro) entered the study (170 MAC, 167 M malmoense, 34 M xenopi). All-cause mortality was high for both groups (44% REClari, 43% RECipro); for MAC it was higher with REClari than with RECipro (48% vs 29%) but for M malmoense (42% vs 56%) and M xenopi (29% vs 47%) it was higher with RECipro (p = 0.006). 3% died from their mycobacterial disease (REClari = RECipro). At the end of treatment, 4% of REClari and 10% of RECipro patients still had positive cultures. Among those with negative cultures at the end of treatment, 6% of the REClari group and 4% of the RECipro group had relapsed. At 5 years 30% of the REClari group were known to have completed treatment as allocated and to be alive and cured compared with 21% of the RECipro group (p = 0.04), but this difference was principally due to those with M malmoense (REClari 38%, RECipro 20%). Patients with MAC or M xenopi were more likely to have a poor outcome than those with M malmoense (p = 0.004), with no difference between REClari and RECipro. Overall, 20% in each group were unable to tolerate the regimen allocated, Cipro being associated with more unwanted effects than Clari (16% vs 9%, p = 0.05). No significant differences in outcomes were found between M vaccae-treated patients and those not treated with M vaccae immunotherapy.
Conclusion: Considering all three species together, there were no differences in outcome between the REClari and RECipro groups. Immunotherapy did not improve outcome. New therapies, optimised management of co-morbid conditions and a more holistic approach must be explored in the hope of improving outcome.