Clarithromycin vs ciprofloxacin as adjuncts to rifampicin and ethambutol in treating opportunist mycobacterial lung diseases and an assessment of Mycobacterium vaccae immunotherapy

Abstract

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 after 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 comorbid conditions and a more holistic approach must be explored in the hope of improving outcome.

Clinical Relevance of Nontuberculous Mycobacteria, Oman

“…Although treatment should be prolonged and pyrazinamide discontinued because of natural resistance to pyrazinamide in NTM, the choice of fi rst-line treatment for TB, without companion drugs such as macrolides or fl uoroquinolones, is supported by a recently published trial of the British Thoracic Society (14).…”

Fatal pulmonary cavitary disease secondary to Mycobacterium xenopi in a patient with sarcoidosis

“…American Thoracic Society has proposed a regimen with clarithromycin, rifampin and ethambutol with the possibility to use moxifloxacin instead of any one of the three drugs. The treatment success rate in patients with pulmonary M. xenopi ranged between 8.8%[13–16] and 73%[17] in six different studies, and the all-cause mortality remains very high. Due to a variety of treatment regimens administered in these studies, an optimal multidrug treatment regimen could not be derived.…”

Cervical abscess in an immunocompetent patient with Mycobacterium malmoense pulmonary disease

“…Based on randomized trials, the British Thoracic Society (BTS) recommends a 12-to 24-month regimen with rifampicin (RMP) and ethambutol (EMB) for pulmonary disease [8]. Although less tolerated and despite the lack of evidence of benefit to date, several authors, including the ATS statement on NTM, commented on the addition of isoniazid, ciprofloxacin or clarithromycin to the regimen with RMP and EMB [11,21,22]. Although in vitro tests suggested an increased susceptibility for a combination with clarithromycin [23] and some resistance to EMB and RMP, there is no evidence that drug susceptibility testing contributes to the choice and response of any treatment regimen [1,8].…”