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

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.

Vitamin A absorption in cystic fibrosis: risk of hypervitaminosis A.

Vitamin A status was examined in nine adult cystic fibrosis patients and six adult control subjects, together with an assessment of their ability to absorb 10,000 IU of retinyl palmitate from a test meal, taken with appropriate pancreatic enzyme supplements. Median baseline values for plasma retinol and carotene, as well as median serum retinol binding protein concentrations, were significantly lower in cystic fibrosis patients than in control subjects. One cystic fibrosis patient had a raised fasting plasma retinyl ester concentration suggestive of chronic hypervitaminosis A, but no symptoms of toxicity. Measures of vitamin A absorption were also significantly lower in cystic fibrosis patients, although there was considerable overlap with control values. No correlation was observed between measures of baseline status and vitamin A absorption. Measurement of plasma retinyl esters may be an appropriate investigation in those patients considered to be at risk of chronic hypervitaminosis A.

Acute haemodynamic effects of nifedipine at rest and during maximal exercise in patients with chronic cor pulmonale.

The pulmonary hypertension of cor pulmonale can be reversed by sustained correction of hypoxia but continuous oxygen treatment poses problems in clinical practice. Alternative methods of relieving pulmonary vasoconstriction have therefore been explored. Eight patients with chronic cor pulmonale (five of them men) were studied to measure the haemodynamic effects of the calcium antagonist nifedipine, both at rest and on maximal, symptom limited exercise. The mean duration of exercise was unchanged by nifedipine (7.8 (SD 3.3) compared with 7.3(3.1) min). Cardiac output rose from 5.2(1.5) l min-1 to 8.6(3.3) 1 min-1 on exercise. Nifedipine increased resting cardiac output by 26%, but did not influence maximal exercise output. It did not significantly alter resting mean pulmonary artery pressure but reduced the level during exercise from 67(15) to 52(11) mm Hg. Nifedipine lowered resting pulmonary vascular resistance (PVR) by 32% and exercise PVR by 28%. It reduced supine mean systemic arterial pressure by 17%, standing pressure by 22%, and pressure at the maximal exercise level by 20%. Nifedipine lowered supine systemic vascular resistance (SVR) by 35%, standing SVR by 28%, and exercise SVR by 20%. Haemodynamic changes were achieved without adverse symptoms, alteration in arterial PO2, or impairment of calculated oxygen delivery. Nifedipine therefore reduced both pulmonary and systemic vasomotor tone at rest and during exercise. It did not alter exercise tolerance, which is probably limited by underlying respiratory disease. It seems possible therefore that nifedipine could delay the development of cor pulmonale, although this hypothesis remains to be tested.