Long-Term Low-Dose Administration of Erythromycin to Patients with Diffuse Panbronchiolitis

Abstract

Although diffuse panbronchiolitis (DPB) has carried a poor prognosis, long-term low-dose administration of erythromycin (EM) is very effective. We administered EM at a daily dose of 400–600 mg to 19 DPB subjects for more than 2 months. Sixteen subjects were relieved from productive cough and dyspnea, and their chest X-ray pictures were improved. We performed a pharmacokinetic study of EM in 11 DPB subjects (8 re-sponders; 3 nonresponders) after the long-term low-dose administration. The maximal serum and sputum levels of EM were below the MICs of clinically pathogenic H. influenzae and P. aeruginosa which were often isolated from the sputum of DPB patients. No difference was observed in the absorption of EM between responded and nonresponders. The results suggested that DPB patients might respond favorably to EM due to mechanisms other than antibacterial activity. Individual variation in the absorption of EM was observed. As EM was effective at very low serum and sputum levels, it was suggested that even 200 mg/day of EM would be effective in DPB patients who had high serum and sputum EM levels and it was necessary to monitor the concentrations of EM in serum and sputum for the treatment of DPB to determine the appropriate dose of EM individually

Effect of 14-Membered Ring Macrolide Therapy on Chronic Respiratory Tract Infections and Polymorphonuclear Leukocyte Activity.

“…While DPBhas a poor prognosis, the long-term administration ofa low dose oferythromycin can provide benefit (3)(4)(5)(6). Interestingly, such a low dose oferythromycin rarely eradicates pathogens from the lower respiratory tract, unlike the conventional doses used in treating an acute exacerbation.…”

“…Although the prognosis of DPBis poor, Kudoh et al (3) reported that the long-term administration of low doses of erythromycin, a 14-membered ring macrolide, is highly effective in improving the clinical symptoms, pulmonary dysfunction, and hypoxia in this disorder (4)(5)(6). These benefits were obtained without the eradication of bacteria from the sputum such as Pseudomonasaeruginosa, which is resistant to erythromycin.…”

Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation

“…11,37 Macrolides have been shown to improve outcome in panbronchiolitis. 38,39 Their beneficial effects are considered to be due to their anti-inflammatory rather than anti-bacterial activities. [40][41][42] Although there has been no report of macrolide use in BO, their mechanisms of action and relatively minor adverse effects warrant a clinical trial.…”

Diffuse panbronchiolitis: an underdiagnosed disease? Study of 4 cases in Brazil

“…We do know that the antibacterial action of the erythromycin against the usual isolated organisms from cultures of sputum of DPB patients (H. influenza and P. aeruginosa) could not be considered as an important mechanism, since the concentration of erythromycin in sputum and serum (with the usual dose of 600 mg daily) are very far below the minimum inhibitory concentration required for these organisms 21 . In spite of this, the use of low dose, long-term macrolide treatment figures as the one with large number of studies showing clinical, functional, and radiological improvement 8,16,[22][23][24] , as well as reduction in the mortality rate 25 .…”