Chest
Volume 136, Issue 6, December 2009, Pages 1569-1575
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Original Research
Respiratory Infections
Therapeutic Effects of Various Initial Combinations of Chemotherapy Including Clarithromycin Against Mycobacterium avium Complex Pulmonary Disease

https://doi.org/10.1378/chest.08-2567Get rights and content

Background

The objective of this study was to find an optimal initial combination chemotherapy that includes clarithromycin (CAM) for treatment-naive patients with Mycobacterium avium complex (MAC) pulmonary disease, as assessed by microbiological conversion using a Mycobacterium growth indicator tube (MGIT).

Methods

Thirty-four patients with treatment-naive MAC pulmonary disease (determined using 1997 American Thoracic Society criteria) were evaluated retrospectively. They demonstrated a nodular and bronchiectatic pattern without cavity on high-resolution CT (HRCT) scans. The following three regimens were administered: regimen A (n = 9) consisted of CAM (400 mg/d), ethambutol (EB) [750 mg/d], and rifampicin (RFP) [450 mg/d]; regimen B (n = 12) consisted of CAM (800 mg/d), EB (750 mg/d), and RFP (450 mg/d); and regimen C (n = 13) consisted of CAM (800 mg/d), EB (1,000 mg/d), and RFP (600 mg/d) during the first 2 months followed by a reduction of the dosage of EB from 1,000 to 750 mg/d. Gender, age, BMI, and HRCT scan finding scores were not significantly different among the three groups. Chemotherapy was continued for 18 months. Sputum culture was periodically assessed by MGIT.

Results

Culture conversion at 18 months in regimen A (55.6%), which included a daily dosage of 400 mg of CAM (9.5 mg/kg), was significantly inferior to that in regimen B (91.7%), which included daily 800 mg of CAM (17.6 mg/kg; p < 0.05), but regimen B and C (92.3%) showed no between-group difference after > 18 months of chemotherapy.

Conclusions

The higher dose of CAM allowed for better culture conversion. Daily combination chemotherapy that includes CAM (800 mg) seems appropriate as an initial treatment against treatment-naive patients with nodular and bronchiectatic MAC pulmonary disease.

Section snippets

Patients and Chemotherapy

We retrospectively evaluated 34 adult patients with noncavitary nodular and bronchiectatic MAC pulmonary disease that had been diagnosed according to 1997 American Thoracic Society diagnostic criteria13 who had been treated at National Minami Yokohama Hospital (Kanagawa, Japan) from 1999 to 2004. All were treatment naive. On arriving at our hospital, the patients had at least one of the following symptoms or complaints: chronic cough; sputum production; hemoptysis; fatigue; and weight loss of >

Results

Among the 10 patients starting regimen A, 1 dropped out because of irregular attendance at the outpatient clinic and a sputum sampling deficit. One patient starting regimen B interrupted chemotherapy because of a drug fever. Two patients receiving regimen C could not complete the treatment because of appetite loss and subjective visual disturbance, respectively. Finally 9, 12, and 13 patients who had completed regimens A, B, and C, respectively, were eligible for retrospective on-treatment

Discussion

The present study demonstrated that higher dose CAM regimens were associated with better culture conversion in MAC-associated bronchiectatic and nodular lung diseases. However, subsequent intensification of early-phase chemotherapy coupled with CAM did not appear to produce an additive effect in this type of MAC pulmonary disease as far as early-phase culture conversion and posttreatment reversion of MAC are concerned.

Although the effect of the CAM dosage on the effectiveness of chemotherapy

Acknowledgments

Author contributions: Drs. Hasegawa, Nishimura, Ohtani, Takeshita, and Fukunaga made substantial contributions to the acquisition, analysis, and interpretation of data. Drs. Hasegawa and Nishimura made substantial contributions to the drafting of the manuscript. Drs. Tasaka and Urano engaged in the radiologic evaluation of HRCT scans. Dr. Ishizaka contributed to the design of the study. Drs. Ishii and Miyairi made substantial contributions to the acquisition of data at outpatient clinic. All

References (0)

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