Clarithromycin (Page 10 of 13)
Decreases in MAC bacteremia or negative blood cultures were seen in the majority of patients in all clarithromycin dosage groups. The mean reductions in MAC colony forming units (CFU) from baseline after 4 weeks of therapy in the 1000 mg (n=32) twice daily and 2000 mg (n=26) twice daily regimen was 2.3 Log CFU compared to 1.5 Log CFU in the clarithromycin 500 mg twice daily (n=35) regimen. A separate trial with a four drug regimen 6 (ciprofloxacin, ethambutol, rifampicin, and clofazimine) had a mean reduction of 1.4 Log CFU.
Clinical outcomes evaluated with the different dosing regimens of clarithromycin monotherapy are shown in Table 14. The 1000 mg and 2000 mg twice daily doses showed significantly better control of bacteremia during the first four weeks of therapy. No significant differences were seen beyond that point. All of the isolates had MIC less than 8 mcg/mL at pre-treatment. Relapse was almost always accompanied by an increase in MIC.
Outcome | Clarithromycin 500 mg twice daily | Clarithromycin 1000 mg twice daily | Clarithromycin 2000 mg twice daily |
One or more negative blood cultures at any time during acute therapy | 61% (30/49) | 59% (29/49) | 52% (25/48) |
Two or more negative blood cultures during acute therapy sustained through study day 84 | 25% (12/49) | 25% (12/49) | 8% (4/48) |
Death or discontinuation by day 84 | 23% (11/49) | 37% (18/49) | 56% (27/48) |
Relapse by day 84 | 14% (7/49) | 12% (6/49) | 13% (6/48) |
Median time to first negative culture (in days) | 54 | 41 | 29 |
Median time to first decrease of at least 1 log CFU (in days) | 29 | 16 | 15 |
Median time to first positive culture or study discontinuation following the first negative culture (in days) | 43 | 59 | 43 |
Clinically Significant Disseminated MAC Disease
Among patients experiencing night sweats prior to therapy, 84% showed resolution or improvement at some point during the 12 weeks of clarithromycin at 500 mg to 2000 mg twice daily doses. Similarly, 77% of patients reported resolution or improvement in fevers at some point. Response rates for clinical signs of MAC are given in Table 15 below.
The median duration of response, defined as improvement or resolution of clinical signs and symptoms, was 2 weeks to 6 weeks.
Since the trial was not designed to determine the benefit of monotherapy beyond 12 weeks, the duration of response may be underestimated for the 25% to 33% of patients who continued to show clinical response after 12 weeks.
Resolution of Fever | Resolution of Night Sweats | ||||
Clarithromycin twice daily dose (mg) | % ever afebrile | % afebrile 6 weeks or more | Clarithromycin twice daily dose (mg) | % ever resolving | % resolving 6 weeks or more |
500 | 67% | 23% | 500 | 85% | 42% |
1000 | 67% | 12% | 1000 | 70% | 33% |
2000 | 62% | 22% | 2000 | 72% | 36% |
Weight Gain Greater Than 3% | Hemoglobin Increase Greater Than 1 gm | ||||
Clarithromycin twice daily dose (mg) | % ever gaining | % gaining 6 weeks or more | Clarithromycin twice daily dose (mg) | % ever increasing | % increasing 6 weeks or more |
500 | 33% | 14% | 500 | 58% | 26% |
1000 | 26% | 17% | 1000 | 37% | 6% |
2000 | 26% | 12% | 2000 | 62% | 18% |
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