Rifabutin as Salvage Therapy for Cases of Chronic Multidrug-Resistant Pulmonary Tuberculosis in Taiwan

Abstract

This study was aimed at assessing the efficacy and tolerability of rifabutin for the re-treatment of cases of chronic, multidrug-resistant pulmonary tuberculosis. The study design was self-controlled, single center. Rifabutin was administered as part of an individual-tailored multidrug regimen. In-patients suffering from pulmonary tuberculosis, infected with Mycobacterium tuberculosis bacilli resistant to isoniazid, rifampicin and other drugs with progressive disease unresponsive to prior courses with standard anti-tuberculosis medications were treated. Overall, 43 patients were enrolled and treated with rifabutin at 300 or 450mg/day according to body weight in conjunction with available anti-tuberculous drugs for a mean time of 353 days (range 42-678). Of these, 36 met all eligibility criteria (i.e. positive baseline culture of sputum with bacilli resistant to rifampicin at least) and were retained for the analysis of efficacy. Seventeen patients (47%) achieved a sustained conversion to a negative culture of sputum in a mean time of 47.7 days with a range of 14-120 days. Treatment prevented deterioration in most patients and resulted in clinical and radiological cure or marked improvement in more than half of cases. No correlation was found between treatment outcome and use of medication concomitant to rifabutin or susceptibility of bacilli to the drugs used. Four deaths occurred due to disease progression, in no case being related to study drugs. Ten patients reported a total of 18 adverse events that led to treatment discontinuation in 5 cases. Rifabutin should be considered for inclusion in regimens for cases of pulmonary multidrug-resistant tuberculosis which fail to respond to previous therapy.

The efficacy of rifabutin for rifabutin-susceptible, multidrug-resistant tuberculosis

“…10,11 Bacteriological conversion was achieved in 34% among 270 patients in a study performed in five nations, 10 and Lee et al reported that 47% of 43 patients achieved sustained sputum conversion with a RFBcontaining regimen in Taiwan. 11 However, as neither study had a control group in order to compare the efficacy of RFB, it was unclear whether the RFB-containing regimen was more effective than conventional therapy that did not use RFB for MDR-TB. Also, RFB susceptibility testing was carried out in only few patients 11 or was not done at all.…”

“…11 However, as neither study had a control group in order to compare the efficacy of RFB, it was unclear whether the RFB-containing regimen was more effective than conventional therapy that did not use RFB for MDR-TB. Also, RFB susceptibility testing was carried out in only few patients 11 or was not done at all. 10 Conversely, ours is the first study to use a control group to better investigate the efficacy of a RFB-containing regimen.…”

“…6,7 Although RFB may have comparable rates of cure and relapse as those of RIF in the treatment of drug-susceptible TB, 8,9 few data on the efficacy of RFB in the treatment of MDR-TB are available. 10,11 Although the level of cross-resistance between RIF and RFB has been reported to be approximately 90%, 12,13 it is known to be relatively low in South Korea, with as many as 20e30% of patients with RFB-susceptible MDR-TB. 14,15 Thus, RFB might be a successful drug for the treatment of a subset of MDR-TB.…”

Comprehensive Treatment of Extensively Drug-Resistant Tuberculosis

“…Finally, when necessary, clinicians reinforced regimens with pyrazinamide and ethambutol (despite extensive prior exposure to these drugs) with drugs for which susceptibility test results were inconsistent, and with amoxicillin–clavulanate, clarithromycin, clofazimine, and rifabutin 35–38. Although evidence of the efficacy of these approaches is limited at best, we cannot exclude the possibility that one or more contributed to treatment success, either by increasing the regimen’s activity or by providing protection against the emergence of resistance to more active agents 39.…”

Mycobacterium tuberculosis in Taiwan

“…36 One study showed that activity of rifabutin against drug-susceptible TB isolates was greater than that of rifampin, however, cross-resistance between rifampin and rifabutin was high in MDRTB isolates. 37 Ethionamide MICs determined by agar dilution and BACTEC 960 MGIT methods ranged from 0.5 to O16 mg/ml. 38 Reported MICs for ofloxacin ranged from 0.25 to 2.0 mg/ml and for ciprofloxacin ranged from 0.5 to 16 mg/ml.…”