Efficacy of Low-Dose Ofloxacin in the Treatment of Multidrug-Resistant Tuberculosis in Indonesia

Mangunnegoro, Hadiarto; Hudoyo, Achmad

doi:10.1159/000048478

Cited by 13 publications

(4 citation statements)

References 7 publications

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“…Characterisation and quantification of the mechanisms of resistance to fluoroquinolones and linezolid are important in order to curb the increase in the number of resistant strains [30,31] and to evaluate the true usefulness of these drugs in the treatment of tuberculosis [32,33] . It may even be possible in the future for inhibitors of these systems to be used as co-adjuvants to improve the activity of these drugs, although further studies would be needed to develop this possibility.…”

Section: Discussionmentioning

confidence: 99%

Importance of the Efflux Pump Systems in the Resistance of <i>Mycobacterium tuberculosis</i> to Fluoroquinolones and Linezolid

Escribano¹,

Rodrı́guez²,

Llorca³

et al. 2007

Chemotherapy

114

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Objective: Our aim was to study the influence of efflux pump systems in the resistance of Mycobacterium tuberculosis to fluoroquinolones and linezolid. Methods: We studied the mutations in gyrA and gyrB genes and the influence of efflux pump systems with 2 inhibitors (reserpine and MC 207.110). Results: The effect of the active efflux system on the decrease in sensitivity to ciprofloxacin, moxifloxacin, levofloxacin, ofloxacin, gatifloxacin and linezolid was studied by investigating the variation in the in vitro activity of these compounds when assayed in association with reserpine and MC 207.110. These inhibitors exhibit activity both in strains that are resistant and in strains that are susceptible to these antibiotics. However, they are seen to be most active in resistant strains, since the minimum inhibitory concentration of the antibiotics studied in these strains was reduced between 2- and 6-fold. Conclusions: Therefore, these mechanisms are involved in the resistance to both compounds. It would be of interest to carry out further studies to determine to what extent these active efflux systems influence resistance to the different groups of drugs used in the treatment of tuberculosis, with a view to the possibility of using the inhibitors of these systems in future therapeutic applications.

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Section: Discussionmentioning

confidence: 99%

Importance of the Efflux Pump Systems in the Resistance of <i>Mycobacterium tuberculosis</i> to Fluoroquinolones and Linezolid

Escribano¹,

Rodrı́guez²,

Llorca³

et al. 2007

Chemotherapy

114

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“…Furthermore, the low relapse rate is a crucial finding. A higher relapse rate has been reported when a low-dose ofloxacin and a shorter duration of treatment (300 mg?day -1 for 12 months with a relapse rate of 20.5% [19] and 400 mg?day -1 for 9 months with a relapse of 11% [21]) was applied. Thus, dosage and treatment duration are important.…”

Section: Outcome Of Pulmonary Mdr-tbmentioning

confidence: 93%

Outcome of pulmonary multidrug-resistant tuberculosis: a 6-yr follow-up study

Chiang¹,

Enarson²,

Yu³

et al. 2006

European Respiratory Journal

104

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A retrospective study was performed to determine factors associated with the outcome of pulmonary multidrug-resistant tuberculosis (MDR-TB) in Taipei, Taiwan.All patients newly diagnosed with pulmonary MDR-TB in a referral centre from 1992-1996 were enrolled and their outcome over the subsequent 6 yrs was determined.A total of 299 patients were identified, comprising 215 (71.9%) males and 84 (28.1%) females with a mean age of 47.3 yrs. The patients received a mean of 3.7 effective drugs. Out of the 299 patients, 153 (51.2%) were cured, 31 (10.4%) failed, 28 (9.4%) died and 87 (29.1%) defaulted. Of the 125 patients receiving second-line drugs with ofloxacin, 74 (59.2%) were cured. Those who received ofloxacin had a lower risk of relapse than those receiving only first-line drugs (hazard ratio (HR) 0.16, 95% confidence interval (CI) 0.03-0.81) and a lower risk of TB-related death than those receiving second-line drugs but not ofloxacin (adjusted HR 0.50, 95% CI 0.31-0.82).In conclusion, multidrug-resistant tuberculosis patients who received ofloxacin were more likely to be cured, and were less likely to die, fail or relapse. The utility of new-generation fluoroquinolones, such as moxifloxacin, in the treatment of multidrug-resistant tuberculosis needs to be evaluated. Default from treatment is a major challenge in the treatment of multidrugresistant tuberculosis.

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“…[42,43] However, studies have also reported reasonably satisfactory responses in shorter periods through regimens incorporating fluoroquinolones like ofloxacin and sparfloxacin. [44][45][46] In general, second-line drugs are more expensive and toxic and treatment, at least in the initial part, should therefore be supervised in a hospital. Therapeutic drug monitoring has been employed.…”

Section: Treatment Of Mdr-tbmentioning

confidence: 99%

Chemotherapy of osteoarticular tuberculosis

Hazra

Laha

2005

Indian J Pharmacol

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Tuberculosis (TB) of the bones and joints is rampant in India with the dorsolumbar spine as the most common site of osseous involvement. For diagnosis, clinical suspicion needs to be confirmed through appropriate laboratory and imaging investigations, and increasingly nowadays, nucleic acid amplification techniques. Chemotherapy remains the cornerstone of management complemented by rest, nutritional support and splinting, as necessary. Operative intervention is required if response to chemotherapy is unsatisfactory and for spinal stabilization. The drugs and regimens are fundamentally similar to those for pulmonary TB. However, there is lack of consensus on the appropriate duration of treatment. The prevailing practice of extending treatment till radiological evidence of healing is complete, may be unnecessary in view of recent reports that 6-9 months of therapy is sufficient for the majority of cases. Relapse rates are not drastically improved by extending treatment to 12 months or even longer, except perhaps in pediatric cases. However, prolonged treatment may be required if surgical debridement is indicated but cannot be done. Multidrugresistant TB should be suspected if disease activity shows no signs of abating after 4-6 months of uninterrupted therapy. These cases are therapeutically challenging and will require second line or experimental antiTB drugs, supported by resistance testing where feasible. Coexistent HIV/AIDS may also necessitate prolonged treatment. Interactions between first line antiTB drugs and antiretroviral medication can complicate matters. Close monitoring is essential in all cases, with dechallenge and cautious reinstitution of drugs in the event of toxicity. While awaiting the arrival of long overdue new antiTB medication, existing drugs and regimens must be used in an informed manner with emphasis on patient compliance.

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Efficacy of Low-Dose Ofloxacin in the Treatment of Multidrug-Resistant Tuberculosis in Indonesia

Cited by 13 publications

References 7 publications

Importance of the Efflux Pump Systems in the Resistance of <i>Mycobacterium tuberculosis</i> to Fluoroquinolones and Linezolid

Importance of the Efflux Pump Systems in the Resistance of <i>Mycobacterium tuberculosis</i> to Fluoroquinolones and Linezolid

Outcome of pulmonary multidrug-resistant tuberculosis: a 6-yr follow-up study

Chemotherapy of osteoarticular tuberculosis

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