The role of moxifloxacin in tuberculosis therapy

Abstract

Tuberculosis (TB) remains a global threat with more than 9 million new infections. Treatment remains difficult and there has been no change in the duration of the standard regimen since the early 1980s. Moreover, many patients are unable to tolerate this treatment and discontinue therapy, increasing the risk of resistance. There is a growing tide of multidrug resistance and few effective antibiotics to tackle the problem. Since the turn of the millennium there has been a surge in interest in developing new therapies for TB and a number of new drugs have been developed. In this review the repurposing of moxifloxacin, an 8-methoxy-fluoroquinolone, for TB treatment is discussed. The evidence that underpins the development of this agent is reviewed. The results of the recently completed phase III trials are summarised and the reasons for the unexpected outcome are explored. Finally, the design of new trials that incorporate moxifloxacin, and that address both susceptible disease and multidrug resistance, is described. @ERSpublications A review of the role of moxifloxacin in tuberculosis therapy http://ow.ly/WaAyC

Mycobacterium tuberculosis Proteome Response to Antituberculosis Compounds Reveals Metabolic “Escape” Pathways That Prolong Bacterial Survival

“…Some among the above-cited compounds have novel mechanisms of action and can kill antibiotic-resistant strains (6)(7)(8)(9), although clinical trials with moxifloxacin were disappointing (10). A growing pipeline of anti-TB compounds is also under development or undergoing clinical trials, and these experimental compounds are anticipated to improve treatment outcomes (11).…”

The evaluation of flouroquinolone use in patients admitted to tuberculosis out-patient clinic

“…Because quinolone resistance generally develops against a common part of the drug group, cross-resistance is frequently observed among quinolones (12-14). However, minimum inhibitor concentrations (MIC) of the new quinolones are lower compared to those of Pulmonologist (n=1), 3 Internal Medicine (n=1), 3 Emergency Physician (n=1) ARB: Acid-resistant bacilli; m±SD: mean±standard deviation; TB: tuberculosis the old quinolones. Therefore, the new quinolones may be effective on bacteria resistant to old quinolones such as ofloxacin (15)(16)(17).…”

“…At present, quinolones are routinely used in the treatment of multi-drug resistant tuberculosis (MDR-TB). In a recently published review, it has been reported that moxifloxacin is as bactericidal as first-generation tuberculosis drugs and this drug should be used in the treatment of MDR-TB routinely and it should be among the first choices for patients that can not tolerate standard treatment (3). There are ongoing studies on the inclusion of moxifloxacin in the standard treatment for shortening the duration of treatment (4-6).…”

Lewofloksacyna i moksyfloksacyna w leczeniu zakażeń bakteryjnych

“…Nowe generacje fluorochinolonów zostały umieszczone w zaleceniach, a ich skuteczność w leczeniu MDR-TB wynika z faktu, iż ta grupa leków cechuje się większą penetracją do wnętrza makrofagów niż ofloksacyna czy cyprofloksacyna [64,65]. Określając wartość MIC dostępnych fluorochinolonów w stosunku do prątka gruź-licy, wykazano duże zróżnicowanie zależne od obecności grupy metoksylowej w pozycji C8 [66,67]. Zwrócono jednak uwagę na fakt, że fluorochinolony ze znaczną aktywnością przeciwbakteryjną ujawniały zbyt dużo działań ubocznych, niekiedy toksycznych, np.…”

“…Aktualnie -zgodnie ze wskazaniami WHO -do leczenia chorych na MDR-TB rekomendowane są lewofloksacyna i moksyfloksacyna [64,66,70,71]. Potwierdza to w pełni metaanaliza 6465 przypadków chorych na gruźlicę, w której porównywano skuteczność m.in.…”