Drug Combinations against Borrelia burgdorferi Persisters In Vitro : Eradication Achieved by Using Daptomycin, Cefoperazone and Doxycycline
Once again we have to thank Prof. Ying Zhang for yet a further study on drug combinations against Borrelia Burgdorferi persisters.
'Daptomycin plus doxycycline and cefoperazone eradicated the most resistant microcolony form of B. burgdorferi persisters and did not yield viable spirochetes upon subculturing, suggesting durable killing that was not achieved by any other two or three drug combinations.'
'As shown in our previous study [16], the stationary phase culture was enriched with morphological variants such as round body form and biofilm-like aggregated microcolony form in increasing proportions in contrast to individual spirochetes found in log phase culture'
This is interesting - 'We also found that miconazole, an imidazole antifungal drug, had high activity against B. burgdorferi persisters when combined with doxycycline and cefoperazone (Table 2). Miconazole has been shown to alter the integrity of lipid membrane [27] and therefore may facilitate the penetration of other drugs such as doxycycline and cefoperazone for improved activity against B. burgdorferi persisters '
Note - 'It is worth noting that short term incubation in subculture studies of antibiotic treated B. burgdorferi is not sufficient to assess the stable eradication of persisters'
'In conclusion, we found there is a hierarchy of B. burgdorferi persisters with increasing antibiotic tolerance as the culture ages from log phase to stationary phase with morphological changes from spirochetal form to round body and microcolony forms. Importantly, we identified drug combinations that have high activity against B. burgdorferi persisters with daptomycin-containing combinations achieving the best activity. The most effective drug combination used daptomycin, cefoperazone and doxycycline which appeared to render resistant microcolony forms of B. burgdorferi unable to resuscitate viability upon subculture, a feature not previously described using any other antibiotic singly or in combinations. While important to state that the role of any persister organisms in human disease is far from elucidated, these findings may have implications for the treatment of certain Lyme disease patients with slow to resolve- or antibiotic-refractory arthritis or possibly stubborn ongoing symptoms. Direct extrapolation of these in vitro findings to human treatment would be unwise and premature. Future studies are needed to confirm whether such combination drug therapy yields benefit in animal models and possibly then in clinical studies.'
Earlier posts on work by Prof Zhang
LymeMD blog has some interesting observations - http://lymemd.blogspot.co.uk/2015/03/potential-for-new-lyme-therapy-bursting.html
Lyme Disease Action have done a report of this recent study
Prof Ying Zhang is due to present at this year's LDA conference
To quote Dr Brian Fallon from the recent PHE meeting talking about emerging research 'it is exciting times'. http://lookingatlyme.blogspot.co.uk/2015/03/dr-fallon-presenting-at-lyme-disease.html
he also said that there were a few interesting tests in the pipeline.
It is interesting to read that Dr Fallon is involved with this research follow the links from this link
Good tests and treatment options for Borrelia persisters could well be on the horizon and not before time. Then maybe they will get down to identifying and looking at better supportive therapies for other co factors causing our health problems.
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