BB:N KYSTAMUOTO JA SEN HOITO!

[Bb]

Lähettäjä: Soijuv Lähetetty: 20.7.2004 13:16

Tutkimuksen mukaan Tinidazole osoittautui tehokkaaksi kystamuotoisten bakteerien hoidossa. Yhdessä makrolidien kanssa, esim klaritromysiini, azitromysiini tai uudempi telitromysiini, se saattaa olla käyttökelpoinen lääke esim kroonisen borrelioosin hoidossa. Tinidazole ei aiheuta yleensä yhtä paljon ongelmia käyttäjilleen kuin meillä yleisemmin käytössä oleva metronidazole. Lyhyillä ab-hoidoilla - tavanomaisilla antibiooteilla kuten doksisykliini, keftriaksone, amoksisilliini jne. - on artikkelin mukaan puutteensa.


An in vitro study of the susceptibility of mobile and cystic forms of Borrelia

burgdorferi to tinidazole Int Microbiol 2004; 7(2):139?142

Koko artikkeli: http://www.im.microbios.org/26June04/09%20Brorson.pdf



Introduction

Borrelia afzelii, B. garinii, and B. burgdorferi, the causative

agents of Lyme borreliosis, are able to rapidly migrate away

from the initial point of infection [19], and may cause longterm

tissue infections frequently leading to a chronic disease

course. Lyme borreliosis can infect several organs, but the

hallmark of this disease is the expanding red rash with central

clearing, called erythema migrans. Unfortunately, many

Borrelia-affected persons will not develop this typical rash. In

a recent study, all erythemas associated with Borrelia garinii

were rapidly forming, and they were large and homogeneous.

This was in contrast to erythemas associated with B. afzelii,

which were generated slowly, small and predominantly annular

[11]. Therefore, infections with B. afzelii may be treated

too late, which contributes to severe late manifestations.

Fourteen days of treatment with penicillin, doxycyclin or

ceftriaxone is often believed to cure the infection, but all

commonly used antibiotics have their shortcomings, and the

frequency of relapses may be highly dependent on the chosen

treatment and the phase of the disease [23−26]. A study of

cytomorphic variations of B. burgdorferi isolates from

patients with or without antibiotic treatment showed that

penicillin can induce membrane-derived vesicles (cysts or

spheroblast L-forms) in vivo [27]. This conversion of mobile

Borrelia to cystic forms was subsequently observed for ceftriaxone,

doxycyclin [17], ciprofloxacin [18] and vancomycin

[12] at concentrations achievable in vivo. The fact that B.

burgdorferi has the ability to convert (and reconvert) to cystic

forms both in vivo and in vitro [1,4−6,10,14,15,21,27,28]

may be regarded as an explanation why the infection may be

persistent and reactivate. Therefore, it is reasonable to suggest

that all germinative forms of the bacterium (and not only

the motile form) should be destroyed so that Lyme borreliosis

can be treated effectively. The aim of this study was to

investigate the susceptibility of motile and cystic forms of B.

burgdorferi to the second-generation amidazole tinidazole.



Results and Discussion

In 1999, we published a study on the treatment of cystic forms

of B. burgdorferi with metronidazole (MZ) [7]. However, this

drug may not be tolerated by all patients. Therefore, the second

generation 5-nitroimidazole tinidazole, which is better

tolerated by most patients and may also be more efficient than

MZ [13] was tested. ................ Therefore, TZ may have more adverse effects on

the DNA in the blebs than MZ. As the content of the blebs is

of great pathogenic importance, TZ may be better suited for

the treatment of Lyme disease [20].



Our results show that TZ as a single agent is not sufficient

to treat Borrelia infections because mobile spirochetes are

highly resistant to this agent. However, TZ has the ability to

inhibit the development of cystic forms and to disrupt spirochetes

and core structures inside the cysts at concentrations

achievable in vivo by the administration of a single 1.5-g

dose [3]. This supports testing the hypothesis that TZ prevents

persistent infections in vivo, as suggested by the observation

of similarities between the aerobic Mycobacterium

tuberculosis and B. burgdorferi: In its coccoid form (L-form),

M. tuberculosis is anaerobic and sensitive to metronidazole

[30]. In addition, tinidazole is also an effective eradicator of

Clostridium difficile and may prevent yeast infection [29],

which may be troublesome during long-term treatment of

Lyme disease. Another advantage of TZ compared to MZ is

its higher accumulation in the cerebrospinal fluid [16]. Dual

medication with TZ and a macrolide (clarithromycin,

azithromycin or the new ketolide telithromycin) might be an

interesting approach to treat borrelioses, and to prevent persistent

infections.