In
Vitro Evaluation of Anti-Tuberculosis Drugs Against Mycobacterium
avium ss. paratuberculosis For
Treatment of Crohn's Disease
I.
Shafran, W. Fenster, C. Piromalli, C. Romero, D. Schwartz, D. Campbell, and S.
Naser
Mycobacterium avium ss.paratuberculosis
(M para) is the causative agent of
Johne's Disease in ruminants and has been implicated in the pathogenesis of
Crohn's disease (CD), a chronic inflammatory bowel disease in humans. Like
members of the M avium complex, M
para is resistant to anti-tuberculosis (anti-TB) drugs. In this study, seven
anti-TB drugs (rifamipcin; RIF, streptomycin; SM, kanamycin; KM, clarithromycin;
CLR, isoniazid; INH, pyrazinamide; PZA and ethambutol; EMB) have been tested
against M para using the Bactec
system. The table below summarizes the MIC50 and MIC99.9 for
the drugs(where 50% and 99.9% respectively of the M para cells were inhibited or killed). To minimize drug
resistance-induced strains, regimens of these drugs have been used for the
treatment of mycobacterial infection. Our data show that a regimen consisting of
RIF:EMB or RIF:CLR resulted in the significant eradication of M para in vitro. In fact,
the RIF:CLR combination produced similar results when used against two clinical
strains of M para that have been
isolated from resected tissue of CD patients. RIF:CLR is recommended for in
vivo eradication of M para because
the spheroplast form of M para has
been suggested as the virulent state of the bacterium in CD. These data also
provide guidelines and possible protocols for the first-line drugs to be used in
the treatment of CD.
|
|
RIF |
ST |
KM
|
CLR |
INH |
PZA |
EMB |
RIF: EMB |
RIF: CLR |
|
|
|
|
|
|
|
|
|
|
|
|
MIC50
(ug/ml) |
>1.0 |
>0.4 |
<1.3 |
<0.2 |
>1.0 |
>5.0 |
<0.5 |
<1.0:
0.2 |
<0.5:
0.2 |
|
MIC99.9
(ug/ml) |
>2.6 |
>3.0 |
<3.0 |
<0.5 |
>1.0 |
>5.0 |
<0.8 |
ND |
<0.5:1.2
or 1.0:0.75 |
Status
|
R |
R |
S |
S |
R |
R |
S |
S |
S |
R =
Resistant
S=
Sensitive
All content copyright ©1999 Dr. Ira Shafran, M.D.