EDITORIAL

RIFAMPICIN RESISTANCE

Asrawati Sofyan, Muhammad Dali Amiruddin

In 1982, Indonesia provide free
treatment to leprosy patients with a
combination of Multi Drug Therapy (MDT)
is a combination of dapsone or DDS
(Diamino Diphenyl Sulfones), or Lam-
prene, clofazimine and rifampicin. Advan-
tages of Multi Drug Therapy (MDT) is
change the concept of long therapy to
prevent the expansion of the disease into
short therapy that cures disease, prevent
drug resistance, improve treatment
adherence from 50% to 95%, prevent
deformity more efficiently and reduce the
number of cases each year.
1.2
Rifampicin
is the most effective anti-leprosy drugs
and brings down the morphological index
in lepromatous leprosy to zero in about
five weeks. It is given orally in a dose of
600 mg once daily, or 450 mg for patient
weighing under 35 kg. Although bacteria
are rapidly killed, the rate of fall of the
bacterial index, the speed of the clinical
improvement and the incidence of type 2
reaction in lepromatous patients are the
same as with dapsone.
1,4,5
Rifampicin
resistance is rare, however, these drugs
should never be prescribed alone or
monotherapy, because it can increase the
resistance, the side effect is damage to
the liver and kidneys. Rifampicin which
serves to inhibit bacterial DNA-dependent
RNA synthesis by inhibiting bacterial DNA-
dependent RNA polymerase. Crystal
structure data and biochemical data
suggest that rifampicin binds to RNA
polymerase at sites adjacent to the active
center of RNA polymerase and inhibit RNA
synthesis with the aim of preventing the
expansion of RNA results beyond 2-3
nucleotides long (mechanism "steric-
occlusion").Resistance to rifampicin arise
from mutations that alter the binding
results of rifampicin on RNA polymerase,
thus decreased affinity for rifampin.
2,4,5

Several methods can be used to detect
such resistance by phenotypic methods,
including methods mouse footpad (MFP),
BACTEC and molecular methods including
PCR-SSCP and DNA sequencing. The
results obtained using the PCR method
consistent with MFP and some of them
confirmed good results, this technique can
be relied upon to identify rifampicin-
resistant strains of M. leprae at 531
position.
4.5
The prevalence of drug
resistance in M. leprae and especially to
rifampicin in Japan in the category of
relapse or intractable cases as many as
24 cases (51%), DDS and RIF: 7 cases;
DDS, RIF and FQ many as 5 cases, and
DDS own 8 cases; RIF only 2 cases and
quinolones as much as 2 cases. Among
the new cases, rifampin resistance was
observed in 4 cases out of 106 cases
(3.8%).
4.5
The development of resistance
in leprosy MDT implementation needed to
prevent the emergence of rifampicin-
resistant mutants. Monitoring of rifampicin-
resistant mutants is important because it is
an important factor in the MDT. To achieve
this, required the addition of field research
and laboratory activities, creation of
networks, identification of the study area;
defines the protocols and implement the
survey. emphasize the importance of
quality skin smears, sites will be chosen
for skin smears and good quality of the
reporting and record keeping.
4.5

REFERENCES
1. Honore N, Cole S T. Molecular basis
of rifampin resistance in M. leprae.
Antimicrob Agents Chemother. 1993;
37: 414-4 18
2. Williams DL, Waguespack C, Eisenach
K, Crawford JT, Portaels F, Salfinger
M, Nolan CM, Abe C, Sticht-Groh V,
Gillis T P. Characterization of rifampin
resistance in pathogenic mycobacteria.
Antimicrob Agents Chemother. 1994;
38: 2380-2386
3. Masters, Susan B.; Trevor, Anthony J.,
Katzung, Bertram G. Katzung &
Trevor's pharmacology. New York:
Lange M edis Books / McGraw Hill,
Medical Pub Division. ISBN 0-07-
142290-0., 2005.
4. WHO. Rifampicin resistance in
Leprosy. Report of an Informal
Consultation National creature Institute
of leprosy and other mycobacterial
disease. India. 2006.p1-16
5. Brycesson A, Pfaltzgraff
RE.Treatment. In: Brycesson A,
Pfaltzgraff RE, editors. Leprosy. 3rd
ed. London: Churchill Livingsone;
1990. p. 57-76.