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Provisional guidance on the role of specific antibiotics in the management of Mycobacterium ulcerans disease (Buruli ulcer):
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Annex 1 - Information on rifampicin, streptomycin and amikacin4
Rifampicin
General information
Group: antimycobacterial agent
Capsule or tablet: 150 mg, 300mg
Rifampicin, a semisynthetic derivative of rifamycin obtained
from Streptomyces mediterranei, is a complex macrocyclic
antibiotic that inhibits ribonucleic acid synthesis in a broad
range of microbial pathogens. Rifampicin is lipid soluble.
Following oral administration, it is rapidly absorbed and
distributed throughout the cellular tissues and body fluids.
A single dose of 600 mg produces a peak serum concentration
of about 10 µg/ml in 2–4 hours, which subsequently decays
with a half-life of 2–3 hours. It is extensively recycled in the
enterohepatic circulation, and metabolites formed by deacetylation
in the liver are eventually excreted in the faeces. Since
resistance readily develops, rifampicin must always be
administered in combination with other effective antimycobacterial
agents.
Clinical information
Uses: Rifampicin is a component of all TB and leprosy chemotherapeutic
regimens currently recommended by WHO.
Administration and dosage: Rifampicin should preferably be given at least 30 minutes
before meals, since absorption is reduced when it is taken with
food. This may not, however, be clinically significant, and food
can reduce intolerance to drugs. Adults and children: 10 mg/kg
(8–12 mg/kg) daily, maximum 600 mg daily.
Contraindications:
Known hypersensitivity to rifamycins. Hepatic dysfunction.
Precautions:
Serious immunological reactions resulting in renal impairment,
haemolysis or thrombocytopenia are on record in patients who
resume taking rifampicin after a prolonged lapse of treatment.
In this rare situation, it should be immediately and definitively
withdrawn. Careful monitoring of liver function is required in
the elderly and in patients who are alcohol dependent or have
hepatic disease. Patients should be warned that treatment
may produce reddish coloration of urine, tears, saliva and
sputum, and that contact lenses may be irreversibly stained.
Side-effects:
Rifampicin is well tolerated by most patients at currently
recommended doses, although gastrointestinal intolerance can
be unacceptably severe. Other adverse effects (fever, influenzalike
syndrome and thrombocytopenia) are more likely to occur
with intermittent administration, and skin rashes are just as
likely. Moderate rises in serum concentrations of bilirubin and
transaminases, which are common at the outset of treatment,
are often transient and without clinical significance. However,
dose-related hepatitis can occur, which is potentially fatal. It
is consequently important not to exceed the maximum total
daily dose of 600 mg.
Drug interactions:
Rifampicin induces hepatic enzymes, and may increase the
dosage requirements of drugs metabolized in the liver. These include corticosteroids, steroid contraceptives, oral hypoglycaemic
agents, oral anticoagulants, phenytoin, cimetidine,
cyclosporin and digitalis glycosides. Since rifampicin reduces
the effectiveness of oral contraceptives, women should be
advised to choose between one of the following two options
for contraception. Firstly, following consultation with a clinician,
the patient may use an oral contraceptive pill containing a
higher dose of estrogen (50 µg). Alternatively, a non-hormonal
method of contraception may be used throughout rifampicin
treatment and for at least one month subsequently. Biliary
excretion of radiocontrast media and sulfobromophthalein
sodium may be reduced and microbiological assays for folic
acid and vitamin B12 disturbed.
Overdosage: Gastric lavage may be of value if undertaken within a few hours
of ingestion. Very large doses of rifampicin may depress central
nervous function. There is no specific antidote and treatment
is supportive.
Storage: Capsules and tablets should be kept in tightly closed containers,
protected from light.
Streptomycin
General information
Group: antimycobacterial agent
Injection (powder for solution for injection): 1 g (as sulfate) in vial
Streptomycin, an aminoglycoside antibiotic derived from
Streptomyces griseus, is used in the treatment of TB and
susceptible Gram-negative infections. After intramuscular administration, streptomycin diffuses readily into the extracellular
component of most body tissues. In adults, a single
injection of 1 g (15 mg/kg) produces a peak serum concentration
of about 30–40 µg/ml in 1–2 hours. The plasma half-life, which
is normally 2–3 hours, is considerably extended in the newborn,
the elderly, and patients with severe renal impairment.
Streptomycin is excreted unchanged in the urine.
Clinical information
Uses: Streptomycin is a component of several TB chemotherapeutic
regimens currently recommended by WHO.
Administration and dosage: Streptomycin must be administered by deep intramuscular
injection. The dose for adults and children is 15 mg/kg body
weight daily. Syringes and needles should be adequately
sterilized to exclude any risk of transmitting viral pathogens.
Drug interactions: Other ototoxic or nephrotoxic drugs should not be administered
to patients receiving streptomycin. These include other
aminoglycoside antibiotics, amphotericin B, cefalosporins,
etacrynic acid, cyclosporin, cisplatin, furosemide, and vancomycin.
Streptomycin may potentiate the effect of neuromuscular
blocking agents administered during anaesthesia.
Side-effects: Severe nausea, vomiting, dizziness, rash and fever. Loss of
hearing has been reported following long-term use. Streptomycin
should not be used in patients with kidney impairment
because it increases the risk of severe toxic reactions. Symptoms
subside and recovery is usually complete after treatment is
stopped. Roaring noises or ringing in the ears are signs that treatment with streptomycin should be stopped. Ototoxicity,
deafness, vertigo or reversible nephrotoxicity may occur.
Overdosage: Haemodialysis can be beneficial. There is no specific antidote
and treatment is supportive.
Storage: Solutions retain their potency for 48 hours after reconstitution
at room temperature and for up to 14 days when refrigerated.
Powder for injection should be stored in tightly closed containers,
protected from light.
Amikacin
General information
Amikacin is an aminoglycoside bactericidal agent, obtained
from Streptomyces. Its bactericidal effect and adverse reactions
are very similar to those of other aminoglycosides.
Clinical information
Presentation and dosage:
Amikacin is presented as a sterile white powder for intramuscular
injection in sealed vials containing the equivalent of
250 mg, 500 mg or 1 g of drug. The drug should be dissolved in
2 ml of 0.9% sodium chloride or water for injection. The optimal
dose is 15 mg/kg body weight, usually 750 mg to 1 g in total,
given daily by deep intramuscular injection or intravenously.
Rotation of injection sites avoids local discomfort.
Side-effects: Side-effects are similar to those associated with streptomycin.
Ototoxicity, deafness, vertigo or reversible nephrotoxicity may
occur.
Precautions: In patients with impaired renal function, the daily dosage
should be reduced and/or the intervals between doses increased,
to avoid accumulation of the drug. In these patients, renal
function should be monitored regularly during antibiotic treatment.
This drug should not be used in pregnant women except
as a last resort.
4 Adapted from (25)
Provisional guidance on the role of specific antibiotics in the management of Mycobacterium ulcerans disease (Buruli ulcer):
1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22
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