~ ATYPICAL TB * MY STORY ~
Below are included some research articles from my Files.
* * *
Below are included some research articles from my Files.
* The Dates at the top indicate time of Recording the items in my Files
Their Publication Dates are included at end of each article.
* Colour highlights are also mine.
* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *
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( Tuesday,
26 May 2009 )
Research for (clofazimine-amikacin-R207910)
Research and comments
*Clarithromycin is the most active MAC antimicrobial
agent and should be part of any drug regimen for treating active MAC disease in
patients with or without AIDS.
*Similarly, azithromycin (600 mg once daily) was
effective in reducing MAC bacteraemia.11 However, in a
head-to-head comparison with clarithromycin, azithromycin was inferior (both
drugs used in combination with ethambutol).12 Clofazimine should
probably not be used at all to treat MAC as it has been associated with reduced
survival.13
Warnings (http://www.medsafe.govt.nz/profs/datasheet/l/Lamprenecap.htm)
Clofazimine has an heterogeneous
distribution throughout the body and a slow elimination rate, accumulating mainly in fatty
tissue, reticuloendothelial system (macrophages, histiocytes and spleen) and
skin. Adverse reactions to clofazimine are mainly linked to its uptake by
tissue and organs. Because of this, the use of high doses for long
periods should be avoided. Daily doses of greater than 100 mg Lamprene should
be given for as short a time as possible (<3 months) and only under close
medical supervision. After prolonged administration in high doses,
clofazimine may accumulate in various organs, body fluids and tissues.
Among the visceras, the jejunum has the highest drug depositions, closely
followed by the spleen. The deposition of large amounts of clofazimine in the
intestinal mucosa cause irritation, leading to gastrointestinal disturbances (e.g.
abdominal pain (sometimes intermittent), nausea, vomiting and diarrhoea),
usually with mild forms, but sometimes with more severe clinical
manifestations. If crystals are deposited in the mesenteric lymph nodes
and/or histiocytes at the lamina propria of the jejunal mucosa, this might lead
to intestinal obstruction. If gastrointestinal symptoms develop during
treatment, the dosage should be reduced or the interval between doses
prolonged. Symptoms may slowly regress on withdrawal of the drug. In the event of persistent diarrhoea or vomiting, the patient should be hospitalised.
bacterial
load, MAC rapidly acquires resistance when treated with single drugs. Active
disease therefore has to be treated with at least two drugs at all times.
When a regimen is failing, at least two new drugs must be added or substituted.
A salvage regimen is concocted from a limited armamentarium after a case-by-case
evaluation. Amikacin or a quinolone (levofloxacin or ciprofloxacin), in
addition to the first line drugs, may be considered.
Introduction
Amikacin
sulfate (AMK) is a broad-spectrum and potent aminoglycoside with limited clinical use
owing to a high dose requirement and renal and audio-vestibular apparatus
toxicity.1-2 Major
drawbacks associated with the use of earlier or conventional liposomal
formulations are the tendency of liposomes to leak drug while in circulation,
the extensive uptake of these liposomes by tissues of reticuloendothelial
systems (RES), and the inability of liposomes to extravasate into infected tissue.3-4 Therefore,
localized liposomal AMK delivery was considered for the treatment of cystic
fibrosis infections in the lungs. Liposomal encapsulation of AMK will give
the required release of drug for a longer time duration at the localized site,
thereby reducing
both the chances of systemic side effects and the frequency of dosing.
The
use of amikacin for first-line therapy is limited, despite its excellent
bactericidal activity against gram-negative organisms. Poor oral absorption, a
short half-life, and serious renal, auditory, and vestibular toxicities
necessitate frequent intravenous administration, with concomitant monitoring of
drug levels to ensure that the levels in plasma remain within a narrow
therapeutic window (26).
Amikacin (Medicine net.com)
HOW TO USE: This medication is
given by injection. It may be injected into a large muscle such as the buttocks
or infused into a vein over 30 minutes to one hour. It is usually given two or
three times a day for 7 to 10 days. Antibiotics work best when the amount of medicine
in your body is kept at a constant level. Do this by using the medication at
evenly spaced intervals throughout the day and night as prescribed. Continue
using this for the full time prescribed. Stopping the medication too soon may
result in ineffective treatment.SIDE EFFECTS: This medication may cause nausea, vomiting or weakness as your body adjusts to the medication. If these effects continue or become severe, inform your doctor. This medication can cause hearing loss or kidney damage especially if used in high doses or for prolonged periods of time. It is important the proper dose be used. The site where the injection is given may be red and irritated for a few days. Notify your doctor if the irritation continues or becomes worse. Notify your doctor immediately if you develop: dizziness, ringing in the ears, hearing loss, skin rash, difficulty breathing, difficult or painful urination, muscle twitching. If you notice other effects not listed above, contact your doctor or pharmacist.
NOTES: Laboratory tests and blood counts will be done routinely while using this to monitor its effects and prevent side effects.
Drugs.com
Renal side
effects
One study has shown that hyperbilirubinemia in
patients with biliary obstruction may also be a predisposing factor to
aminoglycoside nephrotoxicity.
In one prospective, nonrandomized study, patients developed nephrotoxicity in 25% of amikacin courses.
Renal side
effects have included nephrotoxicity (serum creatinine elevations, albuminuria,
presence of red and white cells and casts in urine, azotemia, and oliguria) in
2% to 10% of patients. Predisposing factors include advanced age, preexisting
renal insufficiency, dehydration, and concomitant use of other potentially
nephrotoxic drugs.In one prospective, nonrandomized study, patients developed nephrotoxicity in 25% of amikacin courses.
Discolouration of the conjunctiva, cornea (eyes) and
tears.
Macrolides
Clarithromycin, Azithromycin
Quinolones
Moxifloxacin,ciprofloxacin
or levofloxacin
Aminoglycosides
Amikasin
New
TB Drug May Shorten Treatment Times
A new antibiotic specific to mycobacteria is expected to "dramatically improve TB control programs," according to a report published online December 9th in Science.
Dr. Koen Andries, of Johnson & Johnson Pharmaceutical Research and Development in Beerse, Belgium, and his multinational research team developed a series of compounds, diarylquinolines, which possess potent in vitro activity against several mycobacterial species.
The most active compound of the class, R207910, appears to have a novel target, inhibiting the proton pump of mycobacterial ATP synthase.
There is no concern about an interaction with human ATP synthase, Dr. Andries told Reuters Health during a teleconference, because "when we compare the gene sequence of mycobacterial ATP synthase with the ATP synthase of the human genome, they are quite different." And indeed, phase I trials in humans revealed no adverse effects during 2 weeks of treatment, he added.
Further studies showed that R207910 lacks cross-resistance with other currently used anti-TB agents. In fact, the authors note, 30 different isolates of multiple drug-resistant (MDR) TB strains and 10 fully susceptible strains were susceptible to 0.100 g/mL of R207910, concentrations readily achieved when administered to mice and humans.
The agent appears to be effective against all mycobacteria, including the human pathogens M. tuberculosis, M. kansasii, M. fortuitum, M. abscessus, and Mycobacterium avium complex (MAC).
"In the mouse model, our drug as a monotherapy is as active as the current standard of care, triple therapy with rifampin, isoniazid and pyrazinamide," Dr. Andries said. "Of course, our drug is not to be used as a monotherapy because that would inevitably lead to emergence of resistance, but it does demonstrate the high potency of the compound."
Perhaps even more importantly, "when we compared the results of R207910 combined with isoniazid and pyrazinamide with the standard of care, our combo achieved the same result after 1 month as that obtained after 2 months of standard of care combination therapy."
"We are optimistic that we will be able shorten treatment duration by about 50% based on these data," he added.
He also pointed out that the R207910 combination is compatible with HIV treatment combinations, whereas treatment that includes rifampin is associated with drug-drug interactions that increase the metabolism some HIV agents.
Science 2004.
www.sciencexpress.org/9 December 2004/Page 1/10.1126/science.1106753
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