"Amikacin Sulfate Injection, USP is indicated in the short-term treatment of serious infections due to susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species."
2. Off-label use of amikacin recommended by the World Health Organisation for the treatment of multi-drug-resistant TB -
"When sensitivities are known and the isolate is confirmed as resistant to both INH and RMP, five drugs should be chosen in the following order (based on known sensitivities):
an aminoglycoside (e.g., amikacin, kanamycin) or polypeptide antibiotic (e.g., capreomycin)
a fluoroquinolone: e.g., moxifloxacin (ciprofloxacin should no longer be used)
a thioamide: prothionamide or ethionamide
a macrolide: e.g., clarithromycin
high-dose INH (if low-level resistance)
3. Pathogens specifically identified within the new legislation as having the potential to pose a serious threat to public health -
(A) resistant gram positive pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Staphylococcus aureus, and vancomycin-resistant enterococcus;
(B) multi-drug resistant gram negative bacteria, including Acinetobacter, Klebsiella, Pseudomonas, and E. coli species; (see 1 above)
(C) multi-drug resistant tuberculosis; (see 2 above)
(D) Clostridium difficile.
In the "S.3187 wide-spectrum label" post I suggested that the surrogate endpoints of the NTM study might now support approval of Arikace as a therapy for amikacin-susceptible TB.
The Resident Charlatan observed -
"Arikace works against NTM because it is concentrated inside the cells (fixed macrophages) that take in but cannot kill the NTM by the normal process. By taking in Arikace, the antibiotic is concentrated in the same microenvironment as the NTM bringing the antibiotic (amikacin) to toxic levels for the bacteria. This will probably not work for TB (and INSM is not suggesting any different) because the bacterial cell wall of TB is enriched with three types of mycolic acids that make the bacteria impenetrable by normal antibiotics."
The bit about Mycobacterium tuberculosis having a different cell wall to other mycobacteria was just another one of his lies (and INSM is not suggesting any different).
The WHO recommendation for the use of an aminoglycoside such as amikacin in the treatment of MDR-TB is all the more impressive when one notes that amikacin has a higher ranking that either PZA or EMB.
The standard regimen for routine TB infection involves four drugs - INH, RMP, PZA and EMB.
MDR-TB is any infection resistant to both INH and RMP.
But when treating MDR-TB, amikacin is considered more effective than either of the other two drugs used to treat routine infection.
And as the RC has unwittingly demonstrated, Arikace looks likely to be considerably more effective than amikacin delivered via blood concentration. I have a feeling the WHO is going to be a big fan of Arikace in situations where the funding is available.
But funding is usually a major issue in countries with TB epidemics. However, the country with the World's second largest TB epidemic - China - is estimated to have spent $357 billion on health care in 2011. And is expected to increase that annual spend to $1 trillion by 2020.
An estimated 110,000 Chinese every year develop MDR-TB .....
Gollum...rehdvm clearly stated that the cell wall contains three types of mycolic acid that make treatment difficult. This is true and he is correct. He did not say that the cell wall is different than other mycobacteria.
You lied, Gollum. Shameful behavior on your part. You are misleading investors.
With particular relevance to the pathogens named in Item 3 of the initial post, these data are from a study in Oman from July 2005 to July 2007 of antibiotic resistance via extended spectrum beta-lactamases (ESBLs).
They identified 301 ESBL-producing Escherichia coli and K. pneumoniae strains isolated from clinical samples.
Overall Piperacillin-Tazobactam susceptibility was 57.9 (64.4% E. coli and 43.6% Klebsiella pneumoniae).
Only 29.6 % of ESBLs (24.9% E. coli and 39.6% Klebsiella pneumoniae) were ciprofloxacin susceptible.
98.1% E. coli and 93.1% of Klebsiella pneumoniae were susceptible to Piperacillin-Tazobactam plus Amikacin combination.
73.7% E. coli and 61.4% of Klebsiella pneumoniae were susceptible to Piperacillin-Tazobactam plus Gentamicin combination.
96.7% E. coli and 91.1% of Klebsiella pneumoniae were susceptible to Ciprofloxacin plus Amikacin combination.
41.2% E. coli and 51.5% of Klebsiella pneumoniae were susceptible to Ciprofloxacin plus Gentamicin combination.
"Conclusion: The ESBLs from Oman have similar resistance pattern as those reported from UK and USA. This resistance decreases when these drugs are combined with Amikacin. All ESBLs are susceptible to Carbapenems. However, carbepenam overuse can lead to emergence of carbapenems resistant gram negative bacilli and ESBLs.
Combination of Amikacin plus Piperacillin/Tazobactam is a feasible empirical therapy for ESBLs."
The reference to "empirical therapy" is key - emergency antibiotic treatment provided at a point when the pathogen has yet to be identified via laboratory analysis. From that FDA-sponsored workshop last year on Non-CF bronchiectasis -
"in the unit, in the hospital, we frequently double coverage people with pseudomonal pneumonia, for example, or gram-negative pneumonia, or just empirically before we know what anything is. And a patient with a ventilator-associated pneumonia, or just a rip-roaring severe pseudomonal pneumonia, often gets two drugs of a different class"