Latest Research News on Amikacin : Nov 2020
Pharmacokinetics of amikacin in intensive care unit patients
Objective: To characterize the population pharmacokinetics of amikacin in intensive care unit (ICU) patients and to analyse whether these patients show different kinetic behaviour on the basis of their clinical diagnoses.
Method: The patient population comprised 104 medical ICU patients on amikacin treatment for several presumed or documented Gram‐negative infections. Four study groups were defined according to patients’ clinical diagnosis: sepsis group (n= 39), trauma group (n= 20), pneumonia group (n= 21) and ‘other diagnosis’ group (n= 24). The pharmacokinetic parameters for amikacin in these patients were then compared.
Results: The ICU patients were found to have increased values for the amikacin volume of distribution (0.52 ± 0.21 litres/kg), whereas total amikacin clearance expressed as a linear function of creatinine clearance was Cl (ml/min/kg)= 0.13 ± 0.86 ClCR which is not significantly different from other estimations reported in the literature. However, this relationship revealed statistically significant differences among the four groups of ICU patients. Moreover, the septic and trauma patients showed higher (but not statistically significant) values for the amikacin volume of distribution.
Conclusion: The amikacin pharmacokinetic parameters obtained should allow Bayesian individualization of amikacin doses in patients admitted to medical ICUs, on the basis of their clinical diagnoses. 
Mechanism of Resistance to Amikacin and Kanamycin in Mycobacterium tuberculosis
An A1400G mutation of the rrs gene was identified inMycobacterium tuberculosis (MTB) strain ATCC 35827 and in 13 MTB clinical isolates resistant to amikacin-kanamycin (MICs, >128 μg/ml). High-level cross-resistance may result from such a mutation since MTB has a single copy of the rrs gene. Another mechanism(s) may account for high-level amikacin-kanamycin resistance in two mutants and lower levels of resistance in four clinical isolates, all lacking the A1400G mutation. 
Ototoxicity of Amikacin
Amikacin was used in 77 treatment courses at a dosage of ≥7.5 mg/kg every 8 h, and patients were monitored for ototoxicity by following serial audiograms, serum creatinine, and amikacin blood levels. Patients were leukopenic (58), were infected by gentamicin-resistant organisms (11), or had cystic fibrosis (8). Three patients developed tinnitus, but none had vertigo or nystagmus. Of 55 courses with pre- and post-treatment audiogram, 13 (24%) were associated with development of high-frequency hearing loss, which was usually bilateral. No patient had conversational hearing loss, and audiograms reverted to normal in three patients. Onset of cochlear damage occurred in one patient after therapy was stopped. The group with high-tone hearing loss, in comparison to the group without audiographic changes, received a larger mean total dose (24 versus 9.6 g), were treated for a longer duration (19 versus 9 days), and more frequently had previous aminoglycosides. Fifty-seven percent of patients with a “peak” serum level exceeding 32 μg/ml and 55% of patients with “trough” levels exceeding 10 μg/ml developed cochlear damage. There was no difference between the groups in age, body weight, previous cochlear damage, renal disease before or during therapy, or average daily dose. Both monitoring of blood levels and limiting duration of therapy may prevent amikacin ototoxicity. 
Liposomal Encapsulation of Amikacin Sulphate for Optimizing Its Efficacy and Safety
Aims: The abstract of the current study was to formulate amikacin sulfate in a liposomal formulatiom for enhancing its efficacy and safety.
Place and Duration of Study: Pharmaceutical Technology Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Cairo, Egypt, between 2010-2013.
Methodology: Amikacin sulfate liposomes were prepared by the vortex dispersion method using dipalmitoyl phosphatidyl choline (DPPC), cholesterol (CHOL) and charge inducing agent (CIA). Dicetyl phosphate (DCP) and Stearyl amine (SA) were added as the negative and positive charge inducing agents respectively. Characterization of the prepared amikacin sulphate liposomes was performed. In-vitro release of selected formulations was estimated. A stability study for 45 days was performed. Investigation of the optimum dose for sterilization of amikacin sulfate liposomes was carried out. Selected amikacin sulfate liposomal formulations activities were evaluated against Escherichia coli infection in mice and compared to the free drug.
Results: The entrapment efficiencies ranged from 43.6±1.81 to 62.5±2.57%, the vesicles are well identified and present in a nearly perfect sphere like shape ranging in size from 54.3±11 to 362.1±56 nm and the polydospersity index values of all liposomal formulations were < 0.3. DSC of different liposomal formulations shows a change in transition temperature of the main phospholipids. In-vitro release profiles revealed biphasic release of the drug from liposomes. Physical stability performed at 2-8ºC for 45 days revealed low leakage of drug from all liposomal formulations investigated. Sterilization using gamma radiations revealed that a dose of 25 KGy was the optimum sterilization dose. The results also revealed less number of colonies forming units (cfu/ml) in the case of amikacin sulfate liposomes than the unentrapped drug.
Conclusion: It can be fulfilled from this work that amikacin sulfate liposomes represent promising carrier for delivery of amikacin offering good physical stability, high entrapment effeciencies and controlled drug release. 
Susceptibility Pattern of Extended-Spectrum β-Lactamase (ESBL) Producing Escherichia coli, Klebsiella spp. and Enterobacter spp. to Ciprofloxacin, Amikacin and Imipenem
This study was carried out to determine the susceptibility pattern of Extended-Spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella spp. and Enterobacter spp. to ciprofloxacin, amikacin and imipenem. A total of 100 ESBL producing Escherichia coli, Klebsiella spp. and Enterobacter spp. were studied and identified by double disc synergy test (DDST) and were confirmed phenotypically as ESBL producer by phenotypic confirmatory disc diffusion test (PCDDT). Minimum inhibitory concentrations of ciprofloxacin, amikacin and imipenem among ESBL-producing strains were determined using agar dilution method. Out of 75 DDST positive ESBL-producing E. coli, 71 (94.67%) were also positive by PCDDT. All DDST positive Klebsiella spp. and Enterobacter spp. were also positive by PCDDT. All ESBL-producing E. coli, Klebsiella spp. and Enterobacter spp. were 100% susceptible to imipenem by both agar dilution and disc diffusion method. About 7.04% Escherichia coli, 21.05% Klebsiella spp. were resistant but 100% Enterobacter spp. were susceptible to amikacin by both methods. About 85.92% ESBL-producing Escherichia coli, 73.68% Klebsiella spp. and 33.33% Enterobacter spp. were resistant to ciprofloxacin by agar dilution method but 87.32% Escherichia coli, 78.95% Klebsiella spp. and 50% Enterobacter spp. were resistant to ciprofloxacin by disc diffusion method. ESBL-producing Escherichia coli, Klebsiella spp. and Enterobacter spp. showed high resistance to ciprofloxacin. Imipenem and amikacin were most effective against ESBL positive strains. 
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 El-Ridy, M. S., El-Shamy, A.-E. A., Ramadan, A., Abdel-Rahman, R. F., Awad, G. A., El-Batal, A., Mohsen, A. M. and Darwish, A. B. (2014) “Liposomal Encapsulation of Amikacin Sulphate for Optimizing Its Efficacy and Safety”, Journal of Pharmaceutical Research International, 5(2), pp. 98-116. doi: 10.9734/BJPR/2015/9298.
 Sarker, J., Bakar, S., Barua, R., Sultana, H., Anwar, S., Saleh, A. and Sultana, S. (2015) “Susceptibility Pattern of Extended-Spectrum β-Lactamase (ESBL) Producing Escherichia coli, Klebsiella spp. and Enterobacter spp. to Ciprofloxacin, Amikacin and Imipenem”, Journal of Scientific Research and Reports, 8(1), pp. 1-9. doi: 10.9734/JSRR/2015/16933.