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Critical Care (London, England) Dec 2018Recently, the use of nebulized antibiotics in the intensive care unit, in particular amikacin, has been the subject of much discussion, owing to unconvincing results... (Review)
Review
Recently, the use of nebulized antibiotics in the intensive care unit, in particular amikacin, has been the subject of much discussion, owing to unconvincing results from the latest randomized clinical trials. Here, we examine and reappraise the evidence in favor and against this therapeutic strategy; we then discuss the potential factors that might have played a role in the negative findings of recent clinical trials. Also, we call attention to several factors that are seldom considered by study developers and regulatory agencies, to promote translational research in this field and improve the design of future randomized clinical trials.
Topics: Administration, Inhalation; Amikacin; Anti-Bacterial Agents; Gram-Negative Bacteria; Humans; Intensive Care Units; Pneumonia; Pseudomonas aeruginosa
PubMed: 30558658
DOI: 10.1186/s13054-018-1958-4 -
Critical Reviews in Analytical Chemistry 2022Amikacin (AMK) is one of the commonly used aminoglycoside antibiotics, introduced for clinical use in patients suffering from bacterial infections especially... (Review)
Review
Amikacin (AMK) is one of the commonly used aminoglycoside antibiotics, introduced for clinical use in patients suffering from bacterial infections especially life-threatening gram-negative infections. Due to lack of chromophore in the molecule, the detection of AMK during analysis is a challenge. Thus, pre and post-column derivatization techniques are generally used for AMK estimation. This review focuses on different analytical methods used for detection and quantification of AMK in pure or fixed dose combination pharmaceutical formulations and biological samples. Various reported methods described in the literature include high-performance liquid chromatography techniques, pulsed electrochemical detection techniques, Chemiluminescence techniques, Capillary electrophoresis and immunological methods. High-performance-liquid-chromatography based methods with UV/Vis spectrophotometric, fluorescence and mass spectrometric detection are the most prevailing methods employed for the analysis of AMK. This review could be of significant importance in the area of future AMK analytical method development studies.
Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Humans; Pharmaceutical Preparations
PubMed: 32781828
DOI: 10.1080/10408347.2020.1803042 -
Lancet (London, England) Sep 1977
Comparative Study
Topics: Amikacin; Bacterial Infections; Biological Availability; Gentamicins; Humans; Kanamycin
PubMed: 71471
DOI: 10.1016/s0140-6736(77)92523-5 -
Nature Communications Aug 2023Aminoglycosides are a class of antibiotics that bind to ribosomal RNA and exert pleiotropic effects on ribosome function. Amikacin, the semisynthetic derivative of...
Aminoglycosides are a class of antibiotics that bind to ribosomal RNA and exert pleiotropic effects on ribosome function. Amikacin, the semisynthetic derivative of kanamycin, is commonly used for treating severe infections with multidrug-resistant, aerobic Gram-negative bacteria. Amikacin carries the 4-amino-2-hydroxy butyrate (AHB) moiety at the N amino group of the central 2-deoxystreptamine (2-DOS) ring, which may confer amikacin a unique ribosome inhibition profile. Here we use in vitro fast kinetics combined with X-ray crystallography and cryo-EM to dissect the mechanisms of ribosome inhibition by amikacin and the parent compound, kanamycin. Amikacin interferes with tRNA translocation, release factor-mediated peptidyl-tRNA hydrolysis, and ribosome recycling, traits attributed to the additional interactions amikacin makes with the decoding center. The binding site in the large ribosomal subunit proximal to the 3'-end of tRNA in the peptidyl (P) site lays the groundwork for rational design of amikacin derivatives with improved antibacterial properties.
Topics: Amikacin; Anti-Bacterial Agents; Models, Molecular; Ribosomes; Kanamycin; RNA, Transfer
PubMed: 37537169
DOI: 10.1038/s41467-023-40416-5 -
Current Drug Delivery 2021Amikacin is an aminoglycoside antibiotic used for many gram-negative bacterial infections like infections in the urinary tract, infections in brain, lungs and abdomen....
BACKGROUND
Amikacin is an aminoglycoside antibiotic used for many gram-negative bacterial infections like infections in the urinary tract, infections in brain, lungs and abdomen. Electrochemical determination of amikacin is a challenge in electroanalysis because it shows no voltammetric peak at the surface of bare electrodes.
OBJECTIVE
In this approach, a very simple and easy method for indirect voltammetric determination of amikacin presented in real samples. Gold nanoparticles were electrodeposited at the surface of glassy carbon electrode in constant potential.
METHODS
The effect of several parameters such as time and potential of deposition, pH and scan rates on signal were studied. The cathodic peak current of Au decreased with increasing amikacin concentration. Quantitative analysis of amikacin was performed using differential pulse voltammetry by following cathodic peak current of gold ions.
RESULTS
Two dynamic linear ranges of 1.0 × 10-1.0 × 10 M and 5.0 × 10-1.0 × 10 M were obtained and limit of detection was estimated 3.0× 10 M.
CONCLUSION
The method was successfully determined amikacin in pharmaceutical preparation and human serum. The effect of several interference in determination of amikacin was also studied.
Topics: Amikacin; Electrochemical Techniques; Electrodes; Gold; Humans; Metal Nanoparticles; Oxidation-Reduction
PubMed: 32682378
DOI: 10.2174/1567201817666200719005919 -
Brazilian Journal of Microbiology :... Dec 2021Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical...
Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical and microbiological outcomes of patients treated with amikacin for CRKp infections. We did a retrospective cohort of patients > 18 years old, with CRKp infections treated with amikacin in two tertiary care hospitals in Porto Alegre, Brazil. The impact of clinical factors, antibiotic treatment, and amikacin minimum inhibitory concentration (MIC) on patients' 30-day mortality was assessed. Microbiological clearance and nephrotoxicity (assessed by RIFLE score) were evaluated as secondary outcomes. A Cox regression analysis was done for mortality. We included 84 patients for analysis. Twenty-nine (34.5%) patients died in 30 days. Amikacin MIC values ranged from 0.125 to 8 μg/mL and did not influence on mortality, regardless of the prescribed dose of this antibiotic (P = 0.24). Bacterial clearance occurred in 17 (58.6%) of 29 patients who collected subsequent cultures. Two (16.6%) of the 12 persistently positive cultures changed the amikacin susceptibility profile from susceptible to intermediate. Twenty-nine (37.2%) patients developed acute kidney injury (AKI): risk 13, injury 11, and failure 5. Risk factors for AKI were higher baseline eGFR (P < 0.01) and combination therapy with colistin (P = 0.02). Comparing patients who received combination with colistin vs polymyxin B, AKI occurred in 60.0% vs 20.6%, respectively, P < 0.01. Fifteen of the 16 (16.6%) patients who developed renal injury or failure were receiving colistin. In conclusion, amikacin was an effective treatment for CRKp infections. Within susceptible range, amikacin MIC values did not influence on clinical outcomes. Combination therapy of amikacin and colistin was highly nephrotoxic and should be used with caution.
Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 34191252
DOI: 10.1007/s42770-021-00551-x -
JAMA Mar 1978
Topics: Amikacin; Bacteria; Drug Resistance, Microbial; Kanamycin; United States
PubMed: 628036
DOI: 10.1001/jama.1978.03280370026016 -
Minnesota Medicine Feb 1978
Review
Topics: Amikacin; Bacterial Infections; Dose-Response Relationship, Drug; Half-Life; Humans
PubMed: 162682
DOI: No ID Found -
American Journal of Hospital Pharmacy Jul 1981The antibiotic spectrum, pharmacology, adverse effects, and therapeutic use of amikacin sulfate are reviewed. Amikacin, a semisynthetic analog of kanamycin, is highly... (Review)
Review
The antibiotic spectrum, pharmacology, adverse effects, and therapeutic use of amikacin sulfate are reviewed. Amikacin, a semisynthetic analog of kanamycin, is highly active against most gram-negative bacteria including many gentamicin-resistant strains. Amikacin's pharmacologic properties have been studied extensively in both children and adults. It achieves high, predictable, and prolonged blood concentrations with a favorable therapeutic index. Amikacin does cause nephrotoxicity and ototoxicity; however there is no conclusive evidence that these toxicities differ from those caused by other major aminoglycosides. The effectiveness of amikacin sulfate in the treatment of serious gram-negative bacillary infections is well documented. Amikacin sulfate is an important addition to the antibiotic armamentarium of a hospital with high gentamicin or tobramycin resistance. In hospitals without substantial aminoglycoside resistance, its use is debatable because amikacin has not been shown to have increased clinical efficacy compared with the other aminoglycosides for infections caused by susceptible bacteria.
Topics: Amikacin; Bacteria; Drug Resistance, Microbial; Hearing Disorders; Humans; Kanamycin; Kidney Diseases; Kinetics; Neuromuscular Junction
PubMed: 7020413
DOI: No ID Found -
European Journal of Hospital Pharmacy :... Mar 2022Amikacin is still a widely used aminoglycoside for the treatment of life-threatening infections. The pharmacokinetic parameters of this antibiotic may be altered in...
OBJECTIVES
Amikacin is still a widely used aminoglycoside for the treatment of life-threatening infections. The pharmacokinetic parameters of this antibiotic may be altered in critically ill conditions. Moreover, in the elderly population, pathophysiological changes affect these pharmacokinetic variables, making it difficult to predict the appropriate dose and dosing schedule for amikacin. This study aimed to characterise the pharmacokinetics of amikacin in critically ill elderly patients with renal dysfunction, and to evaluate if the available dose adjustment schedules dependent on renal function would be appropriate for empirical dosing.
METHODS
Critically ill patients aged >60 years with a creatinine clearance of >20 mL/min in need of treatment with amikacin were randomly enrolled. All the patients received approximately 25 mg/kg amikacin. The patients were then divided into three groups according to the stages of their renal dysfunction based on creatinine clearance, and the optimum time to re-dosing was calculated for each group. The pharmacokinetic parameters of the patients were calculated and estimated as population pharmacokinetic data.
RESULTS
Of 30 patients, only 20% attained the target peak levels of amikacin of >64 mg/L. In addition, the mean volume of distribution was 0.47 L/kg. There was a poor correlation between amikacin clearance and creatinine clearance. The difference in amikacin half-life was not statistically significant among any of the stages of renal impairment.
CONCLUSIONS
The initial dosing of amikacin in critically ill elderly patients should not be reduced, even in the context of renal impairment. Regarding the dose adjustment in renal impairment, dosing intervals estimation, no decision can be made based on the creatinine clearance and the first dose individualisation method in terms of the two-sample measurements may be considered as an appropriate strategy.
Topics: Aged; Amikacin; Anti-Bacterial Agents; Critical Illness; Half-Life; Humans; Kidney Diseases; Middle Aged
PubMed: 34588225
DOI: 10.1136/ejhpharm-2021-002986