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Journal of Materials Chemistry. B Jun 2023AMC@SiO core@shell nanocarriers (AMC: amikacin) are realized and contain an exceptionally high drug load of 0.8 mg mg ( 80% AMC of total nanocarrier mass). They are...
AMC@SiO core@shell nanocarriers (AMC: amikacin) are realized and contain an exceptionally high drug load of 0.8 mg mg ( 80% AMC of total nanocarrier mass). They are prepared a solvent-antisolvent approach with AMC nanoparticles formed in a first step, which are then covered and stabilised by a thin silica shell in a one-pot synthesis. In total, the core@shell nanocarriers exhibit a mean diameter of 240 nm with an inner AMC core of 200 nm and an outer silica shell of 20 nm. Subsequent to synthesis, the nanocarriers can be stored in frozen dimethylsulfoxide (DMSO) and applied directly after warming to room temperature with particle contents of 5 mg mL. Size, structure, and composition of the AMC@SiO core@shell nanocarriers are evidenced by electron microscopy (SEM, TEM), spectroscopic methods (EDXS, FT-IR, UV-Vis), as well as X-ray powder diffraction and elemental analysis. As proof-of-concept, the AMC release and the activity of the novel nanocarriers are tested against two relevant, difficult-to-treat and notoriously multidrug resistant, bacterial pathogens: () and (). Colloidal stability, storage stability, high drug load, and activity of the AMC@SiO core@shell nanocarriers are promising for, , aerosol-type pulmonal application.
Topics: Humans; Silicon Dioxide; Amikacin; Spectroscopy, Fourier Transform Infrared; Nanoparticles; Bacterial Infections
PubMed: 37161666
DOI: 10.1039/d2tb02609k -
Bioanalysis Aug 2014Amikacin and kanamycin are frequently used in the treatment of multidrug-resistant TB. The current commercially available immunoassay is unable to analyze kanamycin and...
BACKGROUND
Amikacin and kanamycin are frequently used in the treatment of multidrug-resistant TB. The current commercially available immunoassay is unable to analyze kanamycin and trough levels of amikacin. The objective was therefore to develop a LC-MS/MS method for the quantification of amikacin and kanamycin in human serum.
MATERIALS & METHODS
Using apramycin as internal standard, selectivity, accuracy, precision, recovery, matrix effects and stability were evaluated.
RESULTS
The presented LC-MS/MS method meets the recommendations of the US FDA with a low LLOQ of 250 ng/ml for amikacin and 100 ng/ml for kanamycin. No statistical significant difference was found between the LC-MS/MS method and the immunoassay of amikacin (Architect(®) assay, p = 0.501).
CONCLUSION
The low LLOQ of amikacin and the ability to analyze kanamycin makes the LC-MS/MS method the preferred method for analyzing these aminoglycosides.
Topics: Adult; Aged; Amikacin; Anti-Bacterial Agents; Chromatography, Liquid; Drug Monitoring; Female; Humans; Kanamycin; Male; Middle Aged; Tandem Mass Spectrometry; Young Adult
PubMed: 25331857
DOI: 10.4155/bio.14.191 -
F1000Research 2022Carbapenems are the treatment of choice for multidrug-resistant (MDR) and extensively drug-resistant (XDR) infections, but the emergence of...
Carbapenems are the treatment of choice for multidrug-resistant (MDR) and extensively drug-resistant (XDR) infections, but the emergence of carbapenem-resistant (CRAB) has rendered it ineffective in the vast majority of cases. Combination therapy has grown in popularity over the last decade; this study aims to analyze growth kinetics after exposure to meropenem and ampicillin-sulbactam compared with meropenem and amikacin antibiotic combinations in clinically relevant concentrations. This experimental laboratory study was conducted on the ATCC 19606 isolate and three clinical isolates that were intermediate or resistant to tested antibiotics. Meropenem and ampicillin-sulbactam, as well as meropenem and amikacin, were tested at four different concentrations against isolates. Turbidity measurements were taken at predetermined time points of 0, 1, 2, 4, 6, 8, and 24 hours following exposure; bacterial concentration was enumerated using the agar plate method, with the results plotted in a time-kill curve. A bactericidal effect was achieved in isolates that were intermediate to ampicillin-sulbactam and resistant to meropenem after the administration of meropenem and ampicillin-sulbactam combination with a concentration of 4 µg/ml and 16/8 µg/ml, respectively. The combination of meropenem and ampicillin-sulbactam demonstrated bacteriostatic activity against isolates that were resistant to both antibiotics. Isolates treated with resistant antibiotics showed an increased growth rate compared to the growth control. The combination of meropenem and ampicillin-sulbactam could be a promising combination therapy in treating CRAB infections. The mechanism and degree of antibiotic resistance in the isolates affect the efficacy of antibiotic combinations; further research is needed to corroborate the findings of this study.
Topics: Humans; Meropenem; Acinetobacter baumannii; Amikacin; Kinetics; Anti-Bacterial Agents; Carbapenems; Acinetobacter Infections
PubMed: 36531260
DOI: 10.12688/f1000research.122221.2 -
BMC Infectious Diseases Mar 2021The World Health Organization recommends intravenous amikacin for the treatment of MDR-TB at a dose of 15 mg/kg. However, higher doses are associated with significant...
BACKGROUND
The World Health Organization recommends intravenous amikacin for the treatment of MDR-TB at a dose of 15 mg/kg. However, higher doses are associated with significant toxicity.
METHODS
Patients with MDR-TB treated at our institution receive amikacin at 8-10 mg/kg, with dose adjustment based on therapeutic drug monitoring. We conducted a retrospective cohort study of patients with MDR-TB who received amikacin between 2010 and 2016.
RESULTS
Forty-nine patients were included in the study. The median starting dose of amikacin was 8.9 mg/kg (IQR 8, 10), and target therapeutic drug levels were achieved at a median of 12 days (IQR 5, 26). The median duration of amikacin treatment was 7.2 months (IQR 5.7, 8), and median time to sputum culture conversion was 1 month (IQR 1,2). Six patients (12.2%) experienced hearing loss based on formal audiometry testing (95% CI 4.6-24.8%); 22.2% had subjective hearing loss (95% CI 11.2-37.1%) and 31.9% subjective tinnitus (95% CI 19.1-47.1%). Ten patients (23%) had a significant rise in serum creatinine (95% CI 11.8-38.6%), but only 5 patients had a GFR < 60 at treatment completion. 84% of patients had a successful treatment outcome (95% CI 84-99%).
CONCLUSIONS
Low dose amikacin is associated with relatively low rates of aminoglycoside-related adverse events. We hypothesize that low-dose amikacin can be used as a safe and effective treatment for MDR-TB in situations where an adequate regimen cannot be constructed with Group A and B drugs, and where careful monitoring for adverse events is feasible.
Topics: Adult; Amikacin; Antitubercular Agents; Cohort Studies; Drug Monitoring; Female; Hearing Loss; Humans; Male; Retrospective Studies; Tinnitus; Treatment Outcome; Tuberculosis, Multidrug-Resistant; World Health Organization
PubMed: 33691624
DOI: 10.1186/s12879-021-05947-6 -
Chest Sep 2021In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture... (Randomized Controlled Trial)
Randomized Controlled Trial
Amikacin Liposome Inhalation Suspension for Refractory Mycobacterium avium Complex Lung Disease: Sustainability and Durability of Culture Conversion and Safety of Long-term Exposure.
BACKGROUND
In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture conversion by month 6 in patients with treatment-refractory Mycobacterium avium complex lung disease (ALIS plus GBT, 29% [65/224] vs GBT alone, 8.9% [10/112]; P < .0001).
RESEARCH QUESTION
In patients who achieved culture conversion by month 6 in the CONVERT study, was conversion sustained (negative sputum culture results for 12 months with treatment) and durable (negative sputum culture results for 3 months after treatment) and were there any additional safety signals associated with a full treatment course of 12 months after conversion?
STUDY DESIGN AND METHODS
Adults were randomized 2:1 to receive ALIS plus GBT or GBT alone. Patients achieving culture conversion by month 6 continued therapy for 12 months followed by off-treatment observation.
RESULTS
More patients randomized to ALIS plus GBT (intention-to-treat population) achieved conversion that was both sustained and durable 3 months after treatment vs patients randomized to GBT alone (ALIS plus GBT, 16.1% [36/224] vs GBT alone, 0% [0/112]; P < .0001). Of the patients who achieved culture conversion by month 6, 55.4% of converters (36/65) in the ALIS plus GBT treated arm vs no converters (0/10) in the GBT alone arm achieved sustained and durable conversion (P = .0017). Relapse rates through 3 months after treatment were 9.2% (6/65) in the ALIS plus GBT arm and 30.0% (3/10) in the GBT alone arm. Common adverse events among ALIS plus GBT-treated patients (dysphonia, cough, dyspnea, hemoptysis) occurred mainly within the first 8 months of treatment.
INTERPRETATION
In a refractory population, conversion was sustained and durable in more patients treated with ALIS plus GBT for 12 months after conversion than in those treated with GBT alone. No new safety signals were associated with 12 months of treatment after conversion.
TRIAL REGISTRY
ClinicalTrials.gov; No.: NCT02344004; URL: www.clinicaltrials.gov.
Topics: Administration, Inhalation; Adult; Amikacin; Anti-Bacterial Agents; Bacteriological Techniques; Drug Monitoring; Female; Humans; Liposomes; Long Term Adverse Effects; Lung Diseases; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Sputum; Treatment Outcome
PubMed: 33887244
DOI: 10.1016/j.chest.2021.03.070 -
Veterinary Clinical Pathology Jun 2023Pseudothrombocytopenia may lead to the erroneous diagnosis of thrombocytopenia, resulting in unnecessary testing and treatment. The addition of exogenous substances to...
BACKGROUND
Pseudothrombocytopenia may lead to the erroneous diagnosis of thrombocytopenia, resulting in unnecessary testing and treatment. The addition of exogenous substances to blood samples prior to collection has been shown to mitigate platelet (PLT) clumps in blood samples. Postcollection additives aiming to disaggregate PLT clumps have been largely unexplored.
OBJECTIVES
We aimed to determine if the addition of amikacin to blood samples postcollection aids in the disaggregation of PLT clumps in cats and dogs.
METHODS
For this prospective study, EDTA-collected blood samples from 28 cats and 17 dogs were obtained from a hospital population at UC Davis Veterinary Medical Teaching Hospital. Samples had PLT clumps detected on blood smears and thrombocytopenia per analyzer count. Amikacin was added to samples postcollection, and an additional CBC was performed. Flow cytometry was performed to assess PLT-fibrinogen binding in amikacin-treated aliquots.
RESULTS
PLT-clumped samples treated with amikacin significantly increased PLT numbers by 134% and decreased mean platelet volume (MPV) values by 14% (P ≤ 0.0001) in cats, and increased PLT numbers by 32% (P = 0.04) and increased MPV values by 9% (P = 0.02) in dogs. Mean cell volume (MCV) slightly increased (<4%) for both species. No other CBC parameters were substantially affected by the addition of amikacin. Flow cytometry showed decreased PLT-fibrinogen binding in the majority of cats but was not significant (P > 0.05).
CONCLUSIONS
Adding amikacin to PLT-clumped blood samples postcollection may be a convenient solution for pseudothrombocytopenia in cats and dogs. Future studies are needed to elucidate the mechanism of amikacin and its effectiveness under different storage conditions. This is the first reported use of amikacin postcollection to disaggregate PLT clumps in blood samples from animals.
Topics: Cats; Dogs; Animals; Platelet Count; Amikacin; Edetic Acid; Prospective Studies; Thrombocytopenia; Fibrinogen; Cat Diseases; Dog Diseases
PubMed: 36849708
DOI: 10.1111/vcp.13203 -
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 -
Scientific Reports Jan 2021Modification of outer membrane proteins (OMPs) is the first line of Gram-negative bacteria defence against antimicrobials. Here we point to Proteus mirabilis OMPs and...
Modification of outer membrane proteins (OMPs) is the first line of Gram-negative bacteria defence against antimicrobials. Here we point to Proteus mirabilis OMPs and their role in antibiotic and phage resistance. Protein profiles of amikacin (AMKrsv), phage (Brsv) and amikacin/phage (AMK/Brsv) resistant variants of P. mirabilis were compared to that obtained for a wild strain. In resistant variants there were identified 14, 1, 5 overexpressed and 13, 5, 1 downregulated proteins for AMKrsv, Brsv and AMK/Brsv, respectively. Application of phages with amikacin led to reducing the number of up- and downregulated proteins compared to single antibiotic treatment. Proteins isolated in AMKrsv are involved in protein biosynthesis, transcription and signal transduction, which correspond to well-known mechanisms of bacteria resistance to aminoglycosides. In isolated OMPs several cytoplasmic proteins, important in antibiotic resistance, were identified, probably as a result of environmental stress, e.g. elongation factor Tu, asparaginyl-tRNA and aspartyl-tRNA synthetases. In Brsv there were identified: NusA and dynamin superfamily protein which could play a role in bacteriophage resistance. In the resistant variants proteins associated with resistance mechanisms occurring in biofilm, e.g. polyphosphate kinase, flagella basal body rod protein were detected. These results indicate proteins important in the development of P. mirabilis antibiofilm therapies.
Topics: Amikacin; Anti-Bacterial Agents; Bacterial Infections; Bacterial Outer Membrane Proteins; Bacteriophages; Biofilms; Drug Resistance, Microbial; Gram-Negative Bacteria; Membrane Proteins; Proteus mirabilis
PubMed: 33452316
DOI: 10.1038/s41598-020-80907-9 -
Clinical Laboratory Jun 2022In our study, we evaluated the in vitro activities of plazomicin, amikacin, gentamicin, and tobramycin among fifty carbapenem resistant Klebsiella pneumoniae (CR-Kp)...
BACKGROUND
In our study, we evaluated the in vitro activities of plazomicin, amikacin, gentamicin, and tobramycin among fifty carbapenem resistant Klebsiella pneumoniae (CR-Kp) isolates. Aminoglycoside resistance genes in selected CR-Kp strains were also examined.
METHODS
Minimum inhibitory concentration (MIC) of meropenem, plazomicin, tobramycin, gentamicin, and amikacin were determined by gradient test (G-test) method. In all strains carbapenemase activity was assessed by polymerase chain reaction (PCR). Aminoglycoside modifying enzyme (AME) genes in 14 CR-Kp strains that are resistant to at least one of tobramycin, gentamicin, and amikacin among fifty CR-Kp isolates, and 16S ribosomal methylase genes in 6 CR-Kp strains with plazomicin MIC ≥ 128 mg/L were investigated by PCR method.
RESULTS
The most frequently detected carbapenemase enzyme in the strains in our study was OXA-48 (88%). Aminoglycoside susceptibilities of all isolates were determined; plazomicin 84%, amikacin 66%, gentamicin 50%, tobramycin 18%. The most common AME gene positivities were found, 93% (n = 13) ant(3')-I, 78% (n = 11) aac(6')-Ib, 57% (n = 8) aac(3')-IV, 42% (n = 6) aac(3')-IIa, and 29% (n = 4) aph(3')-VI. Most of the isolates examined for the presence of AME carry at least two or more AME genes. The most common 16S ribosomal methylase gene was rmtH. In our study, MIC values of ≥ 256 µg/mL were found in 6 (12%) of 50 isolates against amikacin, tobramycin, and gentamicin, including plazomicin. At least two 16S ribosomal methylase gene positivity has been shown in these 6 strains.
CONCLUSIONS
In our study, increased in vitro efficacy of plazomicin was shown in CR-Kp isolates comparing to other aminoglycosides. Plazomicin is an effective treatment option against CR-Kp isolates and needs to be sup-ported by clinical studies.
Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Gentamicins; Humans; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Sisomicin; Tobramycin
PubMed: 35704736
DOI: 10.7754/Clin.Lab.2021.210936 -
American Journal of Infection Control Aug 2023Multidrug-resistant bacteria are one of the world's biggest health problems; therefore, improving the spectrum of action of antibiotics could be necessary to reverse...
BACKGROUND
Multidrug-resistant bacteria are one of the world's biggest health problems; therefore, improving the spectrum of action of antibiotics could be necessary to reverse this situation. Amikacin and silver salts have well-known antimicrobial properties. However, both drugs lost their effectiveness against some bacteria, such as Acinetobacter baumannii. This work aims to develop a nanodrug from silver nanoparticles (AgNPs) functionalized with Amikacin against multidrug-resistant Acinetobacter baumannii.
METHODS
AgNPs were produced using the bottom-up methodology and functionalized with Amikacin modified by the carbodiimide-based chemistry, forming AgNPs@Amikacin. Susceptibility tests were performed using Amikacin-resistant Acinetobacter baumannii strains to assess the bacteriostatic and bactericidal potential of the developed nanodrug. The clinical strains were induced to form a biofilm, and biomass quantification and the metabolic activity were determined.
RESULTS
The AgNPs have a hydrodynamic diameter of the particles with a bimodal distribution, with a size of 37.84 nm. The FT-IR spectrum of AgNPs@Amikacin exhibits vibrational modes corresponding to Amikacin, confirming the conjugation to AgNPs. Susceptibility testing demonstrated a minimal inhibitory and bactericidal concentration of < 0.5 µg/mL. The AgNPs@Amikacin reduced the biofilm metabolic activity of Acinetobacter baumannii at rates ≥ 50%, characterized by the minimal biofilm inhibition concentrations.
CONCLUSIONS
Results demonstrate a promising development of a new nanodrug with lower concentrations, less toxicity, and greater efficacy against multidrug-resistant Acinetobacter baumannii.
Topics: Humans; Amikacin; Acinetobacter baumannii; Silver; Metal Nanoparticles; Spectroscopy, Fourier Transform Infrared; Anti-Bacterial Agents; Microbial Sensitivity Tests
PubMed: 36581226
DOI: 10.1016/j.ajic.2022.12.009