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Annals of Surgery Mar 1985Serum concentrations of amikacin following operative wound irrigation were studied in 17 patients having laporatomy and in eight patients having thoracotomy. Irrigation...
Serum concentrations of amikacin following operative wound irrigation were studied in 17 patients having laporatomy and in eight patients having thoracotomy. Irrigation was done with 500 mg of amikacin in 200 ml of saline. The irrigant was reaspirated after 3 minutes. Measurement of amikacin in the irrigant allowed calculation of the retained dose. Serum levels were measured before surgery, and at 30 minutes, 60 minutes, 6 hours, and 12 hours following irrigation. Amikacin was assayed by a microbiological technique. The retained dose after peritoneal irrigation was 350 +/- 128 mg, and after pleural irrigation was 100 +/- 79 mg. The average maximum serum level in the peritoneal irrigation group was 9.4 +/- 6.7 gm/ml; in the thoracotomy group it was 3.5 +/- 1.7. Fourteen of the 17 laparotomy patients but only one of the eight thoracotomy patients had measurable plasma levels at 6 hours. Plasma half-life in the laparotomy group was 2.81 +/- 1.34 hours, and in the thoracotomy group 1.53 +/- 0.83 hours. Interoperative amikacin irrigation, even with immediate aspiration, results in significant absorption in both thoracotomy and laporatomy patients. There was less absorption and a shorter serum half-life in the thoracotomy patients.
Topics: Absorption; Adult; Amikacin; Humans; Inhalation; Intraoperative Period; Kanamycin; Middle Aged; Peritoneum; Pleura; Therapeutic Irrigation
PubMed: 3977436
DOI: 10.1097/00000658-198503000-00013 -
The American Journal of Medicine Jun 1977Treatment with amikacin was evaluated in 15 patients with gram-negative bacteremia. The sources of sepsis were urinary tract (in six patients), abdomen (in five) and...
Treatment with amikacin was evaluated in 15 patients with gram-negative bacteremia. The sources of sepsis were urinary tract (in six patients), abdomen (in five) and miscellaneous sites (in four). Sixteen bacterial pathogens were recovered, including three gentamicin-resistant organisms. All isolates were susceptible to amikacin. Eleven of the 14 patients who could be evaluated fulfilled the criteria for cure, including the three patients with gentamicin-resistant organisms. Three patients failed to respond to amikacin therapy. Monitoring untoward effects revealed eighth nerve toxicity in one patient and nephrotoxicity in one patient. These results indicate that amikacin is effective in the treatment of patients with gram-negative bacteremia, even when caused by gentamicin-resistant bacteria.
Topics: Amikacin; Gentamicins; Hearing Disorders; Humans; Kanamycin; Sepsis
PubMed: 868909
DOI: 10.1016/0002-9343(77)90664-7 -
Annals of Internal Medicine Nov 1978Amikacin is a new aminoglycoside antibiotic that behaves pharmacokinetically similar to kanamycin, gentamicin, and tobramycin. Our study was designed to test whether a...
Amikacin is a new aminoglycoside antibiotic that behaves pharmacokinetically similar to kanamycin, gentamicin, and tobramycin. Our study was designed to test whether a digital computer program could correctly predict amikacin serum concentrations in the clinical setting. A significant relation (P less than 0.0001) was found between 153 measured (bioassayed) and computer-predicted levels from 26 patients. The computer program reliably estimated amikacin serum levels after either intravenous or intramuscular doses. Prediction accuracy was not significantly affected by patient sex, hematocrit, or periods of unstable renal function. Predicted levels were most accurate when based on creatinine clearance corrected to 70 kg body weight or corrected to body surface area. The pharmacokinetic parameters in the computer program were used to generate a new aminoglycoside dosing chart. Ten patients were given amikacin according to this guideline, and the mean peak serum level for the group was 25.6 microgram/ml.
Topics: Adult; Amikacin; Body Weight; Computers; Creatinine; Humans; Injections, Intramuscular; Injections, Intravenous; Kanamycin; Kidney Diseases; Mathematics
PubMed: 717929
DOI: 10.7326/0003-4819-89-5-612 -
Amikacin and gentamicin accumulation pharmacokinetics and nephrotoxicity in critically ill patients.Antimicrobial Agents and Chemotherapy Jan 1981Twenty-five critically ill adults receiving blood level-adjusted doses of amikacin were prospectively studied with serum, urine, and, when possible, tissue amikacin...
Twenty-five critically ill adults receiving blood level-adjusted doses of amikacin were prospectively studied with serum, urine, and, when possible, tissue amikacin concentrations. These data were fitted to a two-compartment pharmacokinetic model. Prolonged urine collections or postmortem tissues (or both) were used to confirm predicted tissue accumulation. Nephrotoxicity was also investigated. Patients were defined as having renal damage if they showed an increase in serum creatinine of greater than 0.5 mg/100 ml, an increase in urine beta 2-microglobulin of greater than 50 mg/day, and presence of urinary casts of greater than 500/ml. Renal damage was attributed to amikacin if there was, in addition to the above, tissue accumulation of amikacin of greater than 600 mg. These patients were matched with 25 patients treated with gentamicin during the same time period. There were no statistical differences between the gentamicin- and amikacin-treated patients in age, sex, weight, base-line creatinine clearance, concurrent cephalosporins or diuretics, treatment duration, site of infection, normalized (amikacin/gentamicin dosing ratio of 3:1) total dose, mortality, or tissue accumulation. More amikacin-treated patients (19 of 25) than gentamicin-treated patients (9 of 25) received prior aminoglycosides (P less than 0.01). The only pharmacokinetic parameter that differed between amikacin and gentamicin was a greater K21 for gentamicin. Nephrotoxicity was observed in 4 gentamicin was a greater K21 for gentamicin. Nephrotoxicity was observed in 4 gentamicin-treated patients (16%) and 5 amikacin-treated patients (20%). At a 3:1 dosing ratio, there were no significant differences between amikacin and gentamicin two-compartment pharmacokinetics and nephrotoxic potential in matched critically ill patients, but the trend of these data showed greater amikacin tissue accumulation. However, at an amikacin/gentamicin dosing ratio of 4:1, their tissue accumulation potential appeared to be almost identical.
Topics: Amikacin; Critical Care; Gentamicins; Half-Life; Humans; Kanamycin; Kidney; Kinetics; Tissue Distribution
PubMed: 7247354
DOI: 10.1128/AAC.19.1.147 -
Antimicrobial Agents and Chemotherapy Oct 2011Amikacin clearance can be increased in burn injury, which is often complicated by renal insufficiency. Little is known about the impact of renal replacement therapies,...
Amikacin clearance can be increased in burn injury, which is often complicated by renal insufficiency. Little is known about the impact of renal replacement therapies, such as continuous venovenous hemofiltration (CVVH), on amikacin pharmacokinetics. We retrospectively examined the clinical pharmacokinetics, bacteriology, and clinical outcomes of 60 burn patients given 15 mg/kg of body weight of amikacin in single daily doses. Twelve were treated with concurrent CVVH therapy, and 48 were not. The pharmacodynamic target of ≥10 for the maximum concentration of drug in serum divided by the MIC (C(max)/MIC) was achieved in only 8.5% of patients, with a small reduction of C(max) in patients receiving CVVH and no difference in amikacin clearance. Mortality and burn size were greater in patients who received CVVH. Overall, 172 Gram-negative isolates were recovered from the blood cultures of 39 patients, with amikacin MIC data available for 82 isolates from 24 patients. A 10,000-patient Monte Carlo simulation was conducted incorporating pharmacokinetic and MIC data from these patients. The cumulative fraction of response (CFR) was similar in CVVH and non-CVVH patients. The CFR rates were not significantly improved by a theoretical 20 mg/kg amikacin dose. Overall, CVVH did not appear to have a major impact on amikacin serum concentrations. The low pharmacodynamic target attainment appears to be primarily due to higher amikacin MICs rather than more rapid clearance of amikacin related to CVVH therapy.
Topics: Adolescent; Adult; Amikacin; Anti-Bacterial Agents; Burns; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hemofiltration; Humans; Male; Middle Aged; Retrospective Studies
PubMed: 21825289
DOI: 10.1128/AAC.00374-11 -
Journal of Infection and Chemotherapy :... Feb 2024Mycobacterium avium complex (MAC) is considered a paramount microbe, especially in East Asia, including Japan. The commonly used commercial Minimum Inhibitory...
Mycobacterium avium complex (MAC) is considered a paramount microbe, especially in East Asia, including Japan. The commonly used commercial Minimum Inhibitory Concentrations (MIC) assay using Middlebrook 7H9 (7H9) medium deviates from the latest Clinical and Laboratory Standards Institute (CLSI) guidelines. Alternatively, measurement with cation-adjusted Mueller-Hinton broth (CAMHB) that conforms to CLSI standards is not yet widely available. Following the approval and commercialization of amikacin liposome inhalation suspension (ALIS) in 2021, a more precise evaluation of amikacin (AMK) susceptibility in MAC is necessary for treatment decisions. In the present study, 33 sputum samples were extracted from 27 patients, and MICs of AMK were compared between the frequently used 7H9 and the recommended CAMHB of the isolated MAC strains. The history of exposure to aminoglycosides for each sample was also added as clinical information. The findings indicated that there was only an 18% concordance rate in MIC between the two media, with 19 samples (58%) indicating lower MICs in 7H9 relative to CAMHB. The 17 samples had a history of exposure to aminoglycosides for periods ranging from 1.5 to 28 months. Specifically, 10 samples were exposed to amikacin by inhalation and intravenous injection, and the remaining seven samples had a history of ALIS inhalation. Samples with a prior utilization of aminoglycosides were significantly predisposed to developing resistance to ALIS compared to those without such a history (P = 0.046). Physicians are encouraged to scrutinize the findings of susceptibility testing utilizing CLSI-endorsed MIC assay using CAMHB medium to ascertain the optimal therapeutic approach.
Topics: Humans; Amikacin; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Anti-Bacterial Agents; Lung Diseases; Culture Media; Microbial Sensitivity Tests
PubMed: 37717608
DOI: 10.1016/j.jiac.2023.09.016 -
Pathologie-biologie May 1985This study addresses circadian variations in the tolerance of mice to a single lethal dose of amikacin. Female mice placed in cages providing constant thermal conditions... (Comparative Study)
Comparative Study
This study addresses circadian variations in the tolerance of mice to a single lethal dose of amikacin. Female mice placed in cages providing constant thermal conditions and lighted from 8 h to 20 h were given a single intraperitoneal injection of 1.6 to 1.9 g/kg amikacin at different times over the 24 hours (8 h, 14 h, 20 h and 2 h) and in two different seasons (november/december and march/april). The number of dead mice was determined every day for seven consecutive days. For a given dose, mortality rate was influenced by the time and season of administration of amikacin. Amikacin toxicity exhibited a peak at 2 h (mean 60%) and nadir at 14 h (mean 47.75%) in november/december, whereas the opposite was true in spring (means 36.6% and 23.3% respectively at 14 h and 2 h). Thus, acute toxicity of amikacin in mice varies throughout the circadian cycle and from season to season. These findings encourage further research in view of achieving optimal use of antibiotics in human clinical practice.
Topics: Amikacin; Animals; Circadian Rhythm; Dose-Response Relationship, Drug; Female; Kanamycin; Mice; Seasons
PubMed: 3897969
DOI: No ID Found -
PloS One 2022Informed antibiotic prescription offers a practical solution to antibiotic resistance problem. With the increasing affordability of different sequencing technologies,...
Informed antibiotic prescription offers a practical solution to antibiotic resistance problem. With the increasing affordability of different sequencing technologies, molecular-based resistance prediction would direct proper antibiotic selection and preserve available agents. Amikacin is a broad-spectrum aminoglycoside exhibiting higher clinical efficacy and less resistance rates in Ps. aeruginosa due to its structural nature and its ability to achieve higher serum concentrations at lower therapeutic doses. This study examines the predictive potential of molecular markers underlying amikacin susceptibility phenotypes in order to provide improved diagnostic panels. Using a predictive model, genes and variants underlying amikacin resistance have been statistically and functionally explored in a large comprehensive and diverse set of Ps. aeruginosa completely sequenced genomes. Different genes and variants have been examined for their predictive potential and functional correlation to amikacin susceptibility phenotypes. Three predictive sets of molecular markers have been identified and can be used in a complementary manner, offering promising molecular diagnostics. armR, nalC, nalD, mexR, mexZ, ampR, rmtD, nalDSer32Asn, fusA1Y552C, fusA1D588G, arnAA170T, and arnDG206C have been identified as the best amikacin resistance predictors in Ps. aeruginosa while faoAT385A, nuoGA890T, nuoGA574T, lptAT55A, lptAR62S, pstBR87C, gidBE126G, gidBQ28K, amgSE108Q, and rplYQ41L have been identified as the best amikacin susceptibility predictors. Combining different measures of predictive performance together with further functional analysis can help design new and more informative molecular diagnostic panels. This would greatly inform and direct point of care diagnosis and prescription, which would consequently preserve amikacin functionality and usefulness.
Topics: Amikacin; Anti-Bacterial Agents; Biomarkers; Microbial Sensitivity Tests; Phenotype; Pseudomonas aeruginosa
PubMed: 35468158
DOI: 10.1371/journal.pone.0267396 -
American Journal of Veterinary Research Aug 1985After IV, IM, and subcutaneous injection of single dosages of amikacin (5, 10, and 20 mg/kg of body weight) in each of 4 dogs, the elimination kinetics of amikacin were... (Comparative Study)
Comparative Study
After IV, IM, and subcutaneous injection of single dosages of amikacin (5, 10, and 20 mg/kg of body weight) in each of 4 dogs, the elimination kinetics of amikacin were determined. The pattern of urinary excretion and cumulative amount excreted unchanged in 24 hours were also determined. Amikacin had a short half-life (approx 1 hour) that was independent of the dosage. Intravenous injection of 10 mg/kg gave apparent volume of distribution of 226 +/- 37 ml/kg and body clearance of 2.64 +/- 0.24 ml/min.kg (mean +/- SD, n = 4). Within 6 hours, greater than 90% of the antibiotic was excreted in the urine, regardless of the route of administration. For isolates of common bacterial species from the canine urinary tract, minimum inhibitory concentrations of amikacin, gentamicin, tobramycin, and kanamycin were determined in vitro. Cumulative percentages were approximately the same for urinary isolates of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and coagulase-positive staphylococci that were susceptible (minimum inhibitory concentrations less than or equal to 32 micrograms/ml) to increasing concentrations of amikacin, gentamicin, and tobramycin, in vitro. Klebsiella pneumoniae was significantly more susceptible to amikacin than were the other bacteria evaluated. Widest variations in susceptibility to aminoglycosides were found with urinary isolates of streptococcal species. For dogs with normal renal function, an amikacin dosage of 10 mg/kg (IM or subcutaneously) is recommended every 8 hours for treatment of systemic infections, and every 12 hours for treatment of urinary tract infections caused by susceptible bacteria.
Topics: Amikacin; Aminoglycosides; Animals; Anti-Bacterial Agents; Bacteria; Dogs; Drug Resistance, Microbial; Half-Life; Injections, Intramuscular; Injections, Intravenous; Injections, Subcutaneous; Kanamycin; Species Specificity
PubMed: 4037511
DOI: No ID Found -
Albrecht Von Graefes Archiv Fur... Aug 1975An experiment was designed to see if an aminoglycoside antibiotic, amikacin, would penetrate the vitreous of rabbits in greater concentrations in the postoperative... (Comparative Study)
Comparative Study
An experiment was designed to see if an aminoglycoside antibiotic, amikacin, would penetrate the vitreous of rabbits in greater concentrations in the postoperative aphakic eye than in the normal eye. Phakic and aphakic eyes were treated with amikacin by topical, subconjunctival, and intramuscular methods separately and combined. Bioassays of aqueous, anterior vitreous, and posterior vitreous revealed that concentrations of amikacin in ocular fluids after intramuscular administration were greater in the aphakic eye as compared to the normal eye; however, concentrations in the vitreous did not reach reliably bactericidal concentrations even when all three methods of administration were combined.
Topics: Absorption; Amikacin; Animals; Aqueous Humor; Cataract Extraction; Endophthalmitis; Kanamycin; Lens, Crystalline; Ophthalmic Solutions; Postoperative Complications; Pseudomonas Infections; Rats; Vitreous Body
PubMed: 1080641
DOI: 10.1007/BF00410030