Amikacin Serum Levels Research Articles

To quantify serum amikacin concentrations in dogs undergoing wound management with topical amikacin (45 mg/mL) 3% carboxymethylcellulose hydrogel. Prospective clinical study. Eleven client-owned dogs. Dogs with naturally occurring wounds, undergoing treatment with topical amikacin gel, were enrolled. A whole blood sample was collected prior to initial application of the gel. Up to a maximum dose of 30 mg/kg of gel, was applied directly on the wound and the wound was bandaged. Serial blood sampling was performed at approximately 2, 4, 8, 12, 18, 24, 32, 40, 48, 56, 64, and 72 h after application of amikacin gel. The sampling schedule was reset following each bandage change and new application of the gel. Up to 20 samples per dog were collected. The Siemens Syva EMIT Amikacin Assay was used to quantify the concentration of amikacin in each blood serum sample. The lower limit of quantification (LLOQ) of the test was 2.5 μg/mL. Amikacin gel was applied a total of 31 times (dose range, 0.1-24.9 mg/kg). A total of 153 samples were analyzed. Five samples in three different dogs were above the LLOQ at approximately 2 h after gel application (range 2.75-3.82 μg/mL). All other samples were below the LLOQ. Routine use of amikacin gel for open wound management did not result in serum amikacin levels above 5 μg/mL. Topical amikacin gel may be a safe treatment option for wounds in dogs with resistant infections or biofilms.

Abstract Background The therapeutic drug monitoring (TDM) of toxic drugs is a routine practice in our 200-bed hospital. Amikacin is not often used except in MDR bacteria. TDM is based on trough and peak levels of aminoglycosides, although AUC TDM may be the way forward, as discussed in the conclusions. According to the literature, measurement of serum amikacin levels is indicated in cases when prolonged aminoglycoside therapy is expected or in patients with compromised renal function and is not recommended for aminoglycoside use for less than 5–7 days or for treatment of mild infections in patients with no risk factors for drug toxicity. Objectives This study delivers some controversy on not to recommend monitoring for aminoglycoside use for less than 5–7 days, or for treatment of mild infections in patients with no risk factors for drug toxicity. Methods A retrospective study was conducted in our hospital between May and June 2023. Five patients aged 62–82 years on amikacin therapy for 5 to 10 days were included, all with Klebsiella pneumoniae OXA-48 UTI. At least two peak and trough samples were collected, and data were submitted to the Precise PK© software for precision dosing. The software is designed to predict population-based levels and patient-based levels. Interpretation of these values by pharmacists delivers optimized/viable amikacin intervals and dose individualized recommendations. Results Results are shown in Table 1. Conclusions Serum amikacin monitoring should guide therapy to ensure adequate levels, especially in Gram-negative resistant bacterial infections. According to these results, with Gram-negative resistant bacteria, it is worth monitoring even the short treatments—as seen in Patient 3. AUC TDM instead of peak TDM might be the way forward— this obviates distribution phase underdosing and delivers more accurate correlation to efficacy after changing intervals.

Therapeutic drug monitoring of Amikacin in hospitalized patients: A pilot study

Background: Bacterial sepsis is highly prevalent among premature infants. Amikacin is an antibiotic widely recommended for the treatment of neonatal sepsis, one of the consequences of which might be nephrotoxicity. The present study aimed to compare the efficacy and nephrotoxicity of multiple daily dosing (MDD) and once-daily dosing (ODD) of amikacin in preterm infants suspected of sepsis. Methods: This triple-blind, randomized, controlled clinical trial was conducted on 40 premature infants suspected of sepsis, who were randomly divided into two groups. In addition to ampicillin, one group was administered with the standard daily dose, and the other group received an ODD of intravenous amikacin. Maximum and minimum serum levels of amikacin and urine neutrophil gelatinase-associated lipocalin (NGAL) were measured in both groups. Data were extracted and analyzed based on the research hypothesis and literature review. Results: No significant differences were observed between the study groups in terms of gender, gestational age, mode of delivery, birth weight, and Apgar score. After the intervention, mean plasma creatinine reduced in both groups, while the mean reduction was significantly higher in the group administered with the ODD of amikacin (P=0.0001). However, mean changes in the urine NGAL had no significant difference between the groups (P=0.635). Minimum and maximum serum levels of amikacin in the study groups indicated a more significant reduction in mean level of the infants administered with the ODD of amikacin compared to the MDD group (P=0.0001). Conclusion: Considering the higher maximum and lower minimum levels of amikacin in the neonates receiving the daily dosage regimen, it seems that this regimen is more effective in the treatment of sepsis in preterm infants. Moreover, no significant difference was observed in the efficacy and nephrotoxicity of the daily amikacin dosing in the premature infants suspected of sepsis compared to those treated by multiple doses of amikacin.

Impact of infusion method on amikacin serum levels in humans

The purpose of this paper was to describe whether there are some relationships between amikacin serum levels and central conduction time in brainstem auditory evoked potentials (BAEP) within therapeutic range levels in newborns as index of drug toxicity in brainstem auditory centers in neonatally exposed infants. We performed a cross-sectional study to compare BAEP from 35 infants under amikacin administration and 24 control infants; both examinations were blinded to investigators. Bivariate and partial correlations were calculated between amikacin and BAEP measurements in treated infants. Amikacin determinations were within therapeutic levels. No clinical alterations in BAEP were found and no differences between amikacin-treated and control infants were found. Significant positive Pearson correlation between latency of I-III interwaves interval and amikacin Cmin serum levels was found and was present when calculations were controlled by partial correlations for gestational age at birth and Apgar score at 5 min. The findings suggest that increased amikacin levels in newborns are related to increased latencies in I-III interwave interval in infants, which may be an early index of brainstem effects of subclinical neurotoxicity of amikacin.

Amikacin is widely used in the treatment of suspected or confirmed neonatal infections. However, dosage regimens are not well defined in this group of patients because of a wide inter-individual pharmacokinetic variability. An individualized goal-oriented amikacin dosage design was applied using population pharmacokinetic data. A dosing chart was developed for neonates during the first 2 days of life, by using population pharmacokinetic parameter values and USCPACK software. This dosing chart based on gestational age (GA) and body weight gives a once-a-day amikacin dosage regimen involving an injection every 24 h. Validation was performed in 57 neonates less than 2 days old, divided into three GA groups and prospectively treated using the dosing chart. Target peak serum levels of amikacin were obtained in 62–80% of patients after the first dose and in 80–100% after the second dose, and trough concentrations were obtained in 100%. This study has confirmed the need for individualization of amikacin dosage regimens in neonates.

The population pharmacokinetics of amikacin, in neonates, was investigated using the nonlinear mixed effects model (NONMEM). One hundred and six steady-state amikacin serum levels were obtained from 53 black neonates with a mean gestational age of 35.1 weeks and mean age at the start of treatment of 3.1 days. A one-compartment model was used to fit the data. The final models for clearance (CL) and volume of distribution (V) were: CL(l.h(-1)) = 0.031WT(1.45) x P and V(l) = 0.316WT(1.44) where WT = birth weight (kg) and P = 1.28 for girls and 1.0 for boys. Inclusion of other fixed effect parameters in the model did not significantly improve the fit of the data. The inter-individual variability for CL and V were 18% and 13%. respectively. Intra-individual variability was 29%. Mean (95% CI) values of CL, V and half-life were 0.048 (0.045, 0.051) l.h(-1).kg(-1), 0.434 (0.414, 0.453) l.kg(-1) and 6.4 (6.2, 6.6) h respectively. Birth weight was an important determinant of both CL and V and, in this data set, gender was also found to influence CL. Mean population pharmacokinetic values were within the range of those previously derived for other neonatal populations using traditional methods.

The aim of the present study was to analyse the pharmacokinetic behaviour of amikacin in intensive care unit (ICU) patients using a mixed-effect model and sparse data collected during routine clinical care. The patient population comprised 158 medical ICU patients divided into two groups: one for computing the population model (n = 120) and the other for validation (n = 38). A 1-compartment model was used and the following covariates were tested for their influence on clearance (CL) and volume of distribution (Vd): age, gender, weight, parenteral nutrition, creatinine clearance, duration of therapy and clinical diagnosis. The nonlinear mixed-effect model (NONMEM) was used to assess the population pharmacokinetic model of amikacin in this patient population. In this study, the final population model accounting for amikacin pharmacokinetics in ICU patients was: CL = 0.93 CL(CR) (1 + 0.22 Trauma), Vd = 0.39 TBW (1 + 0.24 Sepsis), where CL(CR) and TBW corresponded to the patients' creatinine clearance and total bodyweight, respectively. The 'Trauma' and 'Sepsis' variables referred to the clinical diagnosis of the patients. This model was subsequently used to predict amikacin serum levels obtained in the validation population by a priori and Bayesian methods. The predictive performance was adequate for clinical purposes, pointing to the feasibility of our population model to provide reference values for a priori prediction as well as the Bayesian approach for individualisation of amikacin therapy in ICU patients.

Clinical, pharmacokinetic and therapeutic study of amikacin with single daily dose and in combination in neutropenic children with fever

Critically-ill patients receiving total parenteral nutrition show altered amikacin pharmacokinetics

The pharmacokinetic profile of amikacin was analysed by a two-compartment model in 100 critically-ill adult and paediatric patients with normal renal function. In addition the serum amikacin levels in 200 patients randomized to receive a once- or twice-daily dosing regimen are reported. The mean volume of distribution (Vdt) was 0.33 l/kg in the adult patients, 0.50 l/kg in patients 6 to 12 months of age and 0.58 l/kg in patients less than 6 months old. The elimination half-life was prolonged, being 3.45, 2.86 and 5.02 h for the respective age groups (normal 2 h). The clearances dose/AUC) were 0.051, 0.068 and 0.063 l/h/kg respectively. Within each group of patients there was a large variation in the pharmacokinetic parameters, with the Vdt varying by a factor of 6 and the elimination half-life by a factor of 10. All patients receiving a once-daily dose of amikacin had therapeutic peak concentrations. In comparison, therapeutic concentrations were achieved in only 48% of adult and 44% of the paediatric patients receiving the twice-daily dosing regimen. Furthermore the amikacin trough concentrations were significantly higher in the patients who received a divided daily dose. As a consequence of the pharmacokinetic profile of amikacin in critically ill patients a once-daily dosing regimen may be more effective and less toxic than the conventional twice-daily dosing regimen.

Variable serum amikacin levels have been reported in the same patient even after a steady state presumably has been reached. Therefore, the authors investigated the optimal schedule for monitoring serum levels of the drug in 50 neutropenic patients receiving continuous infusion amikacin therapy for infections. We found that levels obtained in the early morning hours were significantly higher than those obtained for the same patient in the evening. As these differences parallel those previously demonstrated for renal function, they may be explained by the pattern of drug clearance by the kidneys. We recommend that blood specimens for the detection of rising serum amikacin levels in a therapeutic setting be obtained in the early morning and at the same time each day so that meaningful comparisons of peak concentrations can be made. However, late evening samples should also be tested whenever dosage modifications are considered so that continuous therapeutic serum concentrations can be ensured.

Amikacin, ethambutol, and rifampin for treatment of disseminated Mycobacterium avium-intracellulare infections in patients with acquired immune deficiency syndrome.

In vitro evaluations of amikacin: an assessment of the currently used methods of disk diffusion and dilution susceptibility, antimicrobial synergy, and the measurement of amikacin concentrations

Antibiotics delivered by an implantable drug pump: A new application for treating osteomyelitis

The purpose of this study was to analyze the role of gestational and postnatal age and of clinical conditions [e.g., respiratory distress syndrome (RDS)] on serum concentrations of amikacin in neonates treated according to commonly recommended dose schedules. Thirty-nine neonates (28.5-42 weeks of gestational age) were treated with the aminoglycoside at a mean dose of 7.2 mg/kg every 12 h for an average period of 6.5 days, and serum levels were monitored throughout treatment. Both gestational and postnatal age influenced amikacin levels. During the first days of life the presence of RDS was found to be strongly associated with amikacin accumulation. Neonates with retarded intrauterine growth according to their gestational age tended to have lower amikacin trough levels in the first days of life. No correlation was found between amikacin serum levels and hematocrit. Peak concentrations of the drug did not correlate with vital or clinical data, probably because of the variability in drug absorption from the intramuscular injection site. These data are discussed in light of the development of renal function and changes in body fluid compartments occurring in the preterm and term neonates during the first weeks of life.

A multicentre prospective randomized study of amikacin and gentamicin in 135 patients with serious infections is presented. Most patients were additionally given a penicillin derivative according to Swedish therapeutic traditions. Synergism was noted in the majority of the tested strains. Clinical cure was recorded in 80% and 76% respectively of the amikacin and gentamicin patient groups. Nephrotoxic reactions were statistically (P less than 0.05) more common in gentamicin-treated patients (20%) than in the amikacin-treated ones (6%) while the corresponding figures for ototoxicity were 16% and 8% respectively (not statistically significant). Pharmacokinetic studies of the drugs showed that with the dose regimens used serum levels of amikacin above 10 times the MIC for the isolated micro-organism were registered during 75% of the 12-hour therapy interval and during 40% of the 8-hour therapy interval for gentamicin. This difference is statistically significant (P less than 0.01). We suggest that the pharmacokinetic advantages of amikacin in comparison to gentamicin might be of practical importance in the prediction of serum levels thereby lowering the risk of toxic reactions.

Aminoglycosides are inactivated by carbenicillin in vitro and in patients with end-stage renal failure. In vitro, amikacin is inactivated to a lesser extent than is gentamicin. In five patients on chronic hemodialysis, serum levels of amikacin alone and after repeated intravenous carbenicillin infusions were determined. Analogous gentamicin studies were conducted with five different patients. Neither amikacin serum levels nor serum clearances were affected by carbenicillin. The mean gentamicin serum half-life was significantly lower in the presence of carbenicillin: 18.4 +/- 8.2 compared with 61.6 +/- 30.7 h. Serum clearance increased significantly. The inactivation of gentamicin by carbenicillin was both time related (greater than 12 h of exposure) and concentration dependent (molar carbenicillin/gentamicin ratios greater than or equal to 39:1). Amikacin would be preferable to gentamicin in patients with end-stage renal failure.

Amikacin sulfate was given to 21 febrile children with neutropenia and cancer for 9 +/- 3 days. Peak serum amikacin levels ranged between 13 and 32 microgram/mL, and trough levels were consistently less than 2 microgram/mL. Renal toxic effects were detected in two children (9.5%) and were extremely mild. Two additional children (16.5%) experienced mild, transient, unilateral, high-frequency hearing losses. The lack of serious renal and auditory impairment suggests that children are at less risk than adults from aminoglycoside therapy.