Amikacin Concentrations Research Articles

Serum amikacin concentrations in dogs with naturally occurring open wounds treated with topical amikacin in carboxymethylcellulose hydrogel.

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.

Antibacterial double-layer calcium phosphate/chitosan composite coating on metal implants for tissue engineering

In this study, four different promising two-layer composite coatings on titanium substrates with antibacterial properties were investigated. Two different types of antibacterial agents were used to impart antibacterial properties to the coatings: antibiotic amikacin (in three different concentrations) and zinc. Chitosan, which also has antibacterial properties, was used as a carrier layer for amikacin on a calcium phosphate coating incorporating zinc. This combination should enable long-term antibacterial properties of a bone implant and thus prevent potential complications during wound healing due to bacterial contamination. To examine the physico-chemical properties of the samples, the elemental, chemical and phase compositions, the thickness and the wettability of the coatings were investigated. The release of amikacin from the chitosan coatings was investigated using high-performance liquid chromatography. Antibacterial activity of the prepared coatings was evaluated against five hospital bacteria strains (Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterococcus faecalis, Klebsiella pneumoniae) and one strain from the microbial strain collection (methicillin-resistant Staphylococcus aureus, ATCC 43300). To investigate the cell toxicity of the composite coating, cell adhesion, proliferation and osteogenic differentiation were tested with mesenchymal stem cells. According to the results, the composite coatings with an amikacin concentration of 5.0 and 7.5 percent by weight have the best biological and antibacterial properties.

Exploring the Potential of Turmeric as a Natural Antibacterial Agent: In Vitro Evaluation of Crude Paste and Aqueous Extract

Background: There is growing concern in the use of natural antimicrobial compounds due to the emergence of antibiotic resistance. One such contender is turmeric (Curcuma longa), an herb known for its usage in medicine for centuries; nowadays, however, its prospects in pharmacology are being actively discussed. Since access and utilization of modern health care is scarce in Bangladesh, such natural cures are worth researching. Objective: To assess the in vitro antibacterial activity of turmeric’s crude paste and aqueous extract against Staphylococcus aureus and Escherichia coli. Methods: The study was carried out in the Department of Pharmacology with the collaboration of Department of Microbiology, Mymensingh Medical College, Bangladesh, over a period of one year from July 2010 to June 2011, and it consisted of three experiments: Effects of crude turmeric paste incorporated in nutrient agar media, Minimum Inhibitory Concentration of Aqueous Turmeric Extract and Amikacin by broth dilution method, and Subculture method to confirm bactericidal effect. Results: CTP demonstrated effective growth of S. aureus at 10% concentration and E. coli at 30% concentration. The MIC of ATE was found to be 800 μg/ml for S. aureus and 2000 μg/ml for E. coli. The MIC for amikacin was 10 μg/ml for both organisms. These effects have been further substantiated in subculture studies regarding their bactericidal properties. Conclusion: From the findings of the current study, it is evident that both turmeric and its crude paste had profound antibacterial effects against S. aureus and E. coli, though the effect of crude paste was observed to be stronger than that of the aqueous extract. Although not as strong as Amikacin, its organic nature and possibility of side effects make it worth pursuing. Hence, this work adds to the literature on the fact that turmeric has health benefits as highlighted by traditional medical practice and points to the need to find new natural sources of .............

Subcutaneous amikacin administration in red-eared sliders (Trachemys scripta elegans) produces prolonged detectable plasma concentrations without biochemistry evidence of impaired renal function.

To establish pilot data on the plasma concentrations of SC amikacin at 2 doses in red-eared sliders and evaluate concurrent plasma biochemistry parameters. 8 adult red-eared sliders (Trachemys scripta elegans). Amikacin was administered SC at target doses of 5 and 10 mg/kg with a 3-week washout period. Blood samples were collected at 0, 24, 48, 72, and 96 hours postadministration. Plasma amikacin concentrations were quantified using liquid chromatography tandem mass spectrometry. Plasma biochemistry analyses were performed before amikacin administration, 1 week post 5-mg/kg administration, and 1 week post 10-mg/kg administration. Mean maximum amikacin plasma concentrations were recorded 24 hours after 5-mg/kg and 10-mg/kg dosing and were 17.5 ± 2.32 µg/mL and 23.6 ± 2.92 µg/mL, respectively. Mean plasma concentrations after 5-mg/kg dosing steadily decreased to 9.1 ± 0.92 µg/mL by 96 hours postadministration. Amikacin remained detectable in all plasma samples 3 weeks post 5-mg/kg dosing with a mean plasma concentration of 1.04 ± 0.22 µg/mL. Mean plasma concentrations after 10-mg/kg dosing did not decrease over the 96-hour study period. There were no clinically relevant changes in biochemistry parameters. Amikacin persists at detectable plasma levels for at least 3 weeks after SC administration of a 5-mg/kg dose in red-eared sliders, which has not previously been reported in any species. No biochemistry changes consistent with renal toxicity occurred after either dose. Use caution with repeated amikacin dosing in this species until further studies can better characterize cumulative amikacin pharmacokinetics and toxic threshold.

Plasma and Tissue Amikacin Concentrations Following Regional Limb Perfusion of Chickens (Gallus gallus domesticus).

Intravenous regional limb perfusion (IVRLP) has been used in the treatment of pododermatitis and distal limb infections, which are significant causes of morbidity in avian species. This intravenous drug administration technique is designed to achieve high drug tissue concentrations while minimizing systemic toxic effects. Amikacin is commonly used for IVRLP in veterinary medicine, but dosing guidelines have not been established for its use in birds. The current study aimed to determine the tissue concentration of amikacin after a single IVRLP administration in healthy, euhydrated leghorn hen chickens (Gallus gallus domesticus). Chickens received a single IVRLP dose of 10 mg/kg amikacin and were euthanatized posttreatment at 1 hour (n = 6), 12 hours (n = 6), and 24 hours (n = 6) to assess tissue and synovial fluid concentrations of amikacin in the injected leg. Mean tissue concentrations were highest 1 hour post-IVRLP (synovial fluid = 153.0 µg/mL, metatarsal pad tissue = 26.05 µg/mL) before declining at the 12- and 24-hour time points. This indicates that administration of amikacin via IVRLP can reach minimum inhibitory concentrations of common bacterial isolates in tissues after a single treatment with 10 mg/kg amikacin. Regional limb perfusion every 24 hours is recommended, although the minimum days of treatment may be case dependent and vary based on response to therapy.

Morphine synovial fluid concentrations after intravenous regional limb perfusion in horses during standing sedation.

Addition of morphine to the perfusate while performing intravenous regional limb perfusion (IVRLP) may be helpful in treating painful infectious orthopaedic conditions of the distal limb. The main objective of this study was to determine synovial morphine concentrations following IVRLP with morphine alone or in combination with amikacin. Randomised cross-over in vivo experiment. Six horses underwent IVRLP with 0.1 mg/kg morphine sulphate diluted to 60 mL using 0.9% NaCl (M group) or combined with 2 g amikacin and 0.9% NaCl (MA group) with a 2-week washout period between treatments. Synovial fluid was collected from the radiocarpal joint (RCJ) at 10, 20, 30, 120, 240, 480, 720 and 1440 min after IVRLP. The tourniquet was removed after the 30-min sample was collected. Synovial concentrations of morphine and major metabolites were measured using liquid chromatography-tandem mass spectrometry. Amikacin concentrations were quantified by a fluorescence polarisation immunoassay. Measurable concentrations of morphine were apparent in the RCJ of all horses. Median CMAX of morphine in the M group was 4753.1 (2115.7-14 934.5) ng/mL and 4477 (3434.3-7363) ng/mL in the MA group (p = 0.5). Median CMAX of synovial amikacin was 322.6 (157.5-1371.6 μg/mL). Limitations include small sample size. Investigators were not blinded to the treatments and a third treatment group where amikacin alone was administered via IVRLP to the study population was not included. IVRLP using morphine is a feasible technique and synovial morphine concentrations were measurable following IVRLP and were not affected when used concurrently with amikacin. Administration of morphine via IVRLP may be beneficial as an analgesic technique for orthopaedic conditions of the distal limb while limiting potential serious systemic side-effects.

Investigation of the Rapid Emergence of Colistin Resistance in a Newborn Infected with KPC-2–Producing Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae

ObjectivesHypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKp) poses a significant threat to public health. This study reports an infection related to hv-CRKp in a premature infant and reveals its colistin resistance and evolutionary mechanisms within the host. MethodsThree KPC-producing CRKp strains were isolated from a patient with sepsis and CRKp osteoarthritis who had been receiving colistin antimicrobial therapy. The minimum inhibitory concentrations (MICs) of ceftazidime, ceftazidime-avibactam (CAZ-AVI), meropenem, imipenem, tigecycline, amikacin, minocycline, sulfamethoxazole/trimethoprim, ciprofloxacin, levofloxacin, aztreonam, cefepime, cefoperazone/sulbactam, piperacillin/tazobactam, and colistin were determined using the microbroth dilution method. The whole-genome sequencing analysis was conducted to determine the sequence types (STs), virulence genes, and antibiotic resistance genes of the three CRKp strains. ResultsWhole-genome sequencing revealed that all three CRKp strains belonged to the ST11 clone and carried a plasmid encoding blaKPC-2. The three strains all possessed the iucABCDiutA virulence cluster, peg-344 gene, and rmpA/rmpA2 genes, defining them as hv-CRKp. Further experiments and whole-genome analysis revealed that a strain of K. pneuomniae had developed resistance to colistin. The mechanism found to be responsible for colistin resistance was a deletion mutation of approximately 9000 bp including the mgrB gene. ConclusionThis study characterizes colistin resistance of the ST11 clone hv-CRKp during colistin treatment and its rapid evolution within the host.

Faster perfusate instillation time results in more systemic leakage of amikacin sulfate when performing intravenous regional limb perfusion in horses.

To evaluate if a difference in synovial amikacin concentrations exists in the radiocarpal joint (RCJ) following different durations of instillation of an IV regional limb perfusion (IVRLP) perfusate. 7 healthy horses. Horses received 2 IVRLPs with 2 g amikacin diluted to 60 mL with 0.9% NaCl via the cephalic vein in a crossover study design with a wash-out period between procedures. Instillation of the perfusate was administered over a 1-minute (technique 1) and 5-minute (technique 5) period. Concentrations of amikacin within the RCJ were measured at time (T) 5, 10, 15, 20, 25, and 30 minutes after instillation of the perfusate. Systemic concentrations of amikacin were measured at T0, 5, 10, 15, 20, 25, 29 minutes, and 1 minute after tourniquet removal (T31). Amikacin concentrations were determined by fluorescence polarization immunoassay. The median maximum concentration (CMAX) of amikacin within the RCJ for technique 1 was 338.4 µg/mL (range, 60 to 4,925 µg/mL), while the median CMAX for technique 5 was higher at 694.8 µg/mL (range, 169.2 to 3,410 µg/mL; P = .398). There was a higher amikacin blood concentration over time for technique 1 compared to technique 5 (P = .004). Administration of perfusate at different rates did not significantly affect synovial concentration of amikacin within the RCJ when performing IVRLP. However, increased systemic leakage was noted when the perfusate was administered over 1 minute, which might affect synovial concentrations in a larger group of horses.

Antibiotic Resistance, Biofilm Formation, and Persistent Phenotype of Klebsiella pneumoniae in a Vietnamese Tertiary Hospital: A Focus on Amikacin.

Klebsiella pneumoniae stands out as a major opportunistic pathogen responsible for both hospital- and community-acquired bacterial infections. This study comprehensively assesses the antibiotic resistance, amikacin persistent patterns, and biofilm-forming ability of 247 isolates of K. pneumoniae obtained from an intensive care unit of a tertiary hospital in Vietnam. Microdilution assays, conducted on a 96-well plate, determined the minimum inhibitory concentrations (MICs) of amikacin. Susceptibility data for other antibiotics were gathered from the antibiogram profile. Stationary-phase bacteria were exposed to 50 × MIC, and viable bacteria counts were measured to determine amikacin persistence. Biofilm forming capacity on 96-well polystyrene surfaces was assessed by biomass and viable bacteria. The prevalence of resistance was notably high across most antibiotics, with 64.8% classified as carbapenem-resistant K. pneumoniae and 81.4% as multidrug resistant. Amikacin, however, exhibited a relatively low rate of resistance. Of the isolates, 58.2% demonstrated a moderate to strong biofilm formation capacity, and these were found to be poorly responsive to amikacin. K. pneumoniae reveals a significant inclination for amikacin persistence, with ∼45% of isolates displaying an antibiotic antibiotic-survival ratio exceeding 10%. The study sheds light on challenges in treating of K. pneumoniae infection in Vietnam, encompassing a high prevalence of antibiotic resistance, a substantial ability to form biofilm, and a notable rate of antibiotic persistence.

Time-dependent pharmacodynamics of amikacin on Mycobacterium abscessus growth and resistance emergence.

Mycobacterium abscessus pulmonary disease is increasing in prevalence globally, particularly for individuals with cystic fibrosis. These infections are challenging to treat due to a high rate of resistance. Amikacin is critical to treatment, but the development of toxicity, amikacin resistance, and treatment failure are significant challenges. Amikacin has been characterized previously as peak-dependent and extended-interval dosing is commonly used. In our hollow fiber infection model of M. abscessus, amikacin exhibited time-dependent rather than the expected peak-dependent pharmacodynamics. Humanized amikacin exposures with more frequent, short-interval dosing (continuous infusion or every 12 hours) yielded improved microbiological response compared to extended-interval dosing (every 24 hours or 1-3 times per week). Short-interval dosing inhibited growth with a mean (SD) maximum Δlog10 colony forming units of -4.06 (0.52), significantly more than extended-interval dosing (P = 0.0013) every 24 hours, -2.40 (0.58), or 1-3 times per week, -2.39 (0.38). Growth recovery, an indicator of resistance emergence, occurred at 6.56 (0.70) days with short-interval dosing but was significantly earlier with extended-interval dosing (P = 0.0032) every 24 hours, 3.88 (0.85) days, and 1-3 times per week, 3.27 (1.72) days. Microbiological response correlated best with the pharmacodynamic index of %T > minimum inhibitory concentration (MIC), with an EC80 for growth inhibition of ~40%T > MIC. We used a previously published population model of amikacin to determine the probability of achieving 40%T > MIC and show that current dosing strategies are far below this target, which may partially explain why treatment failure remains so high for these infections. These data support a cautious approach to infrequent amikacin dosing for the treatment of M. abscessus.IMPORTANCEPulmonary disease caused by Mycobacterium abscessus complex (MABSC) is increasing worldwide, particularly in patients with cystic fibrosis. MABSC is challenging to treat due to high levels of antibiotic resistance. Treatment requires 2-4 antibiotics over more than 12 months and has a significant risk of toxicity but still fails to eradicate infection in over 50% of patients with cystic fibrosis. Antibiotic dosing strategies have been largely informed by common bacteria such as Pseudomonas aeruginosa. The "pharmacodynamic" effects of amikacin, a backbone of MABSC treatment, were thought to be related to maximum "peak" drug concentration, leading to daily or three times weekly dosing. However, we found that amikacin MABSC kill and growth recovery, an indicator of antibiotic resistance, are dependent on how long amikacin concentrations are above the minimum inhibitory concentration, not how high the peak concentration is. Therefore, we recommend a re-evaluation of amikacin dosing to determine if increased frequency can improve efficacy.

Elimination and penetration of amikacin into urine in patients with decreased glomerular filtration rate.

Amikacin monotherapy is recommended for urinary tract infection (UTI) treatment with multi-resistant pathogens. Even though amikacin efficacy in the treatment of UTIs is dependent on its urinary concentration, there are no robust data proving that sufficiently high urinary concentration is reached in patients with reduced glomerular filtration rate (GFR). A prospective study to monitor amikacin penetration into urine of 70 patients [40 males, median (interquartile range) age 70 (65-79) years] with different levels of glomerular filtration decline, including patients treated by dialysis, was conducted. The bactericidal efficacy of amikacin in urine samples has been evaluated. Patients with estimated GFR (eGFR) <30mL/min had significantly lower median amikacin urinary concentration than patients with eGFR >30mL/min (89.75 vs 186.0mg/L, P<.0001; 200.5 vs 830.0mg/L, P<.0001; and 126.0 vs 408.0mg/L, P<.0001 for minimal, maximal and minimal together with maximal concentrations, respectively). The amount of amikacin eliminated in the first 10-13h after dose administration was dependent on eGFR (r2=0.6144, P<.0001). The urinary concentration of amikacin in patients treated by dialysis was indirectly proportional to pH of urine. The plasma concentrations of amikacin did not correlate with urinary levels in patients in either of the GFR categories. Microbiological evaluation showed that the critical urinary concentration for efficacy of amikacin during UTI monotherapy in patients treated by dialysis is 100mg/L. We found that 4 out of 11 patients treated by dialysis did not reach this level during the treatment. Systemic administration of amikacin monotherapy in patients treated by dialysis is questionable as the concentrations of amikacin in their urine are often below the threshold of effectivity. Amikacin plasma concentrations are not a major determinant of amikacin concentration in urine, therefore pulse dosing is neither necessary nor safe in patients treated by dialysis, and may cause undesirable toxicity.

Low-cost and highly sensitive colorimetric and visual detection of amikacin in milk using melamine functionalized gold nanoparticles.

This study developed a rapid, low-cost and highly sensitive analytical method using melamine functionalized gold nanoparticles (MA-Au NPs) as a colorimetric sensor to detect amikacin in milk. The MA-Au NPs were synthesized using a self-assembly process and analyzed using absorption spectroscopy, transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy. The MA-Au NPs exhibited a distinct surface plasmon resonance (SPR) absorption peak at 520 nm and demonstrated excellent spherical dispersion. The reaction parameters were optimized, with a Au NP concentration of 2.0 × 10-7 mol L-1, MA concentration of 1.0 × 10-6 mol L-1, pH of 4.0, and reaction time of 15 minutes. In the optimization experiment, the effects of unmodified Au NPs and MA-Au NPs as colorimetric sensors for amikacin determination were compared. As a specific amount of amikacin was added to the Au NP solution, the reaction solution showed a visible change from wine red to purple and then to blue gray; a red-shift in the absorption spectrum of the solutions was observed, which could also be analyzed using the A640/A520 value, and the color changes were recorded using smartphones for visual detection through RGB (red-green-blue) data image analysis, which made the detection easy and fast. As a result, two approaches were devised using visible absorption spectra and smartphones. A linear correlation was established between the A640/A520 value and the concentration of amikacin in the range of 4.0 to 16.0 × 10-8 mol L-1. The minimal limit of detection (LOD) for absorption spectrum analysis was 3.75 × 10-9 mol L-1, whereas for smartphone analysis, it was 6.0 × 10-8 mol L-1. The recoveries ranged from 103.09% to 104.51%, while the relative standard deviations (RSDs) ranged from 3.76% to 4.25%. The proposed method was used to detect actual milk samples. The results showed that the method is simple, selective, and practical.

Residual concentration of Amikacin in expired drugs

Residual concentration of Amikacin in expired drugs

Can isepamicin be a potential option for extended spectrum beta-lactamases and carbapenemases expressing Escherichiacoli?

BackgroundBeta-lactamase expressing Enterobacterales are challenging to treat. The potency of aminoglycosides as a bactericidal agent has increased interest in using them in combination regimens. In the present study, we evaluated the in-vitro activity of isepamicin and its comparator against phenotypically confirmed ESBL and carbapenemase expressing E. coli isolates. MethodsESBL-E. coli (n = 103) and carbapenemase expressing E. coli (n = 105) collected from various clinical samples were included in this study. The minimum inhibitory concentrations (MICs) of ceftazidime, meropenem, gentamicin, amikacin, and isepamicin were determined using the broth microdilution method according to CLSI guidelines. ResultsIsepamicin potently inhibited 98% of ESBL expressing E. coli isolates and the MIC90 for isepamicin was two-fold lower than that of amikacin. Isepamicin retained its inhibitory activity against 95% of amikacin resistant and 97% of gentamicin resistant ESBL expressing E. coli isolates. There were 31% of amikacin-resistant and 22% of gentamicin-resistant, carbapenemase-expressing E. coli isolates were susceptible to isepamicin. ConclusionThe findings suggest that isepamicin may be useful for treating community acquired urinary tract infection as monotherapy and systemic ESBL-E. coli infection as combination therapy, due to its minimal nephrotoxicity and ototoxicity, compared to other aminoglycosides.

A highly sensitive fluorescence nanosensor for determination of amikacin antibiotics using composites of carbon quantum dots and gold nanoparticles

Amikacin is an aminoglycoside antibiotic widely used to treat various bacterial infections in humans. However, elevated concentrations of amikacin can damage the cochlear nerve. Thus, accurate and rapid amikacin detection is crucial. In this study, we developed an “on-off” fluorescence nanosensor for highly sensitive amikacin determination based on a composite of carbon quantum dots (CQDs) and gold nanoparticles (AuNPs). The method quenches CQD fluorescence (turn-off) when they bind to AuNPs but restores it (turn-on) when amikacin binds and releases the CQDs. Adding Cu2+ enhances sensitivity by cross-linking amikacin-coated AuNPs. Under optimal conditions (pH 4, 1 mM Na2SO4, 1 mM CuSO4), the method achieved a low detection limit of 3.5 × 10-11 M (0.02 ppb), a wide linear range (10-10 to 10-8 M), high precision (RSD < 5 %), and a rapid 2-minute response time. Exceptional selectivity was observed over other antibiotics. The CQDs/AuNPs-based sensor successfully detected amikacin in pharmaceutical and surface water samples. This approach offers a fast on-site analytical method for amikacin detection, with potential applications in clinical and environmental settings.

Comparing minimum inhibitory concentrations of amikacin for pulmonary Mycobacterium avium complex disease: An analysis of culture media differences

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.

Comparison of amikacin lung delivery between AKITA® and eFlow rapid® nebulizers in healthy controls and patients with CF: A randomized cross-over trial

IntroductionNebulization plays a key role in the treatment of cystic fibrosis. The Favorite function couple to jet nebulizers (AKITA®) emerged recently. The aim of this study was to assess the efficiency of the lung delivery by the AKITA® by comparing the urinary concentration of amikacin after nebulization with the AKITA® and the eFlow rapid®, in healthy subjects and patients with CF (PwCF). MethodThe two samples (healthy subjects and PwCF) were randomized (cross-over 1:1) for two nebulizations (500 mg of amikacin diluted in 4 mL of normal saline solution), with the AKITA® and with the eFlow rapid®. The primary endpoint was the amount of urinary excretion of amikacin over 24 h. The constant of elimination (Ke) was calculated based on the maximal cumulative urinary amikacin excretion plotted over time. ResultsThe total amount of urinary amikacin excretion was greater when AKITA® was used in PwCF (11.7 mg (8.2–14.1) vs 6.1 mg (3.7–13.3); p = 0.02) but not different in healthy subjects (14.5 mg (11.7–18.5) vs 12.4 mg (8.0–17.1); p = 0.12). The duration of the nebulization was always shorter with eFlow rapid® than with AKITA® (PwCF: 6.5 ± 0.6 min vs 9.2 ± 1.8 min; p = 0.001 – Healthy: 4.7 ± 1.3 min vs 9.7 ± 1.6 min; p = 0.03). The constant of elimination was similar between the two modalities in CF subjects (0.153 (0.071–0.205) vs 0.149 (0.041–0.182); p = 0.26) and in healthy subjects (0.166 (0.130–0.218) vs 0.167 (0.119–0.210), p = 0.25). Conclusionthe Favorite inhalation is better to deliver a specific amount of drug than a mesh nebulizer (eFlow rapid®) in PwCF but not in healthy subjects.

Effects of a 10% dimethyl sulfoxide solution on radiocarpal joint amikacin pharmacokinetics during intravenous regional limb perfusion in standing sedated horses.

To determine the effect of a 10% dimethyl sulfoxide (DMSO) solution on the peak concentration (CMAX ) of amikacin in the radiocarpal joint (RCJ) during intravenous regional limb perfusion (IVRLP) compared with 0.9% NaCl. Randomized crossover study. Seven healthy adult horses. The horses underwent IVRLP with 2 g of amikacin sulfate diluted to 60 mL using a 10% DMSO or 0.9% NaCl solution. Synovial fluid was collected from the RCJ at 5, 10, 15, 20, 25, and 30 minutes after IVRLP. The wide rubber tourniquet placed on the antebrachium was removed after the 30 min sample. Amikacin concentrations were quantified by a fluorescence polarization immunoassay. The mean CMAX and time to peak concentration (TMAX ) of amikacin within the RCJ were determined. A one-sided paired t-test was used to determine the differences between treatments. The significance level was p < .05. The mean ± SD CMAX in the DMSO group was 1361.8 ± 593 μg/mL and in the 0.9% NaCl group it was 860 ± 481.6 μg/mL (p = .058). Mean TMAX using the 10% DMSO solution was 23 and 18 min using the 0.9% NaCl perfusate (p = .161). No adverse effects were associated with use of the 10% DMSO solution. Although there were higher mean peak synovial concentrations using the 10% DMSO solution no difference in synovial amikacin CMAX between perfusate type was detected (p = .058). Use of a 10% DMSO solution in conjunction with amikacin during IVRLP is a feasible technique and does not negatively affect the synovial amikacin levels achieved. Further research is warranted to determine other effects of using DMSO during IVRLP.

Population pharmacokinetic/pharmacodynamic evaluations of amikacin dosing in critically ill patients undergoing continuous venovenous hemodiafiltration.

The pharmacokinetics/pharmacodynamics (PK/PD) of amikacin in critically ill patients undergoing continuous venovenous hemodiafiltration (CVVHDF) are poorly described, and appropriate dosing is unclear in this patient population. This study aimed to develop a population PK model of amikacin and to provide systemic PK/PD evaluations for different dosing regimens in CVVHDF patients. One hundred and sixty-one amikacin concentration observations from thirty-three CVVHDF patients were pooled to develop the population PK model. Monte Carlo simulations were performed to assess the PK/PD index-based efficacy (Cmax/minimal inhibitory concentration (MIC) > 8 and AUC/MIC > 58.3), nonrisk of drug resistance (T>MIC > 60%) and risk of toxicity (trough concentration > 5 mg/l) for different dosing regimens. A two-compartment model adequately described the concentration data of amikacin. A loading dose of at least 25 mg/kg amikacin is needed to reach the efficacy targets in CVVHDF patients for an MIC of 4 mg/l, and the studied doses could not provide adequate drug exposure and T>MIC > 60% for an MIC ≥ 8 mg/l. The risk of toxicity for amikacin was unacceptably high for the patient population with low clearance. Our study demonstrated that a loading dose of 25-30 mg/kg amikacin is needed to provide adequate PK/PD target attainment in CVVHDF patients for an MIC ≤ 4 mg/l.

Luminescent Sensor with High Sensitivity and Selectivity for Amikacin Detection in a Serum using a Unique Gallium-Organic Framework.

Amikacin is a widely used antibiotic in the treatment of Gram-negative bacteria, but high concentrations of amikacin can cause cochlear nerve damage. Therefore, accurate and quick detection of the concentration of amikacin is desired and important. In this work, we have synthesized a new gallium-organic framework {[(CH3)2(NH2)Ga(PPTA)]·0.5DMF}n (1) (H4PPTA = 4,4',4″,4″'-(1-4-phenlene-bis(pyridine-4,2,6-triyl)) with good solvent and pH stabilities. A structure analysis reveals that 1 is a twofold interpenetrated framework exhibiting a large 1D square aperture with a size of 10.8 Å × 14 Å. The experimental results show that 1 can be used as a stable, fast, and recyclable luminescent probe for the detection of amikacin in aqueous solution and serum. The limit of detection is 2.9 × 10-7 mol/L, which is lower than the harmful concentration of amikacin in human serum. This is the first example of a metal-organic framework used for luminescence sensing of amikacin.