High-dose amikacin for achieving serum target levels in critically ill elderly patients

Abstract

IntroductionTo achieve target concentrations, the application of higher-than-standard doses of amikacin is proposed for the treatment of sepsis due to an increase in volume of distribution and clearance, but little data are available on aminoglycoside administration in critically ill elderly patients.Patients and methodsForty critically ill elderly patients (aged over 65 years) who required amikacin therapy due to severe documented, or suspected gram-negative infections, were randomly assigned to two treatment groups. Group A (20 patients) received 15 mg/kg amikacin and Group B (20 patients) received 25 mg/kg amikacin per day as a single daily dose. All the patients were monitored for renal damage by the daily monitoring of serum creatinine. The amikacin peak (Cmax) and trough (Cmin) serum concentrations were measured on Days 3 and 7 postadministration.ResultsData from 18 patients in Group A and 15 patients in Group B were finally analyzed. On Day 3, the amikacin mean Cmax levels in the standard and high-dose treatment groups were 30.4±11 and 52.3±16.1 µg/mL (P<0.001), and the Cmin levels were 3.2±2.1 and 5.2±2.8 µg/mL, respectively (P=0.035). On Day 7, the Cmax levels in the standard and high-dose groups were 33±7.3 and 60.0±17.6 µg/mL (P=0.001), and the Cmin levels were 3.2±2.9 and 9.3±5.6 µg/mL, respectively (P=0.002). In only six (40%) of the patients in the high-dose groups and none of the patients in the standard-dose group, amikacin Cmax reached the target levels (>64 µg/mL), whereas the amikacin mean Cmin levels in the high-dose group were above the threshold of toxicity (5 µg/mL).ConclusionOur results suggest that the optimum dose of amikacin should be determined for elderly critically ill patients. It seems that higher-than-standard doses of amikacin with more extended intervals might be more appropriate than standard once-daily dosing in the elderly critically ill patients.

Optimized Extraction of Amikacin from Murine Whole Blood

“…Several extraction procedures were performed to maximize Amk recovery from WB. The extraction variables were selected based on previous works performed on plasma samples by other authors [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ], and were iteratively screened according to the heuristic ‘trial and error’ approach. A 5.0 mM aqueous AmkDS solution was always added to a mixture made up of ACN and WB.…”

“…Drug partitioning is often related to sequestration phenomena in tissue and blood cells that can give rise to toxicity concerns due to drug accumulation and secondary interactions [ 7 , 8 ]. Surprisingly, to the best of our knowledge, quantitative analysis of Amk in blood is routinely performed only after extraction from plasma [ 6 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] and no report exists so far on drug extraction from whole blood (WB). This represents an issue as quantification of the drug in plasma does not account for drug partitioning to the blood cell compartment [ 7 ], significantly underrating the drug fraction reaching blood circulation.…”

<p>Antimicrobial activities of ceftazidime&ndash;avibactam, ceftolozane&ndash;tazobactam, and other agents against <em>Escherichia coli</em>, <em>Klebsiella pneumoniae</em>, and <em>Pseudomonas aeruginosa</em> isolated from intensive care units in Taiwan: results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan in 2016</p>

“…In a previous 9-year study between 2003 and 2011, the mean consumption of amikacin (defined daily dose per 1,000 patient-days) was 8, compared to 56 for extended-spectrum cephalosporins, 17 for piperacillin–tazobactam, 22.4 for carbapenems (with an increase each year), and 52 for quinolone 28. However, the emergence of resistant microorganisms warrants further clinical study on the role of aminoglycosides, which have been proposed to be useful as part of combination therapies16,18 or high-dose monotherapy 29,30. Meanwhile, although tigecycline has maintained a high susceptibility rate against Enterobacteriaceae for >10 years since its first use,31 it should be applied cautiously and be limited to the treatment of intra-abdominal and soft tissue infections according to the British guidelines 5…”

Is Holmium Laser Enucleation of the Prostate a Good Surgical Alternative in Benign Prostatic Hyperplasia Management? A Review Article

“…4 Despite the overall promising long-term results and low re-operation rates, these procedures have some minor and major adverse effects such as dysuria, urinary frequency, sexual dysfunction, TUR syndrome, and sepsis associated with peri-operative morbidity; therefore, other therapeutic approaches have been developed to reduce these side effects with the same functional results, including the plasmakinetic resection or enucleation of the prostate, the Holmium laser enucleation or resection of the prostate, and the photoselective vaporization of the prostate (PVP). [4][5][6][7][8] The endoscopic management of BPH that causes bladder outlet obstruction (BOO) is divided into three major categories: vaporization, the resection of tissue, and enucleation. 9 The Holmium laser has a good penetration depth, which helps in staunching blood; it is also used for other urologic surgeries, including urolithiasis, 10,11 bladder tumor, 6 genital skin lesion, 12 and urethrotomy.…”