Extended dosage intervals for aminoglycosides

Rodman, Daniel P.; Maxwell, Alan J.; McKnight, Jerry T.

doi:10.1093/ajhp/51.16.2016

Cited by 10 publications

(15 citation statements)

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“…The results of most pertinent studies suggest equal efficacy with once-daily and multipledaily dosing regimens 3,15,16,[19][20][21][22] ; some researchers have reported superior clinical efficacy with once-daily aminoglycoside administration. 23,24 Much of the literature emphasizes the importance of high peak serum drug concentrations, with the most important aspect of clinical success being related to the peak:MIC ratio.…”

Section: Clinical Efficacy Of Once-daily Dosingmentioning

confidence: 99%

Once-daily aminoglycoside dosing: An update on current literature

Stankowicz

Ibrahim

Brown

2015

American Journal of Health-System Pharmacy

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Section: Clinical Efficacy Of Once-daily Dosingmentioning

confidence: 99%

Once-daily aminoglycoside dosing: An update on current literature

Stankowicz

Ibrahim

Brown

2015

American Journal of Health-System Pharmacy

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“…DiPiro et al [10,11] found a strong correlation between serum concentration and time and a weak correlation between free cefazolin serum concentration and muscle concentration. Cephalosporins have no postantibiotic effect like aminoglycosides [22]. In contrast to aminoglycosides, the antibiotic of cephalosporins is not dependent to the peak level, but it is dependent to a constant plateau concentration, which should be the 10-fold of the MIC 90 [24].…”

Section: Discussionmentioning

confidence: 99%

“…Bleeding and the increase of vascular permeability caused in a decrease of the serum concentrations of proteins like albumin and might support a decrease of the serum concentrations of cefazolin. These lower effective concentrations also result in lower tissue and bone concentrations [9,11,13,22,27]. Therefore bone and tissue concentrations were found to be 10 to 30% of the measured serum concentrations [9][10][11].…”

Section: Discussionmentioning

confidence: 99%

Effect of High-Volume Therapy on Cefazolin Serum Concentrations in Multiple-Trauma Patients

Aufmkolk¹,

Voggenreiter²,

Majetschak³

et al. 2000

Eur J Trauma

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The aim of the study was to determine the effect of volume resuscitation on serum concentrations of cefazolin after severe multiple trauma: prospective and follow-up in a 6-bed trauma intensive care unit, university hospital (10 multiple trauma patients, injury severity score [ISS] > 17 patients).Measurements of serum concentrations were done before, 0.5 and 4 hours after intravenous administration of 2 g cefazolin. The standard regimen of cefazolin administration was 2 g every eighth hour for 48 hours. The data are presented as median, minimum, maximum. Ten patients with an ISS of 29 (18 to 41) points and an age of 32 (22 to 77) years were included. The patients received a total of 9,700 (3,500 to 24,500) ml kristalloid solutions and median 3,800 (500 to 10,400) ml of blood and fresh frozen plasma on the day of the measurements. Before implementation of the measurements, all patients received a total dose of cefazolin between 4 and 10 g. Serum concentrations were 7 (6 to 27) mg/l immediately before start of the infusion (8 hours after the last administration), 186 (36 to 641) mg/l after 0.5 hours and 19 (11 to 60) mg/l at 4 hours after cessation of infusion. The serum concentrations did not correlate with the total doses of cefazolin given before implementation of the measurements.The measured median serum concentrations of cefazolin after an interval of application of 8 hours were much lower than the needed minimum inhibitory serum concentrations against Staphylococcus (10 mg/l). To avoid low minimum serum concentrations and increase the efficacy of prophylactic antibiotic administration a shorter interval of application should probably be chosen.

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“…However, the I‐neb has not been tested in children and little is known about pharmacokinetics (PK) and safety of tobramycin delivered with this nebulizer. This lack of knowledge is especially a risk with drugs such as tobramycin, where high trough concentrations and cumulative exposure can lead to nephro‐ and ototoxicity . Dose recommendations are based on in vitro tests and few in vivo data in adults …”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study

Velzen

Uges

Heijerman

et al. 2019

Brit J Clinical Pharma

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Aims We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I‐neb device to the standard PARI‐LC Plus nebulizer in children with cystic fibrosis. Methods A randomized, open‐label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I‐neb (75 mg) and PARI‐LC Plus (300 mg). Study visits were separated by 1 month, in which 1 of the study nebulizers was used twice daily. Tobramycin PK for both nebulizers was established using measured tobramycin concentrations and Bayesian PK modelling software. Hearing and renal function tests were performed to test for aminoglycoside associated toxicity. In addition to standard estimated glomerular filtration rate values, biomarkers for tubular injury (KIM‐1 and NAG) were measured. Patient and nebulizer satisfaction were assessed. Results Inhalations were well tolerated and serum trough concentrations below the predefined toxic limit were reached with no significant differences in PK parameters between nebulizers. Results of audiometry and estimated glomerular filtration rate revealed no abnormalities. However, increased urinary NAG/creatinine ratios at visit 2 for both nebulizers suggest TIS‐induced subclinical tubular kidney injury. Nebulization time was 50% shorter and patient satisfaction was significantly higher with the I‐neb. Conclusions Nebulization of 75 mg TIS with the I‐neb in children with cystic fibrosis resulted in comparable systemic exposure to 300 mg TIS with the PARI‐LC Plus and was well tolerated and preferred over the PARI‐LC Plus. Long‐term safety of TIS nebulization should be monitored clinically, especially regarding the effects on tubular kidney injury.

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Extended dosage intervals for aminoglycosides

Cited by 10 publications

References 0 publications

Once-daily aminoglycoside dosing: An update on current literature

Once-daily aminoglycoside dosing: An update on current literature

Effect of High-Volume Therapy on Cefazolin Serum Concentrations in Multiple-Trauma Patients

Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study

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