Aminoglycosides

Gilbert, David N.; Leggett, J. E.

doi:10.1016/b978-0-443-06839-3.00026-6

Cited by 23 publications

(33 citation statements)

References 371 publications

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“…This difference can be attributed to several factors that contribute to the modification of the distribution of gentamicin, such as protein binding, blood flow to tissues, membrane permeability, and drug affinity for different tissues (27)(28)(29). The fact that gentamicin is a polar compound with low plasma protein binding (Ͻ30%) makes its V directly related to extracellular body fluid (5). In this respect and during the first 2 years of life, the compartmentalization of body water changes continuously; total body water decreases, and adipose tissue increases (29), resulting in a higher volume of distribution in newborns and infants than that in older children.…”

Section: Discussionmentioning

confidence: 99%

“…Despite their potential for renal toxicity, ototoxicity, and bacterial resistance, several aminoglycosides continue to play an important role in the treatment of infections (3,4). Of the aminoglycosides, gentamicin is one of the most commonly used due to its low cost and broad-spectrum efficacy (5,6). Gentamicin is commonly used to treat infections caused by both Gram-negative and Grampositive bacilli, such as Escherichia coli, Proteus spp., Pseudomonas spp., Serratia spp., and Staphylococcus spp.…”

mentioning

confidence: 99%

“…This change has also being applied to the establishment of gentamicin dosing in pediatrics (1,5,13,14). However, its pharmacokinetics in infants exhibits large inter-and intraindividual variability, mainly due to the developmental changes occurring from the first month of life (15).…”

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confidence: 99%

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Population Pharmacokinetics of Gentamicin and Dosing Optimization for Infants

Medellín‐Garibay

Rueda-Naharro

Peña-Cabia

et al. 2015

Antimicrob Agents Chemother

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The aim of this study was to characterize and validate the population pharmacokinetics of gentamicin in infants and to determine the influences of clinically relevant covariates to explain the inter-and intraindividual variabilities associated with this drug. Infants receiving intravenous gentamicin and with routine therapeutic drug monitoring were consecutively enrolled in the study. Plasma concentration and time data were retrospectively collected from 208 infants (1 to 24 months old) of the Hospital Universitario Severo Ochoa (Spain), of whom 44% were males (mean age [؎ standard deviation], 5.8 ؎ 4.8 months; mean body weight, 6.4 ؎ 2.2 kg). Data analysis was performed with NONMEM 7.2. One-and two-compartment open models were analyzed to estimate the gentamicin population parameters and the influences of several covariates. External validation was carried out in another population of 55 infants. The behavior of gentamicin in infants exhibits two-compartment pharmacokinetics, with total body weight being the covariate that mainly influences central volume (V c ) and clearance (CL); this parameter was also related to creatinine clearance. Both parameters are age related and different from those reported for neonatal populations. On the basis of clinical presentation and diagnosis, a once-daily dosage regimen of 7 mg/kg of body weight every 24 h is proposed for intravenous gentamicin, followed by therapeutic drug monitoring in order to avoid toxicity and ensure efficacy with minimal blood sampling. Gentamicin pharmacokinetics and disposition were accurately characterized in this pediatric population (infants), with the parameters obtained being different from those reported for neonates and children. These differences should be considered in the dosing and therapeutic monitoring of this antibiotic.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Population Pharmacokinetics of Gentamicin and Dosing Optimization for Infants

Medellín‐Garibay

Rueda-Naharro

Peña-Cabia

et al. 2015

Antimicrob Agents Chemother

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“…Although aminoglycosides are distributed almost freely in the extracellular space of most tissues because of their minimal protein binding and high water solubility, they cross biological membranes poorly, so drug concentrations in bronchial secretions are low, thus restricting their efficacy in the treatment of respiratory tract infections (158)(159)(160)(161)(162). Low concentrations of aminoglycosides in the respiratory tract upon intravenous dosing are due to their polycationic charge and their lipid insolubility (163). Data summarized in Table 2 demonstrate that sputum or lung tissue concentrations were significantly increased upon ultrasonic (164), pneumatic (165), and Pari LC Plus Jet (166,167) nebulization using the previous formulations and devices compared to intravenous administration.…”

Section: Serum and Sputum Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Dalhoff¹

2014

Clin Microbiol Rev

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SUMMARY Bacteria adapt to growth in lungs of patients with cystic fibrosis (CF) by selection of heterogeneously resistant variants that are not detected by conventional susceptibility testing but are selected for rapidly during antibacterial treatment. Therefore, total bacterial counts and antibiotic susceptibilities are misleading indicators of infection and are not helpful as guides for therapy decisions or efficacy endpoints. High drug concentrations delivered by aerosol may maximize efficacy, as decreased drug susceptibilities of the pathogens are compensated for by high target site concentrations. However, reductions of the bacterial load in sputum and improvements in lung function were within the same ranges following aerosolized and conventional therapies. Furthermore, the use of conventional pharmacokinetic/pharmacodynamic (PK/PD) surrogates correlating pharmacokinetics in serum with clinical cure and presumed or proven eradication of the pathogen as a basis for PK/PD investigations in CF patients is irrelevant, as minimization of systemic exposure is one of the main objectives of aerosolized therapy; in addition, bacterial pathogens cannot be eradicated, and chronic infection cannot be cured. Consequently, conventional PK/PD surrogates are not applicable to CF patients. It is nonetheless obvious that systemic exposure of patients, with all its sequelae, is minimized and that the burden of oral treatment for CF patients suffering from chronic infections is reduced.

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“…These derivatives enhance many of the therapeutic properties and expand the practical uses of the class. Several comprehensive reviews of the aminoglycosides have been published (Arya 2007;Dozzo and Moser 2010;Gilbert and Leggett 2009;Kirst and Allen 2007;Mitscher 2010).…”

Section: Introductionmentioning

confidence: 99%

Aminoglycoside Antibiotics

Kirst

Marinelli

2013

Antimicrobials

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Aminoglycosides were the second major antibiotic class to be discovered from fermentation of microorganisms. They are structurally characterized by an aminocyclitol that is substituted in several different patterns by amino-and/or neutral sugar moieties. They are potent, bactericidal, water-soluble compounds that are given by parenteral administration. They are especially useful for treatment of infections caused by Gram-negative bacteria, including Pseudomonas aeruginosa. Limitations of the class include the development of microbial resistance by a variety of mechanisms and patient toxicity, especially nephrotoxicity and ototoxicity. Several semi-synthetic derivatives have been developed that have improved features, especially increased activity against resistant strains of bacteria. The newest aminoglycoside, plazomicin, is a semi-synthetic derivative of sisomicin that is undergoing further evaluation in clinical trials.

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Aminoglycosides

Cited by 23 publications

References 371 publications

Population Pharmacokinetics of Gentamicin and Dosing Optimization for Infants

Population Pharmacokinetics of Gentamicin and Dosing Optimization for Infants

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Aminoglycoside Antibiotics

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