Measurement of tobramycin and gentamicin in saliva is not suitable for therapeutic drug monitoring of patients with cystic fibrosis

Spencer, Helen; Kozlowska, Wanda; Davies, Jane C.; Webber, Peter; Chadwick, Maureen V.; Kerr, Jonathan; Makhecha, Sukeshi

doi:10.1016/j.jcf.2005.05.016

Cited by 7 publications

(17 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Strengths of this study include the use of POP‐PK, allowing for the description of nonlinear relations between plasma and saliva gentamicin concentrations with both fixed and random effects, and a relatively large cohort of neonates of different GA receiving varying dosing regimens originating from both a peripheral paediatric ward and NICU, improved the generalizability of the model. Moreover, use of highly sensitive LC–MS/MS allowed for determination of low gentamicin concentrations in small sample volumes with an LLOQ of 0.056 mg/L, which was substantially lower than earlier publications investigating gentamicin in saliva 9–11 . POP‐PK modelling allowed for deviation from scheduled sampling times and identification of covariates.…”

Section: Discussionmentioning

confidence: 91%

See 1 more Smart Citation

Saliva as a sampling matrix for therapeutic drug monitoring of gentamicin in neonates: A prospective population pharmacokinetic and simulation study

Samb

Kruizinga

Tallahi

et al. 2021

Brit J Clinical Pharma

View full text Add to dashboard Cite

Therapeutic drug monitoring (TDM) of gentamicin in neonates is recommended for safe and effective dosing and is currently performed by plasma sampling, which is an invasive and painful procedure. In this study, feasibility of a non-invasive gentamicin TDM strategy using saliva was investigated.Methods: This was a multicentre, prospective, observational cohort study including 54 neonates. Any neonate treated with intravenous gentamicin was eligible for the study. Up to eight saliva samples were collected per patient at different time-points.Gentamicin levels in saliva were determined with liquid chromatography tandem mass-spectrometry (LC-MS/MS). A population pharmacokinetic (PK) model was developed using nonlinear mixed-effects modelling (NONMEM) to describe the relation between gentamicin concentrations in saliva and plasma. Monte Carlo simulations with a representative virtual cohort (n = 3000) were performed to evaluate the probability of target attainment with saliva versus plasma TDM.Results: Plasma PK was adequately described with an earlier published model. An additional saliva compartment describing the salivary gentamicin concentrations was appended to the model with first-order input (k 13 0.023 h À1 ) and first-order elimination (k 30 0.169 h À1 ). Inter-individual variability of k 30 was 38%. Postmenstrual age Amadou Samb and Matthijs Kruizinga contributed equally to this study.The authors confirm that the Principal Investigator for this paper is Timo R. de Haan and that he had direct clinical responsibility for patients.

show abstract

Section: Discussionmentioning

confidence: 91%

“…In the past, several investigators have assessed the use of saliva for TDM of aminoglycosides with varying results 6,8–11 . Berkovitch et al reported a good correlation between plasma and saliva concentrations of gentamicin for a once daily dosing regimen in children 8 .…”

Section: Discussionmentioning

confidence: 99%

Saliva as a sampling matrix for therapeutic drug monitoring of gentamicin in neonates: A prospective population pharmacokinetic and simulation study

Samb

Kruizinga

Tallahi

et al. 2021

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Combined effect of L. gasseri and antibiotics would be suggested to suppress the growth of S. pneumoniae. Because limited amounts of gentamicin in blood is secreted into saliva, sufficient concentration of gentamicin will not be expected in saliva [7]. The help by probiotics will promote better condition of oral cavity.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, treatment and prevention of opportunistic infections at perioperative period are not easy due to the appearance of multidrug resistant bacteria and biofilm formation of opportunistic bacteria [4]. Antimicrobial drugs are used to treat opportunistic infections at the perioperative period, and even if their blood levels increase, sufficient antimicrobials do not migrate to saliva [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Suppression of opportunistic infectious bacteria by lactic acid bacteria and antibacterial drugs

et al. 2019

View full text Add to dashboard Cite

The objective of this study was to investigate inhibitory effect of lactic acid bacteria and antibiotics on the growth of Streptococcus pneumoniae ATCC 33400. Materials and Methods: Antibiotic activities of five oral probiotic candidate bacteria including two strains of Lactobacillus crispatus, Lactobacillus fermentum, Lactobacillus gasseri and Streptococcus mitis and several antibiotics against S. pneumoniae were investigated using radial diffusion assay and competition assay. The biofilm formation of S. pneumoniae in the presence of 50% saturated ammonium sulfate precipitation fraction from L. gasseri and several concentrations of gentamicin were monitored by real time cell analyzer, xCELLigence. Results:The growth of S. pneumoniae was inhibited by two strains of Lactobacillus crispatus, Lactobacillus fermentum and Lactobacillus gasseri. The saturated ammonium sulfate precipitation fraction (0-30% and 30-50%) from L. gasseri effectively inhibited growth of S. pneumoniae. The biofilm formation of S. pneumoniae monitored by real time cell analyzer (xCELLigence) was suppressed by gentamicin in dose dependent manner. Antibacterial substance from L. gasseri against S. pneumoniae was suggested to be small molecular weight substance. Conclusion: L. gasseri inhibited the growth of S. pneumoniae suggesting that L. gasseri will be a candidate of probiotics.

show abstract

“…Amikacin cannot easily diffuse across membranes, such as in the salivary gland [6]. This effect also applies to other aminoglycosides and encourages the use of aerosolised administration [7].…”

mentioning

confidence: 99%

Lack of penetration of amikacin into saliva of tuberculosis patients

et al. 2018

View full text Add to dashboard Cite

In the 2016 update of the World Health Organization treatment guideline for drug-resistant tuberculosis (TB), a shorter multidrug-resistant TB regimen was proposed because of its higher treatment outcomes [1]. However, therapeutic drug monitoring (TDM) is an excellent method to improve clinical outcomes as well and its practice is on the rise [2]. A well-known side-effect of group B injectable anti-TB drugs (e.g. amikacin) is ototoxicity [3]. TDM could also be a solution to minimise side-effects by lowering the drug exposure [4]. In the study by VAN ALTENA et al. [5], TDM was practised using the ratio of peak concentration (Cmax) to minimal inhibitory concentration (MIC) and this resulted in a reduction in patients with hearing loss. Saliva is considered as an alternative matrix for TDM because it is easy, noninvasive and more patient friendly to sample [6]. Studies found a limited penetration of gentamycin and tobramycin into saliva [7], while detectable levels of amikacin in saliva of neonates were reported [8]. Given the low penetration of aminoglycosides into saliva and interest in Cmax for TDM of amikacin, our objective was to study whether the salivary Cmax of amikacin is measurable and useful in salivary TDM.

show abstract

Measurement of tobramycin and gentamicin in saliva is not suitable for therapeutic drug monitoring of patients with cystic fibrosis

Cited by 7 publications

References 3 publications

Saliva as a sampling matrix for therapeutic drug monitoring of gentamicin in neonates: A prospective population pharmacokinetic and simulation study

Saliva as a sampling matrix for therapeutic drug monitoring of gentamicin in neonates: A prospective population pharmacokinetic and simulation study

Suppression of opportunistic infectious bacteria by lactic acid bacteria and antibacterial drugs

Lack of penetration of amikacin into saliva of tuberculosis patients

Contact Info

Product

Resources

About