Target site pharmacokinetics of meropenem: Measurement in human explanted lung tissue by bronchoalveolar lavage, microdialysis and homogenized lung tissue

2021 ◽  
Author(s):  
Michael Paal ◽  
Christina Scharf ◽  
Ann Katrin Denninger ◽  
Luis Ilia ◽  
Charlotte Kloft ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Lung Tissue ◽  
Target Site ◽  
Therapeutic Drug ◽  
Beta Lactam ◽  
Blood Concentrations ◽  
Intensive Care Patients ◽  
Beta Lactam Antibiotics ◽  
Liquid Chromatography Tandem Mass ◽  
Risk Patients

Objectives: Pneumonia is one of the most common infections in intensive care patients, and it is often treated with beta-lactam antibiotics. Even if therapeutic drug monitoring in blood is available, it is unclear whether sufficient concentrations are reached at the target site: the lung. The following study was initiated to fill this knowledge gap. Methods: Various compartments from ten patients` explanted lungs were subjected to laboratory analysis. Meropenem was quantified in serum, bronchoalveolar lavage (BAL), microdialysate and homogenized lung tissue with isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS). BAL represents diluted epithelial lining fluid (ELF), and microdialysate represents interstitial fluid (IF). Differences between target site and blood concentrations were investigated. Results: The median meropenem concentration in blood, ELF, IF and tissue were 26.8, 18.0, 12.1 and 9.1 mg/L, respectively. A total of 37.5% of the target site ELF and IF meropenem concentrations were below the clinical EUCAST breakpoint of 8 mg/L. The median ELF/serum quotient was 61.8% (IQR: 24.8%, 87.6%), the median IF/serum quotient was 35.4% (IQR: 23.8%, 54.3%), and the median tissue/serum quotient was 34.2% (IQR: 28.3%, 38.2%). We observed a substantial interindividual variability between the blood and the compartments (ELF, IF), whereas the intraindividual variability was relatively low. Conclusions: Target site measurement in different lung compartments was feasible and successfully applied in a clinical setting. A relevant amount of 37.5% of the target site concentrations fell under the clinical EUCAST breakpoint, indicating subtherapeutic dosing in high-risk patients receiving perioperative antibiotic prophylaxis in lung transplantation.

Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Burns Patients—A One-Year Prospective Study

2012 ◽  
Vol 34 (2) ◽  
pp. 160-164 ◽  
Author(s):  
Bhavik M. Patel ◽  
Jennifer Paratz ◽  
Natalie C. See ◽  
Michael J. Muller ◽  
Michael Rudd ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Prospective Study ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics ◽  
One Year

scholarly journals Simultaneous Determination of 12 β-Lactam Antibiotics in Human Plasma by High-Performance Liquid Chromatography with UV Detection: Application to Therapeutic Drug Monitoring

2011 ◽  
Vol 55 (10) ◽  
pp. 4873-4879 ◽  
Author(s):  
Marie-Clémence Verdier ◽  
Olivier Tribut ◽  
Pierre Tattevin ◽  
Yves Le Tulzo ◽  
Christian Michelet ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Therapeutic Drug Monitoring ◽  
Simultaneous Determination ◽  
Drug Monitoring ◽  
High Performance ◽  
Therapeutic Drug ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics

ABSTRACTA rapid and specific high-performance liquid chromatography method with UV detection (HPLC-UV) for the simultaneous determination of 12 beta-lactam antibiotics (amoxicillin, cefepime, cefotaxime, ceftazidime, ceftriaxone, cloxacillin, imipenem, meropenem, oxacillin, penicillin G, piperacillin, and ticarcillin) in small samples of human plasma is described. Extraction consisted of protein precipitation by acetonitrile. An Atlantis T3 analytical column with a linear gradient of acetonitrile and a pH 2 phosphoric acid solution was used for separation. Wavelength photodiode array detection was set either at 210 nm, 230 nm, or 298 nm according to the compound. This method is accurate and reproducible (coefficient of variation [CV] < 8%), allowing quantification of beta-lactam plasma levels from 5 to 250 μg/ml without interference with other common drugs. This technique is easy to use in routine therapeutic drug monitoring of beta-lactam antibiotics.

scholarly journals Rational Use of Antibiotics in Neonates: Still in Search of Tailored Tools

Healthcare ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 28 ◽  
Author(s):  
John van den Anker ◽  
Karel Allegaert
Keyword(s):  
Implementation Strategies ◽  
Antibiotic Use ◽  
Therapeutic Drug ◽  
Accurate Information ◽  
Beta Lactam ◽  
Decision Tools ◽  
Beta Lactam Antibiotics ◽  
Empiric Antibiotic ◽  
Access To Knowledge ◽  
Rational Antibiotic Use

Rational medicine use in neonates implies the prescription and administration of age-appropriate drug formulations, selecting the most efficacious and safe dose, all based on accurate information on the drug and its indications in neonates. This review illustrates that important uncertainties still exist concerning the different aspects (when, what, how) of rational antibiotic use in neonates. Decisions when to prescribe antibiotics are still not based on robust decision tools. Choices (what) on empiric antibiotic regimens should depend on the anticipated pathogens, and the available information on the efficacy and safety of these drugs. Major progress has been made on how (beta-lactam antibiotics, aminoglycosides, vancomycin, route and duration) to dose. Progress to improve rational antibiotic use necessitates further understanding of neonatal pharmacology (short- and long-term safety, pharmacokinetics, duration and route) and the use of tailored tools and smarter practices (biomarkers, screening for colonization, and advanced therapeutic drug monitoring techniques). Implementation strategies should not only facilitate access to knowledge and guidelines, but should also consider the most effective strategies (‘skills’) and psychosocial aspects involved in the prescription process: we should be aware that both the decision not to prescribe as well as the decision to prescribe antibiotics is associated with risks and benefits.

scholarly journals Immunoassay Analysis of Kanamycin in Serum Using the Tobramycin Kit

2016 ◽  
Vol 60 (8) ◽  
pp. 4646-4651 ◽  
Author(s):  
J. A. Dijkstra ◽  
A. J. Voerman ◽  
B. Greijdanus ◽  
D. J. Touw ◽  
J. W. C. Alffenaar
Keyword(s):  
Antiviral Agents ◽  
Multidrug Resistant ◽  
Cross Reactivity ◽  
Therapeutic Drug ◽  
Blood Concentrations ◽  
Modified Method ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

ABSTRACTKanamycin is one of the aminoglycosides used in the treatment of multidrug-resistant tuberculosis. Blood concentrations of kanamycin are predictive for the treatment efficacy and the occurrence of side effects, and dose adjustments can be needed to optimize therapy. However, an immunoassay method for the quantification of kanamycin is not commercially available. We modified the existing tobramycin immunoassay to analyze kanamycin. This modified method was tested in a concentration range of 0.3 to 80.0 mg/liter for inaccuracy and imprecision. In addition, the analytical results of the immunoassay method were compared to those obtained by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method using Passing and Bablok regression. Within-day imprecision varied from 2.3 to 13.3%, and between-day imprecision ranged from 0.0 to 11.3%. The inaccuracy ranged from −5.2 to 7.6%. No significant cross-reactivity with other antimicrobials and antiviral agents was observed. The results of the modified immunoassay method were comparable with the LC-MS/MS analytical outcome. This new immunoassay method enables laboratories to perform therapeutic drug monitoring of kanamycin without the need for complex and expensive LC-MS/MS equipment.

Ticarcillin Therapy of Risk Patients with Infections Due to Pseudomonas Aeruginosa

1981 ◽  
Vol 9 (1) ◽  
pp. 44-51 ◽  
Author(s):  
Jürgen Welter ◽  
Dietmar H Wittman ◽  
Volker Freitag
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Evidence ◽  
Surgical Intensive Care Unit ◽  
Beta Lactam ◽  
Surgical Intensive Care ◽  
Severely Injured Patients ◽  
Beta Lactam Antibiotics ◽  
Therapeutic Consequences ◽  
Risk Patients ◽  
Injured Patients

The implication of nosocomial infection due to Pseudomonas aeruginosa is demonstrated by comparing the bacteriological findings with the clinical picture often patients in a surgical intensive care unit. The occurrence of this organism and its resistance to beta-lactam-antibiotics and aminoglycosides is demonstrated. Ticarcillin was administered to ten patients following bacteriological and clinical evidence of infections due to P. aeruginosa. The pathogenicity of P. aeruginosa as an organism complicating the course of severely injured patients is discussed. Therapeutic consequences in regard to possible combination with other antibiotics are suggested.

scholarly journals The Pharmacokinetics of Beta-Lactam Antibiotics Using Scavenged Samples in Pediatric Intensive Care Patients: The EXPAT Kids Study Protocol

2021 ◽  
Vol 12 ◽  
Author(s):  
Stef Schouwenburg ◽  
Enno D. Wildschut ◽  
M. de Hoog ◽  
Birgit C.P. Koch ◽  
Alan Abdulla
Keyword(s):  
Intensive Care ◽  
Pediatric Intensive Care ◽  
Sampling Strategy ◽  
Antibiotic Exposure ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Target Attainment ◽  
Intensive Care Patients ◽  
Beta Lactam Antibiotics ◽  
Dosing Regimens

Background: Emerging evidence supports the importance of optimized antibiotic exposure in pediatric intensive care unit (PICU) patients. Traditional antibiotic dosing is not designed for PICU patients, as the extreme pharmacokinetic (PK) behavior of drugs threatens the achievement of optimal antibiotic treatment outcomes. Scavenged sampling is a sampling strategy which may have positive implications for routine TDM and PK research, as well as monitoring other biomarkers. EXPAT Kids study was designed to analyze whether current empiric dosing regimens of frequently used beta-lactam antibiotics achieve defined therapeutic target concentrations in PICU patients.Methods: A mono-centre, exploratory pharmacokinetic and pharmacodynamic study was designed to assess target attainment of beta-lactam antibiotics. One hundred forty patients will be included within 24 months after start of inclusion. At various time points serum concentration of the study antibiotic (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, and meropenem) are determined. In parallel with these sampling moments, residual material is collected to validate the use of blood of scavenged heparinized astrup syringes for the quantification of antibiotic exposure. The primary outcome is the time that the free (unbound) concentration of the study antibiotic remains above one to four the minimal inhibitory concentration during a dosing interval (100%ƒT &gt; MIC and 100%ƒT&gt;4xMIC). Other included outcomes are disease severity, safety, length of stay, and inflammatory biomarkers.Discussion: Potentially, scavenged sampling may enrich the EXPAT Kids dataset, and reduce additional blood sampling and workload for clinical personnel. The findings from the EXPAT Kids study will lead to new insights in the PK parameters of beta-lactams and consecutive effects on target attainment and clinical outcomes. Is there a need for more precision in dosing? Netherlands Trial Register Number: Trial NL9326.

scholarly journals 1114. Effectiveness and Safety of Beta-lactam Antibiotics with and without Therapeutic Drug Monitoring in Patients with Pseudomonas aeruginosa Pneumonia or Bloodstream Infection

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S650-S650
Author(s):  
Ashlan J Kunz Coyne ◽  
Mohammad H Al-Shaer ◽  
Anthony M Casapao ◽  
Jason Ferreira ◽  
Carmen Isache ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Therapeutic Drug Monitoring ◽  
Bloodstream Infection ◽  
Drug Monitoring ◽  
Clinical Cure ◽  
Therapeutic Drug ◽  
Composite Outcome ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics ◽  
Primary Composite Outcome

Abstract Background Pseudomonas aeruginosa (PSAR) is challenging to treat due to its multiple resistance mechanisms, limited anti-PSAR agents, and population pharmacokinetic (PK) variances. Beta-lactam antibiotics (BLA) are commonly used to treat PSAR infections and although they have a wide therapeutic index, suboptimal exposures may lead to treatment failure and antimicrobial resistance while high exposure may result in adverse effects. Certain patient populations may benefit from BLA therapeutic drug monitoring (TDM) due to their significant PK variability. The purpose of this study was to compare clinical outcomes in patients with PSAR pneumonia (PNA) or bloodstream infection (BSI) receiving BLA with and without the guidance of TDM. Methods Retrospective, parallel cohort study conducted at UF Shands Gainesville and UF Health Jacksonville evaluating five years of patients with PSAR PNA or BSI. TDM group was defined for routine BLA TDM compared to nonroutine BLA TDM service (non-TDM). Patients were excluded if they died before a culture result, transferred in with a positive PSAR culture, were transplant recipients, cystic fibrosis or burn injury patients. The primary outcome was a composite of presumed clinical cure defined as the absence of the following: all-cause in-hospital mortality, escalation, and/or additional antimicrobial therapy for PSAR infection after 48 hours of treatment with primary susceptible regimen due to worsening clinical status or transfer to a higher level of care. Results Two-hundred patients were included (TDM n=95; non-TDM n=105). The overall primary composite outcome of presumed clinical cure occurred in 73% of patients (82% and 75% of the TDM and non-TDM cohorts, respectively; p=0.301). A post-hoc multivariate analysis was conducted to assess predictors of not attaining clinical cure. Conclusion While there was no difference in the primary composite outcome of presumed clinical cure, future studies can use these data to assess TDM patient selection and whether a bundled care approach of BLA regimens with known clinical benefit, early TDM-guided dose optimization, and continued clinical assessment improves outcomes in patients with PSAR PNA or BSI compared to use of each modality individually. Disclosures All Authors: No reported disclosures

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