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

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 1825. Optimizing β-lactam Therapy in Surgical Intensive Care Unit Patients Using Therapeutic Drug Monitoring

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S40-S41
Author(s):  
Mohammad H Al-Shaer ◽  
Eric Rubido ◽  
Daniel Lee ◽  
Kenneth Klinker ◽  
Charles Peloquin
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Clinical Cure ◽  
Surgical Intensive Care Unit ◽  
Therapeutic Drug ◽  
Surgical Intensive Care ◽  
Days Of Therapy ◽  
Unit Increase

Abstract Background Therapeutic drug monitoring (TDM) is a powerful tool to optimize antibiotic exposure. It seldom has been used for β-lactams (BLs). We present our BL data in patients admitted to the surgical intensive care unit (SICU). Methods This retrospective study included SICU patients at UF Health (2016 and 2018) who received BL therapy and had TDM. Data collected included demographics, APACHE scores, platelet count, serum creatinine (Scr), infection source, cultures/susceptibilities, BL regimens, and plasma concentrations. Clinical cure was defined as resolution of infection-related symptoms at the end of therapy. Microbiologic eradication was defined as eradication of causative organism from the primary source out to 30 days after therapy. Pharmacokinetic and statistical analyses were performed on Phoenix v8.0 and JMP Pro v14. Results A total of 127 patients were included. Table 1 shows the baseline characteristics. The median age was 55 years, and weight was 83 kg. Eighty-three (65%) were male. P. aeruginosa was the most common isolated bacteria (n = 38). Lung was the most common source of infection (n = 50). Table 2 summarizes the median (IQR) doses, infusion times, calculated free trough concentrations (fCmin) of common BLs, and the reported minimum inhibitory concentrations (MICs). Calculated median time above the MIC (fT > MIC) for 66 (52%) patients was 100%. A total of 99 (79%) patients had clinical cure and 67 (61%) patients had microbiologic eradication. For efficacy, the Cmin/MIC ratio predicted the microbiologic eradication in wound infections only (n = 15, OR 1.09 [95% CI 1.01–1.24]). Using stepwise regression, 1-unit increase fT > MIC and APACHE score was associated with 0.84 decrease (P = 0.03) and 0.62 increase (P = 0.004) in days of therapy, respectively. For safety, Figure 2 shows the increase in Scr vs. BL free area under the concentration–time curve from time zero to end of the dosing interval (fAUC0-tau). Cefepime fAUC0-tau predicted neurotoxicity (OR per 20 unit increase 1.08 [95% CI: 1.01–1.18]). Conclusion In SICU patients, increase in fT > MIC was associated with shorter treatment duration, and fAUC0-tau increase was associated with an increase in Scr and incidence of neurotoxicity. TDM is warranted in this population to optimize therapy. Disclosures All Authors: No reported Disclosures.

Barriers and facilitators in the clinical implementation of beta-lactam therapeutic drug monitoring in critically ill patients

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Alan Abdulla ◽  
Puck van den Broek ◽  
Tim M.J. Ewoldt ◽  
Anouk E. Muller ◽  
Henrik Endeman ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Barriers And Facilitators ◽  
Therapeutic Drug ◽  
Clinical Implementation ◽  
Beta Lactam

scholarly journals 1101. Implementing a Beta-Lactam Therapeutic Drug Monitoring Program: Experience from a Large Academic Medical Center

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S642-S642
Author(s):  
Venugopalan Veena ◽  
Malva Hamza ◽  
Barbara A Santevecchi ◽  
Kathryn DeSear ◽  
Kartikeya Cherabuddi ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Dosage Adjustment ◽  
Total Serum ◽  
Therapeutic Drug ◽  
Beta Lactam ◽  
Dose Individualization ◽  
Material Support ◽  
Drug Concentrations ◽  
Drug Registry

Abstract Background Beta-lactams (BL) are the cornerstone of antimicrobial treatment for infections. Beta-lactam therapeutic drug monitoring (BL-TDM) optimizes drug concentrations to ensure maximal efficacy and minimal toxicity. The goals of this study were to describe the implementation process of a BL-TDM program and to further describe our experience using BL-TDM in clinical practice. Methods This was a retrospective review of adult patients with available BL-TDM between January 2016 and November 2019 at the University of Florida (UF) Health Shands Hospital. Total serum concentrations of BL were measured in the Infectious Diseases Pharmacokinetics Lab (IDPL) at UF, using a validated ultrahigh pressure liquid chromatography assay with triple quadrupole mass spectroscopy (LC-MS-MS). At our institution, TDM is available for 11 BLs and in-house assays are performed from Mon-Fri for most BLs. Results A total of 3,030 BL concentrations were obtained. An analysis was performed on the first BL-TDM encounter in 1,438 patients. The median age was 57 years (IQR, 41-69) and the median BMI was 27.5 kg/m2 (IQR, 22.5-34.5). On the day of BL-TDM, the median serum creatinine was 0.83 (IQR, 0.59-1.30). Fifty-one percent of patients (n=735) were in an ICU at the time of BL-TDM with a median SOFA score of 6 (IQR, 3-9). BL-TDM was most frequently performed on cefepime (61%, n=882), piperacillin (15%, n=218), and meropenem (11%, n=151). The BL was administered as a continuous infusion in 211 (15%) patients. An interim analysis of 548 patients showed that BL-TDM was performed a median of 2 days (IQR, 1-4) from the start of BL therapy and resulted in a dosage adjustment in 26% (n=145). Conclusion BL-TDM was performed in older, non-obese patients with normal renal function. Over half of the evaluated patients were in an ICU at the time of TDM. This finding emphasizes the value of BL-TDM in the ICU setting because altered pharmacokinetics during critical illness has been linked to enhanced BL clearance. Interestingly, BL-TDM resulted in dosage adjustment in 1 in 4 patients who were receiving licensed BL dosing regimens, thus highlighting the role of TDM in dose individualization. BL-TDM was performed most commonly within the 72-hours of therapy initiation. Early BL-TDM has been shown to improve patient outcomes and should be promoted. Disclosures Venugopalan Veena, PharmD, Melinta (Other Financial or Material Support, Received a stipend for participation in a drug registry)Merck (Other Financial or Material Support, Received a stipend for participation in a drug registry) Charles A. Peloquin, Pharm.D., Nothing to disclose

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