A UHPLC–MS/MS method for the simultaneous determination of piperacillin and tazobactam in plasma (total and unbound), urine and renal replacement therapy effluent

Naicker, Saiyuri; Valero, Yarmarly C. Guerra; Meija, Jenny L. Ordenez; Lipman, Jeffrey; Roberts, Jason A.; Wallis, Steven C.; Parker, Suzanne L.

doi:10.1016/j.jpba.2017.10.023

Cited by 29 publications

(29 citation statements)

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“…HPLC was performed to measure PIP concentrations while the combination of PIP and tazobactam (PIP/TAZ) was administered to the patients. Recent evidence, however, suggests that the PK alterations of both PIP and TAZ are almost equal in healthy adults [58] and critically ill patients [59,60]. β-lactamase inhibition with tazobactam occurs rapidly, within 20-30 min [58] and additionally, piperacillin inhibits tubular excretion of tazobactam [61].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic drug monitoring-guided continuous infusion of piperacillin/tazobactam significantly improves pharmacokinetic target attainment in critically ill patients: a retrospective analysis of four years of clinical experience

Richter

Frey²,

Röhr³

et al. 2019

Infection

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Purpose Standard dosing and intermittent bolus application (IB) are important risk factors for pharmacokinetic (PK) target non-attainment during empirical treatment with β-lactams in critically ill patients, particularly in those with sepsis and septic shock. We assessed the effect of therapeutic drug monitoring-guided (TDM), continuous infusion (CI) and individual dosing of piperacillin/tazobactam (PIP) on PK-target attainment in critically ill patients. Methods This is a retrospective, single-center analysis of a database including 484 patients [933 serum concentrations (SC)] with severe infections, sepsis and septic shock who received TDM-guided CI of PIP in the intensive care unit (ICU) of an academic teaching hospital. The PK-target was defined as a PIP SC between 33 and 64 mg/L [fT > 2-4 times the epidemiological cutoff value (ECOFF) of Pseudomonas aeruginosa (PSA)]. Results PK-target attainment with standard dosing (initial dose) was observed in 166 patients (34.3%), whereas only 49 patients (10.1%) demonstrated target non-attainment. The minimum PK-target of ≥ 33 mg/L was overall realized in 89.9% (n = 435/484) of patients after the first PIP dose including 146 patients (30.2%) with potentially harmful SCs ≥ 100 mg/L. Subsequent TDM-guided dose adjustments significantly enhanced PK-target attainment to 280 patients (62.4%) and significantly reduced the fraction of potentially overdosed (≥ 100 mg/L) patients to 4.5% (n = 20/449). Renal replacement therapy (RRT) resulted in a relevant reduction of PIP clearance (CL PIP ): no RRT CL PIP 6.8/6.3 L/h (median/IQR) [SCs n = 752, patients n = 405], continuous veno-venous hemodialysis (CVVHD) CL PIP 4.3/2.6 L/h [SCs n = 160, n = 71 patients], intermittent hemodialysis (iHD) CL PIP 2.6/2.3 L/h [SCs n = 21, n = 8 patients]). A body mass index (BMI) of > 40 kg/m 2 significantly increased CL PIP 9.6/7.7 L/h [SC n = 43, n = 18 patients] in these patients. Age was significantly associated with supratherapeutic PIP concentrations (p < 0.0005), whereas high CrCL led to non-target attainment (p < 0.0005). Patients with target attainment (33-64 mg/L) within the first 24 h exhibited the lowest hospital mortality rates (13.9% [n = 23/166], p < 0.005). Those with target non-attainment demonstrated higher mortality rates (≤ 32 mg/L; 20.8% [n = 10/49] ≥ 64 mg/L; 29.4% [n = 79/269]). Conclusion TDM-guided CI of PIP is safe in critically ill patients and improves PK-target attainment. Exposure to defined PK-targets impacts patient mortality while lower and higher than intended SCs may influence the outcome of critically ill patients. Renal function and renal replacement therapy are main determinants of PK-target attainment. These results are only valid for CI of PIP and not for prolonged or intermittent bolus administration of PIP.

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Section: Discussionmentioning

confidence: 99%

Therapeutic drug monitoring-guided continuous infusion of piperacillin/tazobactam significantly improves pharmacokinetic target attainment in critically ill patients: a retrospective analysis of four years of clinical experience

Richter

Frey²,

Röhr³

et al. 2019

Infection

Self Cite

View full text Add to dashboard Cite

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“…To evaluate the linearity of this HPLC method, plasma calibration curves were determined in triplicate on three separate days. The correlation coefficients and the calibration ranges for each compound are reported in Table 1 The calibration ranges were defined in accordance with the expected plasma concentration in patients (McWhinney et al, 2010; Naicker et al, 2018; Xie et al, 2014; Zheng et al, 2019).…”

Section: Methods Validationmentioning

confidence: 99%

A new HPLC–DAD method for contemporary quantification of 10 antibiotics for therapeutic drug monitoring of critically ill pediatric patients

Cairoli

Simeoli

Tarchi

et al. 2020

Biomedical Chromatography

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The common practice of therapeutic drug monitoring (TDM) involves the quantification of drug plasma concentrations at a specific time in a dosing window. Although TDM for antibiotics is not considered mandatory, it may represent a valid tool for clinicians in order to limit antibiotic resistance and avoid therapeutic failures. The aim of our study was to develop and validate a high‐performance liquid chromatography–diode array detection method for simultaneous quantification of 10 antibiotics in plasma. This method has a fast analytical procedure that uses the same chromatographic conditions to quantify ceftazidime, ceftriaxone, meropenem, ertapenem, ciprofloxacin, tigecycline, ampicillin, levofloxacin and piperacillin, plus the β‐lactamase inhibitor tazobactam. Method validation was ensured by testing selectivity, accuracy, precision, limits of detection and quantification, recovery and stability. The calibration ranges, established accordingly to the expected plasma concentration in patients, showed a coefficient of determination >0.996 for all compounds. Within‐ and between‐days precisions reported a coefficient of variation >15%. Similarly, the accuracy evaluation reported a relative standard deviation of <10% for each antibiotic. The recovery ranged between 97 and 103% for all compounds. This method could represent a useful tool for TDM of antibiotics.

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“…Total drug concentrations were determined by separate validated high performance liquid chromatography with tandem mass spectrometry. 11,12 Samples and withinbatch calibrators and quality controls were prepared by protein precipitation, and the extracts separated on C18 stationary phase. To isolate the unbound fraction for analysis, protein-bound drug was removed from the plasma sample with Centrifree centrifugal filter devices (Merck Millipore, Tullagreen, Ireland).…”

Section: Bioanalysismentioning

confidence: 99%

Insufficient plasma concentrations of empiric anti‐pseudomonal beta‐lactam antibiotics in critically ill patients with suspected sepsis

Mangalore

Padiglione

Martin

et al. 2020

Pharmacy Practice and Res

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Aim To determine if empirical anti‐pseudomonal beta‐lactam antibiotic (BLA) dosing achieves adequate drug exposure in septic patients. Method A single‐centre, prospective pharmacokinetic study was conducted in Intensive Care Unit (ICU) patients with sepsis, receiving empirical therapy with piperacillin/tazobactam or meropenem. The pharmacokinetic/pharmacodynamic (PK/PD) targets were free BLA concentrations above the MIC at the mid‐point (Concentration A, 50%f T > MIC) and end of the dosing interval (Concentration B, 100% fT > MIC). Sub‐therapeutic concentrations were defined as concentration A < MIC, and sub‐optimal as concentration B < MIC. The MIC breakpoint for Pseudomonas aeruginosa, as defined by The European Committee on Antimicrobial Susceptibility Testing (EUCAST) (available from ) was used. Results Of the 37 eligible patients, 20 were receiving piperacillin/tazobactam (TZP), and 17 meropenem (MEM). PK data were available for 36 patients (concentration A) and 34 patients (concentration B). The median measured plasma concentrations (mg/L) were: piperacillin for doses 4 g 8‐hourly and 4 g 6‐hourly – concentration A 53.9 [14.38–123.71] and 36.44 [13.38–107.45], concentration B 8.01 [2.57–71.08] and 27.31 [3.32–59.76], MEM for doses 1 g 8‐hourly and 2 g 8‐hourly – concentration A 12.49 [7.35–23.63] and 30.5, concentration B 7.47 [2.97–11.33] and 9.31. 27.8% (10 of 36) of patients had sub‐therapeutic concentrations (concentration A) and 50% (17 of 34) had sub‐optimal concentrations (concentration B). Conclusion Our study confirms that sub‐therapeutic unbound plasma anti‐pseudomonal BLA concentrations are common in critically ill septic patients and underscores the urgent need for future trials exploring the efficacy of BLA therapeutic drug monitoring in these patients.

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A UHPLC–MS/MS method for the simultaneous determination of piperacillin and tazobactam in plasma (total and unbound), urine and renal replacement therapy effluent

Cited by 29 publications

References 28 publications

Therapeutic drug monitoring-guided continuous infusion of piperacillin/tazobactam significantly improves pharmacokinetic target attainment in critically ill patients: a retrospective analysis of four years of clinical experience

Therapeutic drug monitoring-guided continuous infusion of piperacillin/tazobactam significantly improves pharmacokinetic target attainment in critically ill patients: a retrospective analysis of four years of clinical experience

A new HPLC–DAD method for contemporary quantification of 10 antibiotics for therapeutic drug monitoring of critically ill pediatric patients

Insufficient plasma concentrations of empiric anti‐pseudomonal beta‐lactam antibiotics in critically ill patients with suspected sepsis

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