Teicoplanin use in adult patients with haematological malignancy: Exploring relationships between dose, trough concentrations, efficacy and nephrotoxicity

Byrne, Catherine J.; Egan, Suzanne; Fennell, Jérôme; O'Byrne, Philomena; Enright, Helen; Deasy, Evelyn; Ryder, Sheila A.; D’Arcy, Deirdre M.; McHugh, Johnny

doi:10.1016/j.ijantimicag.2015.05.019

Cited by 34 publications

(42 citation statements)

References 25 publications

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“…Such was the case in the current study, with only seven patients being evaluable for assessment of teicoplanin efficacy, and therefore, no further insight into the appropriate trough concentration target for teicoplanin in hematological malignancy patients was gained. Nevertheless, the mean Ϯ SD trough 48 h-total of 18.6 Ϯ 12.3 mg/liter and the mean Ϯ SD trough 72 h-total of 22.8 Ϯ 15.2 mg/liter, observed in successful cases in the current study, were consistent with the findings of previous studies suggesting a target trough concentration of 20 mg/liter (15,16). While our data do not allow determination of the MIC value that this trough concentration target relates to, it might be prudent to consider higher levels of exposure for patients with infections with pathogens with MICs of Ͼ1 mg/liter.…”

Section: Discussionsupporting

confidence: 93%

“…The regression analyses showed that renal function is an important consideration for appropriate initial teicoplanin dosing, which is in keeping with the findings of recently published studies (16,27,28). Although the impact of renal function on trough concentrations was stronger at 72 h than at 48 h, the results suggest that in patients with enhanced renal function, achieving target trough concentrations may be difficult unless very high loading doses, such as doses of Ͼ20 mg/kg, are used.…”

Section: Discussionsupporting

confidence: 85%

“…The target trough total concentration was 20 mg/liter, and the target trough unbound concentration was 1.5 mg/liter, assuming 92.5% protein binding. These targets were based on those suggested from previously published studies (13,15,16).…”

Section: Methodsmentioning

confidence: 99%

“…Assessment of the response to teicoplanin therapy was conducted using the same methods and definitions previously described by Byrne et al (16).…”

Section: Methodsmentioning

confidence: 99%

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Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy

Byrne

Roberts

McWhinney

et al. 2017

Antimicrob Agents Chemother

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The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of Ն20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h (P Ͻ 0.05). For an average hematological malignancy patient (creatinine clearance ϭ 70 ml/ min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.)

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

“…Assessment of the response to teicoplanin therapy was conducted using the same methods and definitions previously described by Byrne et al (16).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy

Byrne

Roberts

McWhinney

et al. 2017

Antimicrob Agents Chemother

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“…In a recent study, Byrne et al [16 ]reported that the mean C min of teicoplanin was significantly higher in successful treatments than in failed treatments. The mean C min of successful and failed cases of coagulase-negative staphylococcal central line-associated bloodstream infection was 19.6 ± 5.1 and 13.3 ± 5.5 mg/L, respectively.…”

Section: Discussionmentioning

confidence: 99%

Optimal Trough Concentration of Teicoplanin in Febrile Neutropenic Patients with Hematological Malignancy

et al. 2017

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Background: Teicoplanin is a glycopeptide antibiotic currently used for the treatment of methicillin-resistant Staphylococcus aureus. The need for therapeutic drug monitoring of teicoplanin has been increasingly highlighted as important. It is generally accepted that whereas a plasma trough concentration (C_min) of ≥10 mg/L is appropriate for the majority of infections, it should exceed 20 mg/L for severe infections. The target C_min of teicoplanin in patients with febrile neutropenia (FN) has not been reported. The aim of this study was to estimate the target C_min for the treatment of FN in patients with hematological malignancy. Methods: In this retrospective, single-center, observational cohort study, the records of 52 hospitalized patients with hematological malignancy who were treated with teicoplanin for FN due to bacteriologically documented or presumptive gram-positive infections were analyzed. Results: A significant difference in the first C_min of teicoplanin was observed between the response and nonresponse groups in patients with bacteremia. The areas under the receiver operating characteristic curves were 0.80 for clinical efficacy. The cut-off value of teicoplanin C_min on days 4-6 was 15.2 mg/L (sensitivity 80.0%, specificity 75.0%). Conclusions: The authors propose a target teicoplanin C_min of ≥15.2 mg/L for FN in patients with hematological malignancy.

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Evaluating the optimal dose of teicoplanin with therapeutic drug monitoring: not too high for adverse event, not too low for treatment efficacy

Kim

Kang

Huh

et al. 2019

Eur J Clin Microbiol Infect Dis

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Teicoplanin use in adult patients with haematological malignancy: Exploring relationships between dose, trough concentrations, efficacy and nephrotoxicity

Cited by 34 publications

References 25 publications

Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy

Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy

Optimal Trough Concentration of Teicoplanin in Febrile Neutropenic Patients with Hematological Malignancy

Evaluating the optimal dose of teicoplanin with therapeutic drug monitoring: not too high for adverse event, not too low for treatment efficacy

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