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Effects of biobanking conditions on six antibiotic substances in human serum assessed by a novel evaluation protocol

  • Johannes Zander EMAIL logo , Barbara Maier , Michael Zoller , Gundula Döbbeler , Lorenz Frey , Daniel Teupser and Michael Vogeser
Published/Copyright: July 21, 2015

Abstract

Background: Although therapeutic drug monitoring (TDM) for antibiotics in critically ill patients is recommended by expert panels, no commercial tests are available for most antibiotics. Therefore, we previously developed a multi-analyte method for the quantification of piperacillin, tazobactam, cefepime, meropenem, ciprofloxacin and linezolid in serum. However, limited stability data were available, and the relevant studies did not address the coefficients of variation of the methods applied, which may be important for verifying the storage dependency of the observed effects. Here we aimed to evaluate the storage effects of antibiotics by applying a novel evaluation protocol.

Methods: Serum-based test samples were aliquoted and stored at room temperature, 4 °C, −20 °C or −80 °C for up to 180 days. Using an innovative evaluation protocol (considering the coefficient of variation, p-value, and criterion of monotony of observed changes), we assessed whether relevant changes (defined as ≥15% in comparison with baseline) were storage dependent (defined as substantial changes).

Results: Storage at −80 °C for up to 180 days did not lead to substantial changes for any analyte. In contrast, storage at −20 °C induced substantial decreases after ≥7 days for piperacillin, tazobactam, cefepime and meropenem; after 90 days at −20 °C, only ≤23% of the initial concentrations were found for these parameters. No substantial changes were observed for linezolid and ciprofloxacin at any storage condition. All of the observed substantial changes were monotonic decreases.

Conclusions: We recommend a storage temperature of −80 °C for β-lactam antibiotics. The applied evaluation protocol yielded conclusive results and may be generally useful for stability studies.


Corresponding author: Johannes Zander, Institute of Laboratory Medicine, Hospital of the Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377 Munich, Germany, Phone: +49 89 440052448, E-mail:
aJohannes Zander and Barbara Maier contributed equally to this work.

Acknowledgments

This study was supported by a Mérieux Research Grant (day of acceptance: 5 February 2013) (Institut Mérieux, Lyon, France).

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Bode-Böger SM, Schopp B, Tröger U, Martens-Lobenhoffer J, Kalousis K, Mailänder P. Intravenous colistin in a patient with serious burns and borderline syndrome: the benefits of therapeutic drug monitoring. Int J Antimicrob Agents 2013;42:357–60.10.1016/j.ijantimicag.2013.06.009Search in Google Scholar

2. Bodmann Klaus-Friedrich GB. Empfehlungen zur kalkulierten parenteralen Intitialtherapie bakterieller Erkrankungen bei Erwachsenen Update. Chemother J 2010;19:179–255.Search in Google Scholar

3. David MD, Gill MJ. Potential for underdosing and emergence of resistance in Acinetobacter baumannii during treatment with colistin. J Antimicrob Chemother 2008;61:962–4.10.1093/jac/dkn009Search in Google Scholar

4. Mazzei T, Novelli A. Pharmacological rationale for antibiotic treatment of intra-abdominal infections. J Chemother 2009;21(Suppl 1):19–29.10.1179/joc.2009.21.Supplement-1.19Search in Google Scholar

5. McKenzie C. Antibiotic dosing in critical illness. J Antimicrob Chemother 2011;66(Suppl 2):ii25–31.10.1093/jac/dkq516Search in Google Scholar

6. Forrest A, Nix DE, Ballow CH, Goss TF, Birmingham MC, Schentag JJ. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother 1993;37:1073–81.10.1128/AAC.37.5.1073Search in Google Scholar

7. Gonçalves-Pereira J, Póvoa P. Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of β-lactams. Crit Care 2011;15:R206.10.1186/cc10441Search in Google Scholar

8. Roberts JA, Abdul-Aziz MH, Lipman J, Mouton JW, Vinks AA, Felton TW, et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis 2014;14:498–509.10.1016/S1473-3099(14)70036-2Search in Google Scholar

9. Zoller M, Maier B, Hornuss C, Neugebauer C, Döbbeler G, Nagel D, et al. Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study. Crit Care 2014;18:R148.10.1186/cc13984Search in Google Scholar PubMed PubMed Central

10. Pea F, Viale P, Furlanut M. Antimicrobial therapy in critically ill patients: a review of pathophysiological conditions responsible for altered disposition and pharmacokinetic variability. Clin Pharmacokinet 2005;44:1009–34.10.2165/00003088-200544100-00002Search in Google Scholar PubMed

11. Rayner CR, Forrest A, Meagher AK, Birmingham MC, Schentag JJ. Clinical pharmacodynamics of linezolid in seriously ill patients treated in a compassionate use programme. Clin Pharmacokinet 2003;42:1411–23.10.2165/00003088-200342150-00007Search in Google Scholar PubMed

12. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41:580–637.10.1097/CCM.0b013e31827e83afSearch in Google Scholar

13. Deutsche Vereinte Gesellschaft für Klinische Chemie und Laboratoriumsmedizin. Die Qualität diagnostischer Proben. Heidelberg, Germany: Becton Dickinson Diagnostics, 2012.Search in Google Scholar

14. World Health Organization. Use of anticoagulants in diagnostic laboratory investigations. Geneva: WHO, 2002.Search in Google Scholar

15. Arzuaga A, Isla A, Gascón AR, Maynar J, Martín A, Solinís MA, et al. Quantitation and stability of piperacillin and tazobactam in plasma and ultrafiltrate from patients undergoing continuous venovenous hemofiltration by HPLC. Biomed Chromatogr 2005;19:570–8.10.1002/bmc.482Search in Google Scholar

16. Augey V, Grosse PY, Albert G, Audran M, Bressolle F. High-performance liquid chromatographic determination of tazobactam and piperacillin in human plasma and urine. Chromatogr B Biomed Appl 1996;682:125–36.10.1016/0378-4347(96)00049-7Search in Google Scholar

17. Boak LM, Li J, Nation RL, Rayner CR. High-performance liquid chromatographic method for simple and rapid determination of linezolid in human plasma. Biomed Chromatogr 2006;20:782–6.10.1002/bmc.597Search in Google Scholar

18. Cherti N, Kinowski JM, Lefrant JY, Bressolle F. High-performance liquid chromatographic determination of cefepime in human plasma and in urine and dialysis fluid using a column-switching technique. J Chromatogr B Biomed Sci Appl 2001;754: 377–86.10.1016/S0378-4347(00)00630-7Search in Google Scholar

19. Cios A, Kuś K, Szymura-Oleksiak J. Determination of linezolid in human serum by reversed-phase high-performance liquid chromatography with ultraviolet and diode array detection. Acta Pol Pharm 2013;70:631–41.Search in Google Scholar

20. Cohen-Wolkowiez M, White NR, Bridges A, Benjamin DK Jr, Kashuba AD. Development of a liquid chromatography-tandem mass spectrometry assay of six antimicrobials in plasma for pharmacokinetic studies in premature infants. J Chromatogr B Analyt Technol Biomed Life Sci 2011;879:3497–506.10.1016/j.jchromb.2011.09.031Search in Google Scholar

21. Colin P, De Bock L, T’jollyn H, Boussery K, Van Bocxlaer J. Development and validation of a fast and uniform approach to quantify β-lactam antibiotics in human plasma by solid phase extraction-liquid chromatography-electrospray-tandem mass spectrometry. Talanta 2013;103:285–93.10.1016/j.talanta.2012.10.046Search in Google Scholar

22. Elkhaïli H, Linger L, Monteil H, Jehl F. High-performance liquid chromatographic assay for cefepime in serum. J Chromatogr B Biomed Sci Appl 1997;690:181–8.10.1016/S0378-4347(96)00406-9Search in Google Scholar

23. Elkhaïli H, Niedergang S, Pompei D, Linger L, Leveque D, Jehl F. High-performance liquid chromatographic assay for meropenem in serum. J Chromatogr B Biomed Appl 1996;686:19–26.10.1016/S0378-4347(96)00205-8Search in Google Scholar

24. Grondin C, Zhao W, Fakhoury M, Jacqz-Aigrain E. Determination of ciprofloxacin in plasma by micro-liquid chromatography-mass spectrometry: an adapted method for neonates. Biomed Chromatogr 2011;25:827–32.10.1002/bmc.1523Search in Google Scholar PubMed

25. Isla A, Arzuaga A, Maynar J, Gascón AR, Solinís MA, Corral E, et al. Determination of ceftazidime and cefepime in plasma and dialysate-ultrafiltrate from patients undergoing continuous veno-venous hemodiafiltration by HPLC. J Pharm Biomed Anal 2005;39:996–1005.10.1016/j.jpba.2005.05.027Search in Google Scholar PubMed

26. Legrand T, Chhun S, Rey E, Blanchet B, Zahar JR, Lanternier F, et al. Simultaneous determination of three carbapenem antibiotics in plasma by HPLC with ultraviolet detection. J Chromatogr B Analyt Technol Biomed Life Sci 2008;875:551–6.10.1016/j.jchromb.2008.09.020Search in Google Scholar PubMed

27. Muchohi SN, Thuo N, Karisa J, Muturi A, Kokwaro GO, Maitland K. Determination of ciprofloxacin in human plasma using high-performance liquid chromatography coupled with fluorescence detection: application to a population pharmacokinetics study in children with severe malnutrition. J Chromatogr B Analyt Technol Biomed Life Sci 2011;879:146–52.10.1016/j.jchromb.2010.11.032Search in Google Scholar PubMed PubMed Central

28. Nemutlu E, Kir S, Katlan D, Beksaç MS. Simultaneous multiresponse optimization of an HPLC method to separate seven cephalosporins in plasma and amniotic fluid: application to validation and quantification of cefepime, cefixime and cefoperazone. Talanta 2009;80:117–26.10.1016/j.talanta.2009.06.034Search in Google Scholar PubMed

29. Swoboda S, Ober M, Anagnostakos K, Geiss HK, Weigand MA, Hoppe-Tichy T. A simple isocratic HPLC assay to determine linezolid concentrations in different biomatrices for in vivo and in vitro studies. Clin Chem Lab Med 2007;45:1019–22.10.1515/CCLM.2007.247Search in Google Scholar PubMed

30. Tobin CM, Sunderland J, White LO, MacGowan AP. A simple, isocratic high-performance liquid chromatography assay for linezolid in human serum. J Antimicrob Chemother 2001;48:605–8.10.1093/jac/48.5.605Search in Google Scholar PubMed

31. Watabe S, Yokoyama Y, Nakazawa K, Shinozaki K, Hiraoka R, Takeshita K, et al. Simultaneous measurement of pazufloxacin, ciprofloxacin, and levofloxacin in human serum by high-performance liquid chromatography with fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci 2010;878:1555–61.10.1016/j.jchromb.2010.04.012Search in Google Scholar PubMed

32. Zander J, Maier B, Suhr A, Zoller M, Frey L, Teupser D, et al. Quantification of piperacillin, tazobactam, cefepime, meropenem, ciprofloxacin and linezolid in serum using an isotope dilution UHPLC-MS/MS method with semi-automated sample preparation. Clin Chem Lab Med 2015;53:781–91.10.1515/cclm-2014-0746Search in Google Scholar PubMed

33. Zander J, Maier B, Zoller M, Teupser D, Vogeser M. Quantification of linezolid in serum by LC-MS/MS using semi-automated sample preparation and isotope dilution internal standardization. Clin Chem Lab Med 2014;52:381–9.10.1515/cclm-2013-0594Search in Google Scholar PubMed

34. Van Geijlswijk IM, van Zanten AR, van der Meer YG. Reliable new high-performance liquid chromatographic method for the determination of ciprofloxacin in human serum. Ther Drug Monit 2006;28:278–81.10.1097/01.ftd.0000189823.43236.90Search in Google Scholar PubMed

35. Oddoze C, Lombard E, Portugal H. Stability study of 81 analytes in human whole blood, in serum and in plasma. Clin Biochem 2012;45:464–9.10.1016/j.clinbiochem.2012.01.012Search in Google Scholar PubMed

36. Zander J, Bruegel M, Kleinhempel A, Becker S, Petros S, Kortz L, et al. Effect of biobanking conditions on short-term stability of biomarkers in human serum and plasma. Clin Chem Lab Med 2014;52:629–39.10.1515/cclm-2013-0705Search in Google Scholar PubMed

37. Fraser CG. Reference change values. Clin Chem Lab Med 2011;50:807–12.Search in Google Scholar

38. Brinkman JW, de Zeeuw D, Lambers Heerspink HJ, Gansevoort RT, Kema IP, de Jong PE, et al. Apparent loss of urinary albumin during long-term frozen storage: HPLC vs. immunonephelometry. Clin Chem 2007;53:1520–6.10.1373/clinchem.2007.088823Search in Google Scholar PubMed

39. Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrot M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436–72.10.1093/clinchem/48.3.436Search in Google Scholar

40. European Medicines Agency. ICH Topic Q 1 E. Evaluation of stability data. Note for guidance on evaluation of stability data (CPMP/ICH/420/02). London, UK: European Medicines Agency, 2003.Search in Google Scholar

41. Food and Drug Administration. FDA guidance for industry: bioanalytical method. Validation. Rockville, MD: US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, 2001.Search in Google Scholar

42. ICH Expert Working Group. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. Evaluation for stability data. QIE. 2003.Search in Google Scholar

43. Dirar AM, Daleel AA, Kamal EA. Effect of storage time and temperature on some serum analytes. Int J Pathol 2010;8: 68–71.Search in Google Scholar

44. Surveillance der Antibiotika-Anwendung und der bakteriellen Resistenzen auf Intensivstationen. SARI information for antibiotic consumption over the time of all intensive care units participating at SARI. Available from: http://sari.eu-burden.info/auswertung/down/AD-ZEIT.pdf. Accessed 2 January, 2015.Search in Google Scholar


Supplemental Material:

The online version of this article (DOI: 10.1515/cclm-2015-0325) offers supplementary material, available to authorized users.


Received: 2015-4-7
Accepted: 2015-6-19
Published Online: 2015-7-21
Published in Print: 2016-2-1

©2016 by De Gruyter

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