Similar articles

Abstract: polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

多黏菌素B治疗药物监测专家共识：中国药理学会治疗药物监测研究专业委员会及上海市医学会感染与化疗专科分会发起制定

[1]AvedissianSN, MiglisC, KubinCJ, et al., 2018. Polymyxin B pharmacokinetics in adult cystic fibrosis patients. Pharmacotherapy, 38(7):730-738.

[2]AzadMAK, NationRL, VelkovT, et al., 2019. Mechanisms of polymyxin-induced nephrotoxicity. In: Li J, Nation RL, Kaye KS (Eds.), Polymyxin Antibiotics: From Laboratory Bench to Bedside. Springer, Cham, p.305-319.

[3]BeggEJ, BarclayML, DuffullSB, 1995. A suggested approach to once-daily aminoglycoside dosing. Br J Clin Pharmacol, 39(6):605-609.

[4]BehzadiP, BaráthZ, GajdácsM, 2021. It’s not easy being green: a narrative review on the microbiology, virulence and therapeutic prospects of multidrug-resistant Pseudomonas aeruginosa. Antibiotics, 10(1):42.

[5]BergenPJ, BulittaJB, ForrestA, et al., 2010. Pharmacokinetic/pharmacodynamic investigation of colistin against Pseudomonas aeruginosa using an in vitro model. Antimicrob Agents Chemother, 54(9):3783-3789.

[6]BergenPJ, ForrestA, BulittaJB, et al., 2011a. Clinically relevant plasma concentrations of colistin in combination with imipenem enhance pharmacodynamic activity against multidrug-resistant Pseudomonas aeruginosa at multiple inocula. Antimicrob Agents Chemother, 55(11):5134-5142.

[7]BergenPJ, TsujiBT, BulittaJB, et al., 2011b. Synergistic killing of multidrug-resistant Pseudomonas aeruginosa at multiple inocula by colistin combined with doripenem in an in vitro pharmacokinetic/pharmacodynamic model. Antimicrob Agents Chemother, 55(12):5685-5695.

[8]Bielecka-OderA, 2018. Safety and security regulations against biological threats. In: Radosavljevic V, Banjari I, Belojevic G (Eds.), Defence Against Bioterrorism: Methods for Prevention and Control. Springer, Dordrecht, p.151-176.

[9]BulittaJB, YangJC, YohonnL, et al., 2010. Attenuation of colistin bactericidal activity by high inoculum of Pseudomonas aeruginosa characterized by a new mechanism-based population pharmacodynamic model. Antimicrob Agents Chemother, 54(5):2051-2062.

[10]BurkinMA, GalvidisIA, SurovoyYA, et al., 2021. Development of ELISA formats for polymyxin B monitoring in serum of critically ill patients. J Pharm Biomed Anal, 204:114275.

[11]CaiYY, LeeW, KwaAL, 2015. Polymyxin B versus colistin: an update. Expert Rev Anti-Infect Ther, 13(12):1481-1497.

[12]CDC, 2019. Antibiotic Resistance Threats in the United States. CDC, Atlanta, USA.

[13]CheahSE, WangJP, NguyenVTT, et al., 2015. New pharmacokinetic/pharmacodynamic studies of systemically administered colistin against Pseudomonas aeruginosa and Acinetobacter baumannii in mouse thigh and lung infection models: smaller response in lung infection. J Antimicrob Chemother, 70(12):3291-3297.

[14]ChenN, GuoJH, XieJ, et al., 2022. Population pharmacokinetics of polymyxin B: a systematic review. Ann Transl Med, 10(4):231.

[15]ChenWQ, LiuHF, WangQL, et al., 2021. Estimation of the area under concentration-time curve of polymyxin B based on limited sampling concentrations in Chinese patients with severe pneumonia. Eur J Clin Pharmacol, 77(1):95-105.

[16]Chinese Pharmacopoeia Commission, 2020. 9012 Guidelines for Validation of Quantitative Analysis Methods for Biological Samples. China Medical Science Press, Beijing, China, p.466-472 (in Chinese).

[17]CiftciA, IzdesS, AltintasND, 2018. Factors determining nephrotoxicity and mortality in critical care patients receiving colistin. J Infect Dev Ctries, 11(12):912-918.

[18]CovelliJ, RuszajD, StraubingerR, et al., 2017. The development and validation of a simple liquid chromatography-tandem mass spectrometry method for polymyxin B1 and B2 quantification in different matrices. J Chromatogr B, 1065-1066:112-118.

[19]de VeldeF, MoutonJW, de WinterBCM, et al., 2018. Clinical applications of population pharmacokinetic models of antibiotics: challenges and perspectives. Pharmacol Res, 134:280-288.

[20]DengY, XuB, LiX, et al., 2021. Exploration of LC-MS/MS method for therapeutic drug monitoring and clinical application of polymyxin B. Chin Pharm J, 56(15):‍1249-1254 (in Chinese).

[21]DerisZZ, YuHH, DavisK, et al., 2012. The combination of colistin and doripenem is synergistic against Klebsiella pneumoniae at multiple inocula and suppresses colistin resistance in an in vitro pharmacokinetic/pharmacodynamic model. Antimicrob Agents Chemother, 56(10):5103-5112.

[22]Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society, 2019. The Expert Consensus on the Standards of Therapeutic Drug Monitoring (2019 Edition). Eval Anal Drug-Use Hosp China, 19(8):‍897-898, 902 (in Chinese).

[23]Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society, Hospital Pharmacy Committee of Chinese Pharmaceutical Association, Evidence-Based Pharmacy Committee of Chinese Pharmaceutical Association, et al., 2020. The Expert Consensus on the Interpretation of Therapeutic Drug Monitoring. Chin J Hosp Pharm, 40(23):2389-2395 (in Chinese).

[24]Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society, Pharmaceutical Bioanalysis Committee, China Pharmaceutical Association, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 2021. Expert Consensus on Quality Assurance of Chromatographic Technology for Therapeutic Drug Monitoring (2021 Edition). Chin Pharm J, 56(17):1443-1448 (in Chinese).

[25]DudhaniRV, TurnidgeJD, NationRL, et al., 2010a. fAUC/MIC is the most predictive pharmacokinetic/pharmacodynamic index of colistin against Acinetobacter baumannii in murine thigh and lung infection models. J Antimicrob Chemother, 65(9):1984-1990.

[26]DudhaniRV, TurnidgeJD, CoulthardK, et al., 2010b. Elucidation of the pharmacokinetic/pharmacodynamic determinant of colistin activity against Pseudomonas aeruginosa in murine thigh and lung infection models. Antimicrob Agents Chemother, 54(3):1117-1124.

[27]DugganJX, 2019. Quantification below the LLOQ in regulated LC-MS/MS assays: a review of bioanalytical considerations and cautions. Bioanalysis, 11(8):797-814.

[28]FratoniAJ, NicolauDP, KutiJL, 2021. A guide to therapeutic drug monitoring of β‍-lactam antibiotics. Pharmacotherapy, 41(2):220-233.

[29]FureyA, MoriartyM, BaneV, et al., 2013. Ion suppression; A critical review on causes, evaluation, prevention and applications. Talanta, 115:104-122.

[30]GalesAC, CastanheiraM, JonesRN, et al., 2012. Antimicrobial resistance among Gram-negative bacilli isolated from Latin America: results from SENTRY Antimicrobial Surveillance Program (Latin America, 2008‍‒‍2010). Diagn Microbiol Infect Dis, 73(4):354-360.

[31]GulS, KuscuF, AydemirH, et al., 2016. Risk factors for colistin-associated acute kidney injury: a multicenter study from Turkey. Jpn J Infect Dis, 69(2):109-112.

[32]HermesDM, PittCP, LutzL, et al., 2013. Evaluation of heteroresistance to polymyxin B among carbapenem-susceptible and -resistant Pseudomonas aeruginosa. J Med Microbiol, 62(8):1184-1189.

[33]JavanAO, ShokouhiS, SahraeiZ, 2015. A review on colistin nephrotoxicity. Eur J Clin Pharmacol, 71(7):801-810.

[34]JiaXD, GuoCH, YinZ, et al., 2022. Risk factors for acute kidney injury induced by intravenous polymyxin B in Chinese patients with severe infection. Infect Drug Resist, 15:1957-1965.

[35]JonesRN, Guzman-BlancoM, GalesAC, et al., 2013. Susceptibility rates in Latin American nations: report from a regional resistance surveillance program (2011). Braz J Infect Dis, 17(6):672-681.

[36]KubinCJ, NelsonBC, MiglisC, et al., 2018. Population pharmacokinetics of intravenous polymyxin B from clinical samples. Antimicrob Agents Chemother, 62(3):e01493-17.

[37]LakotaEA, LandersdorferCB, NationRL, et al., 2018. Personalizing polymyxin B dosing using an adaptive feedback control algorithm. Antimicrob Agents Chemother, 62(7):e00483-18.

[38]LanckohrC, BoeingC, de WaeleJJ, et al., 2021. Antimicrobial stewardship, therapeutic drug monitoring and infection management in the ICU: results from the international A-TEAMICU survey. Ann Intensive Care, 11:131.

[39]LandersdorferCB, WangJP, WirthV, et al., 2018. Pharmacokinetics/pharmacodynamics of systemically administered polymyxin B against Klebsiella pneumoniae in mouse thigh and lung infection models. J Antimicrob Chemother, 73(2):462-468.

[40]LiJ, TurnidgeJ, MilneR, et al., 2001. In vitro pharmacodynamic properties of colistin and colistin methanesulfonate against Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob Agents Chemother, 45(3):781-785.

[41]LiJ, NationRL, TurnidgeJD, et al., 2006. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis, 6(9):589-601.

[42]LiYQ, ChenKF, DingJJ, et al., 2021. External evaluation of published population pharmacokinetic models of polymyxin B. Eur J Clin Pharmacol, 77(12):1909-1917.

[43]LiuXF, YuZW, WangY, et al., 2020. Therapeutic drug monitoring of polymyxin B by LC-MS/MS in plasma and urine. Bioanalysis, 12(12):845-855.

[44]LiuXF, ChenYC, YangHJ, et al., 2021. Acute toxicity is a dose-limiting factor for intravenous polymyxin B: a safety and pharmacokinetic study in healthy Chinese subjects. J Infect, 82(2):207-215.

[45]LunnDJ, BestN, ThomasA, et al., 2002. Bayesian analysis of population PK/PD models: general concepts and software. J Pharmacokinet Pharmacodyn, 29(3):271-307.

[46]ManchandaniP, ThamlikitkulV, DubrovskayaY, et al., 2018. Population pharmacokinetics of polymyxin B. Clin Pharmacol Ther, 104(3):534-538.

[47]MengM, WangLX, LiuS, et al., 2016. Simultaneous quantitation of polymyxin B1, polymyxin B2 and polymyxin B1-1 in human plasma and treated human urine using solid phase extraction and liquid chromatography-tandem mass spectrometry. J Chromatogr B, 1012-1013:23-36.

[48]MiglisC, RhodesNJ, AvedissianSN, et al., 2018. Population pharmacokinetics of polymyxin B in acutely ill adult patients. Antimicrob Agents Chemother, 62(3):e01475-17.

[49]NaesensM, KuypersDRJ, SarwalM, 2009. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol, 4(2):481-508.

[50]NangSC, AzadMAK, VelkovT, et al., 2021. Rescuing the last-line polymyxins: achievements and challenges. Pharmacol Rev, 73(2):679-728.

[51]OlaitanAO, MorandS, RolainJM, 2014. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front Microbiol, 5:643.

[52]PaiMP, NeelyM, RodvoldKA, et al., 2014. Innovative approaches to optimizing the delivery of vancomycin in individual patients. Adv Drug Deliv Rev, 77:50-57.

[53]PanuwetP, HunterRE, D'SouzaPE, et al., 2016. Biological matrix effects in quantitative tandem mass spectrometry-based analytical methods: advancing biomonitoring. Crit Rev Anal Chem, 46(2):93-105.

[54]PheK, LeeY, McDaneldPM, et al., 2014. In vitro assessment and multicenter cohort study of comparative nephrotoxicity rates associated with colistimethate versus polymyxin B therapy. Antimicrob Agents Chemother, 58(5):2740-2746.

[55]PogueJM, TamVH, 2019. Toxicity in patients. In: Li J, Nation RL, Kaye KS (Eds.), Polymyxin Antibiotics: From Laboratory Bench to Bedside. Springer, Cham, p.289-304.

[56]PogueJM, JonesRN, BradleyJS, et al., 2020. Polymyxin susceptibility testing and interpretive breakpoints: recommendations from the United States Committee on Antimicrobial Susceptibility Testing (USCAST). Antimicrob Agents Chemother, 64(2):e01495-19.

[57]RobertsJA, KirkpatrickCMJ, LipmanJ, 2011. Monte Carlo simulations: maximizing antibiotic pharmacokinetic data to optimize clinical practice for critically ill patients. J Antimicrob Chemother, 66(2):227-231.

[58]RybakMJ, LeJ, LodiseTP, et al., 2020. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm, 77(11):835-864.

[59]SandriAM, LandersdorferCB, JacobJ, et al., 2013. Population pharmacokinetics of intravenous polymyxin B in critically ill patients: implications for selection of dosage regimens. Clin Infect Dis, 57(4):524-531.

[60]SongFH, 2011. “Cross-talk” in scheduled multiple reaction monitoring caused by in-source fragmentation in herbicide screening with liquid chromatography electrospray tandem mass spectrometry. J Agric Food Chem, 59(9):4361-4364.

[61]SunL, ChenWQ, DengZX, et al., 2009. Microbiological assay for quantitative determination of polyoxin B. Process Biochem, 44(3):361-364.

[62]TamVH, SchillingAN, VoG, et al., 2005. Pharmacodynamics of polymyxin B against Pseudomonas aeruginosa. Antimicrob Agents Chemother, 49(9):3624-3630.

[63]TamVH, LeeLS, NgTM, et al., 2020. Performance of population pharmacokinetic models in predicting polymyxin B exposures. Microorganisms, 8(11):1814.

[64]TheuretzbacherU, GottwaltS, BeyerP, et al., 2019. Analysis of the clinical antibacterial and antituberculosis pipeline. Lancet Infect Dis, 19(2):e40-e50.

[65]ThomasTA, BrounEC, AbildskovKM, et al., 2012. High performance liquid chromatography-mass spectrometry assay for polymyxin B1 and B2 in human plasma. Ther Drug Monit, 34(4):398-405.

[66]TsujiBT, PogueJM, ZavasckiAP, et al., 2019. International consensus guidelines for the optimal use of the polymyxins: endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy, 39(1):10-39.

[67]WangJS, GaoY, DorshorstDW, et al., 2017. Development of a multi-matrix LC-MS/MS method for urea quantitation and its application in human respiratory disease studies. J Pharm Biomed Anal, 133:96-104.

[68]WangPL, ZhangQW, QinZF, et al., 2020. A simple and robust liquid chromatography with tandem mass spectrometry analytical method for therapeutic drug monitoring of plasma and cerebrospinal fluid polymyxin B1 and B2. Ther Drug Monit, 42(5):716-723.

[69]WangPL, ZhangQW, ZhuZF, et al., 2021. Comparing the population pharmacokinetics of and acute kidney injury due to polymyxin B in Chinese patients with or without renal insufficiency. Antimicrob Agents Chemother, 65(2):e01900-20.

[70]WangPL, XingH, ZhangF, et al., 2022. Population pharmacokinetics of polymyxin B in critically ill patients receiving continuous venovenous haemofiltration. Int J Antimicrob Agents, 60(1):106599.

[71]WenYX, QuQ, LongWM, et al., 2022. Nephrotoxicity and efficacy assessment of polymyxin B use in renal transplant patients. Infect Drug Resist, 15:275-283.

[72]WichaSG, MärtsonAG, NielsenEI, et al., 2021. From therapeutic drug monitoring to model-informed precision dosing for antibiotics. Clin Pharmacol Ther, 109(4):928-941.

[73]WongG, SimeFB, LipmanJ, et al., 2014. How do we use therapeutic drug monitoring to improve outcomes from severe infections in critically ill patients? BMC Infect Dis, 14:288.

[74]ZavasckiAP, NationRL, 2017. Nephrotoxicity of polymyxins: is there any difference between colistimethate and polymyxin B? Antimicrob Agents Chemother, 61(3):e02319-16.

[75]ZavasckiAP, GoldaniLZ, CaoGY, et al., 2008. Pharmacokinetics of intravenous polymyxin B in critically ill patients. Clin Infect Dis, 47(10):1298-1304.

[76]ZhangXJ, QiSY, DuanXG, et al., 2021. Clinical outcomes and safety of polymyxin B in the treatment of carbapenem-resistant Gram-negative bacterial infections: a real-world multicenter study. J Transl Med, 19(1):431.