Prospective evaluation of improving fluoroquinolone exposure using centralised therapeutic drug monitoring (TDM) in patients with tuberculosis (PERFECT): a study protocol of a prospective multicentre cohort study

被引：5

作者：

van den Elsen, Simone H. J. ^{[1
]}

Sturkenboom, Marieke G. G. ^{[1
]}

Akkerman, Onno ^{[2
,3
]}

Barkane, Linda ^{[4
]}

Bruchfeld, Judith ^{[5
,6
]}

Eather, Geoffrey ^{[7
,8
]}

Heysell, Scott K. ^{[9
]}

Hurevich, Henadz ^{[10
]}

Kuksa, Liga ^{[4
]}

Kunst, Heinke ^{[11
]}

Kuhlin, Johanna ^{[5
,6
]}

Manika, Katerina ^{[12
]}

Moschos, Charalampos ^{[13
]}

Mpagama, Stellah G. ^{[14
]}

Munoz Torrico, Marcela ^{[15
]}

Skrahina, Alena ^{[10
]}

Sotgiu, Giovanni ^{[16
]}

Tadolini, Marina ^{[17
]}

Tiberi, Simon ^{[18
]}

Volpato, Francesca ^{[17
]}

van der Werf, Tjip S. ^{[2
,19
]}

Wilson, Malcolm R. ^{[7
,8
]}

Zuniga, Joaquin ^{[20
,21
]}

Touw, Daan J. ^{[1
]}

Migliori, Giovanni B. ^{[22
]}

Alffenaar, Jan-Willem ^{[1
,23
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharm & Pharmacol, Groningen, Netherlands

[2] Univ Groningen, Univ Med Ctr Groningen, Dept Pulm Dis & TB, Groningen, Netherlands

[3] Univ Groningen, Univ Med Ctr Groningen, TB Ctr Beatrixoord, Haren, Netherlands

[4] Riga East Univ Hosp, TB & Lung Dis Clin, Dept Multidrug Resistant TB, Riga, Latvia

[5] Karolinska Inst, Dept Med, Div Infect Dis, Stockholm, Sweden

[6] Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden

[7] Princess Alexandra Hosp, Dept Resp Med, Woolloongabba, Qld, Australia

[8] Princess Alexandra Hosp, Metro South Clin TB Serv, Woolloongabba, Qld, Australia

[9] Univ Virginia, Div Infect Dis & Int Hlth, Charlottesville, VA USA

[10] Republican Sci & Pract Ctr Pulmonol & TB, Minsk, BELARUS

[11] Queen Mary Univ London, Barts Hlth NHS Trust, Blizard Inst, Dept Resp Med, London, England

[12] Aristotle Univ Thessaloniki, G Papanikolaou Hosp, Resp Infect Unit, Pulm Dept, Thessaloniki, Greece

[13] Sotiria Hosp Chest Dis, Drug Resistant TB Unit, Athens, Greece

[14] Kibongoto Infect Dis Hosp, Kilimanjaro, Tanzania

[15] Inst Nacl Enfermedades Resp, Clin TB, Mexico City, DF, Mexico

[16] Univ Sassari, Dept Med Surg & Expt Sci, Clin Epidemiol & Med Stat Unit, Sassari, Italy

[17] Univ Bologna, Alma Mater Studiorum, Unit Infect Dis, Dept Med & Surg Sci, Bologna, Italy

[18] Queen Mary Univ London, Blizard Inst, Dept Infect, Barts Hlth NHS Trust, London, England

[19] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands

[20] Inst Nacl Enfermedades Resp, Lab Immunobiol & Genet, Mexico City, DF, Mexico

[21] Tecnol Monterrey, Escuela Med & Ciencias Salud, Mexico City, DF, Mexico

[22] Ist Clin Sci Maugeri IRCCS, Serv Epidemiol Clin Malattie Resp, Tradate, Italy

[23] Univ Sydney, Fac Med & Hlth, Sydney Pharm Sch, Sydney, NSW, Australia

来源：

BMJ OPEN | 2020年 / 10卷 / 06期

关键词：

tuberculosis; clinical pharmacology; organisation of health services; infectious diseases; MULTIDRUG-RESISTANT TUBERCULOSIS; ARTIFICIAL-INTELLIGENCE; TB; MOXIFLOXACIN; MANAGEMENT; REGIMENS; OUTCOMES;

D O I：

10.1136/bmjopen-2019-035350

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

IntroductionGlobal multidrug-resistant tuberculosis (MDR-TB) treatment success rates remain suboptimal. Highly active WHO group A drugs moxifloxacin and levofloxacin show intraindividual and interindividual pharmacokinetic variability which can cause low drug exposure. Therefore, therapeutic drug monitoring (TDM) of fluoroquinolones is recommended to personalise the drug dosage, aiming to prevent the development of drug resistance and optimise treatment. However, TDM is considered laborious and expensive, and the clinical benefit in MDR-TB has not been extensively studied. This observational multicentre study aims to determine the feasibility of centralised TDM and to investigate the impact of fluoroquinolone TDM on sputum conversion rates in patients with MDR-TB compared with historical controls.Methods and analysisPatients aged 18 years or older with sputum smear and culture-positive pulmonary MDR-TB will be eligible for inclusion. Patients receiving TDM using a limited sampling strategy (t=0and t=5hours) will be matched to historical controls without TDM in a 1:2 ratio. Sample analysis and dosing advice will be performed in a centralised laboratory. Centralised TDM will be considered feasible if >80% of the dosing recommendations are returned within 7days after sampling and 100% within 14 days. The number of patients who are sputum smear and culture-negative after 2months of treatment will be determined in the prospective TDM group and will be compared with the control group without TDM to determine the impact of TDM.Ethics and disseminationEthical clearance was obtained by the ethical review committees of the 10 participating hospitals according to local procedures or is pending (online supplementary file 1). Patients will be included after obtaining written informed consent. We aim to publish the study results in a peer-reviewed journal.Trial registration numberClinicalTrials.gov Registry (NCT03409315).

引用

页数：7

共 49 条

[1] Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis [J].

Ahmad, Nafees ;

Ahuja, Shama D. ;

Akkerman, Onno W. ;

Alffenaar, Jan-Willem C. ;

Anderson, Laura F. ;

Baghaei, Parvaneh ;

Bang, Didi ;

Barry, Pennan M. ;

Bastos, Mayara L. ;

Behera, Digamber ;

Benedetti, Andrea ;

Bisson, Gregory P. ;

Boeree, Martin J. ;

Bonnet, Maryline ;

Brode, Sarah K. ;

Brust, James C. M. ;

Cai, Ying ;

Caumes, Eric ;

Cegielski, J. Peter ;

Centis, Rosella ;

Chan, Pei-Chun ;

Chan, Edward D. ;

Chang, Kwok-Chiu ;

Charles, Macarthur ;

Cirule, Andra ;

Dalcolmo, Margareth Pretti ;

D'Ambrosio, Lia ;

de Vries, Gerard ;

Dheda, Keertan ;

Esmail, Aliasgar ;

Flood, Jennifer ;

Fox, Gregory J. ;

Frechet-Jachym, Mathilde ;

Fregona, Geisa ;

Gayoso, Regina ;

Gegia, Medea ;

Gler, Maria Tarcela ;

Gu, Sue ;

Guglielmetti, Lorenzo ;

Holtz, Timothy H. ;

Hughes, Jennifer ;

Isaakidis, Petros ;

Jarlsberg, Leah ;

Kempker, Russell R. ;

Keshavjee, Salmaan ;

Khan, Faiz Ahmad ;

Kipiani, Maia ;

Koenig, Serena P. ;

Koh, Won-Jung ;

Kritski, Afranio .

LANCET, 2018, 392 (10150) :821-834

[2] Integrating Pharmacokinetics and Pharmacodynamics in Operational Research to End Tuberculosis [J].

Alffenaar, Jan-Willem C. ;

Gumbo, Tawanda ;

Dooley, Kelly E. ;

Peloquin, Charles A. ;

Mcilleron, Helen ;

Zagorski, Andre ;

Cirillo, Daniela M. ;

Heysell, Scott K. ;

Silva, Denise Rossato ;

Migliori, Giovanni Battista .

CLINICAL INFECTIOUS DISEASES, 2020, 70 (08) :1774-1780

[3] Therapeutic Drug Monitoring: The Need for Practical Guidance [J].

Alffenaar, Jan-Willem C. ;

Heysell, Scott K. ;

Mpagama, Stellah G. .

CLINICAL INFECTIOUS DISEASES, 2019, 68 (06) :1065-1066

[4] Multidrug-resistant tuberculosis: pharmacokinetic and pharmacodynamic science [J].

Alffenaar, Jan-Willem C. ;

Migliori, Giovanni Battista ;

Gumbo, Tawanda .

LANCET INFECTIOUS DISEASES, 2017, 17 (09) :898-898

[5] Therapeutic Drug Monitoring in Tuberculosis: Practical Application for Physicians [J].

Alffenaar, Jan-Willem C. ;

Tiberi, Simon ;

Verbeeck, Roger K. ;

Heysell, Scott K. ;

Grobusch, Martin P. .

CLINICAL INFECTIOUS DISEASES, 2017, 64 (01) :104-+

[6] Acquired Drug Resistance: We Can Do More Than We Think! [J].

Alffenaar, Jan-Willem C. ;

Gumbo, Tawanda ;

Aarnoutse, Rob E. .

CLINICAL INFECTIOUS DISEASES, 2015, 60 (06) :969-+

[7] Comparison of the Pharmacokinetics of Two Dosage Regimens of Linezolid in Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis Patients [J].

Alffenaar, Jan-Willem C. ;

van Altena, Richard ;

Harmelink, Ilse M. ;

Filguera, Patricia ;

Molenaar, Esther ;

Wessels, A. Mireille A. ;

van Soolingen, Dick ;

Kosterink, Jos G. W. ;

Uges, Donald R. A. ;

van der Werf, Tjip S. .

CLINICAL PHARMACOKINETICS, 2010, 49 (08) :559-565

[8] Early interventions for diabetes related tuberculosis associate with hastened sputum microbiological clearance in Virginia, USA [J].

Alkabab, Yosra ;

Keller, Suzanne ;

Dodge, Denise ;

Houpt, Eric ;

Staley, Deborah ;

Heysell, Scott .

BMC INFECTIOUS DISEASES, 2017, 17

[9]

[Anonymous], 2012, GLOB TUB REP 2012

[10] Linezolid-based Regimens for Multidrug-resistant Tuberculosis (TB): A Systematic Review to Establish or Revise the Current Recommended Dose for TB Treatment [J].

Bolhuis, Mathieu S. ;

Akkerman, Onno W. ;

Sturkenboom, Marieke G. G. ;

Ghimire, Samiksha ;

Srivastava, Shashikant ;

Gumbo, Tawanda ;

Alffenaar, Jan-Willem C. .

CLINICAL INFECTIOUS DISEASES, 2018, 67 :S327-S335

← 1 2 3 4 5 →