BİR İLAÇ MONOGRAFI : MEROPENEM-VABORBAKTAM

Yıl 2018, Cilt: 2 Sayı: 1, 50 - 57, 30.04.2018

Hande Toptan , Mustafa Altındiş

Öz

Meropenem
Vaborbaktam yakın zamanda Amerika’da kullanıma sunulmuş, iki faz III
çalışmasını başarıyla tamamlamış yeni bir β-laktamaz inhibitörlü karbapenem
kombinasyonudur. Kimyasal yapısı, etki mekanizması ve yan etki profili
bakımından diğer β-laktam antibiyotiklerle benzerlik taşımakla birlikte
antibakteriyel etkinliği açısından birçok üstünlüğe sahip olduğu belirtilmektedir.
Başta Klebsiella pneumoniae carbapenemase (KPC) olmak üzere belirli bazı
karbapenemaz türleri üzerinde etkili bulunması bu üstünlüğün en önemli
sebebidir. Karbapenem dirençli bakterilerle gerçekleştirilen TANGO II’de mümkün
olan en iyi tedavi ile meropenem-vaborbaktam alan hasta grupları kıyaslanmış,
meropenem-vaborbaktamın beklenenin üzerinde üstünlük sağlamasıyla çalışma
planlanandan önce sonlandırılmıştır. Günümüzde Meropenem – vaborbaktam
kombinasyonu dirençli Gram negatif bakterilerle meydana gelen komplike idrar
yolları enfeksiyonu / pyelonefrit için ruhsatlandırılmış; ventilatör ilişkili
pnömoni için Faz III çalışmaları devam etmektedir.

Anahtar Kelimeler

Meropenem-vaborbaktam, Karpabepenem dirençli Enterobacteriaceae, KPC bakteriler, Metallo-beta-laktamazlar, Karbapenemazlar

Kaynakça

• 1. US Department of Health and Human Services Centers for Disease Control and Prevention. 2013. Antibiotic resistance threats in the United States, 2013. http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf. Erişim tarihi: 10 Nisan 2018.
• 2. Öztürk H, Ozkirimli E, Özgür A. Classification of Beta-lactamases and penicillin binding proteins using ligand-centric network models. PLoS One. 2015;10(2):e0117874.
• 3. Bush K, Jacoby GA. Updated functional classification of betalactamases. Antimicrob Agents Chemother. 2010;54(3):969–76.4. Drawz SM, Papp-Wallace KM, Bonomo RA. New b-lactamase inhibitors: a therapeutic renaissance in an MDR world. Antimicrob Agents Chemother. 2014;58(4):1835–46.
• 5. Hecker SJ, Reddy KR, Totrov M, Hirst GC, Lomovskaya O, Griffith DC, et al. Discovery of a cyclic boronic acid b-lactamase inhibitor (RPX7009) with utility vs class A serine carbapenemases. J Med Chem. 2015;58(9):3682–92.
• 6. Munson E, Huband MD, Castanheira M, Fedler KA, Flamm RK. Determination of MIC and disk diffusion quality control guidelines for meropenem-vaborbactam, a novel carbapenem/boronic acid β-lactamase inhibitor combination. Diagn Microbiol InfectDis. 2018; 90(4): 324-328.
• 7. Rodriguez Bano, J.CRE: Combination or monotherapy? ECCMID2018 CONGRESS, ORAL PRESENTATİON, April 2018, Madrid.
• 8. Zhanel GG, Wiebe R, Dilay L, et al. Comparative review of the carbapenems. Drugs. 2007;67:1027-1052.
• 9. Merrem® (meropenem prospektüs). Wilmington, DE: AstraZeneca Pharmaceuticals, LP; 2016.
• 10. Vabomere® (meropenem/vaborbactam prospektüs). Parsippany, NJ: The Medicines Company; 2017.
• 11. Lomovskaya O, Sun D, Rubio-Aparicio D, et al. Vaborbactam: spectrum of beta-lactamase inhibition and impact of resistance mechanisms on activity in Enterobacteriaceae. Antimicrob Agents Chemother. 2017;61:e01443-17.
• 12. Castanheira M, Huband MD, Mendes RE, Flamm RK. Meropenem-vaborbactam tested against contemporary Gram-negative isolates collected worldwide during 2014, including carbapenem-resistant, KPC-producing, multidrugresistant, and extensively drug-resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2017;61:e00567-17.
• 13. Castanheira M, Rhomberg PR, Flamm RK, Jones RN. Effect of the beta-lactamase inhibitor vaborbactam combined with meropenem against serine carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2016;60(9):5454–8.
• 14. Lapuebla A, Abdallah M, Olafisoye O, Cortes C, Urban C, Quale J, et al. Activity of meropenem combined with RPX7009, a novel β-lactamase inhibitor, against gram-negative clinical isolates in New York City. Antimicrob Agents Chemother. 2015;59(8):4856–60.
• 15. Hackel MA, Lomovskaya O, Dudley MN, Karlowsky JA, Sahm DF. In vitro activity of meropenem-vaborbactam against clinical isolates of KPC-positive Enterobacteriaceae. Antimicrob Agents Chemother. 2017;62:pii: e01904-17.
• 16. Goldstein EJ, Citron DM, Tyrrell KL, Merriam CV. In vitro activity of biapenem plus RPX7009, a carbapenem combined with a serine beta-lactamase inhibitor, against anaerobic bacteria. Antimicrob Agents Chemother. 2013;57(6):2620–30.
• 17. Wenzler E, Gotfried MH, Loutit JS, Durso S, Griffith DC, Dudley MN, et al. Meropenem-RPX7009 concentrations in plasma, epithelial lining fluid, and alveolar macrophages of healthy adult subjects. Antimicrob Agents Chemother. 2015;59(12):7232–9.
• 18. Griffith DC, Loutit JS, Morgan EE, Durso S, Dudley MN. Phase 1 study of the safety, tolerability, and pharmacokinetics of the β-lactamase inhibitor vaborbactam (RPX7009) in healthy adult subjects. Antimicrob Agents Chemother. 2016;60:6326-6332.
• 19. The Medicines Company. The Medicines Company announces positive top-line results for phase 3 TANGO 1 clinical trial of Carbavance. http://www.themedicinescompany.com/investors/news/medicines-company-announces-positive-top-line-resultsphase-3-tango-1-clinical-trial. Erişim tarihi: 10 Nisan 2018.
• 20. Walsh TJ, Bhowmick T, Darouiche RO, et al. Meropenemvaborbactam (Vabomere) vs. piperacillin-tazobactam in TANGO I (a phase 3, randomized, double-blind trial): outcomes by baseline MIC in adults with cUTI or AP. ID Week 2017 poster bildirisi; 7 Ekim 2017; San Diego, CA.
• 21. Kaye KS, Vazquez J, Mathers A, et al. Meropenemvaborbactam (Vabomere) vs. best available therapy for CRE infections: TANGO II randomized, controlled phase 3 study results. ID Week 2017 poster bildirisi; 7 Ekim 2017; San Diego, CA.
• 22. The Medicines Company. The Medicines Company announces TANGO-2 trial of meropenem-vaborbactam (formerly, Carbavance) stopped early for superior benefit-risk compared to best available therapy for CRE. http://www.themedicinescompany.com/investors/news/medicinescompany-announces-tango-2-trial-meropenem-vaborbactamformerly-carbavance. Erişim tarihi: 10 Nisan 2018.
• 23. Wunderink R, Giamarellos-Bourboulis EJ, Rahav G, et al. Meropenem-vaborbactam (Vabomere) vs. best available therapy for carbapenem-resistant Enterobacteriaceae infections in TANGO II: primary outcomes by site of infection. ID Week 2017 poster bildirisi; 7 Ekim 2017; San Diego, CA.
• 24. Lomovskaya O, Castanheira M, Vazquez J, et al. Assessment of MIC increases with meropenem-vaborbactam (Vabomere) and ceftazidime-avibactam in TANGO II (a phase 3 study of the treatment of CRE infections. ID Week 2017 poster bildirisi; 7 Ekim 2017; San Diego, CA.
• 25. The Medicines Company. A study of meropenem-vaborbactam versus piperacillin/tazobactam in participants with hospital-acquired and ventilator-associated bacterial pneumonia (TANGOIII). https://clinicaltrials.gov/ct2/show/study/NCT03006679?term=vaborbactam&rank=2. Erişim tarihi: 10 Nisan 2018.
• 26. Paterson D, Kwak EJ, Bhowmick T, et al. Meropenemvaborbactam (Vabomere) vs. best available therapy for carbapenem-resistant Enterobactericeae in TANGO II: outcomes in immunocompromised patients. ID Week 2017 poster bildirisi; 7 Ekim 2017; San Diego, CA.
• 27. Mathers A, Hope W, Kaye KS, et al. Meropenem-vaborbactam (Vabomere): outcomes in subjects with renal impairment in phase 3 studies TANGO I and II. ID Week 2017 poster bildirisi; 7 Ekim 2017; San Diego, CA.
• 28. Spriet I, Goyens J, Meersseman W, Wilmer A, Willems L, Van Paesschen W. Interaction between valproate and meropenem: a retrospective study. Ann Pharmacother. 2007; 41: 1130-1136.
• 29. Kidd JM, Avery LM, Asempa TE, Nicolau DP, Kuti JL. Physical compatibility of meropenem and vaborbactam with select intravenous drugs during simulated Y-site administration. Clin Ther. 2018;40:261-269.