OpenLB
Open Library of Bioscience
Advanced Search
Infectious diseases and therapy
Apr 12, 2025;

Meropenem-Vaborbactam for Treatment of Carbapenem-Resistant Enterobacterales: A Narrative Review of Clinical Practice Evidence.

Matteo Bassetti, Daniele Roberto Giacobbe, Antonio Vena, Garyphallia Poulakou, Gian Maria Rossolini, Alex Soriano, David P Nicolau
Author Information
  1. Matteo Bassetti: Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy. matteo.bassetti@hsanmartino.it.
  2. Daniele Roberto Giacobbe: Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy. ORCID
  3. Antonio Vena: Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
  4. Garyphallia Poulakou: 3rd Department of Internal Medicine and Laboratory, Medical School, National and Kapodistrian University of Athens, Sotiria General Hospital, Athens, Greece.
  5. Gian Maria Rossolini: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
  6. Alex Soriano: Department of Infectious Diseases, Hospital Clinic of Barcelona, IDIBAPS, Ciberinfect Ciber in infectious Diseases, ISCIII, Madrid, Spain.
  7. David P Nicolau: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.
PMID: 40216659 DOI: 10.1007/s40121-025-01146-x

Abstract

Among drug-resistant bacteria, carbapenem-resistant Enterobacterales (CRE) are a major clinical challenge with limited options for treatment. In the last several years, new treatment options have emerged for CRE, including meropenem-vaborbactam (MVB). MVB was studied clinically in the TANGO-I and TANGO-II trials, which evaluated the combination in complicated urinary tract infections and in different types of CRE infections, respectively. To date, clinical data on the efficacy of MVB in treatment of CRE remain limited, but are needed to understand the efficacy of a drug in routine practice. Eight retrospective studies have investigated the use of MVB for CRE. In these analyses, the overall clinical success rate varied from 60 to 75%, while mortality rates at 30 days ranged from about 15 to 30%. Most of these investigations involved patients with KPC-producing CRE strains, but also patients with Gram-negative infections, of which 80% were CRE. In addition, a number of small case series and case reports have emerged describing the use of MVB. In both retrospective studies and case series/reports, there appeared to be no major safety concerns. Collectively, these data have shown that MVB can be considered to have promising efficacy in severe Klebsiella pneumoniae carbapenemase (KPC)-producing-CRE infections and is safe and well tolerated.

Keywords

Antimicrobial resistance KPC Observational studies

References

  1. WHO. Antibiotic resistance 2020. Available from: https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance .
  2. WHO. Antimicrobial resistance 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance .
  3. WHO. Global antimicrobial resistance and use surveillance system (GLASS) Report 2021. Available from: https://iris.who.int/bitstream/handle/10665/341666/9789240027336-eng.pdf .
  4. Lutgring J. Carbapenem-resistant Enterobacteriaceae: an emerging bacterial threat. Semin Diagn Pathol. 2019;36(3):182–6. [PMID: 31056277]
  5. Papp-Wallace K, Endimiani A, Taracila M, et al. Carbapenems: past, present, and future. Antimicrob Agents Chemother. 2011;55(11):4943–60. [PMID: 21859938]
  6. Bonomo R, Burd E, Conly J, et al. Carbapenemase-producing organisms: a global scourge. Clin Infect Dis. 2018;66(8):1290–7. [PMID: 29165604]
  7. Hall BG, Barlow M. Revised Ambler classification of beta-lactamases. J Antimicrob Chemother. 2005;55(6):1050–1. [PMID: 15872044]
  8. van Duin D, Doi Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence. 2017;8(4):460–409. [PMID: 27593176]
  9. CDC. Available at: https://arpsp.cdc.gov/profile/arln/cre . Accessed 8 Jan 2025.
  10. Lee YR, Baker NT. Meropenem-vaborbactam: a carbapenem and beta-lactamase inhibitor with activity against carbapenem-resistant Enterobacteriaceae. Eur J Clin Microbiol Infect Dis. 2018;37(8):1411–9. [PMID: 29675787]
  11. Ding L, Shen S, Chen J, et al. Klebsiella pneumoniae carbapenemase variants: the new threat to global public health. Clin Microbiol Rev. 2023;36(4): e0000823. [PMID: 37937997]
  12. Tsivkovski R, Lomovskaya O. Potency of Vaborbactam is less affected than that of avibactam in strains producing KPC-2 mutations that confer resistance to ceftazidime-avibactam. Antimicrob Agents Chemother. 2020;64(4):e01936-19. [PMID: 32015028]
  13. Wilson WR, Kline EG, Jones CE, et al. Effects of KPC Variant and Porin genotype on the in vitro activity of Meropenem-Vaborbactam against Carbapenem-resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2019;63(3):e02048-18. [PMID: 30617090]
  14. Kelly A, Mathema B, Larson E. Carbapenem-resistant Enterobacteriaceae in the community: a scoping review. Int J Antimicrob Agents. 2017;50(2):127–34. [PMID: 28647532]
  15. van Duin D, Paterson D. Multidrug-resistant bacteria in the community: an update. Infect Dis Clin North Am. 2020;34(4):709–22. [PMID: 33011046]
  16. Zilberberg M, Nathanson B, Sulham K, et al. Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis. BMC Infect Dis. 2017;17(1):279. [PMID: 28415969]
  17. Martin A, Fahrbach K, Zhao Q, et al. Association between carbapenem resistance and mortality among adult, hospitalized patients with serious infections due to Enterobacteriaceae: results of a systematic literature review and meta-analysis. Open Forum Infect Dis. 2018. https://doi.org/10.1093/ofid/ofy150 . [DOI: 10.1093/ofid/ofy150]
  18. Tompkins K, van Duin D. Treatment for carbapenem-resistant Enterobacterales infections: recent advances and future directions. Eur J Clin Microbiol Infect Dis. 2021;40(10):2053–68. [PMID: 34169446]
  19. van Duin D, Kaye K, Neuner E, et al. Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. Diagn Microbiol Infect Dis. 2013;75(2):115–20. [PMID: 23290507]
  20. Rychlickova J, Kubickova V, Suk P, et al. Challenges of colistin use in ICU and therapeutic drug monitoring: a literature review. Antibiotics (Basel). 2023;12(3):437. [PMID: 36978303]
  21. 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. https://doi.org/10.1128/AAC.01443-17 . [DOI: 10.1128/AAC.01443-17]
  22. Novelli A, Del Giacomo P, Rossolini GM, et al. Meropenem/vaborbactam: a next generation beta-lactam beta-lactamase inhibitor combination. Expert Rev Anti Infect Ther. 2020;18(7):643–55. [PMID: 32297801]
  23. Cienfuegos-Gallet AV, Shashkina E, Chu T, et al. In vitro activity of meropenem-vaborbactam plus aztreonam against metallo-beta-lactamase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2024;68(4): e0134623. [PMID: 38426743]
  24. Kaye K, Bhowmick T, Metallidis S, et al. Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on clinical cure or improvement and microbial eradication in complicated urinary tract infection: the TANGO I randomized clinical trial. JAMA. 2018;319(8):788–99. [PMID: 29486041]
  25. Lawandi A, Yek C, Kadri SS. IDSA guidance and ESCMID guidelines: complementary approaches toward a care standard for MDR Gram-negative infections. Clin Microbiol Infect. 2022;28(4):465–9. [PMID: 35150882]
  26. Tamma PD, Heil EL, Justo JA, et al. Infectious Diseases Society of America 2024 guidance on the treatment of antimicrobial-resistant gram-negative infections. Clin Infect Dis. 2024. https://doi.org/10.1093/cid/ciae403 . [DOI: 10.1093/cid/ciae403]
  27. Shields R, McCreary E, Marini R, et al. Early experience with meropenem-vaborbactam for treatment of carbapenem-resistant Enterobacteriaceae infections. Clin Infect Dis. 2019;71(3):667–71. [>PMCID: ]
  28. Blonde L, Khunti K, Harris S, et al. Interpretation and impact of real-world clinical data for the practicing clinician. Adv Ther. 2018;35(11):1763–74. [PMID: 30357570]
  29. FDA. FDA approves new antibacterial drug 2017. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-new-antibacterial-drug .
  30. Wunderink R, Giamarellos-Bourboulis E, Rahav G, et al. Effect and safety of meropenem-vaborbactam versus best-available therapy in patients with carbapenem-resistant Enterobacteriaceae infections: the TANGO II randomized clinical trial. Infect Dis Ther. 2018;7(4):439–55. [PMID: 30270406]
  31. Bassetti M, Giacobbe DR, Patel N, et al. Efficacy and safety of meropenem-vaborbactam versus best available therapy for the treatment of carbapenem-resistant Enterobacteriaceae infections in patients without prior antimicrobial failure: a post hoc analysis. Adv Ther. 2019;36(7):1771–7. [PMID: 31098989]
  32. Bokesch PM, Arrieta AC, Bradley JS, et al. 1676. PK, Safety and Tolerability of VABOMERE® (meropenem-vaborbactam) in Infants, Children and Adolescents. Open Forum Infect Dis. 2023;10(Supplement_2).
  33. Fornari C, Arrieta A, Bradley JS, et al. Dose rationale for the use of meropenem/vaborbactam combination in paediatric patients with Gram-negative bacterial infections. Br J Clin Pharmacol. 2024;90(10):2597–610. [PMID: 38925918]
  34. Jorgensen SCJ, Rybak MJ. Meropenem and vaborbactam: stepping up the battle against carbapenem-resistant Enterobacteriaceae. Pharmacotherapy. 2018;38(4):444–61. [PMID: 29427523]
  35. Ackley R, Roshdy D, Meredith J, et al. Meropenem-vaborbactam versus ceftazidime-avibactam for treatment of carbapenem-resistant Enterobacteriaceae infections. Antimicrob Agents Chemother. 2020;64(5):2313–9.
  36. Zilberberg MD, Nathanson BH, Redell MA, et al. Comparative outcomes of meropenem-vaborbactam vs ceftazidime-avibactam among adults hospitalized with an infectious syndrome in the US, 2019–2021. Antibiotics (Basel). 2025. https://doi.org/10.3390/antibiotics14010029 . [DOI: 10.3390/antibiotics14010029]
  37. Tumbarello M, Raffaelli F, Cascio A, et al. Compassionate use of meropenem/vaborbactam for infections caused by KPC-producing Klebsiella pneumoniae: a multicentre study. JAC Antimicrob Resist. 2022;4(1):dlac022. [PMID: 35265842]
  38. Alosaimy S, Langf A, Morrisette T, et al. Real-world, multicenter experience with meropenem-vaborbactam for gram-negative bacterial infections including carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. Open Forum Infect Dis. 2021;8(8):371.
  39. Zhang H, Cressman L, Lautenbach E. Real-world clinical outcomes of meropenem/vaborbactam for treatment of carbapenem-resistant Enterobacterales infections. J Glob Antimicrob Resist. 2021;27:299–302. [PMID: 34775130]
  40. Tiseo G, Galfo V, Riccardi N, et al. Real-world experience with meropenem/vaborbactam for the treatment of infections caused by ESBL-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae. Eur J Clin Microbiol Infect Dis. 2024. https://doi.org/10.1007/s10096-024-04758-2 . [DOI: 10.1007/s10096-024-04758-2]
  41. Tumbarello M, Raffaelli F, Giannella M, et al. Outcomes and predictors of mortality in patients with KPC-Kp infections treated with meropenem vaborbactam: an observational multicenter study. Open Forum Infect Dis. 2024. https://doi.org/10.1093/ofid/ofae273 . [DOI: 10.1093/ofid/ofae273]
  42. Belati A, Fiore Bavaro D, Diella L, et al. Meropenem/vaborbactam plus aztreonam as a possible treatment strategy for bloodstream infections caused by ceftazidime/avibactam-resistant klebsiella pneumoniae: a retrospective case series and literature review. Antibiotics (Basel). 2022;11(3):373. [PMID: 35326836]
  43. Alataby H, Atemnkeng F, Bains S, et al. A COVID-19 case complicated by candida dubliniensis and klebsiella pneumoniae-carbapenem-resistant Enterobacteriaceae. J Med Cases. 2020;11(12):403–6. [PMID: 33984080]
  44. Athanas V, Neuner E, Hassouna H, et al. Meropenem-Vaborbactam as salvage therapy for ceftazidime-avibactam-resistant klebsiella pneumoniae bacteremia and abscess in a liver transplant recipient. Antimicrob Agents Chemother. 2018. https://doi.org/10.1128/AAC.01551-18 . [DOI: 10.1128/AAC.01551-18]
  45. Belati A, Novara R, Fiore Bavaro D, et al. Thoracic aorta graft infection by avibactam-resistant KPC-producing K. pneumoniae treated with meropenem/vaborbactam: a case report and literature review. Infez Med. 2022;30(2):277–84. [PMID: 35693053]
  46. Jorgensen SCJ, McDonald P, Mynatt R, et al. Averting the post-antibiotic era: successful use of meropenem/vaborbactam for carbapenem-resistant Serratia marcescens and Enterobacter aerogenes bacteraemia in a haemodialysis patient. J Antimicrob Chemother. 2018;73(12):3529–31. [PMID: 30188993]
  47. Oliva A, Curtolo A, Volpicelli L, et al. Synergistic meropenem/vaborbactam plus fosfomycin treatment of KPC producing K. pneumoniae septic thrombosis unresponsive to ceftazidime/avibactam: from the bench to the bedside. Antibiotics (Basel). 2021;10(7):781. [PMID: 34199072]
  48. Tiseo G, Falcone M, Loeonildi A, et al. Meropenem-vaborbactam as salvage therapy for ceftazidime-avibactam-, cefiderocol-resistant ST-512 Klebsiella pneumoniae-producing KPC-31, a D179Y variant of KPC-3. Open Forum Infect Dis. 2021. https://doi.org/10.1093/ofid/ofab141 . [DOI: 10.1093/ofid/ofab141]
  49. Larcher R, Laffont-Lozes P, Naciri T, et al. Continuous infusion of meropenem-vaborbactam for a KPC-3-producing Klebsiella pneumoniae bloodstream infection in a critically ill patient with augmented renal clearance. Infection. 2023. https://doi.org/10.1007/s15010-023-02055-2 . [DOI: 10.1007/s15010-023-02055-2]
  50. Volpicelli L, Cairoli S, Al Ismail D, et al. Simultaneous post-neurosurgical ventriculitis and bacteraemia by two different strains of KPC-producing K. pneumoniae successfully treated with meropenem/vaborbactam and high dose of fosfomycin. J Glob Antimicrob Resist. 2024;37:86–90. [PMID: 38519025]
  51. Giuliano G, Sambo M, Castellani P, et al. Meropenem-vaborbactam as intrathecal-sparing therapy for the treatment of carbapenem-resistant K. pneumoniae shunt-related ventriculitis: two case reports and review of the literature. Eur J Clin Microbiol Infect Dis. 2024. https://doi.org/10.1007/s10096-024-04986-6 . [DOI: 10.1007/s10096-024-04986-6]
  52. Laffont-Lozes P, Naciri T, Pantel A, et al. First case report of a vertebral osteomyelitis caused by carbapenem-resistant Enterobacter cloacae treated with imipenem/cilastatin/relebactam prolonged infusion then meropenem/vaborbactam in continuous infusion. Front Pharmacol. 2024;15:1347306. [PMID: 39545060]
  53. Gainey A, Burch A-K, Brownstein M, et al. Combining bacteriophages with cefiderocol and meropenem/vaborbactam to treat a pan-drug resistant Achromobacter species infection in a pediatric cystic fibrosis patient. Pediatr Pulmonol. 2020;55(11):2990–4. [PMID: 32662948]
  54. Hanretty A, Kaur I, Evangelista A, et al. Pharmacokinetics of the meropenem component of meropenem-vaborbactam in the treatment of KPC-producing Klebsiella pneumoniae bloodstream infection in a pediatric patient. Pharmacotherapy. 2018;38(12):e87–91. [PMID: 30300440]
  55. Alexander EL, Loutit J, Tumbarello M, et al. Carbapenem-resistant enterobacteriaceae infections: results from a retrospective series and implications for the design of prospective clinical trials. Open Forum Infect Dis. 2017;4(2): ofx063. [PMID: 28584849]
  56. Dhillon S. Meropenem/vaborbactam: a review in complicated urinary tract infections. Drugs. 2018;78(12):1259–70. [PMID: 30128699]
  57. Alosaimy S, Jorgesen S, Langf A, et al. Real-world multicenter analysis of clinical outcomes and safety of meropenem-vaborbactam in patients treated for serious gram-negative bacterial infections. Open Forum Infect Dis. 2020;7(3):ofaa051. [PMID: 32161775]
  58. Lodise TP, Berger A, Altincatal A, et al. Antimicrobial resistance or delayed appropriate therapy-does one influence outcomes more than the other among patients with serious infections due to carbapenem-resistant versus carbapenem-susceptible enterobacteriaceae? Open Forum Infect Dis. 2019;6(6): ofz194. [PMID: 31198817]
  59. Zilberberg MD, Nathanson BH, Redell M, et al. 2817. Outcomes of timely vs. delayed meropenem/vaborbactam treatment of infections with CRE among adults hospitalized in the US, 2019–2021. Open Forum Infect Dis. 2023. https://doi.org/10.1093/ofid/ofad500.2428 . [DOI: 10.1093/ofid/ofad500.2428]
  60. Marino A, Campanella E, Stracquadanio S, et al. Ceftazidime/avibactam and meropenem/vaborbactam for the management of enterobacterales infections: a narrative review, clinical considerations, and expert opinion. Antibiotics. 2023;12(10):1521. [PMID: 37887222]
  61. Louie A, Castanheira M, Liu W, et al. Pharmacodynamics of beta-lactamase inhibition by NXL104 in combination with ceftaroline: examining organisms with multiple types of beta-lactamases. Antimicrob Agents Chemother. 2012;56(1):258–70. [PMID: 22024819]
  62. Rahal JJ, Urban C, Segal-Maurer S. Nosocomial antibiotic resistance in multiple gram-negative species: experience at one hospital with squeezing the resistance balloon at multiple sites. Clin Infect Dis. 2002;34(4):499–503. [PMID: 11797177]
  63. Bhavnani SM, Trang M, Griffith DC, et al. Pharmacokinetic-pharmacodynamic target attainment analyses as support for meropenem-vaborbactam dosing regimens and susceptibility breakpoints. Antimicrob Agents Chemother. 2022;66(12): e0213021. [PMID: 36374023]
Journal Article Review
Article has an altmetric score of 2

Word Cloud

Created with Highcharts 10.0.0CREMVBinfectionsclinicaltreatmentefficacystudiescasemajorlimitedoptionsemergeddataretrospectiveusepatientsKPCAmongdrug-resistantbacteriacarbapenem-resistantEnterobacteraleschallengelastseveralyearsnewincludingmeropenem-vaborbactamstudiedclinicallyTANGO-ITANGO-IItrialsevaluatedcombinationcomplicatedurinarytractdifferenttypesrespectivelydateremainneededunderstanddrugroutinepracticeEightinvestigatedanalysesoverallsuccessratevaried6075%mortalityrates30 daysranged1530%investigationsinvolvedKPC-producingstrainsalsoGram-negative80%additionnumbersmallseriesreportsdescribingseries/reportsappearedsafetyconcernsCollectivelyshowncanconsideredpromisingsevereKlebsiellapneumoniaecarbapenemase-producing-CREsafewelltoleratedMeropenem-VaborbactamTreatmentCarbapenem-ResistantEnterobacterales:NarrativeReviewClinicalPracticeEvidenceAntimicrobialresistanceObservational

Similar Articles

Cited By