Skip to main content
SpringerLink
Log in

Recognizing and Overcoming Resistance to New Beta-Lactam/Beta-Lactamase Inhibitor Combinations

  • Antimicrobial Development and Drug Resistance (K Claeys and A Vega, Section Editors)
  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To describe the mechanisms and clinical relevance of emergent resistance to three recently introduced beta-lactamase inhibitor combinations (BLICs) active against resistant Gram-negative organisms: ceftolozane-tazobactam, ceftazidime-avibactam, and meropenem-vaborbactam.

Recent Findings

Despite their recent introduction into practice, clinical reports of resistance to BLICs among typically susceptible organisms have already emerged, in some cases associated with therapeutic failure. The resistance mechanisms vary by agent, including mutations in beta-lactamase active sites, upregulation of efflux pumps, and alterations in the structure or expression of porin channels. These changes may confer cross-resistance or, rarely, increased susceptibility to related agents. Clinicians need to be aware of the potential for initial or emergent resistance to BLICs and ensure appropriate antimicrobial susceptibility testing is performed. Dose optimization and novel combinations of agents may play a role in preventing and managing resistance.

Summary

Recently approved BLICs have provided important new therapeutic options against resistant Gram-negative organisms, but are already coming up against emergent resistance. Awareness of the potential for resistance, early detection, and dose optimization may be important in preserving the utility of these agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2009;48:1–12.

    Google Scholar 

  2. Bush K. Past and present perspectives on β-lactamases. Antimicrob Agents Chemother. 2018;62:e01076-18. Incredibly useful and updated perspective on beta-lactamases from one of the leaders in the field.

  3. Livermore DM. Beta-lactamases in laboratory and clinical resistance. Clin Microbiol Rev. 1995;8:557–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Babic M, Hujer AM, Bonomo RA. What’s new in antibiotic resistance? Focus on beta-lactamases. Drug Resist Updat Rev Comment Antimicrob Anticancer Chemother. 2006;9:142–56.

    CAS  Google Scholar 

  5. Naas T, Oueslati S, Bonnin RA, Dabos ML, Zavala A, Dortet L, et al. Beta-lactamase database (BLDB)—structure and function. J Enzyme Inhib Med Chem. 2017;32:917–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Zapun A, Contreras-Martel C, Vernet T. Penicillin-binding proteins and beta-lactam resistance. FEMS Microbiol Rev. 2008;32:361–85.

    CAS  PubMed  Google Scholar 

  7. Bellido F, Veuthey C, Blaser J, Bauernfeind A, Pechère JC. Novel resistance to imipenem associated with an altered PBP-4 in a Pseudomonas aeruginosa clinical isolate. J Antimicrob Chemother. 1990;25:57–68.

    CAS  PubMed  Google Scholar 

  8. Neuwirth C, Siébor E, Duez JM, Péchinot A, Kazmierczak A. Imipenem resistance in clinical isolates of Proteus mirabilis associated with alterations in penicillin-binding proteins. J Antimicrob Chemother. 1995;36:335–42.

    CAS  PubMed  Google Scholar 

  9. Moyá B, Beceiro A, Cabot G, Juan C, Zamorano L, Alberti S, et al. Pan-β-lactam resistance development in Pseudomonas aeruginosa clinical strains: molecular mechanisms, penicillin-binding protein profiles, and binding affinities. Antimicrob Agents Chemother. 2012;56:4771–8.

    PubMed  PubMed Central  Google Scholar 

  10. Pagès J-M, James CE, Winterhalter M. The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria. Nat Rev Microbiol. 2008;6:893–903.

    PubMed  Google Scholar 

  11. Fernández L, Hancock REW. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin Microbiol Rev. 2012;25:661–81.

    PubMed  PubMed Central  Google Scholar 

  12. Pagès J-M, Peslier S, Keating TA, Lavigne J-P, Nichols WW. Role of the outer membrane and porins in susceptibility of β-lactamase-producing Enterobacteriaceae to ceftazidime-avibactam. Antimicrob Agents Chemother. 2015;60:1349–59.

    PubMed  Google Scholar 

  13. Chalhoub H, Sáenz Y, Nichols WW, Tulkens PM, Van Bambeke F. Loss of activity of ceftazidime-avibactam due to MexAB-OprM efflux and overproduction of AmpC cephalosporinase in Pseudomonas aeruginosa isolated from patients suffering from cystic fibrosis. Int J Antimicrob Agents. 2018;52:697–701.

    CAS  PubMed  Google Scholar 

  14. Solomkin J, Hershberger E, Miller B, Popejoy M, Friedland I, Steenbergen J, et al. Ceftolozane/tazobactam plus metronidazole for complicated intra-abdominal infections in an era of multidrug resistance: results from a randomized, double-blind, phase 3 trial (ASPECT-cIAI). Clin Infect Dis Off Publ Infect Dis Soc Am. 2015;60:1462–71.

    CAS  Google Scholar 

  15. Wagenlehner FM, Umeh O, Steenbergen J, Yuan G, Darouiche RO. Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI). Lancet Lond Engl. 2015;385:1949–56.

    CAS  Google Scholar 

  16. Rodríguez-Martínez J-M, Poirel L, Nordmann P. Extended-spectrum cephalosporinases in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2009;53:1766–71.

    PubMed  PubMed Central  Google Scholar 

  17. Cabot G, Bruchmann S, Mulet X, Zamorano L, Moyà B, Juan C, et al. Pseudomonas aeruginosa ceftolozane-tazobactam resistance development requires multiple mutations leading to overexpression and structural modification of AmpC. Antimicrob Agents Chemother. 2014;58:3091–9.

    PubMed  PubMed Central  Google Scholar 

  18. Fraile-Ribot PA, Cabot G, Mulet X, Periañez L, Martín-Pena ML, Juan C, et al. Mechanisms leading to in vivo ceftolozane/tazobactam resistance development during the treatment of infections caused by MDR Pseudomonas aeruginosa. J Antimicrob Chemother. 2018;73:658–63.

    CAS  PubMed  Google Scholar 

  19. Zamudio R, Hijazi K, Joshi C, Aitken E, Oggioni MR, Gould IM. Phylogenetic analysis of resistance to ceftazidime/avibactam, ceftolozane/tazobactam and carbapenems in piperacillin/tazobactam-resistant Pseudomonas aeruginosa from cystic fibrosis patients. Int J Antimicrob Agents. 2019;53:774–80.

    CAS  PubMed  Google Scholar 

  20. Barnes MD, Taracila MA, Rutter JD, Bethel CR, Galdadas I, Hujer AM, et al. Deciphering the evolution of cephalosporin resistance to ceftolozane-tazobactam in Pseudomonas aeruginosa. mBio. 2018;9:e02085-18.

  21. Bassetti M, Castaldo N, Cattelan A, Mussini C, Righi E, Tascini C, et al. Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience. Int J Antimicrob Agents. 2019;53:408–15. This study describes the clinical experience with ceftolozane/tazobactam across 22 hospitals in Italy. It details clinical outcomes, resistance rates, and characteristics associated with clinical failure.

    CAS  PubMed  Google Scholar 

  22. Haidar G, Philips NJ, Shields RK, Snyder D, Cheng S, Potoski BA, et al. Ceftolozane-tazobactam for the treatment of multidrug-resistant Pseudomonas aeruginosa infections: clinical effectiveness and evolution of resistance. Clin Infect Dis Off Publ Infect Dis Soc Am. 2017;65:110–20.

    CAS  Google Scholar 

  23. So W, Shurko J, Galega R, Quilitz R, Greene JN, Lee GC. Mechanisms of high-level ceftolozane/tazobactam resistance in Pseudomonas aeruginosa from a severely neutropenic patient and treatment success from synergy with tobramycin. J Antimicrob Chemother. 2019;74:269–71.

    PubMed  Google Scholar 

  24. Skoglund E, Abodakpi H, Rios R, Diaz L, De La Cadena E, Dinh AQ, et al. In vivo resistance to ceftolozane/tazobactam in Pseudomonas aeruginosa arising by AmpC- and non-AmpC-mediated pathways. Case Rep Infect Dis. 2018;2018:9095203.

    PubMed  PubMed Central  Google Scholar 

  25. Xiao AJ, Miller BW, Huntington JA, Nicolau DP. Ceftolozane/tazobactam pharmacokinetic/pharmacodynamic-derived dose justification for phase 3 studies in patients with nosocomial pneumonia. J Clin Pharmacol. 2016;56:56–66.

    CAS  PubMed  Google Scholar 

  26. VanScoy BD, Mendes RE, Castanheira M, McCauley J, Bhavnani SM, Jones RN, et al. Relationship between ceftolozane-tazobactam exposure and selection for Pseudomonas aeruginosa resistance in a hollow-fiber infection model. Antimicrob Agents Chemother. 2014;58:6024–31.

    PubMed  PubMed Central  Google Scholar 

  27. Natesan S, Pai MP, Lodise TP. Determination of alternative ceftolozane/tazobactam dosing regimens for patients with infections due to Pseudomonas aeruginosa with MIC values between 4 and 32 mg/L. J Antimicrob Chemother. 2017;72:2813–6.

    CAS  PubMed  Google Scholar 

  28. Rico Caballero V, Almarzoky Abuhussain S, Kuti JL, Nicolau DP. Efficacy of human-simulated exposures of ceftolozane-tazobactam alone and in combination with amikacin or colistin against multidrug-resistant Pseudomonas aeruginosa in an in vitro pharmacodynamic model. Antimicrob Agents Chemother. 2018;62.

  29. Gómez-Junyent J, Benavent E, Sierra Y, El Haj C, Soldevila L, Torrejón B, et al. Efficacy of ceftolozane/tazobactam, alone and in combination with colistin, against multidrug-resistant Pseudomonas aeruginosa in an in vitro biofilm pharmacodynamic model. Int J Antimicrob Agents. 2019;53:612–9.

    PubMed  Google Scholar 

  30. Zasowski EJ, Rybak JM, Rybak MJ. The β-lactams strike back: ceftazidime-avibactam. Pharmacotherapy. 2015;35:755–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Coleman K. Diazabicyclooctanes (DBOs): a potent new class of non-β-lactam β-lactamase inhibitors. Curr Opin Microbiol. 2011;14:550–5.

    CAS  PubMed  Google Scholar 

  32. Bush K, Bradford PA. Interplay between β-lactamases and new β-lactamase inhibitors. Nat Rev Microbiol. 2019;17:295–306.

    CAS  PubMed  Google Scholar 

  33. Wagenlehner FM, Sobel JD, Newell P, Armstrong J, Huang X, Stone GG, et al. Ceftazidime-avibactam versus doripenem for the treatment of complicated urinary tract infections, including acute pyelonephritis: RECAPTURE, a phase 3 randomized trial program. Clin Infect Dis Off Publ Infect Dis Soc Am. 2016;63:754–62.

    CAS  Google Scholar 

  34. Mazuski JE, Gasink LB, Armstrong J, Broadhurst H, Stone GG, Rank D, et al. Efficacy and safety of ceftazidime-avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infection: results from a randomized, controlled, double-blind, phase 3 program. Clin Infect Dis Off Publ Infect Dis Soc Am. 2016;62:1380–9.

    CAS  Google Scholar 

  35. Torres A, Zhong N, Pachl J, Timsit J-F, Kollef M, Chen Z, et al. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis. 2018;18:285–95.

    CAS  PubMed  Google Scholar 

  36. Carmeli Y, Armstrong J, Laud PJ, Newell P, Stone G, Wardman A, et al. Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study. Lancet Infect Dis. 2016;16:661–73.

    CAS  PubMed  Google Scholar 

  37. Livermore DM, Warner M, Jamrozy D, Mushtaq S, Nichols WW, Mustafa N, et al. In vitro selection of ceftazidime-avibactam resistance in Enterobacteriaceae with KPC-3 carbapenemase. Antimicrob Agents Chemother. 2015;59:5324–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Livermore DM, Mushtaq S, Barker K, Hope R, Warner M, Woodford N. Characterization of β-lactamase and porin mutants of Enterobacteriaceae selected with ceftaroline + avibactam (NXL104). J Antimicrob Chemother. 2012;67:1354–8.

    CAS  PubMed  Google Scholar 

  39. Shields RK, Nguyen MH, Press EG, Chen L, Kreiswirth BN, Clancy CJ. In vitro selection of meropenem resistance among ceftazidime-avibactam-resistant, Meropenem-susceptible Klebsiella pneumoniae isolates with variant KPC-3 Carbapenemases. Antimicrob Agents Chemother. 2017;61.

  40. Compain F, Arthur M. Impaired inhibition by avibactam and resistance to the ceftazidime-avibactam combination due to the D179Y substitution in the KPC-2 β-lactamase. Antimicrob Agents Chemother. 2017;61.

  41. Haidar G, Clancy CJ, Shields RK, Hao B, Cheng S, Nguyen MH. Mutations in blaKPC-3 that confer ceftazidime-avibactam resistance encode novel KPC-3 variants that function as extended-spectrum β-lactamases. Antimicrob Agents Chemother. 2017;61.

  42. Compain F, Dorchène D, Arthur M. Combination of amino acid substitutions leading to CTX-M-15-mediated resistance to the ceftazidime-avibactam combination. Antimicrob Agents Chemother. 2018;62.

  43. Nelson K, Hemarajata P, Sun D, Rubio-Aparicio D, Tsivkovski R, Yang S, et al. Resistance to ceftazidime-avibactam is due to transposition of KPC in a porin-deficient strain of Klebsiella pneumoniae with increased efflux activity. Antimicrob Agents Chemother. 2017;61:e00989-17

  44. Kazmierczak KM, Biedenbach DJ, Hackel M, Rabine S, de Jonge BLM, Bouchillon SK, et al. Global dissemination of blaKPC into bacterial species beyond Klebsiella pneumoniae and in vitro susceptibility to ceftazidime-avibactam and aztreonam-avibactam. Antimicrob Agents Chemother. 2016;60:4490–500.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Winkler ML, Papp-Wallace KM, Hujer AM, Domitrovic TN, Hujer KM, Hurless KN, et al. Unexpected challenges in treating multidrug-resistant gram-negative bacteria: resistance to ceftazidime-avibactam in archived isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2015;59:1020–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Sanz-García F, Hernando-Amado S, Martínez JL. Mutation-driven evolution of Pseudomonas aeruginosa in the presence of either ceftazidime or ceftazidime-avibactam. Antimicrob Agents Chemother. 2018;62.

  47. Humphries RM, Yang S, Hemarajata P, Ward KW, Hindler JA, Miller SA, et al. First report of ceftazidime-avibactam resistance in a KPC-3-expressing Klebsiella pneumoniae isolate. Antimicrob Agents Chemother. 2015;59:6605–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Shields RK, Potoski BA, Haidar G, Hao B, Doi Y, Chen L, et al. Clinical outcomes, drug toxicity, and emergence of ceftazidime-avibactam resistance among patients treated for carbapenem-resistant Enterobacteriaceae infections. Clin Infect Dis Off Publ Infect Dis Soc Am. 2016;63:1615–8. This key reference describes the development of clinical resistance to ceftazidime-avibactam with as few as 10 days of exposure, further emphasizing the need for additional data to better understand how to avert such cases.

    CAS  Google Scholar 

  49. Shields RK, Nguyen MH, Press EG, Chen L, Kreiswirth BN, Clancy CJ. Emergence of ceftazidime-avibactam resistance and restoration of carbapenem susceptibility in Klebsiella pneumoniae carbapenemase-producing K pneumoniae: a case report and review of literature. Open Forum Infect Dis. 2017;4:ofx101.

    PubMed  PubMed Central  Google Scholar 

  50. Giddins MJ, Macesic N, Annavajhala MK, Stump S, Khan S, McConville TH, et al. Successive emergence of ceftazidime-avibactam resistance through distinct genomic adaptations in blaKPC-2-harboring Klebsiella pneumoniae sequence type 307 isolates. Antimicrob Agents Chemother. 2018;62. This reference is important as it highlights the balance and quick shift between susceptibility and resistance with certain antibiotic selections.

  51. Thomson GK, Snyder JW, McElheny CL, Thomson KS, Doi Y. Coproduction of KPC-18 and VIM-1 carbapenemases by Enterobacter cloacae: implications for newer β-lactam-β-lactamase inhibitor combinations. J Clin Microbiol. 2016;54:791–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Both A, Büttner H, Huang J, Perbandt M, Belmar Campos C, Christner M, et al. Emergence of ceftazidime/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate. J Antimicrob Chemother. 2017;72:2483–8.

    CAS  PubMed  Google Scholar 

  53. King M, Heil E, Kuriakose S, Bias T, Huang V, El-Beyrouty C, et al. Multicenter study of outcomes with ceftazidime-avibactam in patients with carbapenem-resistant Enterobacteriaceae infections. Antimicrob Agents Chemother. 2017;61:e00449-17.

  54. Wunderink RG, Giamarellos-Bourboulis EJ, Rahav G, Mathers AJ, Bassetti M, Vazquez J, 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;7:439–55.

    PubMed  PubMed Central  Google Scholar 

  55. Shields RK, Nguyen MH, Chen L, Press EG, Kreiswirth BN, Clancy CJ. Pneumonia and renal replacement therapy are risk factors for ceftazidime-avibactam treatment failures and resistance among patients with carbapenem-resistant Enterobacteriaceae infections. Antimicrob Agents Chemother. 2018;62:e02497–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Mojica MF, Ouellette CP, Leber A, Becknell MB, Ardura MI, Perez F, et al. Successful treatment of bloodstream infection due to Metallo-β-lactamase-producing Stenotrophomonas maltophilia in a renal transplant patient. Antimicrob Agents Chemother. 2016;60:5130–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Shaw E, Rombauts A, Tubau F, Padullés A, Càmara J, Lozano T, et al. Clinical outcomes after combination treatment with ceftazidime/avibactam and aztreonam for NDM-1/OXA-48/CTX-M-15-producing Klebsiella pneumoniae infection. J Antimicrob Chemother. 2018;73:1104–6.

    CAS  PubMed  Google Scholar 

  58. Castanheira M, Rhomberg PR, Flamm RK, Jones RN. Effect of the β-lactamase inhibitor vaborbactam combined with meropenem against serine carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2016;60:5454–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, et al. Imipenem-relebactam and meropenem-vaborbactam: two novel carbapenem-β-lactamase inhibitor combinations. Drugs. 2018;78:65–98.

    CAS  PubMed  Google Scholar 

  60. Lomovskaya O, Sun D, Rubio-Aparicio D, Nelson K, Tsivkovski R, Griffith DC, et al. Vaborbactam: Spectrum of beta-lactamase inhibition and impact of resistance mechanisms on activity in Enterobacteriaceae. Antimicrob Agents Chemother. 2017;61. This article discusses meropenem-vaborbactam's main mechanism of resistance—outer membrane porins—and specifies which specific porin (aka OmpK36) increases the need for higher vaborbactam concentrations.

  61. Dhillon S. Meropenem/vaborbactam: a review in complicated urinary tract infections. Drugs. 2018;78:1259–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Kaye KS, Bhowmick T, Metallidis S, Bleasdale SC, Sagan OS, Stus V, 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;319:788–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Sun D, Rubio-Aparicio D, Nelson K, Dudley MN, Lomovskaya O. Meropenem-vaborbactam resistance selection, resistance prevention, and molecular mechanisms in mutants of KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2017;61.

  64. Wilson WR, Kline EG, Jones CE, Morder KT, Mettus RT, Doi Y, 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.

  65. Pfaller MA, Huband MD, Mendes RE, Flamm RK, Castanheira M. In vitro activity of meropenem/vaborbactam and characterisation of carbapenem resistance mechanisms among carbapenem-resistant Enterobacteriaceae from the 2015 meropenem/vaborbactam surveillance programme. Int J Antimicrob Agents. 2018;52:144–50.

    CAS  PubMed  Google Scholar 

  66. Livermore DM, Winstanley TG, Shannon KP. Interpretative reading: recognizing the unusual and inferring resistance mechanisms from resistance phenotypes. J Antimicrob Chemother. 2001;48(Suppl 1):87–102.

    CAS  PubMed  Google Scholar 

  67. Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: the phantom menace. J Antimicrob Chemother. 2012;67:1597–606.

    CAS  PubMed  Google Scholar 

  68. Martínez-Martínez L. Extended-spectrum beta-lactamases and the permeability barrier. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2008;14(Suppl 1):82–9.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of California San Francisco School of Pharmacy, 533 Parnassus Ave, U-503 Box 0622, San Francisco, CA, 94143, USA

    Stephanie Ho, Trang Trinh & Conan MacDougall

  2. University of California San Francisco Medical Center, San Francisco, CA, USA

    Lynn Nguyen

Authors
  1. Stephanie Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lynn Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Trang Trinh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Conan MacDougall
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Conan MacDougall.

Ethics declarations

Conflict of Interest

Stephanie Ho, Lynn Nguyen, and Trang Trinh declare no conflicts of interest.Conan MacDougall has received honoraria from Shionogi Pharmaceuticals and has served on an advisory board for Paratek Pharmaceuticals.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Antimicrobial Development and Drug Resistance

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ho, S., Nguyen, L., Trinh, T. et al. Recognizing and Overcoming Resistance to New Beta-Lactam/Beta-Lactamase Inhibitor Combinations. Curr Infect Dis Rep 21, 39 (2019). https://doi.org/10.1007/s11908-019-0690-9

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11908-019-0690-9

Keywords

Search

Navigation