Brink, AdrianCoetzee, JenniferRichards, Guy A.Feldman, CharlesLowman, WarrenTootla, Hafsah D.Miller, Malcolm G.A.Niehaus, Abraham J.Wasserman, SeanPerovic, OlgaGovind, Chetna N.Schellack, NatalieMendelson, Marc2023-02-272023-02-272022-10-20Brink, A.J., Coetzee, J., Richards, G.A., et al. Best practices: Appropriate use of the new β-lactam/β-lactamase inhibitor combinations, ceftazidime-avibactam and ceftolozane-tazobactam in South Africa. Southern African Journal of Infectious Diseases 2022; 37(1), a453. https://DOI.org/10.4102/sajid.v37i1.453.2312-0053 (print)2313-1810 (online)10.4102/sajid.v37i1.453https://repository.up.ac.za/handle/2263/89842Antibiotic stewardship of hospital-acquired infections because of difficult-to-treat resistant (DTR) Gram-negative bacteria is a global challenge. Their increasing prevalence in South Africa has required a shift in prescribing in recent years towards colistin, an antibiotic of last resort. High toxicity levels and developing resistance to colistin are narrowing treatment options further. Recently, two new β-lactam/β-lactamase inhibitor combinations, ceftazidime-avibactam and ceftolozane-tazobactam were registered in South Africa, bringing hope of new options for management of these life-threatening infections. However, with increased use in the private sector, increasing levels of resistance to ceftazidime-avibactam are already being witnessed, putting their long-term viability as treatment options of last resort, in jeopardy. This review focuses on how these two vital new antibiotics should be stewarded within a framework that recognises the resistance mechanisms currently predominant in South Africa’s multi-drug and DTR Gram-negative bacteria. Moreover, the withholding of their use for resistant infections that can be treated with currently available antibiotics is a critical part of stewardship, if these antibiotics are to be conserved in the long term.en© 2022. The Authors. Licensee: AOSIS. This work is licensed under the Creative Commons Attribution License.Antimicrobial stewardship (AMS)β-Lactamase inhibitor combinationsCeftazidimeavibactamCeftolozane-tazobactamGram-negativesPseudomonas aeruginosaEnterobacteralesBeta-lactam (β-Lactam)Beta-lactamase (β-Lactam)Difficult-to-treat resistant (DTR)Article