Best practices: Appropriate use of the new β-lactam/ β-lactamase inhibitor combinations, ceftazidime- avibactam and ceftolozane-tazobactam in South Africa

Antibiotic 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 beta-lactam/beta-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.

Automated summary

Antibiotic stewardship in South Africa is facing challenges due to difficult-to-treat resistant Gram-negative bacteria causing hospital-acquired infections. The use of colistin, a last-resort antibiotic, has been increasing, but its toxicity and developing resistance limit treatment options. The registration of two new antibiotics, ceftazidime-avibactam and ceftolozane-tazobactam, brings hope for managing these life-threatening infections. However, the increasing resistance to ceftazidime-avibactam in the private sector jeopardizes their long-term viability as last-resort treatment options.