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

Adrian J Brink¹, Jennifer Coetzee², Guy A Richards³, Charles Feldman⁴, Warren Lowman^{5

6

7}, Hafsah D Tootla⁸, Malcolm G A Miller⁹, Abraham J Niehaus¹⁰, Sean Wasserman^{11

12}, Olga Perovic^{13

14}, Chetna N Govind^{15

16}, Natalie Schellack¹⁷, Marc Mendelson¹¹

Affiliations

¹ Division of Medical Microbiology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
² Division of Microbiology, Ampath National Reference Laboratory, Centurion, South Africa.
³ Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁴ Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁵ Department of Clinical Microbiology, Pathcare/Vermaak Pathologists, Gauteng, South Africa, South Africa.
⁶ Department Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
⁷ Department of Clinical Microbiology and Infection Prevention and Control, Wits Donald Gordon Medical Centre, Johannesburg, South Africa.
⁸ Division of Medical Microbiology, National Health Laboratory Service, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.
⁹ Division of Critical Care, Department of Anaesthesia and Perioperative Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
¹⁰ Department of Medical Microbiology, Ampath Laboratory Services, Cape Town, South Africa.
¹¹ Division of Infectious Diseases and HIV Medicine, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
¹² Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
¹³ National Institute for Communicable Disease, National Health Laboratory Services, Johannesburg, South Africa.
¹⁴ School of Pathology, Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁵ Department of Medical Microbiology, Lancet Laboratories, KwaZulu-Natal, Durban, South Africa.
¹⁶ Antimicrobial Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
¹⁷ Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.

PMID: 36338193
PMCID: PMC9634826
DOI: 10.4102/sajid.v37i1.453

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

Adrian J Brink et al. S Afr J Infect Dis. 2022.

. 2022 Oct 20;37(1):453.

doi: 10.4102/sajid.v37i1.453. eCollection 2022.

Authors

Affiliations

¹ Division of Medical Microbiology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
² Division of Microbiology, Ampath National Reference Laboratory, Centurion, South Africa.
³ Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁴ Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁵ Department of Clinical Microbiology, Pathcare/Vermaak Pathologists, Gauteng, South Africa, South Africa.
⁶ Department Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
⁷ Department of Clinical Microbiology and Infection Prevention and Control, Wits Donald Gordon Medical Centre, Johannesburg, South Africa.
⁸ Division of Medical Microbiology, National Health Laboratory Service, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.
⁹ Division of Critical Care, Department of Anaesthesia and Perioperative Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
¹⁰ Department of Medical Microbiology, Ampath Laboratory Services, Cape Town, South Africa.
¹¹ Division of Infectious Diseases and HIV Medicine, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
¹² Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
¹³ National Institute for Communicable Disease, National Health Laboratory Services, Johannesburg, South Africa.
¹⁴ School of Pathology, Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁵ Department of Medical Microbiology, Lancet Laboratories, KwaZulu-Natal, Durban, South Africa.
¹⁶ Antimicrobial Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
¹⁷ Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.

PMID: 36338193
PMCID: PMC9634826
DOI: 10.4102/sajid.v37i1.453

Abstract

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 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.

Keywords: Enterobacterales; Gram-negatives; Pseudomonas aeruginosa; antimicrobial stewardship; ceftazidime-avibactam; ceftolozane-tazobactam; β-lactam/β-lactamase inhibitor combinations.

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Conflict of interest statement

The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.

Figures

**FIGURE 1**
Conceptual approach to β-lactamase inhibitor therapy for severe infections.

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

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

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Conflict of interest statement

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