The changing landscape of antimicrobial resistance and use in South Africa: The need for access to new antibiotics: A position paper
DOI:
https://doi.org/10.7196/SAMJ.2024.v114i10.2348Keywords:
antimicrobial resistance, antimicrobial use, antibiotic stewardship, AwaRE antibioticsAbstract
Antibiotic resistance is a global threat, with a disproportionate burden of mortality in low- and middle-income countries. It is increasing in both the public and private healthcare sectors within South Africa, especially in Gram-negative organisms, and is associated with increased use of World Health Organization watch and reserve antibiotics. There is a need for improved access to new antibiotics to treat infections caused by drug-resistant organisms in order to limit side-effects and improve patient outcomes of currently available antibiotics. We propose the responsible introduction of these new antibiotics with both administrative and clinical oversight in order to preserve the longevity of these precious antibiotics.
References
1. World Health Organization. Ten threats to global health in 2019. Geneva: WHO, 2019. https://www. who.int/news-room/feature-stories/ten-threats-to-global-health-in-2019 (accessed 3 July 2020).
2. Murray CJ, Shunji Ikuta K, Sharara F, et al. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet 2022;399(10325):629-655. https://doi.org/10.1016/S0140-6736(21)02724-0.
3. Sartorius B, Gray AP, Davis Weaver N, et al. The burden of bacterial antimicrobial resistance in the WHO African region in 2019: A cross-country systematic analysis. Lancet Glob Health 2023;
12(2):E201-E216. https://doi.org/10.1016/S2214-109X(23)00539-9
4. HolmesAH,MooreLSP,SundsfjordA,etal.Understandingthemechanismsanddriversofantimicrobial
resistance. Lancet 2016;387(10014):176-187. https://doi.org/10.1016/S0140-6736(15)00473-0
5. Sharma A, Singh A, Dar MA, et al. Menace of antimicrobial resistance in LMICs: Current surveillance practices and control measures to tackle hostility. J Infect Public Health 2022;15(2):172-181. https://
doi.org/10.1016/J.JIPH.2021.12.008
6. MorielDG,PiccioliD,RasoMM,PizzaM.Theoverlookedbacterialpandemic.SeminImmunopathol 2024; 45(4-6):481-491. https://doi.org/10.1007/S00281-023-00997-1
7. Daulaire N, Bang A, Tomson G, Kalyango JN, Cars O. Universal access to effective antibiotics is essential for tackling antibiotic resistance. J Law Med Ethics 2015;43(Suppl 3):S17-S21. https://doi. org/10.1111/JLME.12269
8. Abubakar U, Amir O, Rodríguez-Baño J. Healthcare-associated infections in Africa: A systematic review and meta-analysis of point prevalence studies. J Pharm Policy Pract 2022;15(1):1-16. https:// doi.org/10.1186/S40545-022-00500-5
9. National Department of Health, South Africa. Surveillance for antimicrobial resistance and consumption of antibiotics in South Africa 2018 - 2022. Pretoria: NDoH, 2024.
10. Pillay T, Pillay DG, Adhikari M, Pillay A, Sturm AW. An outbreak of neonatal infection with Acinetobacter linked to contaminated suction catheters. J Hosp Infect 1999;43(4)299-304. https://doi. org/10.1016/S0195-6701(99)90426-7
11. Snyman Y, Whitelaw AC, Reuter S, et al. Clonal expansion of colistin-resistant Acinetobacter baumannii isolates in Cape Town, South Africa. Int J Infect Dis 2020;91:94-100. https://doi. org/10.1016/j.ijid.2019.11.021
12. Acinetobacter baumannii cluster reported in neonatal unit of KwaZulu-Natal hospital. Outbreak News Today, 2022. https://outbreaknewstoday.com/acinetobacter-baumannii-cluster-reported-in-neonatal- unit-of-kwazulu-natal-hospital-58138/ (accessed 3 March 2024).
13. Lowe M, Shuping L, Perovic O. Carbapenem-resistant Enterobacterales in patients with bacteraemia at tertiary academic hospitals in South Africa, 2019 - 2020: An update. S Afr Med J 2022;112(8):542-552. https://doi.org/10.7196/SAMJ.2022.V112I8.16351
14. Venter H, Ruan Z, Evans BA, et al. Molecular characterisation of Acinetobacter baumannii isolates from bloodstream infections in a tertiary-level hospital in South Africa. Front Microbiol 2022;13:863129. https://doi.org/10.3389/fmicb.2022.863129
15. Perovic IO, Duse A, Chibabhai V, et al. Acinetobacter baumannii complex, national laboratory-based surveillance in South Africa, 2017 to 2019. PLoS ONE 2022;17:e0271355. https://doi.org/10.1371/ journal.pone.0271355
16. Browne AJ, Chipeta MG, Haines-Woodhouse G, et al. Global antibiotic consumption and usage in humans, 2000 - 18: A spatial modelling study. Articles Lancet Planet Health 2021;5(12):893-904. https://doi.org/10.1016/S2542-5196(21)00280-1
17. Moore DP, Chetty T, Pillay A,.Antibiotic and antifungal use in paediatric departments at three academic hospitals in South Africa. IJID Regions 2024;10:151-158. https://doi.org/10.1016/J.IJREGI.2023.12.004
18. Mthombeni TC, Riétte Burger J, Lubbe MS, Julyan M. Antibiotic prescribing to inpatients in Limpopo, South Africa: A multicentre point-prevalence survey. Antimicrob Resist Infect Contr 2023;12(1):103.
19. Chetty T, Pillay A, Balakrishna Y, et al. Healthcare-associated infections drive antimicrobial prescribing in pediatric departments at three academic hospitals in South Africa. Pediatr Infect Dis J 2023;42(8):E283-289. https://doi.org/10.1097/INF.0000000000003954
20. Labuschagne Q, Schellack N, Gous A, et al. Colistin: Adult and paediatric guideline for South Africa, 2016. S Afr J Infect Dis 2016;31(1):3-7. https://doi.org/10.1080/23120053.2016.1144285.
21. Chibabhai V, Bekker A, Black M, et al. Appropriate use of colistin in neonates, infants and children: Interim guidance. S Afr J Infect Dis 2023;38(1):555 https://doi.org/10.4102/SAJID.V38I1.555
22. Paul M, Carrara E, Retamar P, et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram- negative bacilli (endorsed by European Society of Intensive Care Medicine). Clin Microbiol Infect 2022;28(4):521-547. https://doi.org/10.1016/j.cmi.2021.11.025
23. Brink AJ, Coetzee J, Richards GA, et al. Best practices: Appropriate use of the new B-lactam/ B-lactamase inhibitor combinations, ceftazidime-avibactam and ceftolozone-taxabactam in South Africa. S Afr J Infect Dis 2022;37(1):453. https://doi.org/10.4102/sajid.v37i1.453
24. Wang J, Pan Y, Shen J, Xu Y. The efficacy and safety of tigecycline for the treatment of bloodstream infections: A systematic review and meta-analysis. Ann Clin Microbiol Antimicrob 2017;16(1):24 .https://doi.org/10.1186/S12941-017-0199-8
25. Zha L, Pan L, Guo J, French N, Villanueva EV, Tefsen B. Effectiveness and safety of high dose tigecycline for the treatment of severe infections: A systematic review and meta-analysis. Adv Ther 2020;37(3):1049-1064. https://doi.org/10.1007/S12325-020-01235-Y
26. Gong J, Su D, Shang J, et al. Efficacy and safety of high-dose tigecycline for the treatment of infectious diseases: A meta-analysis. Medicine 2019;98:e17091. https://doi.org/10.1097/MD.0000000000017091
27. Almangour TA, Ghonem L, Aljabri A, et al. Ceftazidime-avibactam versus colistin for the treatment of infections due to carbapenem-resistant enterobacterales: A multicenter cohort study. Infect Drug Resist 2022;15:211-221. https://doi.org/10.2147/IDR.S349004
28. Karampatakis T, Tsergouli K, Lowrie K. Efficacy and safety of ceftazidime-avibactam compared to other antimicrobials for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae strains, a systematic review and meta-analysis. Microb Pathog 2023;179:106090. https:// doi.org/10.1016/J.MICPATH.2023.106090
29. Bradley JS, Broadhurst H, Cheng K, et al. Safety and efficacy of ceftazidime-avibactam plus metronidazole in the treatment of children ≥3 months to <18 years with complicated intra-abdominal infection: Results from a phase 2, randomized, controlled trial. Pediatr Infect Dis J 2019;38(8):816-824. https://doi.org/10.1097/INF.0000000000002392
30. Bradley JS, Roilides E, Broadhurst H, et al. Safety and efficacy of ceftazidime-avibactam in the treatment of children ≥3 months to <18 years with complicated urinary tract infection: Results from a phase 2 randomized, controlled trial. Pediatr Infect Dis J 2019;38(9):920-928. https://doi.org/10.1097/ INF.0000000000002395
31. Meng H, Zhao Y, An Q, Zhu B, Cao Z, Lu J. Use of ceftazidime-avibactam for suspected or confirmed carbapenem-resistant organisms in children: A retrospective study. Infect Drug Resist 2023;16:5815- 5824. https://doi.org/10.2147/IDR.S426326
32. Iosifidis E, Chorafa E, Agakidou E, et al. Use of ceftazidime-avibactam for the treatment of extensively drug-resistant or pan drug-resistant Klebsiella pneumoniae in neonates and children <5 years of age. Pediatr Infect Dis J 2019;38(8):812-815. https://doi.org/10.1097/INF.0000000000002344
33. Tootla HD, Copelyn J, Botha A, Brink AJ, Eley B. Using ceftazidime-avibactam for persistent carbapenem-resistant Serratia marcescens infection highlights antimicrobial stewardship challenges with new beta-lactam-inhibitor combination antibiotics. S Afr Med J 2021;111(8):729-731. https://doi. org/10.7196/SAMJ.2021.V111I8.15762
34. Falcone M, Daikos GL, Tiseo G, et al. Efficacy of ceftazidime-avibactam plus aztreonam in patients with bloodstream infections caused by metallo-β-lactamase-producing Enterobacterales. Clin Infect Dis 2021;72(11):1871-1878. https://doi.org/10.1093/cid/ciaa586
35. Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America 2023 guidance on the treatment of antimicrobial resistant gram-negative infections. Clin Infect Dis 2023 Jul 18:ciad428. https://doi.org/10.1093/CID/CIAD428
36. Liu J, Shu Y, Zhu F, et al. Comparative efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for multiple drug-resistant and extensively drug-resistant Acinetobacter baumannii infections: A systematic review and network meta-analysis. J Glob Antimicrob Resist 2021;24:136-147. https://doi.org/10.1016/J.JGAR.2020.08.021
37. Kaye KS, Shorr AF, Wunderink RG, et al. Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: A multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK). Lancet Infect Dis 2023;23(9):1072-1084. https://doi.org/10.1016/S1473-3099(23)00184-6.
38. Shields RK, Paterson DL, Tamma PD. Navigating available treatment options for carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex infections. Clin Infect Dis 2023;76(Suppl 2):S179-S193. https://doi.org/10.1093/CID/CIAD094
39. Bassetti M, Echols R, Matsunaga Y, et al. Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): A randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial. Lancet Infect Dis 2021;21(2):226-240. https://doi.org/10.1016/S1473-3099(20)30796-9
40. Falcone M, Tiseo G, Leonildi A, et al. Cefiderocol- compared to colistin-based regimens for the treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2022;66(5):e0214221. https://doi.org/10.1128/AAC.02142-21
41. Pascale R, Pasquini Z, Bartoletti M, et al. Cefiderocol treatment for carbapenem-resistant Acinetobacter baumannii infection in the ICU during the COVID-19 pandemic: A multicentre cohort study. JAC Antimicrob Resist 2021;3(4):dlab174. https://doi.org/10.1093/JACAMR/DLAB174
42. Shields RK, Potoski BA, Haidar G, et al. Clinical outcomes, drug toxicity, and emergence of ceftazidime-avibactam resistance among patients treated for carbapenem-resistant Enterobacteriaceae infections. Clin Infect Dis 2016;63(12):1615-1618. https://doi.org/10.1093/CID/CIW636
43. Fendian ÁM, Albanell-Fernández M, Tuset M, et al. Real-life data on the effectiveness and safety of cefiderocol in severely infected patients: A case series. Infect Dis Ther 2023;12(4):1205-1216. https:// doi.org/10.1007/S40121-023-00776-3
44. Dramowski A, Velaphi S, Reubenson G, et al. National Neonatal Sepsis Task Force launch: Supporting infection prevention and surveillance, outbreak investigation and antimicrobial stewardship in neonatal units in South Africa. S Afr Med J 2020;110(5):360-363. https://doi.org/10.7196/SAMJ.2020. V110I5.14564
45. Nana T, Bhoora S, Chibabhai V. Trends in the epidemiology of urinary tract infections in pregnancy at a tertiary hospital in Johannesburg: Are contemporary treatment recommendations appropriate? S Afr J Infect Dis 2021;36(1):328. https://doi.org/10.4102/SAJID.V36I1.328
46. Reddy K, Ramsamy Y, Swe Swe-Han K, et al. Antimicrobial resistance and antimicrobial stewardship in South Africa: A survey of healthcare workers in academic and nonacademic hospitals. Antimicrob Stewardship Healthcare Epidemiol 2023;3:e202. https://doi.org/10.1017/ASH.2023.483.
47. Hutton G, Chase C, Kennedy-Walker RJ. Costs of health care associated infections from inadequate water and sanitation in health care facilities in eastern and southern Africa. Washington, DC: World Bank, 2024. https://doi.org/10.1596/1813-9450-10708
Downloads
Published
Issue
Section
License
Copyright (c) 2024 H Finlayson, V Chibabhai, P Jeena, S Kolman, W Lowman, T C Manzini, T Nana, J Nuttall, A Parker, P Skosana, V Ueckermann, A Wise

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Licensing Information
The SAMJ is published under an Attribution-Non Commercial International Creative Commons Attribution (CC-BY-NC 4.0) License. Under this license, authors agree to make articles available to users, without permission or fees, for any lawful, non-commercial purpose. Users may read, copy, or re-use published content as long as the author and original place of publication are properly cited.
Exceptions to this license model is allowed for UKRI and research funded by organisations requiring that research be published open-access without embargo, under a CC-BY licence. As per the journals archiving policy, authors are permitted to self-archive the author-accepted manuscript (AAM) in a repository.
Publishing Rights
Authors grant the Publisher the exclusive right to publish, display, reproduce and/or distribute the Work in print and electronic format and in any medium known or hereafter developed, including for commercial use. The Author also agrees that the Publisher may retain in print or electronic format more than one copy of the Work for the purpose of preservation, security and back-up.