Bell Sara F E, Ware Robert S, Lewis David A, Lahra Monica M, Whiley David M
Centre for Clinical Research, The University of Queensland, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
Menzies Health Institute Queensland and School of Medicine and Dentistry, Griffith University, Nathan, QLD, Australia.
Lancet Microbe. 2023 Jul;4(7):e544-e551. doi: 10.1016/S2666-5247(23)00071-X. Epub 2023 Jun 16.
Neisseria gonorrhoeae treatment guided by molecular antimicrobial susceptibility assays could improve treatment options and antimicrobial stewardship; however, few commercial assays are available. We aimed to investigate antimicrobial susceptibility of N gonorrhoeae isolates in New South Wales, Australia, and estimate the potential usefulness of hypothetical combinations of rapid molecular antimicrobial susceptibility assays.
In this proof-of-principle, population-based, retrospective analysis, we assessed N gonorrhoeae susceptibility data for ceftriaxone, azithromycin, ciprofloxacin, and penicillin. Isolates were previously collected as part of the Australian Gonococcal Surveillance Programme between Jan 1, 2008, and Dec 31, 2019. All cultured N gonorrhoeae isolates with susceptibility data to all four antimicrobials were included. However, only one isolate was included if several isolates originated from the same individual within 13 days of the previous isolate originating from that individual, and there were less than two standard double-dilution minimum inhibitory concentrations between the isolates. We assessed the use of different combinations of hypothetical antimicrobial susceptibility assays and treatment combinations in terms of their ability to minimise overall ceftriaxone use, and use specifically in isolates with decreased susceptibility to ceftriaxone, compared with standard non-assay-guided empirical ceftriaxone treatment.
We included 23 089 N gonorrhoeae isolates. The prevalence of antimicrobial sensitivity fluctuated significantly during the study. Isolates with decreased susceptibility to ceftriaxone were more likely to be resistant to one or more antimicrobials than isolates without decreased susceptibility (782 [98·6%] of 793 vs 10 661 [47·8%] of 22 296), particularly ciprofloxacin (p<0·0001) and penicillin (p<0·0001). Compared with empirical ceftriaxone treatment, we estimated that strategies based on the use of hypothetical antimicrobial susceptibility would reduce ceftriaxone use (p<0·0001). However, because of co-resistance, most assay-directed treatment strategies, including those involving use of assays for two antibiotics, would result in only moderate reductions in ceftriaxone use among isolates with decreased susceptibility to ceftriaxone.
Individualised treatment guided by molecular antimicrobial susceptibility diagnostics could help to reduce overall ceftriaxone use in gonorrhoea. However, the use of these assays needs to be informed by the non-random nature of co-resistance among circulating N gonorrhoeae strains.
Australian Government and Queensland Government.
由分子抗菌药物敏感性检测指导的淋病奈瑟菌治疗可改善治疗选择并促进抗菌药物管理；然而，可用的商业检测方法很少。我们旨在调查澳大利亚新南威尔士州淋病奈瑟菌分离株的抗菌药物敏感性，并评估快速分子抗菌药物敏感性检测的假设组合的潜在效用。
在这项基于人群的原理验证性回顾性分析中，我们评估了淋病奈瑟菌对头孢曲松、阿奇霉素、环丙沙星和青霉素的敏感性数据。这些分离株先前作为澳大利亚淋球菌监测计划的一部分，于2008年1月1日至2019年12月31日期间收集。纳入了所有对这四种抗菌药物均有敏感性数据的培养淋病奈瑟菌分离株。然而，如果同一人的多个分离株在先前分离株之后的13天内获得，且这些分离株之间的标准双倍稀释最低抑菌浓度相差不到两个，则只纳入其中一个分离株。我们评估了假设的抗菌药物敏感性检测和治疗组合的不同组合在将头孢曲松总体使用量降至最低方面的作用，以及与标准的非检测指导经验性头孢曲松治疗相比，在对头孢曲松敏感性降低的分离株中的具体使用情况。
我们纳入了23089株淋病奈瑟菌分离株。在研究期间，抗菌药物敏感性的流行率波动显著。对头孢曲松敏感性降低的分离株比敏感性未降低的分离株更有可能对一种或多种抗菌药物耐药（793株中的782株[98.6%]对22296株中的10661株[47.8%]），尤其是环丙沙星（p<0.0001）和青霉素（p<0.0001）。与经验性头孢曲松治疗相比，我们估计基于使用假设的抗菌药物敏感性的策略会减少头孢曲松的使用（p<0.0001）。然而，由于共同耐药性，大多数检测指导的治疗策略，包括那些涉及使用两种抗生素检测的策略，在对头孢曲松敏感性降低的分离株中只会使头孢曲松的使用量适度减少。
由分子抗菌药物敏感性诊断指导的个体化治疗有助于减少淋病中头孢曲松的总体使用。然而，这些检测方法的使用需要考虑到循环淋病奈瑟菌菌株中共同耐药性的非随机性质。
澳大利亚政府和昆士兰州政府。
