Lau Chee Lan, Ramli Ramliza, Periyasamy Petrick, Tan Toh Leong, Neoh Hui-Min, Yusof Aliza Mohamad, Zainal Abidin Zainina, Zulkifli Chia Noranati, Mohd Saaid Mohd Syazwan, Abdul Aziz Munirah, Naina-Mohamed Isa
Department of Pharmacology, Pharmacoepidemiology and Drug Safety Unit, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia.
Pharmacy Department, Hospital Canselor Tuanku Muhriz, Cheras, Kuala Lumpur, Malaysia.
Microbiol Spectr. 2025 Jun 18:e0286324. doi: 10.1128/spectrum.02863-24.
Delayed antibiotics increase mortality in bloodstream infection (BSI). Direct-from-blood-culture disk diffusion antibiotic susceptibility testing (dAST) forecasts susceptibility earlier than conventional susceptibility testing (cAST). The study aimed to evaluate dAST performance and its impact on antibiotic adjustment in BSI. In this Malaysian single-center prospective study, dAST was performed and interpreted according to breakpoints by Clinical and Laboratory Standards Institute (CLSI) guidelines. The turnaround time (TAT), categorical agreements (CA), and predictive values of dAST for susceptibility by cAST were determined among positive blood cultures (PBC) between November 2022 and November 2023. The active and WHO AWaRe antibiotics administered before and after dAST results were compared. Of the 318 PBCs, the median of TAT was earlier than cAST by 35 hours. The CA for 3,561 organism-antibiotics combinations was 91.5%, with 3.6% very major errors (VME), 3.3% major errors (ME), and 5.2% minor errors (mE). The dAST achieved CA above 90% for with cefoxitin (98.5%), with ceftazidime (100%), and with ampicillin/sulbactam (100%). For Enterobacterales, most combinations were above 90%, including ampicillin (95.1%), ceftriaxone (95.7%), and meropenem (95.7%), though those of the aminopenicillin/inhibitor combinations were above 80%. Most errors were attributed to mEs. Among 159 BSI, the prescribing of active antibiotics improved significantly following dAST (73.0% versus 89.3%, < 0.001) but not WHO Access antibiotics (35.8% versus 35.2%, = 0.188). dAST had good CAs for most antibiotics, allowing earlier improvement in active antibiotics. The modest change in WHO Access antibiotics prescribing reveals practice gaps in need of antimicrobial stewardship.
Global deaths attributable to antimicrobial resistance are rising. Hence, rapid susceptibility testing is essential for timely antibiotic de-escalation to mitigate antimicrobial resistance (AMR) development from exposure to broad-spectrum antibiotics. Compared to the costly advanced technology, direct disk diffusion from blood culture (diffusion antibiotic susceptibility testing [dAST]) is an affordable method that can be quickly adopted. However, the reliability of dAST in informing susceptibility was mainly reported from Western countries and scarcely from other regions, including Southeast Asia, where the AMR burden is high. This study from Malaysia adds insights into the performance of dAST and the potential to apply it in similar resource-limited settings from the same region. Furthermore, assessing the dAST's influence on antibiotic prescribing identifies the gap in implementation to guide areas of improvement for optimizing clinical utility.
延迟使用抗生素会增加血流感染(BSI)的死亡率。直接从血培养进行纸片扩散法抗生素敏感性试验(dAST)比传统敏感性试验(cAST)能更早预测敏感性。本研究旨在评估dAST的性能及其对BSI中抗生素调整的影响。在这项马来西亚单中心前瞻性研究中,dAST按照临床和实验室标准协会(CLSI)指南的断点进行操作和解释。在2022年11月至2023年11月期间,对阳性血培养(PBC)样本测定dAST的周转时间(TAT)、分类一致性(CA)以及相对于cAST的敏感性预测值。比较了dAST结果前后使用的活性抗生素和世界卫生组织基本药物清单(WHO AWaRe)中的抗生素。在318份PBC样本中,TAT的中位数比cAST早35小时。3561种微生物 - 抗生素组合的CA为91.5%,其中3.6%为极重大错误(VME),3.3%为重大错误(ME),5.2%为轻微错误(mE)。dAST对头孢西丁的CA达到98.5%,对头孢他啶的CA达到100%,对氨苄西林/舒巴坦的CA达到100%。对于肠杆菌科细菌,大多数组合的CA高于90%,包括氨苄西林(95.1%)、头孢曲松(95.7%)和美罗培南(95.7%),不过氨基青霉素/抑制剂组合的CA高于80%。大多数错误归因于轻微错误。在159例BSI中,dAST结果出来后,活性抗生素的处方开具情况有显著改善(73.0%对89.3%,P < 0.001),但世界卫生组织基本药物清单中的抗生素处方开具情况没有显著变化(35.8%对35.2%,P = 0.188)。dAST对大多数抗生素具有良好的CA,能使活性抗生素更早得到改善。世界卫生组织基本药物清单中抗生素处方开具情况的适度变化揭示了抗菌药物管理方面需要填补的实践空白。
全球因抗菌药物耐药性导致的死亡人数正在上升。因此,快速敏感性试验对于及时进行抗生素降阶梯治疗以减轻因接触广谱抗生素而产生的抗菌药物耐药性(AMR)发展至关重要。与成本高昂的先进技术相比,直接从血培养进行纸片扩散法(扩散抗生素敏感性试验[dAST])是一种可快速采用的经济实惠的方法。然而,dAST在告知敏感性方面的可靠性主要来自西方国家,在包括东南亚在内的其他地区报道较少,而东南亚的AMR负担较重。这项来自马来西亚的研究为dAST的性能以及在同一地区类似资源有限环境中应用它的潜力提供了新见解。此外,评估dAST对抗生素处方的影响可确定实施过程中的差距,以指导改进领域,优化临床效用。