Janssen Zan, Martini Helena, Vanstokstraeten Robin, Vandoorslaer Kristof, Wybo Ingrid, Honacker Eveline Van, Piérard Denis
National Reference Center for Toxigenic Corynebacteria, Department of Microbiology and Infection Control, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium.
Antibiotics (Basel). 2025 Feb 6;14(2):160. doi: 10.3390/antibiotics14020160.
: Despite a significant reduction in diphtheria incidence and mortality due to vaccination, antitoxin therapy and antibiotic treatments, a concerning resurgence is occurring in Europe. Resistance to penicillins and macrolides is emerging, resulting in a growing challenge for diphtheria management. This retrospective study aims to evaluate and compare antibiotic susceptibilities of both toxigenic and . : Susceptibilities were assessed using broth microdilution-the gold standard-disk diffusion and the gradient method, and analyzed on the basis of the EUCAST breakpoint tables for the interpretation of MICs and zone diameters. Antimicrobial resistance genes and mutations were detected by analyzing whole-genome sequences (WGS). : A small number of isolates were resistant to the first-choice antimicrobial classes, penicillins and macrolides, while higher resistance rates were observed for ciprofloxacin (29%), tetracycline (38%) and trimethoprim-sulfamethoxazole (SXT, 85%). A good correlation was found with resistance genes and mutations detected by WGS. isolates were susceptible to all tested antibiotics, except clindamycin, to which this species is naturally resistant, and a few ciprofloxacin resistances not confirmed by WGS. Diffusion techniques were found to be acceptable alternatives, but false susceptible results were detected for ciprofloxacin and tetracycline by disk diffusion and ciprofloxacin and SXT by gradient diffusion. : Penicillins and macrolides remain the first-choice antibiotics for the treatment of diphtheria. However, antimicrobial susceptibility testing is needed for all toxigenic and isolates, as resistance is emerging. Antimicrobial susceptibility testing should not be limited to penicillins and macrolides, but be extended to other antibiotics. When WGS is performed for epidemiological purposes, resistance genes and mutations should be looked for.
尽管由于疫苗接种、抗毒素治疗和抗生素治疗，白喉的发病率和死亡率显著降低，但欧洲仍出现了令人担忧的回升。对青霉素和大环内酯类药物的耐药性正在出现，给白喉的治疗带来了越来越大的挑战。这项回顾性研究旨在评估和比较产毒和非产毒白喉棒状杆菌的抗生素敏感性。使用肉汤微量稀释法（金标准）、纸片扩散法和梯度法评估敏感性，并根据欧盟药敏试验委员会（EUCAST）的折点表对最低抑菌浓度（MIC）和抑菌圈直径进行分析。通过分析全基因组序列（WGS）检测抗菌药物耐药基因和突变。少数白喉棒状杆菌分离株对首选抗菌药物类别青霉素和大环内酯类耐药，而环丙沙星（29%）、四环素（38%）和甲氧苄啶-磺胺甲恶唑（SXT，85%）的耐药率较高。发现与WGS检测到的耐药基因和突变有良好的相关性。除克林霉素（该菌种天然耐药）和少数未被WGS证实的环丙沙星耐药菌株外，白喉棒状杆菌分离株对所有测试抗生素敏感。发现扩散技术是可接受的替代方法，但纸片扩散法检测环丙沙星和四环素以及梯度扩散法检测环丙沙星和SXT时出现了假敏感结果。青霉素和大环内酯类仍然是治疗白喉的首选抗生素。然而，由于耐药性正在出现，所有产毒和非产毒白喉棒状杆菌分离株都需要进行抗菌药物敏感性测试。抗菌药物敏感性测试不应局限于青霉素和大环内酯类，而应扩展到其他抗生素。当出于流行病学目的进行WGS时，应寻找耐药基因和突变。
