Andreoni Federica, Zürcher Claudia, Tarnutzer Andrea, Schilcher Katrin, Neff Andrina, Keller Nadia, Marques Maggio Ewerton, Poyart Claire, Schuepbach Reto A, Zinkernagel Annelies S
Division of Infectious Diseases and Hospital Epidemiology.
Division of Clinical Pathology.
J Infect Dis. 2017 Jan 15;215(2):269-277. doi: 10.1093/infdis/jiw229.
Group A Streptococcus (GAS) has acquired an arsenal of virulence factors, promoting life-threatening invasive infections such as necrotizing fasciitis. Current therapeutic regimens for necrotizing fasciitis include surgical debridement and treatment with cell wall-active antibiotics. Addition of clindamycin (CLI) is recommended, although clinical evidence is lacking. Reflecting the current clinical dilemma, an observational study showed that only 63% of the patients with severe invasive GAS infection received CLI. This work thus aimed to address whether CLI improves necrotizing fasciitis outcome by modulating virulence factors of CLI-susceptible and CLI-resistant GAS in vitro and in vivo. Treatment with CLI reduced extracellular DNase Sda1 and streptolysin O (SLO) activity in vivo, whereas subinhibitory CLI concentrations induced expression and activity of SLO, DNase, and Streptococcus pyogenes cell envelope protease in vitro. Our in vivo results suggest that CLI should be administered as soon as possible to patients with necrotizing fasciitis, while our in vitro studies emphasize that a high dosage of CLI is essential.
A组链球菌（GAS）已经获得了一系列毒力因子，可引发诸如坏死性筋膜炎等危及生命的侵袭性感染。目前针对坏死性筋膜炎的治疗方案包括外科清创术以及使用细胞壁活性抗生素进行治疗。尽管缺乏临床证据，但仍建议加用克林霉素（CLI）。一项观察性研究反映了当前的临床困境，该研究表明，在严重侵袭性GAS感染患者中，只有63%的患者接受了CLI治疗。因此，这项研究旨在探讨CLI是否通过在体外和体内调节对CLI敏感和耐药的GAS的毒力因子来改善坏死性筋膜炎的治疗效果。CLI治疗在体内降低了细胞外DNA酶Sda1和链球菌溶血素O（SLO）的活性，而亚抑菌浓度的CLI在体外诱导了SLO、DNA酶和化脓性链球菌细胞包膜蛋白酶的表达和活性。我们的体内研究结果表明，坏死性筋膜炎患者应尽快使用CLI，而我们的体外研究强调高剂量的CLI至关重要。
