Sandhu Gagangeet, Piraino Samuel T, Piticaru Joshua
Division of Critical Care, Department of Medicine, St Joseph's Hospital, Syracuse, NY; and.
Department of Pharmacy, St Joseph's Hospital, Syracuse, NY.
Am J Ther. 2022;29(3):e275-e278. doi: 10.1097/MJT.0000000000001487. Epub 2022 Mar 4.
Severe SARS-CoV-2 (COVID) pneumonia is characterized by marked inflammation. Current guidelines recommend the addition of the tocilizumab to dexamethasone in critically ill patients. In randomized trials, the use of tocilizumab was not associated with a statistically significant increased risk of secondary infections but concerns remain.
Do patients with severe COVID pneumonia treated with tocilizumab experienced high rates of secondary infection.
We performed a retrospective electronic chart review of patients with COVID pneumonia who received tocilizumab and dexamethasone (n = 62) from January 2021 to October 2021 and compared them with a cohort of patients (n = 49) who received only dexamethasone and admitted from July 2020 to December 2020 (before institutional use of tocilizumab). Patients received tocilizumab only if they had acute hypoxic respiratory failure and were felt to be clinically worsening. Patients were deemed to have a secondary infection only if a diagnosis of infection was confirmed via positive cultures.
Sixty-six patients received tocilizumab; of which, 30 (45.5%) subsequently had culture-positive secondary infections compared with 24.5% of controls. Thirty-one patients (47.0%) who received tocilizumab died by the time of analysis, 14 (45.2%) of whom had a secondary infection. Gram-negative bacterial infections predominated, followed by fungal infections. Patients who received tocilizumab had over twice as many gram-negative pneumonias (30.3% vs. 14.3%).
Patients with severe COVID pneumonia treated with tocilizumab experienced high rates of secondary infection. Although the benefit of tocilizumab in reducing mortality is well-established and almost certainly outweighs secondary infection risks, we question if the "real-world" infection rates are much higher than those reported in trials or if the infection risk could be mitigated with dose reductions in tocilizumab without losing the mortality benefit. Further study into the infection risk, and risk-benefit analysis of dose adjustments, of tocilizumab in the critical care setting is warranted.
重症严重急性呼吸综合征冠状病毒2（SARS-CoV-2，即新冠病毒）肺炎的特点是炎症明显。当前指南建议在重症患者中，在使用地塞米松的基础上加用托珠单抗。在随机试验中，使用托珠单抗与继发感染风险的统计学显著增加无关，但仍存在担忧。
接受托珠单抗治疗的重症新冠病毒肺炎患者继发感染率是否较高？
我们对2021年1月至2021年10月期间接受托珠单抗和地塞米松治疗的新冠病毒肺炎患者（n = 62）进行了回顾性电子病历审查，并将他们与2020年7月至2020年12月期间（在机构开始使用托珠单抗之前）仅接受地塞米松治疗的一组患者（n = 49）进行比较。仅当患者出现急性低氧性呼吸衰竭且临床症状恶化时才给予托珠单抗治疗。只有通过阳性培养确诊感染时，患者才被视为发生继发感染。
66例患者接受了托珠单抗治疗；其中，30例（45.5%）随后出现培养阳性的继发感染，而对照组为24.5%。到分析时，接受托珠单抗治疗的31例患者（47.0%）死亡，其中14例（45.2%）发生了继发感染。革兰阴性菌感染占主导，其次是真菌感染。接受托珠单抗治疗的患者革兰阴性菌肺炎的发生率是对照组的两倍多（30.3%对14.3%）。
接受托珠单抗治疗的重症新冠病毒肺炎患者继发感染率较高。尽管托珠单抗在降低死亡率方面的益处已得到充分证实，且几乎肯定超过继发感染风险，但我们质疑“现实世界”中的感染率是否远高于试验报告的感染率，或者是否可以通过降低托珠单抗剂量来降低感染风险，同时又不失去死亡率方面的益处。有必要对重症监护环境中托珠单抗的感染风险以及剂量调整的风险效益分析进行进一步研究。
