Department of Health Sciences (DISSAL), University of Genoa.
Clinica Malattie Infettive, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Curr Opin Infect Dis. 2022 Dec 1;35(6):568-574. doi: 10.1097/QCO.0000000000000884. Epub 2022 Oct 3.
To discuss empirical therapy for severe infections due to Gram-negative bacteria with difficult-to-treat resistance (GNB-DTR) in current clinical practice, focusing in particular on the positioning of novel therapeutic agents and rapid diagnostic tests.
The current era of novel agents active against GNB-DTR and showing differential activity against specific determinants of resistance is an unprecedented scenario, in which the clinical reasoning leading to the choice of the empirical therapy for treating severe GNB-DTR infections is becoming more complex, but it also allows for enhanced treatment precision.
Novel agents should be used in line with antimicrobial stewardship principles, aimed at reducing selective pressure for antimicrobial resistance. However, this does not mean that they should not be used. Indeed, excesses in restrictive uses may be unethical by precluding access to the most effective and less toxic treatments for patients with severe GNB-DTR infections. Given these premises (the 'how'), empirical treatment with novel agents should be considered in all patients with risk factors for GNB-DTR and severe clinical presentation of acute infection (the 'when'). Furthermore, empirical novel agents should preferably be continued only for a few hours, until de-escalation, modification, or confirmation (as targeted therapy) is made possible by the results of rapid diagnostic tests (the 'how long').
讨论目前临床实践中针对革兰氏阴性菌（GNB）耐药性严重感染（GNB-DTR）的经验性治疗，特别关注新型治疗药物和快速诊断检测的定位。
目前针对 GNB-DTR 具有活性且针对特定耐药决定因素具有不同活性的新型药物的出现是一个前所未有的情况，这使得导致选择治疗严重 GNB-DTR 感染的经验性治疗的临床推理变得更加复杂，但也允许提高治疗精度。
新型药物应根据抗菌药物管理原则使用，旨在降低抗菌药物耐药性的选择压力。然而，这并不意味着不应使用它们。实际上，过度限制使用可能不道德，因为它会排除对患有严重 GNB-DTR 感染的患者使用最有效和毒性较低的治疗方法。鉴于这些前提（“如何”），所有具有 GNB-DTR 风险因素和急性感染严重临床表现的患者都应考虑使用新型药物进行经验性治疗（“何时”）。此外，只有在快速诊断检测结果（“如何”）允许进行降级、修改或确认（作为靶向治疗）时，才应优选继续使用新型经验性药物几个小时。
