Plaisance Connor J, Borne Grant E, Daniel Charles P, Wagner Maxwell J, Shelvan Anitha, Mathew Jibin, Ahmadzadeh Shahab, Paladini Antonella, Varrassi Giustino, Shekoohi Sahar, Kaye Alan D
School of Medicine, Louisiana State University Health Sciences Center, Shreveport, USA.
Department of Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA.
Cureus. 2024 Jan 13;16(1):e52230. doi: 10.7759/cureus.52230. eCollection 2024 Jan.
With increasing resistance to conventional antibiotic treatments, especially among gram-negative bacilli, the search for new antibiotics has become critical on a global scale. Among infections with multidrug-resistant bacteria is hospital-acquired pneumonia (HAP), which is nosocomial pneumonia in patients who have been hospitalized for more than 48 hours. HAP carries a high mortality rate and continues to be a challenge with regard to adequate treatment. The typical multidrug-resistant gram negatives found in HAP include , , and . Many new antibiotics have been studied and tested against these pathogens as possible solutions, and the search continues. Cefiderocol, a novel siderophore cephalosporin, is effective against these pathogens. Cefiderocol is an iron-chelating agent that makes use of iron pumps on the membrane of bacteria via a catechol moiety on the C3 side chain of the molecule. This allows for easy access into the cytoplasm, where it can inhibit peptidoglycan synthesis by binding to penicillin-binding proteins. Cefiderocol displays linear pharmacokinetics and is mainly excreted through the kidneys. It is well tolerated in healthy individuals but may need adjustments of dosage in patients with impaired renal function. Studies have shown that both healthy subjects and those with impaired renal function experienced some adverse effects, including nausea, diarrhea, abdominal pain, and increased creatinine kinase; however, these adverse effects were limited and experienced in placebo groups. It has demonstrated efficacy in treating infections caused by many multidrug-resistant gram-negative pathogens and has demonstrated high stability against many classes of b-lactamases. There have been multiple phase 3 trials, such as the CREDIBLE-CR trial and the APEKS-NP trial, that demonstrated efficacy in treated nosocomial pneumonia caused by multidrug-resistant gram negatives, such as carbapenem-resistant , , and , compared to the best available treatment. While clinical data remain limited, a few studies are showing clinical efficacy and few adverse effects. Cefiderocol demonstrated effectivity in treating multidrug-resistant gram-negative pneumonia in patients with multiple comorbidities, such as chronic kidney disease, chronic-obstructive pulmonary disease, and diabetes mellitus. Cefiderocol shows promise as a novel antimicrobial agent in treating multidrug-resistant gram-negative in HAP.
随着对传统抗生素治疗的耐药性不断增加，尤其是在革兰氏阴性杆菌中，寻找新型抗生素在全球范围内已变得至关重要。医院获得性肺炎（HAP）是多重耐药菌感染之一，它是指住院超过48小时的患者发生的医院内肺炎。HAP死亡率高，在充分治疗方面仍然是一项挑战。HAP中常见的典型多重耐药革兰氏阴性菌包括 、 和 。许多新型抗生素已针对这些病原体进行了研究和测试，作为可能的解决方案，并且研究仍在继续。头孢地尔，一种新型铁载体头孢菌素，对这些病原体有效。头孢地尔是一种铁螯合剂，它通过分子C3侧链上的儿茶酚部分利用细菌膜上的铁泵。这使得它能够轻松进入细胞质，在那里它可以通过与青霉素结合蛋白结合来抑制肽聚糖合成。头孢地尔呈现线性药代动力学，主要通过肾脏排泄。它在健康个体中耐受性良好，但肾功能受损的患者可能需要调整剂量。研究表明，健康受试者和肾功能受损者都出现了一些不良反应，包括恶心、腹泻、腹痛和肌酸激酶升高；然而，这些不良反应是有限的，并且在安慰剂组中也有出现。它已证明在治疗由许多多重耐药革兰氏阴性病原体引起的感染方面有效，并且对许多类β-内酰胺酶具有高稳定性。已经进行了多项3期试验，如CREDIBLE-CR试验和APEKS-NP试验，与现有最佳治疗方法相比，这些试验证明了在治疗由多重耐药革兰氏阴性菌引起的医院内肺炎方面的有效性，如耐碳青霉烯类 、 和 。虽然临床数据仍然有限，但一些研究显示出临床疗效且不良反应较少。头孢地尔在治疗患有多种合并症（如慢性肾病、慢性阻塞性肺疾病和糖尿病）的患者的多重耐药革兰氏阴性肺炎方面显示出有效性。头孢地尔作为一种新型抗菌剂在治疗HAP中的多重耐药革兰氏阴性菌方面显示出前景。
