Introduction: A major public health problem is the emergence of anti-gram-negative antimicrobial resistance worldwide. Cefiderocol is a new agent targeting Gram-negative bacteria, including strains with resistance to carbapenems.
Aim of the study: Analysis of the efficiency of cefiderocol in the treatment of infections caused by gram-negative bacteria, the drug's mechanism of action and pharmacokinetics and pharmacodynamics of the drug.
Material and Methods: Search of the PubMed database using the following keywords: cefiderocol, resistance, gram negative bacteria. Only full-length articles were taken into consideration.
Results: The studies show that cefiderocol is active against Enterobacteriaceae, P. aeruginosa, B. cepacia and A. baumannii and effective in the treatment of pneumonia in both non-ventilated and ventilated patients. Moreover, it has been used in the treatment of sepsis as a rescue therapy.
Conclusion: Cefiderocol is an effective treatment for infections caused by gram-negative bacteria. However, more research is needed to learn more about the use of this drug, side effects and resistance mechanisms

Gorczyca, Kamila

Jastrzębska, Ilona

Kołodziej, Magdalena

Wieczorek, Michał

Węgorowski, Paweł

English

Akademicka Platforma Czasopism

1KOŁODZIEJ, Magdalena, GORCZYCA, Kamila, JASTRZĘBSKA, Ilona, WĘGOROWSKI, Paweł & WIECZOREK, Michał. The solution todrug resistance of Gram-negative bacteria – Cefiderocol. Journal of Education, Health and Sport. 2023;33(1):17-21. eISSN 2391-8306. DOIhttp://dx.doi.org/10.12775/JEHS.2023.33.01.002https://apcz.umk.pl/JEHS/article/view/43777https://zenodo.org/record/7962694The journal has had 40 points in Ministry of Education and Science of Poland parametric evaluation. Annex to the announcement of the Minister of Education and Science of December 21, 2021. No. 32343.Has a Journal's Unique Identifier: 201159. Scientific disciplines assigned: Physical Culture Sciences (Field of Medical sciences and health sciences); Health Sciences (Field of Medical Sciences and Health Sciences).Punkty Ministerialne z 2019 - aktualny rok 40 punktów. Załącznik do komunikatu Ministra Edukacji i Nauki z dnia 21 grudnia 2021 r. Lp. 32343. Posiada Unikatowy Identyfikator Czasopisma: 201159.Przypisane dyscypliny naukowe: Nauki o kulturze fizycznej (Dziedzina nauk medycznych i nauk o zdrowiu); Nauki o zdrowiu (Dziedzina nauk medycznych i nauk o zdrowiu).© The Authors 2023;This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, PolandOpen Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the originalauthor (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike.(http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited.The authors declare that there is no conflict of interests regarding the publication of this paper.Received: 29.04.2023. Revised: 10.05.2023. Accepted: 23.05.2023. Published: 23.05.2023.The solution to drug resistance of Gram-negative bacteria – CefiderocolMagdalena Kołodziej 1, https://orcid.org/0000-0002-6597-1559, magdalenakolodziej502@gmail.comKamila Gorczyca 2, https://orcid.org/0000-0002-7976-0509, kamila.gorczyca@o2.plIlona Jastrzębska 1, https://orcid.org/0000-0001-6754-529X, ilonaj14@gmail.comDr Paweł Węgorowski 3, https://orcid.org/0000-0001-6077-7653, wegorpl@wp.plDr Michał Wieczorek 3, https://orcid.org/0000-0002-3204-5022, wieczorek.michal@gmail.com1- Medical University of Lublin,2- Department of Obstetrics and Perinatology, Medical University of Lublin3- Vincent Pol University in Lublin.Corresponding authors: Magdalena Kołodziej, magdalenakolodziej502@gmail.com;AbstractIntroduction: A major public health problem is the emergence of anti-gram-negative antimicrobial resistance worldwide.Cefiderocol is a new agent targeting Gram-negative bacteria, including strains with resistance to carbapenems.Aim of the study: Analysis of the efficiency of cefiderocol in the treatment of infections caused by gram-negativebacteria, the drug's mechanism of action and pharmacokinetics and pharmacodynamics of the drug.Material and Methods: Search of the PubMed database using the following keywords: cefiderocol, resistance, gramnegative bacteria. Only full-length articles were taken into consideration.17Results: The studies show that cefiderocol is active against Enterobacteriaceae, P. aeruginosa, B. cepacia and A.baumannii and effective in the treatment of pneumonia in both non-ventilated and ventilated patients. Moreover, it hasbeen used in the treatment of sepsis as a rescue therapy.Conclusion: Cefiderocol is an effective treatment for infections caused by gram-negative bacteria. However, moreresearch is needed to learn more about the use of this drug, side effects and resistance mechanisms.Keywords: cefiderocol, resistance, gram negative bacteriaIntroductionA major public health problem is the emergence of anti-gram-negative antimicrobial resistance worldwide. Cefiderocol isa new agent targeting Gram-negative bacteria, including strains with resistance to carbapenems [1].Gram-negative bacteria resistant to carbapenems of clinical importance include, first of all, Pseudomonas aeruginosa,Acinetobacter baumannii, Enterobacteriaceae [2]. Enterobacteriacae produce both B-lactamase and extended-spectrumcarbapenemase, while Pseudomonas and Acetinobacter produce carbapenemases [3]. Colistin and tigecycline are used asfirst-line drugs in the treatment of infections caused by these pathogens, but their effectiveness is uncertain, even whenused in combination with other drugs. Recently, several new drugs with activity against certain carbapenem-resistantpathogens have either been approved for clinical use or are in the final stages of research. These include meropenem-vaborbactam, ceftazidime-avibactam, ceftolozane-tazobactam and cefiderocol [2].Materials, Methods and Purpose:The purpose of this article was to analyse the efficiency of cefiderocol in the treatment of infections caused by gram-negative bacteria, the drug's mechanism of action and pharmacokinetics and pharmacodynamics of the drug. During thesearch of the PubMed database the following keywords were used: cefiderocol, resistance, gram negative bacteria.Only full-length articles were taken into consideration.The mechanism of actionCefiderocol is a new cephalosporin with siderophore properties in which the catechol side chain forms a chelatedcomplex with iron [2,4]. Siderophoris an iron chelating agent and facilitates the absorption of iron, which is needed forthe survival of the bacteria [5]. The siderophore group absorbs iron from the environment. A complex composed ofsiderophore iron and of the antibiotic binds the iron transporter on the outside of the bacterial membrane and is actively18transported inside. Thanks to this, it bypasses the defence systems of the microorganism. This action is referred to as the"Trojan horse strategy" and uses an iron transporter to improve the penetration of the antibiotic [6].Pharmacokinetics and pharmacodynamics of the drugStructurally, cefiderocol is similar to cefepime and ceftazidime [1,7]. Cefiderocol is eliminated in 60-70% in the urineunchanged, and no accumulation was observed in health patients after a 1-h infusion of 1000 mg [8,9]. The coefficiencyof variation in volume of distribution and clearance in subjects with normal renal function for cefiderocol Has beenreported as 15.8 (15%) L and 4.70 (27%) L/h. In addition, there is no proof of significant interactions of this newcephalosporin with other medications [5]. The therapeutic dose of cefiderocol is 2g and is usually well tolerated inpatients. In addition, no side effects have been reported after the supratherapeutic dose of 4g. Additionally, cefiderocolhas no significant effect on ECG parameters, including the QT interval [10].Studies using cefiderocolCefiderocol has been studied in 2 radomized trials. These were phase 3 studies and involved patients with cancer andpneumonia in the second study. Mortality rates were similar with meropenem [11]. One study used cefiderocol to treat A.baumanii infection. It showed that patients who received cefiderocol had a lower risk of 30-day mortality compared tocontrols [12]. In another study, 65% of patients with nosocomial pneumonia, who were taking cefiderocol, achieved aclinical improvement compared with 67% of those taking meropenem [13]. Cefiderocol was approved in 2019 by theFDA for the treatment of infections caused by gram-negative bacteria, in particular complicated urinary tract infections[14]. The 2021 IDSA guidelines recommend the use of cefiderocol for the treatment of pneumonia [15].The use of cefiderocolCefiderocol is active against Enterobacteriaceae, P. aeruginosa, B. cepacia and A. baumannii [16]. In addition, it is activein vitro against all classes of beta-lactamases that are produced by Gram-negative bacteria (classes A, B and D) [17]. It isused to treat pneumonia [18] in both non-ventilated and ventilated patients. Additionally, cefiderocol is one of thetreatment options for ventilator-associated pneumonia [19]. Moreover, it has been used in the treatment of sepsis as arescue therapy and is used in patients with complications of urinary tract infections [20].Table 1. Range of activity of individual drugsCeftolozane-tazobactam Pseudomonas aeruginosa, EnterobacteriaceaeCeftazidime-avibactam Enterobacteriaceae, Pseudomonas aeruginosa,Stenotrophomonas maltophiliaCefiderocol Pseudomonas aeruginosa, Klebsiella pneumoniae,Acinetobacter baumannii, Stenotrophomonas maltophiliaSource: Own study based on: [20–23].19DiscussionCefiderocol is a new cephalosporin that is active against carbamenem-resistant Gram-negative bacteria both in vivo andin vitro. No clinically significant adverse effects have been reported in studies conducted with this drug. The impact ofcefiderocol on the iron economy is not yet well explained [24] however the mechanism of action of the drug provides itshigh concentration in the blood. In addition, the mechanisms of resistance to this drug have not been thoroughly studied[6].ConclusionCefiderocol is an effective treatment for infections caused by gram-negative bacteria. It is necessary to optimize the useof new antibiotics, guaranteeing patients the best treatment, while delaying the emergence of resistance to cefiderocol.However, more research is needed to learn more about the use of this drug, side effects and resistance mechanisms.References:1. Sato, T.; Yamawaki, K. Cefiderocol: Discovery, Chemistry, and In Vivo Profiles of a Novel SiderophoreCephalosporin. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2019, 69, S538–S543, doi:10.1093/cid/ciz826.2. Doi, Y. Treatment Options for Carbapenem-Resistant Gram-Negative Bacterial Infections. Clin. Infect. Dis. Off.Publ. Infect. Dis. Soc. Am. 2019, 69, S565–S575, doi:10.1093/cid/ciz830.3. Kanj, S.S.; Bassetti, M.; Kiratisin, P.; Rodrigues, C.; Villegas, M.V.; Yu, Y.; van Duin, D. Clinical Data fromStudies Involving Novel Antibiotics to Treat Multidrug-Resistant Gram-Negative Bacterial Infections. Int. J.Antimicrob. Agents 2022, 60, 106633, doi:10.1016/j.ijantimicag.2022.106633.4. 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The solution to drug resistance of Gram-negative bacteria – Cefiderocol

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The solution to drug resistance of Gram-negative bacteria – Cefiderocol

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