Cefiderocol in Combating Carbapenem-Resistant <i>Acinetobacter baumannii</i>: Action and Resistance
<i>Acinetobacter baumannii</i> (<i>A. baumannii</i>) has emerged as a prominent multidrug-resistant (MDR) pathogen, significantly complicating treatment strategies due to its formidable resistance mechanisms, particularly against carbapenems. Reduced membrane permeability, ac...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/12/11/2532 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850267545439830016 |
|---|---|
| author | Bahman Yousefi Setayesh Kashanipoor Payman Mazaheri Farnaz Alibabaei Ali Babaeizad Shima Asli Sina Mohammadi Amir Hosein Gorgin Tahereh Alipour Valentyn Oksenych Majid Eslami |
| author_facet | Bahman Yousefi Setayesh Kashanipoor Payman Mazaheri Farnaz Alibabaei Ali Babaeizad Shima Asli Sina Mohammadi Amir Hosein Gorgin Tahereh Alipour Valentyn Oksenych Majid Eslami |
| author_sort | Bahman Yousefi |
| collection | DOAJ |
| description | <i>Acinetobacter baumannii</i> (<i>A. baumannii</i>) has emerged as a prominent multidrug-resistant (MDR) pathogen, significantly complicating treatment strategies due to its formidable resistance mechanisms, particularly against carbapenems. Reduced membrane permeability, active antibiotic efflux, and enzymatic hydrolysis via different β-lactamases are the main resistance mechanisms displayed by <i>A. baumannii</i>, and they are all effective against successful treatment approaches. This means that alternate treatment approaches, such as combination therapy that incorporates beta-lactams, β-lactamase inhibitors, and novel antibiotics like cefiderocol, must be investigated immediately. Cefiderocol, a new catechol-substituted siderophore cephalosporin, improves antibacterial activity by allowing for better bacterial membrane penetration. Due to its unique structure, cefiderocol can more efficiently target and destroy resistant bacteria by using iron transport systems. Through its inhibition of peptidoglycan formation through binding to penicillin-binding proteins (PBPs), cefiderocol avoids conventional resistance pathways and induces bacterial cell lysis. The possibility of resistance development due to β-lactamase synthesis and mutations in PBPs, however, emphasizes the need for continued investigation into cefiderocol’s efficacy in combination treatment regimes. Cefiderocol’s siderophore mimic mechanism is especially important in iron-limited conditions because it can use ferric-siderophore transporters to enter cells. Additionally, its passive diffusion through bacterial porins increases its intracellular concentrations, making it a good option for treating carbapenem-resistant <i>A. baumannii</i>, especially in cases of severe infections and ventilator-associated diseases (IVACs). Cefiderocol may reduce MDR infection morbidity and mortality when combined with customized antimicrobial treatments, but further investigation is needed to improve patient outcomes and address <i>A. baumannii</i> resistance issues. |
| format | Article |
| id | doaj-art-7d0397c52cd9477a96be189168d764a4 |
| institution | OA Journals |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-7d0397c52cd9477a96be189168d764a42025-08-20T01:53:44ZengMDPI AGBiomedicines2227-90592024-11-011211253210.3390/biomedicines12112532Cefiderocol in Combating Carbapenem-Resistant <i>Acinetobacter baumannii</i>: Action and ResistanceBahman Yousefi0Setayesh Kashanipoor1Payman Mazaheri2Farnaz Alibabaei3Ali Babaeizad4Shima Asli5Sina Mohammadi6Amir Hosein Gorgin7Tahereh Alipour8Valentyn Oksenych9Majid Eslami10Cancer Research Center, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 35147-99442, IranCancer Research Center, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 35147-99442, IranCancer Research Center, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 35147-99442, IranCancer Research Center, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 35147-99442, IranCancer Research Center, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 35147-99442, IranCancer Research Center, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 35147-99442, IranStudent Research Committee, School of Medicine, Semnan University of Medical Sciences, Semnan 35147-99442, IranStudent Research Committee, School of Medicine, Semnan University of Medical Sciences, Semnan 35147-99442, IranNervous System Stem Cell Research Center, Semnan University of Medical Sciences, Semnan 35147-99442, IranDepartment of Clinical Science, University of Bergen, 5020 Bergen, NorwayDepartment of bacteriology and Virology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 35147-99442, Iran<i>Acinetobacter baumannii</i> (<i>A. baumannii</i>) has emerged as a prominent multidrug-resistant (MDR) pathogen, significantly complicating treatment strategies due to its formidable resistance mechanisms, particularly against carbapenems. Reduced membrane permeability, active antibiotic efflux, and enzymatic hydrolysis via different β-lactamases are the main resistance mechanisms displayed by <i>A. baumannii</i>, and they are all effective against successful treatment approaches. This means that alternate treatment approaches, such as combination therapy that incorporates beta-lactams, β-lactamase inhibitors, and novel antibiotics like cefiderocol, must be investigated immediately. Cefiderocol, a new catechol-substituted siderophore cephalosporin, improves antibacterial activity by allowing for better bacterial membrane penetration. Due to its unique structure, cefiderocol can more efficiently target and destroy resistant bacteria by using iron transport systems. Through its inhibition of peptidoglycan formation through binding to penicillin-binding proteins (PBPs), cefiderocol avoids conventional resistance pathways and induces bacterial cell lysis. The possibility of resistance development due to β-lactamase synthesis and mutations in PBPs, however, emphasizes the need for continued investigation into cefiderocol’s efficacy in combination treatment regimes. Cefiderocol’s siderophore mimic mechanism is especially important in iron-limited conditions because it can use ferric-siderophore transporters to enter cells. Additionally, its passive diffusion through bacterial porins increases its intracellular concentrations, making it a good option for treating carbapenem-resistant <i>A. baumannii</i>, especially in cases of severe infections and ventilator-associated diseases (IVACs). Cefiderocol may reduce MDR infection morbidity and mortality when combined with customized antimicrobial treatments, but further investigation is needed to improve patient outcomes and address <i>A. baumannii</i> resistance issues.https://www.mdpi.com/2227-9059/12/11/2532<i>Acinetobacter baumannii</i>β-lactamasecarbapenemcefiderocolPBP |
| spellingShingle | Bahman Yousefi Setayesh Kashanipoor Payman Mazaheri Farnaz Alibabaei Ali Babaeizad Shima Asli Sina Mohammadi Amir Hosein Gorgin Tahereh Alipour Valentyn Oksenych Majid Eslami Cefiderocol in Combating Carbapenem-Resistant <i>Acinetobacter baumannii</i>: Action and Resistance Biomedicines <i>Acinetobacter baumannii</i> β-lactamase carbapenem cefiderocol PBP |
| title | Cefiderocol in Combating Carbapenem-Resistant <i>Acinetobacter baumannii</i>: Action and Resistance |
| title_full | Cefiderocol in Combating Carbapenem-Resistant <i>Acinetobacter baumannii</i>: Action and Resistance |
| title_fullStr | Cefiderocol in Combating Carbapenem-Resistant <i>Acinetobacter baumannii</i>: Action and Resistance |
| title_full_unstemmed | Cefiderocol in Combating Carbapenem-Resistant <i>Acinetobacter baumannii</i>: Action and Resistance |
| title_short | Cefiderocol in Combating Carbapenem-Resistant <i>Acinetobacter baumannii</i>: Action and Resistance |
| title_sort | cefiderocol in combating carbapenem resistant i acinetobacter baumannii i action and resistance |
| topic | <i>Acinetobacter baumannii</i> β-lactamase carbapenem cefiderocol PBP |
| url | https://www.mdpi.com/2227-9059/12/11/2532 |
| work_keys_str_mv | AT bahmanyousefi cefiderocolincombatingcarbapenemresistantiacinetobacterbaumanniiiactionandresistance AT setayeshkashanipoor cefiderocolincombatingcarbapenemresistantiacinetobacterbaumanniiiactionandresistance AT paymanmazaheri cefiderocolincombatingcarbapenemresistantiacinetobacterbaumanniiiactionandresistance AT farnazalibabaei cefiderocolincombatingcarbapenemresistantiacinetobacterbaumanniiiactionandresistance AT alibabaeizad cefiderocolincombatingcarbapenemresistantiacinetobacterbaumanniiiactionandresistance AT shimaasli cefiderocolincombatingcarbapenemresistantiacinetobacterbaumanniiiactionandresistance AT sinamohammadi cefiderocolincombatingcarbapenemresistantiacinetobacterbaumanniiiactionandresistance AT amirhoseingorgin cefiderocolincombatingcarbapenemresistantiacinetobacterbaumanniiiactionandresistance AT taherehalipour cefiderocolincombatingcarbapenemresistantiacinetobacterbaumanniiiactionandresistance AT valentynoksenych cefiderocolincombatingcarbapenemresistantiacinetobacterbaumanniiiactionandresistance AT majideslami cefiderocolincombatingcarbapenemresistantiacinetobacterbaumanniiiactionandresistance |