Hamad, M., Al-Marzooq, F., Orive, G. & Al-Tel, T. H. Superbugs but no drugs: Steps in averting a post-antibiotic era. Drug Discov. Today 24, 2225–2228 (2019).
Murray, C. J. et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet 399, 629–655 (2022).
Prestinaci, F., Pezzotti, P. & Pantosti, A. Antimicrobial resistance: A global multifaceted phenomenon. Pathog Glob Health 109, 309–318 (2015).
Hamad, M. et al. Antibacterial activity of small molecules which eradicate methicillin-resistant Staphylococcus aureus persisters. Front. Microbiol. 13, 823394 (2022).
Daoud, L. & Al Marzooq, F. PGN-015 – Cefiderocol: A new weapon to fight antibiotic resistant Klebsiella pneumoniae. Int. J. Antimicrob. Agents 58, 21003824 (2021).
Ito, A. et al. In vitro antibacterial properties of cefiderocol, a novel siderophore cephalosporin, against gram-negative bacteria. Antimicrob. Agents Chemother. 62, 10. https://doi.org/10.1128/aac.01454-17 (2017).
Sato, T. & Yamawaki, K. Cefiderocol: Discovery, chemistry, and in vivo profiles of a novel siderophore cephalosporin. Clin. Infect. Dis. 69, S538–S543 (2019).
Zhanel, G. G. et al. Cefiderocol: A siderophore cephalosporin with activity against carbapenem-resistant and multidrug-resistant gram-negative bacilli. Drugs 79, 271–289 (2019).
Maseda, E. & de la Rica, A. S. The role of cefiderocol in clinical practice. Rev. Esp. Quimioter. 35, 39–44 (2022).
Viale, P., Sandrock, C. E., Ramirez, P., Rossolini, G. M. & Lodise, T. P. Treatment of critically ill patients with cefiderocol for infections caused by multidrug-resistant pathogens: Review of the evidence. Ann. Intensive Care 13, 52 (2023).
Timsit, J. F. et al. Cefiderocol for the treatment of infections due to metallo-b-lactamase–producing pathogens in the CREDIBLE-CR and APEKS-NP phase 3 randomized studies. Clin. Infect. Dis. 75, 1081–1084 (2022).
Delgado-Valverde, M., Portillo-Calderón, I., Recacha, E., Pérez-Palacios, P. & Pascual, A. In vitro activity of cefiderocol compared to other antimicrobials against a collection of metallo-beta-lactamase-producing gram-negative bacilli from Southern Spain. Microbiol. Spectr. 11, e04936-e5022 (2023).
González-Bello, C., Rodríguez, D., Pernas, M., Rodríguez, Á. & Colchón, E. β-Lactamase inhibitors to restore the efficacy of antibiotics against superbugs. J. Med. Chem. 63, 1859–1881 (2020).
Olney, K. B., Thomas, J. K. & Johnson, W. M. Review of novel β-lactams and β-lactam/β-lactamase inhibitor combinations with implications for pediatric use. Pharmacother. J. Hum. Pharmacol. Drug Ther. 43, 713–731 (2023).
Kang, S.-J., Kim, D.-H. & Lee, B.-J. Metallo-β-lactamase inhibitors: A continuing challenge for combating antibiotic resistance. Biophys. Chem. 309, 107228 (2024).
Papp-Wallace, K. M. The latest advances in β-lactam/β-lactamase inhibitor combinations for the treatment of Gram-negative bacterial infections. Expert Opin. Pharmacother. 20, 2169–2184 (2019).
Fontana, R., Cornaglia, G., Ligozzi, M. & Mazzariol, A. The final goal: penicillin-binding proteins and the target of cephalosporins. Clin. Microbiol. Infect. 6(Suppl 3), 34–40 (2000).
Liu, B. et al. Discovery of taniborbactam (VNRX-5133): A broad-spectrum serine- and metallo-β-lactamase inhibitor for carbapenem-resistant bacterial infections. J. Med. Chem. 63, 2789–2801 (2020).
Hamrick, J. C. et al. VNRX-5133 (Taniborbactam), a broad-spectrum inhibitor of serine- and metallo-β-lactamases, restores activity of cefepime in Enterobacterales and Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 64, 10. https://doi.org/10.1128/aac.01963-19 (2020).
Wagenlehner, F. M. et al. Cefepime-taniborbactam in complicated urinary tract infection. N. Engl. J. Med. 390, 611–622 (2024).
Sun, D. et al. Intrinsic antibacterial activity of xeruborbactam in vitro: Assessing spectrum and mode of action. Antimicrob. Agents Chemother. 66, e0087922 (2022).
Karakonstantis, S., Rousaki, M. & Kritsotakis, E. I. Cefiderocol: Systematic review of mechanisms of resistance, heteroresistance and in vivo emergence of resistance. Antibiotics (Basel) 11, 723 (2022).
Daoud, L. et al. Extreme resistance to the novel siderophore-cephalosporin cefiderocol in an extensively drug-resistant Klebsiella pneumoniae strain causing fatal pneumonia with sepsis: Genomic analysis and synergistic combinations for resistance reversal. Eur. J. Clin. Microbiol. Infect. Dis. 42, 1395–1400 (2023).
Yue, W. W., Grizot, S. & Buchanan, S. K. Structural evidence for iron-free citrate and ferric citrate binding to the TonB-dependent outer membrane transporter FecA. J. Mol. Biol. 332, 353–368 (2003).
Grinter, R. & Lithgow, T. The structure of the bacterial iron–catecholate transporter Fiu suggests that it imports substrates via a two-step mechanism. J. Biol. Chem. 294, 19523–19534 (2019).
Tosi, M. et al. Multidrug resistant bacteria in critically ill patients: a step further antibiotic therapy. J. Emerg. Crit. Care Med. 2, (2018).
Hoeksema, M., Jonker, M. J., Brul, S. & ter Kuile, B. H. Effects of a previously selected antibiotic resistance on mutations acquired during development of a second resistance in Escherichia coli. BMC Genomics 20, 284 (2019).
Odoyo, E. et al. Environmental contamination across multiple hospital departments with multidrug-resistant bacteria pose an elevated risk of healthcare-associated infections in Kenyan hospitals. Antimicrob. Resist. Infect. Control 12, 22 (2023).
Simner, P. J. et al. Progressive development of cefiderocol resistance in Escherichia coli during therapy is associated with an increase in blaNDM-5 copy number and gene expression. Clin. Infect. Dis. 75, 47–54 (2022).
Jousset, A. B. et al. Population analysis of Escherichia coli sequence type 361 and reduced cefiderocol susceptibility, France. Emerg. Infect. Dis. 29, 1877–1881 (2023).
Kocer, K. et al. Genomic modification of TonB and emergence of small-colony phenotype in VIM- and NDM-producing Escherichia coli following cefiderocol exposure in vitro. Antimicrob. Agents Chemother. 67, e00118-e123 (2023).
Al-Marzooq, F. et al. Genomic approach to evaluate the intrinsic antibacterial activity of novel diazabicyclooctanes (zidebactam and nacubactam) against clinical Escherichia coli isolates from diverse clonal lineages in the United Arab Emirates. J. Infect. Public Health 18, 102761 (2025).
Vila, A. J. et al. P-1370. Molecular bases and mechanistic insights of NDM-mediated resistance to cefiderocol. Open Forum Infect. Dis. 12, ofae631.1547 (2025).
Poirel, L. et al. NDM-35-producing ST167 Escherichia coli highly resistant to β-lactams including cefiderocol. Antimicrob. Agents Chemother. 66, e00311-e322 (2022).
Raro, O. H. F., Le Terrier, C., Nordmann, P. & Poirel, L. Impact of extended-spectrum chromosomal AmpC (ESAC) of Escherichia coli on susceptibility to cefiderocol. Microbiol. Spectr. 12, e00704-e724 (2024).
Simner, P. J. et al. An NDM-producing Escherichia coli clinical isolate exhibiting resistance to cefiderocol and the combination of ceftazidime-avibactam and aztreonam: Another step towards Pan-β-lactam resistance. Open Forum Infect. Dis. https://doi.org/10.1093/ofid/ofad276 (2023).
Fröhlich, C., Sørum, V., Tokuriki, N., Johnsen, P. J. & Samuelsen, Ø. Evolution of β-lactamase-mediated cefiderocol resistance. J. Antimicrob. Chemother. 77, 2429–2436 (2022).
Ahn, K. et al. Nosocomial outbreak caused by NDM-5 and OXA-181 carbapenemase co-producing Escherichia coli. Infect. Chemother. 51, 177–182 (2019).
He, W.-Y. et al. Characterization of an international high-risk Escherichia coli ST410 clone coproducing NDM-5 and OXA-181 in a food market in China. Microbiol. Spectr. 11, e04727-e4822 (2023).
Baek, J. Y. et al. Plasmid analysis of Escherichia coli isolates from South Korea co-producing NDM-5 and OXA-181 carbapenemases. Plasmid 104, 102417 (2019).
Abid, F. B. et al. Molecular characterization of clinical carbapenem-resistant Enterobacterales from Qatar. Eur. J. Clin. Microbiol. Infect. Dis. 40, 1779–1785 (2021).
Wang, Q. et al. Occurrence of high levels of cefiderocol resistance in carbapenem-resistant Escherichia coli before its approval in China: A report from China CRE-network. Microbiol. Spectr. 10, e02670-e2721 (2022).
Giufrè, M. et al. Emergence of NDM-5-producing Escherichia coli sequence type 167 clone in Italy. Int. J. Antimicrob. Agents 52, 76–81 (2018).
Al-Marzooq, F., Ghazawi, A., Allam, M., Collyns, T. & Saleem, A. Novel variant of New Delhi metallo-beta-lactamase (blaNDM-60) discovered in a clinical strain of Escherichia coli from the United Arab Emirates: An emerging challenge in antimicrobial resistance. Antibiotics 13, 1158 (2024).
Al-Marzooq, F., Ghazawi, A., Allam, M. & Collyns, T. Deciphering the genetic context of the emerging OXA-484-producing carbapenem-resistant Escherichia coli from ST167 high-risk clone in the United Arab Emirates. Eur. J. Clin. Microbiol. Infect. Dis. https://doi.org/10.1007/s10096-025-05082-z (2025).
Sands, K. et al. Acquisition of Escherichia coli carrying extended-spectrum ß-lactamase and carbapenemase genes by hospitalised children with severe acute malnutrition in Niger. Nat. Commun. 16, 6751 (2025).
Z, Z. et al. Genetic diversity and characteristics of bla NDM-positive plasmids in Escherichia coli. PubMed (2021).
Pitout, J. D. D. & Chen, L. The significance of epidemic plasmids in the success of multidrug-resistant drug pandemic extraintestinal pathogenic Escherichia coli. Infect. Dis. Ther. 12, 1029–1041 (2023).
Ding, M. et al. Subinhibitory antibiotic concentrations promote the horizontal transfer of plasmid-borne resistance genes from Klebsiella pneumoniae to Escherichia coli. Front. Microbiol. 13, 1017092 (2022).
Lerminiaux, N. A. & Cameron, A. D. S. Horizontal transfer of antibiotic resistance genes in clinical environments. Can. J. Microbiol. 65, 34–44 (2019).
Zhang, Y., Kashikar, A., Brown, C. A., Denys, G. & Bush, K. Unusual Escherichia coli PBP 3 insertion sequence identified from a collection of carbapenem-resistant Enterobacteriaceae tested in vitro with a combination of ceftazidime-, ceftaroline-, or aztreonam-avibactam. Antimicrob. Agents Chemother. 61, e00389-e417 (2017).
Sauvage, E. et al. Crystal structure of penicillin-binding protein 3 (PBP3) from Escherichia coli. PLoS ONE 9, e98042 (2014).
Lan, P. et al. Catecholate siderophore receptor CirA impacts cefiderocol susceptibility in Klebsiella pneumoniae. Int. J. Antimicrob. Agents 60, 106646 (2022).
McElheny, C. L., Fowler, E. L., Iovleva, A., Shields, R. K. & Doi, Y. In vitro evolution of cefiderocol resistance in an NDM-producing Klebsiella pneumoniae due to functional loss of CirA. Microbiol. Spectr. 9, e01779-e1821 (2021).
Daoud, L., Al-Marzooq, F., Moubareck, C. A., Ghazawi, A. & Collyns, T. Elucidating the effect of iron acquisition systems in Klebsiella pneumoniae on susceptibility to the novel siderophore-cephalosporin cefiderocol. PLoS ONE 17, e0277946 (2022).
Moeck, G. S. & Coulton, J. W. TonB-dependent iron acquisition: Mechanisms of siderophore-mediated active transport. Mol. Microbiol. 28, 675–681 (1998).
Pinkert, L. et al. Antibiotic conjugates with an artificial MECAM-based siderophore are potent agents against gram-positive and gram-negative bacterial pathogens. J. Med. Chem. 64, 15440–15460 (2021).
Le Terrier, C., Nordmann, P., Sadek, M. & Poirel, L. In vitro activity of cefepime/zidebactam and cefepime/taniborbactam against aztreonam/avibactam-resistant NDM-like-producing Escherichia coli clinical isolates. J. Antimicrob. Chemother. 78, 1191–1194 (2023).
Le Terrier, C., Nordmann, P., Buchs, C. & Poirel, L. Effect of modification of penicillin-binding protein 3 on susceptibility to ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam, cefepime-taniborbactam, and cefiderocol of Escherichia coli strains producing broad-spectrum β-lactamases. Antimicrob. Agents Chemother. 68, e0154823 (2024).
Le Terrier, C. et al. Relative inhibitory activities of the broad-spectrum β-lactamase inhibitor xeruborbactam in comparison with taniborbactam against metallo-β-lactamases produced in Escherichia coli and Pseudomonas aeruginosa. Antimicrob. Agents Chemother. https://doi.org/10.1128/aac.01570-23 (2024).
Daoud, L., Al-Marzooq, F., Ghazawi, A., Anes, F. & Collyns, T. High efficacy and enhanced synergistic activity of the novel siderophore-cephalosporin cefiderocol against multidrug-resistant and extensively drug-resistant Klebsiella pneumoniae from inpatients attending a single hospital in the United Arab Emirates. J. Infect. Public Health 16, 33–44 (2023).
Gurevich, A., Saveliev, V., Vyahhi, N. & Tesler, G. QUAST: Quality assessment tool for genome assemblies. Bioinformatics 29, 1072–1075 (2013).
Alzayer, M. et al. Genomic insights into the diversity, virulence, and antimicrobial resistance of group B Streptococcus clinical isolates from Saudi Arabia. Front. Cell. Infect. Microbiol. 14, 1377993 (2024).
Saini, P. et al. Genomic insights into virulence, antimicrobial resistance, and adaptation acumen of Escherichia coli isolated from an urban environment. MBio 15, e03545-e3623 (2024).
Seemann, T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 30, 2068–2069 (2014).
Alcock, B. P. et al. CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res. 48, D517–D525 (2020).
Argimón, S. et al. Microreact: Visualizing and sharing data for genomic epidemiology and phylogeography. Microb. Genom. 2, e000093 (2016).
Zhou, Z. et al. GrapeTree: Visualization of core genomic relationships among 100,000 bacterial pathogens. Genome Res. 28, 1395–1404 (2018).
Achtman, M. et al. Multilocus sequence typing as a replacement for serotyping in Salmonella enterica. PLoS Pathog. 8, e1002776 (2012).
Jolley, K. A. et al. Ribosomal multilocus sequence typing: Universal characterization of bacteria from domain to strain. Microbiology (Reading) 158, 1005–1015 (2012).
Blanc, D. S., Magalhães, B., Koenig, I., Senn, L. & Grandbastien, B. Comparison of whole genome (wg-) and core genome (cg-) MLST (BioNumericsTM) versus SNP variant calling for epidemiological investigation of Pseudomonas aeruginosa. Front. Microbiol. 11, 1729 (2020).
Zhou, Z. et al. The EnteroBase user’s guide, with case studies on Salmonella transmissions, Yersinia pestis phylogeny, and Escherichia core genomic diversity. Genome Res. 30, 138–152 (2020).
Beghain, J., Bridier-Nahmias, A., Le Nagard, H., Denamur, E. & Clermont, O. ClermonTyping: an easy-to-use and accurate in silico method for Escherichia genus strain phylotyping. Microb. Genom. 4, e000192 (2018).
Clermont, O., Christenson, J. K., Denamur, E. & Gordon, D. M. The Clermont Escherichia coli phylo-typing method revisited: Improvement of specificity and detection of new phylo-groups. Environ. Microbiol. Rep. 5, 58–65 (2013).
Rahimi, Z., Malekzadegan, Y., Bahador, A., Azimzadeh, M. & Haghighi, M. A. Phylogenetic study, distribution of virulence genes and antibiotic resistance profiles of Escherichia coli isolated from Bushehr coastal water. Gene Rep. 26, 101473 (2022).
Clermont, O. et al. Characterization and rapid identification of phylogroup G in Escherichia coli, a lineage with high virulence and antibiotic resistance potential. Environ. Microbiol. 21, 3107–3117 (2019).
Heberle, H., Meirelles, G. V., da Silva, F. R., Telles, G. P. & Minghim, R. InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams. BMC Bioinform. 16, 169 (2015).
Chung, N. C., Miasojedow, B., Startek, M. & Gambin, A. Jaccard/Tanimoto similarity test and estimation methods for biological presence-absence data. BMC Bioinform. 20, 644 (2019).
Pal, C., Bengtsson-Palme, J., Kristiansson, E. & Larsson, D. G. J. Co-occurrence of resistance genes to antibiotics, biocides and metals reveals novel insights into their co-selection potential. BMC Genomics 16, 964 (2015).
CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 34rd ed. (2024).
Karlowsky, J. A., Hackel, M. A., Bouchillon, S. K. & Sahm, D. F. In vitro activity of WCK 5222 (cefepime–zidebactam) against worldwide collected gram-negative bacilli not susceptible to carbapenems. Antimicrob. Agents Chemother. 64, e01432-e1520 (2020).
eucast: Clinical breakpoints and dosing of antibiotics. https://www.eucast.org/clinical_breakpoints.
Al-Marzooq, F., Ghazawi, A., Tariq, S., Daoud, L. & Collyns, T. Discerning the role of polymyxin B nonapeptide in restoring the antibacterial activity of azithromycin against antibiotic-resistant Escherichia coli. Front. Microbiol. 13, 998671 (2022).
