Lakhasly

2.5.7 Acinetobacter. baumannii
One of the most concerning mechanisms conferring carbapenem resistance to A. baumannii and other Gram-negative bacteria is the presence of mobile carbapenemase genes, encoded by genetic elements that can easily spread among bacteria and consequently, between patients and facilities. Carbapenemase enzymes encoded by genes can be classified into molecular classes such as class A [e.g., Klebsiella pneumoniae carbapenemase (blaKPC)], class B [e.g., Active-on-Imipenem (blaIMP), New Delhi metallo-β-lactamase (blaNDM), and Verona integron-encoded metallo-β-lactamase (blaVIM)], and class D [e.g., Oxacillinase (blaOXA-23-like, blaOXA-24/40-like, blaOXA-48-like, and blaOXA-58-like)]. Varying frequencies of these carbapenemase genes in A. baumannii have been reported globally, with class D carbapenemase genes most often detected(Sabour et al.,2024)
has been reported to show the presence of type AmpC chromosomal cephalosporinases, extended-spectrum B_lactamases, type D chromosomal (OXA-51), and plasmid (OXA-23, OXA-24, OXA-58, OXA143, and OXA 134) Carbapenemases, type A Carbapenemases (KPC and GES), and type B Carbapenemases (metallo-ß-lactamases), with the alteration of porins and efflux pumps(Requena_Cabello et al 2023)
Acinetobacter baumanii Resistance to carbapenems is mainly mediated through acquired OXA-type carbapenem-hydrolyzing class D B lactamases [oxacillinases (OXAs)], encoded byblaoxA-23-like, blaoxA-40-like, blaoxA-58-like, blaoxA143-like, and blaoxA-235-like, Some variants of the intrinsic OXA-51-like carbapenemase confer carbapenem resistance when overexpressed via ISAbal. Less frequently, carbapenem resistance in A.baumanii is mediated through class B metallo-beta-lactamases (MBLs) such as IMP, NDM, SIM, and VIM and only rarely by class A KPC and GES beta-lactamases(Müller et al 2023).
2.5.8 Citrobacter ferundii
C. freundii develops resistance to antibiotics by several mechanisms including the production of B-lactamases that hydrolyze the ẞ-lactam ring of antibiotics. Within the genome of C. freundii, the ẞ-lactamase blaCMY (AmpC) genes are present that produce, The AmpC ẞ-lactamase is regulated by the AmpR which is located upstream of the AmpC, The AmpR mutant showed low expression of AmpC whereas constitutive expression of AmpR resulted in high production of AmpC. The induciblevector encoded AmpC ẞ-lactamases with AmpR have been studied in E. cloacae, Morganella morganii, and C. freundii. For instance, ACT-1, DHA-1, and CMY-13 are plasmid-encoded ẞ-lactamases and their inducible expression gave resistance to cephalosporins. Cloacae, M. morganii, and C. freundii respectively. InC. Freund, the presence of f-lactam antibiotic increased the cytoplasmic anhydromuropeptides which bind to AmpR and activatedAmpC while the absence of activating ligand-like peptidoglycan recycled product repressed AmpC expression, Previously, Ryuichi and coworkers determined the AmpC ẞ-lactamase expression level with or without AmpR and their results suggested that the resistance of CFE-1 (plasmid-encoded AmpC ẞ-lactamase) to cephalosporins is due to the substitution of Asp135Ala inAmpR of C. freundii )Tariq et al 2023).

2.5.9Enterobacter hormaechei
The most common antimicrobial resistance mechanisms in such microorganisms include the acquisition of mobile genetic elements(MGEs) from other Enterobacterales and the overexpression of efflux pumps, The predominant cause of resistance to B-lactams is the production of B-lactamases, which inactivate the drug by hydrolyzing the B-lactam ring. Based on the amber scheme, B-lactamases are grouped into four classes: the class B metalloenzymes, also known as Metallo-B-lactamases (MBLs); and the serine-reactive hydrolases (classes A, C, and D)[11]. ECC strains are intrinsically resistant to cephalosporins due to the production of thechromosomalcephalosporinaseblaACT-16whereas the spread of acquired B-lactamases has been often documented, such as the class A extended-spectrum beta-lactamases (ESBLs) of the CTX-M and SHV families as well as carbapenemases, such as the VIM- and NDMtypes (class B), KPC-2 (class A) and OXA-48 (class).(Mavroidi et al 2023).
In addition, overexpression of the β-lactamase AmpC, the occurrence of extended-spectrum β-lactamases (ESBLs), such as TEM, CTX-M, and SHV, membrane-associated mechanisms, such as outer membrane permeability, and the overexpression of efflux pumps have been demonstrated to contribute to carbapenem resistance in ECC. The acquisition of the carbapenem resistance genes is most often transferred by mobile genetic elements (MGEs), such as plasmids and transposons, which can be easily transferred between different species. Globally, NDM is the main CHβL conferring carbapenem resistance in CREC. However, regional differences in the distribution of CREC CHβLs have been observed, with KPC being predominant in North America, OXA-48 and VIM being predominant in Europe, and NDM being the most prevalent in China

A multinational surveillance study based on multi-locus sequence typing (MLST) revealed substantial clonal diversity of CREC, and ST114, ST93, ST90, and ST78 were potential high-risk clones globally widespread in 37 countries (Peirano et al., 2018). Risk factor analysis for CREC acquisition has shown ICU admission, prior antimicrobial exposure, and invasive(Han, M et al 2023).