Antibiotic resistance in patients with liver cirrhosis: Prevalence and current approach to tackle

Table 1 Examples of intrinsic (natural) antibiotic resistance pathways in bacteria

Resistance mechanism	Molecule/process involved	Resistance to antibiotic	Primary host	Genome-encoded	Plasmid-encoded
Decrease in bacterial wall permeability	Reduced porin expression	Different antibiotics	Gram-negative bacteria	oprD gene	No
Increase in efflux	Tripartite RND pump family	Different antibiotics	Gram-negative bacteria	Yes	Yes
Antibiotic inactivation by chemical group transfer	Modification	Aminoglycosides	Gram-negative and Gram-positive bacteria	Yes	Yes
	Oxidation	Tetracyclines	Many bacteria	Tet(X) genes	Yes
Antibiotic hydrolysis	AmpC beta-lactamases	Broad-spectrum beta-lactams	Gram-negative bacteria: Enterobacteriaceae	Yes	Yes
	Carbapenemases	A variety of beta-lactams	Enterobacteriaceae	Yes	Yes
Modification of antibiotic target	Modification of peptidoglycan precursors	Glycopeptides: vancomycin	Gram-positive cocci: Enterococcaceae	vanC, vanD operons	vanA gene claster
	Alteration of LPS	Polymyxins: colistin	Gram-negative: Enterobacteriaceae	Yes	Yes
	Exchange of conventional PBP to PBP2a	Beta-lactams	Staphylococcaceae	mecA gene	Yes

RND: Resistance-nodulation-division pump family; LPS: Lipopolysaccharide; PBP: Penicillin binding protein.

Table 2 Examples of acquired antibiotic resistance in bacteria

Metabolic process	Molecule/reaction involved	Resistance to antibiotic	Host	Genome encoded	Plasmid encoded
Decrease in bacterial wall permeability	Modified porins	Many antibiotics	Gram-negative bacteria	Loss or mutated oprD mutations in porin operon
Increase in efflux	RND pump family	Many antibiotics	Gram-negative bacteria; S. aureus	Mutations in mtr region, mexEF-oprN	RND with NDM-1
	Efflux pump	Fluoroquinolones	S. aureus	Amplification of norA gene
Enzymatic antibiotic inactivation	Oxidation	Tetracyclines	Many bacteria		Mobile Tet(X)
Antibiotic hydrolysis	ESBLs	Broad-spectrum beta-lactams	Gram-negative bacteria	Yes	Yes
Modification of antibiotic target	RNA polymerase RpoB	Rifampicin	S. aureus	Mutated RpoB gene
	DNA gyrase GyrA and topoisomerase IV ParC	Quinolones Fluoroquinolones	S. aureus; K. pneumoniae	QRDR	Yes
	DHPS and DHFR	Trimethoprim–sulfamethoxazole	Gram-negative bacteria	Mutated dfrA gene	Yes
	Altered rRNA	Macrolides: erythromycin, Oxazolidinones: linezolid	Staphylococcus spp.; Streptococcus spp.	Mutated rRNA operon	Yes
	Modification of peptidoglycan precursors	Vancomycin	Enterococcaceae, Staphyloccaceae	Mutated van genes, vanR/van S controls	Yes
	Enoyl-ACP reductase	Triclosan	P. aeruginosa	Alternative fabV gene
	Addition of moieties to LPS	Colistin	Enterobacter spp.	Mutated TSC genes	mcr
	Transpeptidase moiety of PBP	Methicillin and other beta-lactams	Staphylococcus spp.	mecA gene	SCCmec
	Dihydropteroate synthase	Sulphonamides		Mutated sul1/2 gene

RND: Family of resistance–nodulation–division efflux pumps; NDM-1: New Delhi metalo-beta-lactamase 1; ESBLs: Extended spectrum of beta-lactamases; QRDR: quinolone resistance determine region; DHPS: Dihydropteroate synthase; DHFR: Dihydrofolate reductase; TSC: Two-component system; mcr: Mobile colistin resistance; LPS: Lipopolysaccharide; PBP: Penicillin binding protein; SCCmec: Staphylococcal cassette chromosome.