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. Author manuscript; available in PMC: 2021 Sep 16.
Published in final edited form as: Microb Pathog. 2021 Jun 10;158:105040. doi: 10.1016/j.micpath.2021.105040

Table 1.

Evolutionary trends in β-lactamase resistance development.

β-lactamases Mechanisms Resistance Strains β-lactam Antibiotics References
CTX-M family
CTX-M-3, CTX-M-15, CTX-M-16, CTX-M-19, CTX-M-27 Hydrolyze, mutation, ESBLs E. coli Ceftazidime [73,74]
CTX-M-9, CTX-M-13, CTX-M-14. Plasmid mediated, tnpA gene transposon, insert sequence ISEcp-1 on plasmid ESBLs Enterobacteriaceae, E. coli,
Klebsiella pneumoniae 		Cefotaxime, Ceftazidime [75–77]
CTX-M-32 Asp-240Gly substitution E. coli Cefotaxime, ceftazidime, and aztreonam [78]
CTX-M-2, CTX-M-39 Plasmid mediated ESBLs, substitution of arginine E. coli Cefotaxime
CTX-M-32 Asp-240Gly substitution of ESBLs E. coli Ceftazidime [78]
CTX-M-14 CTX-M-15, CTX-M-57 along with qnrB and qnrS Plasmid mediated substitution of ESBLs, Active efflux E. coli,
Klebsiella pneumoniae 		Ceftazidime and quinolones [79]
CTX-M Single nucleotide mutation Salmonella spp. Ceftriaxone [42]
CTX-M-2, CTX-M-3, CTX-M-14 Plasmid mediated substitution of ESBLs E. coli,
Klebsiella. pneumoniae 		Cephalosporin [36,37]
CTX-M-14 Plasmid mediated substitution of ESBLs E. coli,
Klebsiella. Pneumoniae 		Cefotaxime and ceftazidime [35]
TEM Family
TEM-30, TEM-34, TEM-40, TEM-51 Single amino acid substitution E. coli Cefoxitin
TEM-1, TEM-30, TEM-33, Plasmid mediated ESBLs E. coli Cefotaxime
TEM-3, TEM-4, TEM-133 Mutations L21F, E104K, and R164S E. coli,
Klebsiella. pneumoniae 		Ceftazidime, Cefotaxime [80]
TEM-1 along with qnrB and qnrS Plasmid mediated ESBLs substitution, active efflux E. coli,
. Klebsiella. pneumoniae 		Ceftazidime and quinolones [81]
TEM-34, TEM-40 Single amino acid gene mutations E. coli,
. Klebsiella. pneumoniae 		Cefotaxime, Clavulanic acid [44]
TEM-1 Single nucleotide mutation ESBLs Salmonella spp. Nalidixic acid, ampicillin, ceftriaxone cotrimoxazole, chloramphenicol, and ciprofloxacin [42]
SHV Family
SHV-1 Gene mutation, hydrolysis Enterobacteriaceae,
K. pneumoniae 		Penicillins,
1st generation cephalosporin		 [82]
SHV-5, SHV-12 Plasmid mediated ESBLs, substitution E. coli,
K. pneumoniae 		Cefotaxime
SHV-36 Mutation E. coli and E. cloacae Cephalosporinss [42]
SHV-2, SHV-5, SHV-12 along with qnrB and qnrS Plasmid mediated ESBLs substitution, Active efflux E. coli,
K. pneumoniae 		Ceftazidime and quinolones [81]
SHV-1, SHV-11, SHV-12, SHV-18, SHV-28 Amino acid mutation E. coli,
K. pneumoniae 		Penicillin, amoxicillin, oxacillin, cefoxitin,
Cefotaxime		 [38]
SHV-1, SHV-10 Acylation of the S130G enzyme,
Reduced carbamylation		 E. coli Avibactam,
Diazabicyclooctane		 [55]
KPC
KPC-1 Carbapenem-hydrolyzing β-lactamase, Alterations in porin expression
 K. pneumoniaee Cephalosporins, aztreonam,  imipenem, meropenem [60]
KPC-1 Carbapenem-hydrolyzing β-lactamase, Enterobacteriaceae species Cephalosporins, aztreonam, [59]
KPC-2, KPC-3 Carbapenem-hydrolyzing β-lactamase K. pneumoniae ST258 Cephalosporins, Penicillin, [83]
KPC-2 Plasmid mediated Carbapenem-hydrolyzing β-lactamase K. pneumonia ST11 Ceftazidime, cefoxitin, piperacillin/tazobactam, cefoperazone/sulbactam [84]
KPC-kp pkp28 plasmid mediated, hydrolysis K. pneumoniae Cephalosporins [42]
Carbapenemase NDM
NDM-1 ESBLs, Porin impermeability K. pneumoniae,
E. coli 		Imipenem, ertapenem, meropenem
NDM-1 Plasmid mediated resistance K. pneumoniae,
E. coli 		Imipenem, ertapenem,
Meropenem, aztreonam		 [85]
NDM-1 Plasmid mediated blaNDM-1 K. pneumoniae ST11
K. pneumoniae ST14		 Imipenem, ertapenem, meropenem [86]
NDM-1 Plasmid mediated blaNDM-1 K. pneumoniae All β-lactams except aztreonam [87]
NDM+KPC Plasmid mediated enzymatic degradation Enterobacteriaceae All carbapenem
NDM-1 bla NDM-1 Salmonella Spp. Ampicillin
Amoxicillin-clavulanic acid
Piperacillin-tazobactam
Ceftriaxone
Trimethoprim-sulfamethoxazole		 [88]
NDM-1 IncN plasmid p46 with ISCR1 element K. pneumonia,
E. coli 		Carbapenems [73,89]
NDM-1 Plasmid mediated blaNDM-1 Acinetobacter baumannii strains of ST1 Carbapenems [90]
NDM-1 blaNDM-1 on transposon Acinetobacter spp. Meropenem [58,66]
NDM-1 + qnrB + aac +SHV-11 blaNDM-1 and outer membrane loss E. coli Multidrug resistance [57]
NDM-1 + KPC-3, gyrA, gyrB, parC, pare and armA Plasmid mediated blaNDM-1, and loss of porins Enterobacter cloacae Multidrug resistance [91]
OXA Family
OXA Single amino acid mutation E. coli,
P. aeruginosa 		Cefoxitin [92]
OXA-2 Plasmid mediated ESBLs substitution E. coli Cefotaxime
OXA-10, OXA17, OXA-74 No OprD production Pseudomonas aeruginosa Cefipime and cefotaxime [65]
OXA-48 ESBLs, Porin impermeability K. pneumoniae,
E. coli 		Imipenem, ertapenem, meropenem
OXA-23, OXA-58 Hydrolysis by oxacillinase Acinetobacter spp. Meropenem [58,66]
KPC
KPC-1 Carbapenem-hydrolyzing β-lactamase, Alterations in porin expression K. pneumoniae Cephalosporins, aztreonam,  imipenem, meropenem [60]
KPC-1 Carbapenem-hydrolyzing β-lactamase, Enterobacteriaceae species Cephalosporins, aztreonam, [59]
KPC-2, KPC-3 Carbapenem-hydrolyzing β-lactamase K. pneumoniae ST258 Cephalosporins, Penicillin, [83]
KPC-2 Plasmid mediated Carbapenem-hydrolyzing β-lactamase K. pneumonia ST11 Ceftazidime, cefoxitin, piperacillin/tazobactam, cefoperazone/sulbactam [93]
KPC-kp pkp28 plasmid mediated, hydrolysis K. pneumoniae Cephalosporins [61]
Carbapenemase NDM
NDM-1 ESBLs, Porin impermeability K. pneumoniae,
E. coli 		Imipenem, ertapenem, meropenem [81]
NDM-1 Plasmid mediated resistance K. pneumonia,
E. coli 		Imipenem, ertapenem,
Meropenem, aztreonam		 Fisher and Mobashery, 2014; Bakour et al., 2015)
NDM-1 Plasmid mediated blaNDM-1 K. pneumoniae ST11
K. pneumoniae ST14		 Imipenem, ertapenem, meropenem [50,51]
NDM-1 Plasmid mediated blaNDM-1 K. pneumoniae All β-lactams except aztreonam [69]
NDM+KPC Plasmid mediated enzymatic degradation Enterobacteriaceae All carbapenem [94]
NDM-1 bla NDM-1 Salmonella Spp. Ampicillin
Amoxicillin-clavulanic acid
Piperacillin-tazobactam
Ceftriaxone
Trimethoprim-sulfamethoxazole
NDM-1 IncN plasmid p46 with ISCR1 element K. pneumoniae,
E. coli 		Carbapenems [95]
NDM-1 Plasmid mediated blaNDM-1 Acinetobacter baumannii strains of ST1 Carbapenems [84]
NDM-1 blaNDM-1 on transposon Acinetobacter spp. Meropenem [58,66]
NDM-1 + qnrB + aac +SHV-11 blaNDM-1 and outer membrane loss E. coli Multidrug resistance [73,74]
NDM-1 + KPC-3, gyrA, gyrB, parC, pare and armA Plasmid mediated blaNDM-1, and loss of porins Enterobacter cloacae Multidrug resistance [57]
AmpC β-lactamases
AmpC Mutations at positions −42 and −32 of the ampC promoter region E. coli Cefoxitin [96,97]
DHA-1 Plasmid mediated hydrolyzing β-lactamase K. pneumoniae ST11 Ceftazidime, cefoxitin, piperacillin/tazobactam, cefoperazone/sulbactam [81]
AmpC Overexpression of MexXY-OprM and MexAB-OprM Pseudonomas aeruginosa Cefipime and cefotaxime [65]
AmpC overexpression of the ampC gene and hydrolysis of oxyimino cephalosporins Enterobacteriaceae Cephalosporins [23]
AmpC Less generation and low activation of ampC leads to confine the β-lactams in periplasmic region Enterobacteriaceae Cephalosporin [96,97]
AmpC + TEM Mutation in genes E. coli Amoxicillin, cefixime, nalidixic acid, gentamicin, ceftriaxone, ceftazidime, TMP, difloxacin, cefotaxime,
AmpC + CTX-M Mutation in promoter at position −31 E. coli Cefpodoxime [98]
AmpC blaAmpC over production, Mutation in efflux parts, PBP3 mutation Pseudomonas aeruginosa Ceftazidime [80]