Drug Information

Drug (ID: DG00085) and It's Reported Resistant Information

• Name: Ceftriaxone
• Synonyms: Biotrakson; CTRX; Cefatriaxone; Ceftriaxon; Ceftriaxona; Ceftriaxonum; Ceftriazone; Longacef; Longaceph; Rocefin; Rocephin; Rocephine; CEFTRIAXONE SODIUM; Ceftriaxone intravenous; Ro 139904; Ceftriaxona [INN-Spanish]; Ceftriaxone (INN); Ceftriaxone (TN); Ceftriaxone [USAN:JAN]; Ceftriaxone, Disodium Salt; Ceftriaxonum [INN-Latin]; DRG-0071; Ro13-9904; Rocephin (TN); Ceftriaxone, Disodium Salt, Hemiheptahydrate; Ro-13-9904; (6R,7R)-7-(2-(2-Amino-4-thiazolyl)glyoxylamido)-8-oxo-3-(((1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-as-triazin-3-yl)thio)methyl)-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7(sup 2)-(Z)-(O-methyloxime), sesquaterhydrate; (6R,7R)-7-({(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(methyloxy)imino]acetyl}amino)-3-{[(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[(2-methyl-5,6-dioxo-1H-1,2,4-triazin-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino}-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 7beta-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino}-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)sulfanyl]methyl}-3,4-didehydrocepham-4-carboxylic acid
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (8 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [2], [3], [4]
  Escherichia coli intestinal infection [ICD-11: 1A03]; [5]
  Gonococcal infection [ICD-11: 1A72]; [6]
  Gonorrhea [ICD-11: 1A70]; [7]
  Meningococcal disease [ICD-11: 1C1C]; [8]
  Non-tuberculous mycobacteria infection [ICD-11: 1B21]; [9]
  Pneumonia [ICD-11: CA40]; [5]
  Salmonellosis [ICD-11: 1A09]; [10]
• Target: Bacterial Penicillin binding protein (Bact PBP); NOUNIPROTAC; [1]
• Formula: C18H18N8O7S3
• IsoSMILES: CN1C(=NC(=O)C(=O)N1)SCC2=C(N3[C@@H]([C@@H](C3=O)NC(=O)/C(=N\\OC)/C4=CSC(=N4)N)SC2)C(=O)O
• InChI: 1S/C18H18N8O7S3/c1-25-18(22-12(28)13(29)23-25)36-4-6-3-34-15-9(14(30)26(15)10(6)16(31)32)21-11(27)8(24-33-2)7-5-35-17(19)20-7/h5,9,15H,3-4H2,1-2H3,(H2,19,20)(H,21,27)(H,23,29)(H,31,32)/b24-8-/t9-,15-/m1/s1
• InChIKey: VAAUVRVFOQPIGI-SPQHTLEESA-N
• PubChem CID: 5479530
• ChEBI ID: CHEBI:29007
• TTD Drug ID: D07ACT
• VARIDT ID: DR00553
• INTEDE ID: DR2655
• DrugBank ID: DB01212

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  DISM: Drug Inactivation by Structure Modification

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [2], [3], [4]

• Molecule Alteration: Missense mutation; p.D240G
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH10B; 316385
• In Vitro Model: Citrobacter freundii 2526/96; 546
• In Vitro Model: Escherichia coli isolates; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: We have reported recently the DNA sequence of another Beta-lactamase, CTX- M-15, from Indian enterobacterial isolates that were resistant to both cefotaxime and ceftazidime.CTX-M-15 has a single amino acid change [Asp-240-Gly (Ambler numbering)]7 compared with CTX-M-3.

Key Molecule: Beta-lactamase (BLA) [10]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Enterobacter cloacae infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Enterobacter cloacae strains ENLA-1; 550
• In Vitro Model: Escherichia coli strain ECAA-1; 562
• In Vitro Model: Escherichia coli strain ECLA-1; 562
• In Vitro Model: Escherichia coli strain ECLA-2; 562
• In Vitro Model: Escherichia coli strain ECLA-4; 562
• In Vitro Model: Escherichia coli strain ECZK-1; 562
• In Vitro Model: Escherichia coli strain ECZP-1; 562
• In Vitro Model: Escherichia coli strain ECZU-1; 562
• In Vitro Model: Escherichia coli strain HK225f; 562
• In Vitro Model: Klebsiella pneumoniae strains KPAA-1; 573
• In Vitro Model: Klebsiella pneumoniae strains KPBE-2; 573
• In Vitro Model: Klebsiella pneumoniae strains KPGE-1; 573
• In Vitro Model: Klebsiella pneumoniae strains KPGE-2; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-1; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-10; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-2; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-3; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-4; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-5; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-6; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-7; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-8; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-9; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-1; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-10; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-11; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-12; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-13; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-4; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-6; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-7; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-8; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-9; 573
• In Vitro Model: Salmonella enterica serotype wien strain SWLA-1; 149384
• In Vitro Model: Salmonella enterica serotype wien strain SWLA-2; 149384
• Experiment for Molecule Alteration: Hybridization experiments assay
• Experiment for Drug Resistance: Microdilution method assay
• Mechanism Description: Of 60 strains with reduced susceptibility to expanded-spectrum cephalosporins which had been collected, 34 (24Klebsiella pneumoniae, 7Escherichia coli, 1Enterobacter cloacae, and 2Salmonella entericaserotypewien) hybridized with the intragenic blaSHVprobe. TheblaSHVgenes were amplified by PCR, and the presence ofblaSHV-ESBLwas established in 29 strains by restriction enzyme digests of the resulting 1,018-bp amplimers as described elsewhere. These results were confirmed by the nucleotide sequencing of all 34 amplimers. Five strains contained SHV non-ESBL enzymes.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: TolC family outer membrane protein (TOLC) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Acinetobacter baumannii AYE WT; 509173
• In Vitro Model: Acinetobacter baumannii AYE detaabuO; 509173
• In Vitro Model: Acinetobacter baumannii AYE detaabuO Omega abuO; 509173
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay; E-strip test assay
• Mechanism Description: AbuO, an OMP, confers broad-spectrum antimicrobial resistance via active efflux in A. baumannii.

Escherichia coli intestinal infection [ICD-11: 1A03]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [5]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli JM109; 562
• Experiment for Molecule Alteration: PCR and molecular characterization assay
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: CTX-M-55 is a novel ceftazidime-resistant CTX-M extended-spectrum Beta-lactamase, which reduced susceptibility.

Key Molecule: Beta-lactamase (BLA) [10]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Enterobacter cloacae strains ENLA-1; 550
• In Vitro Model: Escherichia coli strain ECAA-1; 562
• In Vitro Model: Escherichia coli strain ECLA-1; 562
• In Vitro Model: Escherichia coli strain ECLA-2; 562
• In Vitro Model: Escherichia coli strain ECLA-4; 562
• In Vitro Model: Escherichia coli strain ECZK-1; 562
• In Vitro Model: Escherichia coli strain ECZP-1; 562
• In Vitro Model: Escherichia coli strain ECZU-1; 562
• In Vitro Model: Escherichia coli strain HK225f; 562
• In Vitro Model: Klebsiella pneumoniae strains KPAA-1; 573
• In Vitro Model: Klebsiella pneumoniae strains KPBE-2; 573
• In Vitro Model: Klebsiella pneumoniae strains KPGE-1; 573
• In Vitro Model: Klebsiella pneumoniae strains KPGE-2; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-1; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-10; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-2; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-3; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-4; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-5; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-6; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-7; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-8; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-9; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-1; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-10; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-11; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-12; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-13; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-4; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-6; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-7; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-8; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-9; 573
• In Vitro Model: Salmonella enterica serotype wien strain SWLA-1; 149384
• In Vitro Model: Salmonella enterica serotype wien strain SWLA-2; 149384
• Experiment for Molecule Alteration: Hybridization experiments assay
• Experiment for Drug Resistance: Microdilution method assay
• Mechanism Description: Of 60 strains with reduced susceptibility to expanded-spectrum cephalosporins which had been collected, 34 (24Klebsiella pneumoniae, 7Escherichia coli, 1Enterobacter cloacae, and 2Salmonella entericaserotypewien) hybridized with the intragenic blaSHVprobe. TheblaSHVgenes were amplified by PCR, and the presence ofblaSHV-ESBLwas established in 29 strains by restriction enzyme digests of the resulting 1,018-bp amplimers as described elsewhere. These results were confirmed by the nucleotide sequencing of all 34 amplimers. Five strains contained SHV non-ESBL enzymes.

Salmonellosis [ICD-11: 1A09]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [10]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Salmonella enterica infection [ICD-11: 1A09.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Enterobacter cloacae strains ENLA-1; 550
• In Vitro Model: Escherichia coli strain ECAA-1; 562
• In Vitro Model: Escherichia coli strain ECLA-1; 562
• In Vitro Model: Escherichia coli strain ECLA-2; 562
• In Vitro Model: Escherichia coli strain ECLA-4; 562
• In Vitro Model: Escherichia coli strain ECZK-1; 562
• In Vitro Model: Escherichia coli strain ECZP-1; 562
• In Vitro Model: Escherichia coli strain ECZU-1; 562
• In Vitro Model: Escherichia coli strain HK225f; 562
• In Vitro Model: Salmonella enterica serotype wien strain SWLA-1; 149384
• In Vitro Model: Salmonella enterica serotype wien strain SWLA-2; 149384
• In Vitro Model: Klebsiella pneumoniae strains kPAA-1; 573
• In Vitro Model: Klebsiella pneumoniae strains kPBE-2; 573
• In Vitro Model: Klebsiella pneumoniae strains kPGE-1; 573
• In Vitro Model: Klebsiella pneumoniae strains kPGE-2; 573
• In Vitro Model: Klebsiella pneumoniae strains kPLA-1; 573
• In Vitro Model: Klebsiella pneumoniae strains kPLA-10; 573
• In Vitro Model: Klebsiella pneumoniae strains kPLA-2; 573
• In Vitro Model: Klebsiella pneumoniae strains kPLA-3; 573
• In Vitro Model: Klebsiella pneumoniae strains kPLA-4; 573
• In Vitro Model: Klebsiella pneumoniae strains kPLA-5; 573
• In Vitro Model: Klebsiella pneumoniae strains kPLA-6; 573
• In Vitro Model: Klebsiella pneumoniae strains kPLA-7; 573
• In Vitro Model: Klebsiella pneumoniae strains kPLA-8; 573
• In Vitro Model: Klebsiella pneumoniae strains kPLA-9; 573
• In Vitro Model: Klebsiella pneumoniae strains kPZU-1; 573
• In Vitro Model: Klebsiella pneumoniae strains kPZU-10; 573
• In Vitro Model: Klebsiella pneumoniae strains kPZU-11; 573
• In Vitro Model: Klebsiella pneumoniae strains kPZU-12; 573
• In Vitro Model: Klebsiella pneumoniae strains kPZU-13; 573
• In Vitro Model: Klebsiella pneumoniae strains kPZU-4; 573
• In Vitro Model: Klebsiella pneumoniae strains kPZU-6; 573
• In Vitro Model: Klebsiella pneumoniae strains kPZU-7; 573
• In Vitro Model: Klebsiella pneumoniae strains kPZU-8; 573
• In Vitro Model: Klebsiella pneumoniae strains kPZU-9; 573
• Experiment for Molecule Alteration: Hybridization experiments assay
• Experiment for Drug Resistance: Microdilution method assay
• Mechanism Description: Of 60 strains with reduced susceptibility to expanded-spectrum cephalosporins which had been collected, 34 (24Klebsiella pneumoniae, 7Escherichia coli, 1Enterobacter cloacae, and 2Salmonella entericaserotypewien) hybridized with the intragenic blaSHVprobe. TheblaSHVgenes were amplified by PCR, and the presence ofblaSHV-ESBLwas established in 29 strains by restriction enzyme digests of the resulting 1,018-bp amplimers as described elsewhere. These results were confirmed by the nucleotide sequencing of all 34 amplimers. Five strains contained SHV non-ESBL enzymes.

Gonorrhea [ICD-11: 1A70]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Probable peptidoglycan D,D-transpeptidase PenA (PENA) [11], [12], [13]

• Molecule Alteration: Missense mutation; p.A311V
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Key Molecule: Probable peptidoglycan D,D-transpeptidase PenA (PENA) [11], [12], [13]

• Molecule Alteration: Missense mutation; p.T316P
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Key Molecule: Probable peptidoglycan D,D-transpeptidase PenA (PENA) [11], [12], [13]

• Molecule Alteration: Missense mutation; p.A311V+p.T316P
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Key Molecule: Probable peptidoglycan D,D-transpeptidase PenA (PENA) [11], [12], [13]

• Molecule Alteration: Missense mutation; p.T483S
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Key Molecule: Probable peptidoglycan D,D-transpeptidase PenA (PENA) [11], [12], [13]

• Molecule Alteration: Missense mutation; p.T483S+p.A311V+p.T316P
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Type IV pilus biogenesis and competence protein PilQ (PILQ) [7]

• Molecule Alteration: Missense mutation; p.G666K
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae PR100; 485
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Antibiotic resistance mediated by penC is the result of a Glu-666 to Lys missense mutation in the pilQ gene that interferes with the formation of the SDS-resistant high-molecular-mass PilQ secretin complex, disrupts piliation, and decreases transformation frequency by 50-fold.

ICD-12: Respiratory system diseases

Pneumonia [ICD-11: CA40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [5]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Klebsiella pneumoniae [ICD-11: CA40.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Klebsiella pneumoniae isolates; 573
• Experiment for Molecule Alteration: PCR and molecular characterization assay
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: CTX-M-55 is a novel ceftazidime-resistant CTX-M extended-spectrum Beta-lactamase, which reduced susceptibility.

Key Molecule: Beta-lactamase (BLA) [10]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Klebsiella pneumoniae infection [ICD-11: CA40.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Enterobacter cloacae strains ENLA-1; 550
• In Vitro Model: Escherichia coli strain ECAA-1; 562
• In Vitro Model: Escherichia coli strain ECLA-1; 562
• In Vitro Model: Escherichia coli strain ECLA-2; 562
• In Vitro Model: Escherichia coli strain ECLA-4; 562
• In Vitro Model: Escherichia coli strain ECZK-1; 562
• In Vitro Model: Escherichia coli strain ECZP-1; 562
• In Vitro Model: Escherichia coli strain ECZU-1; 562
• In Vitro Model: Escherichia coli strain HK225f; 562
• In Vitro Model: Klebsiella pneumoniae strains KPAA-1; 573
• In Vitro Model: Klebsiella pneumoniae strains KPBE-2; 573
• In Vitro Model: Klebsiella pneumoniae strains KPGE-1; 573
• In Vitro Model: Klebsiella pneumoniae strains KPGE-2; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-1; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-10; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-2; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-3; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-4; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-5; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-6; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-7; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-8; 573
• In Vitro Model: Klebsiella pneumoniae strains KPLA-9; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-1; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-10; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-11; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-12; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-13; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-4; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-6; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-7; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-8; 573
• In Vitro Model: Klebsiella pneumoniae strains KPZU-9; 573
• In Vitro Model: Salmonella enterica serotype wien strain SWLA-1; 149384
• In Vitro Model: Salmonella enterica serotype wien strain SWLA-2; 149384
• Experiment for Molecule Alteration: Hybridization experiments assay
• Experiment for Drug Resistance: Microdilution method assay
• Mechanism Description: Of 60 strains with reduced susceptibility to expanded-spectrum cephalosporins which had been collected, 34 (24Klebsiella pneumoniae, 7Escherichia coli, 1Enterobacter cloacae, and 2Salmonella entericaserotypewien) hybridized with the intragenic blaSHVprobe. TheblaSHVgenes were amplified by PCR, and the presence ofblaSHV-ESBLwas established in 29 strains by restriction enzyme digests of the resulting 1,018-bp amplimers as described elsewhere. These results were confirmed by the nucleotide sequencing of all 34 amplimers. Five strains contained SHV non-ESBL enzymes.

References

• Ref 1: AbuO, a TolC-like outer membrane protein of Acinetobacter baumannii, is involved in antimicrobial and oxidative stress resistance. Antimicrob Agents Chemother. 2015 Feb;59(2):1236-45. doi: 10.1128/AAC.03626-14. Epub 2014 Dec 15.
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