Drug (ID: DG00163) and It's Reported Resistant Information
Name
Cefotaxime
Synonyms
Cefotaxim; Cefotaxima; Cefotaximum; Cephotaxim; Cephotaxime; Claforan; Klaforan; Cefotaxim Hikma; Cefotaxime acid; CE3; RU 24662; Cefotaxim Hikma (TN); Cefotaxima [INN-Spanish]; Cefotaxime (INN); Cefotaxime [INN:BAN]; Cefotaximum [INN-Latin]; Claforan (TN); Ru-24756; Claforan (*Sodium salt*)
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Indication
In total 1 Indication(s)
Bacterial infection [ICD-11: 1A00-1C4Z]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (6 diseases)
Anaerobic bacterial infection [ICD-11: 1A09]
[2], [3]
Bacterial infection [ICD-11: 1A00-1C4Z]
[4]
Escherichia coli intestinal infection [ICD-11: 1A03]
[4]
Malaria [ICD-11: 1F45]
[1]
Non-tuberculous mycobacteria infection [ICD-11: 1B21]
[5]
Pneumonia [ICD-11: CA40]
[6]
Target Bacterial DD-carboxypeptidase (Bact vanYB) VANY_ENTFA [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C16H17N5O7S2
IsoSMILES
CC(=O)OCC1=C(N2[C@@H]([C@@H](C2=O)NC(=O)/C(=N\\OC)/C3=CSC(=N3)N)SC1)C(=O)O
InChI
1S/C16H17N5O7S2/c1-6(22)28-3-7-4-29-14-10(13(24)21(14)11(7)15(25)26)19-12(23)9(20-27-2)8-5-30-16(17)18-8/h5,10,14H,3-4H2,1-2H3,(H2,17,18)(H,19,23)(H,25,26)/b20-9-/t10-,14-/m1/s1
InChIKey
GPRBEKHLDVQUJE-QSWIMTSFSA-N
PubChem CID
5742673
ChEBI ID
CHEBI:204928
TTD Drug ID
D0D1HA
INTEDE ID
DR2226
DrugBank ID
DB00493
Type(s) of Resistant Mechanism of This Drug
  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
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Anaerobic bacterial infection [ICD-11: 1A00-1A09]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Beta-lactamase (BLA) [2], [3]
Molecule Alteration Expression
Up-regulation
Resistant Disease Anaerobic Bacterial infection [ICD-11: 1A00-1A09]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli HB101 634468
Escherichia coli JM109 562
Acidaminococcus fermentans RYC-MR95 905
Acidaminococcus fermentans RYC4093 905
Acidaminococcus fermentans RYC4356 905
Escherichia coli RYC1000 562
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Agar dilution method assay; broth microdilution method assay
Mechanism Description A. intestini is the first Gram-negative coccus with demonstrated resistance to beta-lactam antibiotics. The reference genome of the A. intestini strain RyC-MR95, which was isolated from a perianal abscess of a European male diabetic patient, contains the aci1 gene, which encodes the ACI-1 class A beta-lactamase that confers resistance to penicillins and extended-spectrum cephalosporins.
Bacterial infection [ICD-11: 1A00-1C4Z]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Beta-lactamase (BLA) [7]
Molecule Alteration Missense mutation
p.Y104A+p.N110D+p.E175Q+p.S179A
Resistant Disease Bacterial infection [ICD-11: 1A00-1C4Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Acinetobacter baumannii CIP70.10 470
Klebsiella pneumoniae kP3 1290996
Pseudomonas aeruginosa PU21 287
Experiment for
Molecule Alteration
Whole genome sequence assay; Allelic frequency measurement assay
Experiment for
Drug Resistance
MIC assay
Mechanism Description K. pneumoniae kP3 was resistant to all Beta-lactams, including carbapenems, and expressed the carbapenem-hydrolyzing Beta-lactamase OXA-181, which differs from OXA-48 by four amino acid substitutions. Compared to OXA-48, OXA-181 possessed a very similar hydrolytic profile.
Key Molecule: Beta-lactamase (BLA) [8]
Molecule Alteration Missense mutation
p.Y221H
Resistant Disease Bacterial infection [ICD-11: 1A00-1C4Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Escherichia coli EC13 562
Experiment for
Molecule Alteration
Whole genome sequencing assay
Experiment for
Drug Resistance
Disk diffusion test assay
Mechanism Description The CMY-136 Beta-lactamase, a Y221H point mutant derivative of CMY-2,confers an increased level of resistance to ticarcillin, cefuroxime, cefotaxime, and ceftolozane/tazobactam.
Key Molecule: Beta-lactamase (BLA) [9]
Molecule Alteration Mutantion
p.V231S
Resistant Disease Bacterial infection [ICD-11: 1A00-1C4Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli DH10B 316385
Escherichia coli VA1171/10 562
Experiment for
Molecule Alteration
Whole genome sequence assay; Allelic frequency measurement assay
Experiment for
Drug Resistance
Quadruple disc test assay
Mechanism Description Molecular methods revealed a novel, plasmid-localized variant of CMY-2 with a substitution of valine 231 for serine (V231S), which was designated CMY-42. Like the CMY-2-like AmpC beta-lactamase CMY-30, carrying the substitution V231G, CMY-42 displayed increased activity toward expanded spectrum cephalosporins.
Key Molecule: Beta-lactamase (BLA) [10], [11], [12]
Molecule Alteration Missense mutation
p.V84I+p.A184V
Resistant Disease Bacterial infection [ICD-11: 1A00-1C4Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli JM109 562
Mechanism Description The TEM Beta-lactamases are among the best-studied antibiotic resistance enzymes around.TEM-1, the first TEM allele identified, was isolated from penicillin-resistant bacteria in 1963.
Key Molecule: Beta-lactamase (BLA) [11], [13], [14]
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
Citrobacter freundii 2526/96 546
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: Metallo-beta-lactamase (VIM1) [4]
Molecule Alteration Expression
Inherence
Resistant Disease Achromobacter xylosoxydans infection [ICD-11: 1A00-1C4Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli 668369
Achromobacter xylosoxydans subsp. denitrificans AX-22 85698
Escherichia coli MkD-135 562
Pseudomonas aeruginosa 10145/3 287
Experiment for
Molecule Alteration
DNA extraction and Sequencing assay
Experiment for
Drug Resistance
Macrodilution broth method assay
Mechanism Description A. xylosoxydans AX22 exhibited broad-spectrum resistance to Beta-lactams and aminoglycosides. The Beta-lactam resistance pattern (including piperacillin, ceftazidime, and carbapenem resistance) was unusual for this species, and the high-level carbapenem resistance suggested the production of an acquired carbapenemase. In fact, carbapenemase activity was detected in a crude extract of AX22 (specific activity, 184 +/- 12 U/mg of protein), and this activity was reduced (>80%) after incubation of the crude extract with 2 mM EDTA, suggesting the presence of a metallo-Beta-lactamase determinant.
Key Molecule: Beta-lactamase (BLA) [11], [15]
Molecule Alteration Missense mutation
p.V77A+p.D114N+p.S140A+p.N288D
Resistant Disease Bacterial infection [ICD-11: 1A00-1C4Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Citrobacter freundii strain 2524/96 546
Citrobacter freundii strain 2525/96 546
Citrobacter freundii strain 2526/96 546
Escherichia coli strain 2527/96 562
Experiment for
Drug Resistance
Agar dilution method assay
Mechanism Description Sequencing has revealed that C. freundii isolates produced a new CTX-M-3 enzyme which is very closely related to the CTX-M-1/MEN-1 Beta-lactamase.
Escherichia coli intestinal infection [ICD-11: 1A03]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Metallo-beta-lactamase (VIM1) [4]
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 668369
Achromobacter xylosoxydans subsp. denitrificans AX-22 85698
Escherichia coli MkD-135 562
Pseudomonas aeruginosa 10145/3 287
Experiment for
Molecule Alteration
DNA extraction and Sequencing assay
Experiment for
Drug Resistance
Macrodilution broth method assay
Mechanism Description Electroporation of Escherichia coli DH5alpha with the purified plasmid preparation yielded ampicillin-resistant transformants which contained a plasmid apparently identical to pAX22 (data not shown). DH5alpha(pAX22) produced carbapenemase activity (specific activity of crude extract, 202 +/- 14 U/mg of protein) and, compared to DH5alpha, exhibited a decreased susceptibility to several Beta-lactams.
Non-tuberculous mycobacteria infection [ICD-11: 1B21]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [5]
Molecule Alteration Expression
Up-regulation
Resistant Disease Cutaneous bacterial infection [ICD-11: 1B21.4]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Acinetobacter baumannii isolates 470
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
Broth microdilution method assay; Agar dilution method assay
Mechanism Description The isolate was resistant to antibiotics other than ampicillin-sulbactam and colistin, suggesting drug resistance due to carbapenemase production by OXA-23.carbapenem resistance in the isolated carbapenem-resistant A. baumannii strain was at least partially conferred by bla OXA-23-like carbapenemase.
Malaria [ICD-11: 1F45]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: CAM-1 carbapenemase (CAM1) [1]
Molecule Alteration Expression
Up-regulation
Resistant Disease Pseudomonas infection [ICD-11: 1F45.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Pseudomonas aeruginosa N17-01167 287
Pseudomonas aeruginosa N17-01173 287
Pseudomonas aeruginosa N17-02436 287
Pseudomonas aeruginosa N17-02437 287
Experiment for
Molecule Alteration
Whole genome sequencing assay
Experiment for
Drug Resistance
Vitek 2 assay; Etest assay
Mechanism Description A novel class B Beta-lactamase gene, blaCAM-1, exhibited resistance to imipenem, meropenem, doripenem, cefotaxime, ceftazidime, cefoxitin, piperacillin/tazobactam, ceftazidime/avibactam and ceftolozane/tazobactam.
ICD-12: Respiratory system diseases
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Pneumonia [ICD-11: CA40]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Bcr/CflA family efflux transporter (BCML) [6]
Molecule Alteration Expression
Inherence
Resistant Disease Klebsiella pneumoniae infection [ICD-11: CA40.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli DH10B 316385
Escherichia coli strain NCTC 50192 562
Klebsiella pneumoniae strain ORI-1 573
Experiment for
Molecule Alteration
PCR and hybridization experiments assay
Experiment for
Drug Resistance
Agar dilution technique assay
Mechanism Description Klebsiella pneumoniae ORI-1 strain harbored a ca. 140-kb nontransferable plasmid, pTk1, that conferred an extended-spectrum cephalosporin resistance profile antagonized by the addition of clavulanic acid, tazobactam, or imipenem. The gene for GES-1 (Guiana extended-spectrum beta-lactamase) was cloned, and its protein was expressed in Escherichia coli DH10B, where this pI-5. 8 beta-lactamase of a ca. 31-kDa molecular mass conferred resistance to oxyimino cephalosporins (mostly to ceftazidime). GES-1 is weakly related to the other plasmid-located Ambler class A extended-spectrum beta-lactamases (ESBLs).
Key Molecule: Bcr/CflA family efflux transporter (BCML) [6]
Molecule Alteration Expression
Acquired
Resistant Disease Klebsiella pneumoniae infection [ICD-11: CA40.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli DH10B 316385
Escherichia coli strain NCTC 50192 562
Klebsiella pneumoniae strain ORI-1 573
Experiment for
Molecule Alteration
PCR and hybridization experiments assay
Experiment for
Drug Resistance
Agar dilution technique assay
Mechanism Description Beta-Lactam MICs for k. pneumoniae ORI-1 and Escherichia coli DH10B harboring either the natural plasmid pTk1 or the recombinant plasmid pC1 were somewhat similar and might indicate the presence of an ESBL. In all cases, the ceftazidime MICs were higher than those of cefotaxime and aztreonam. Beta-Lactam MICs were always lowered by the addition of clavulanic acid or tazobactam, less so by sulbactam, and uncommonly by imipenem.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Bcr/CflA family efflux transporter (BCML) [6]
Molecule Alteration Expression
Antagonism
Sensitive Disease Klebsiella pneumoniae infection [ICD-11: CA40.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli DH10B 316385
Escherichia coli strain NCTC 50192 562
Klebsiella pneumoniae strain ORI-1 573
Experiment for
Molecule Alteration
PCR and hybridization experiments assay
Experiment for
Drug Resistance
Agar dilution technique assay
Mechanism Description Inhibition studies, as measured by IC50 values with benzylpenicillin as the substrate, showed that GES-1 was inhibited by clavulanic acid (5 uM) and tazobactam (2.5 uM) and strongly inhibited by imipenem (0.1 uM). Beta-Lactam MICs were always lowered by the addition of clavulanic acid or tazobactam, less so by sulbactam, and uncommonly by imipenem.
Key Molecule: OmpK37 (OMPK37) [16]
Molecule Alteration Expression
Inherence
Sensitive Disease Klebsiella pneumoniae infection [ICD-11: CA40.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli 668369
Klebsiella pneumoniae strain CSUB10R 573
Klebsiella pneumoniae strain CSUB10S 573
Klebsiella pneumoniae strain LB4 573
Klebsiella pneumoniae strain LB66 573
Klebsiella pneumoniae strain SD8 573
Experiment for
Molecule Alteration
Southern blotting assay
Experiment for
Drug Resistance
Microdilution method assay
Mechanism Description Due to its porin deficiency, strain CSUB10R is more resistant to Beta-lactams than is parental strain CSUB10S. As expected, for k. pneumoniae CSUB10R expressing Ompk36 or Ompk35, the MICs reverted to values similar to those observed for strain CSUB10S.
References
Ref 1 Identification of a novel metallo-Beta-lactamase, CAM-1, in clinical Pseudomonas aeruginosa isolates from Canada. J Antimicrob Chemother. 2019 Jun 1;74(6):1563-1567. doi: 10.1093/jac/dkz066.
Ref 2 ACI-1 from Acidaminococcus fermentans: characterization of the first beta-lactamase in Anaerobic cocci. Antimicrob Agents Chemother. 2000 Nov;44(11):3144-9. doi: 10.1128/AAC.44.11.3144-3149.2000.
Ref 3 ACI-1 beta-lactamase is widespread across human gut microbiomes in Negativicutes due to transposons harboured by tailed prophages. Environ Microbiol. 2018 Jun;20(6):2288-2300. doi: 10.1111/1462-2920.14276. Epub 2018 Aug 7.
Ref 4 In70 of plasmid pAX22, a bla(VIM-1)-containing integron carrying a new aminoglycoside phosphotransferase gene cassette. Antimicrob Agents Chemother. 2001 Apr;45(4):1249-53. doi: 10.1128/AAC.45.4.1249-1253.2001.
Ref 5 Daptomycin .J Antimicrob Chemother. 2018 Jan 1;73(1):1-11. doi: 10.1093/jac/dkx349. 10.1093/jac/dkx349
Ref 6 Biochemical sequence analyses of GES-1, a novel class A extended-spectrum beta-lactamase, and the class 1 integron In52 from Klebsiella pneumoniae. Antimicrob Agents Chemother. 2000 Mar;44(3):622-32. doi: 10.1128/AAC.44.3.622-632.2000.
Ref 7 Characterization of OXA-181, a carbapenem-hydrolyzing class D beta-lactamase from Klebsiella pneumoniae. Antimicrob Agents Chemother. 2011 Oct;55(10):4896-9. doi: 10.1128/AAC.00481-11. Epub 2011 Jul 18.
Ref 8 Genetic, Biochemical, and Structural Characterization of CMY-136 Beta-Lactamase, a Peculiar CMY-2 Variant. ACS Infect Dis. 2019 Apr 12;5(4):528-538. doi: 10.1021/acsinfecdis.8b00240. Epub 2019 Mar 7.
Ref 9 CMY-42, a novel plasmid-mediated CMY-2 variant AmpC beta-lactamase. Microb Drug Resist. 2011 Jun;17(2):165-9. doi: 10.1089/mdr.2010.0137. Epub 2011 Mar 9.
Ref 10 Natural evolution of TEM-1 Beta-lactamase: experimental reconstruction and clinical relevance. FEMS Microbiol Rev. 2010 Nov;34(6):1015-36. doi: 10.1111/j.1574-6976.2010.00222.x.
Ref 11 Identifying novel Beta-lactamase substrate activity through in silico prediction of antimicrobial resistance. Microb Genom. 2021 Jan;7(1):mgen000500. doi: 10.1099/mgen.0.000500.
Ref 12 Nucleotide sequence of the ampicillin resistance gene of Escherichia coli plasmid pBR322. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3737-41. doi: 10.1073/pnas.75.8.3737.
Ref 13 Plasmid-mediated extended-spectrum beta-lactamase (CTX-M-3 like) from India and gene association with insertion sequence ISEcp1. FEMS Microbiol Lett. 2001 Jul 24;201(2):237-41. doi: 10.1111/j.1574-6968.2001.tb10762.x.
Ref 14 Biochemical analysis of the ceftazidime-hydrolysing extended-spectrum beta-lactamase CTX-M-15 and of its structurally related beta-lactamase CTX-M-3. J Antimicrob Chemother. 2002 Dec;50(6):1031-4. doi: 10.1093/jac/dkf240.
Ref 15 Cefotaxime-resistant Enterobacteriaceae isolates from a hospital in Warsaw, Poland: identification of a new CTX-M-3 cefotaxime-hydrolyzing beta-lactamase that is closely related to the CTX-M-1/MEN-1 enzyme. Antimicrob Agents Chemother. 1998 Apr;42(4):827-32. doi: 10.1128/AAC.42.4.827.
Ref 16 Identification and characterization of a new porin gene of Klebsiella pneumoniae: its role in beta-lactam antibiotic resistance. J Bacteriol. 1999 May;181(9):2726-32. doi: 10.1128/JB.181.9.2726-2732.1999.

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