Drug Information
Drug (ID: DG00163) and It's Reported Resistant Information
Name |
Cefotaxime
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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)
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Structure | |||||
Drug Resistance Disease(s) |
Disease(s) with Clinically Reported Resistance for This Drug
(6 diseases)
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]
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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
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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
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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
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InChIKey |
GPRBEKHLDVQUJE-QSWIMTSFSA-N
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ChEBI ID | |||||
TTD Drug ID | |||||
INTEDE ID | |||||
DrugBank ID |
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
Anaerobic bacterial infection [ICD-11: 1A00-1A09]
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Drug Inactivation by Structure Modification (DISM) | ||||
Key Molecule: Beta-lactamase (BLA) | [2], [3] | |||
Molecule Alteration | Expression | Up-regulation |
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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]
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Drug Inactivation by Structure Modification (DISM) | ||||
Key Molecule: Beta-lactamase (BLA) | [7] | |||
Molecule Alteration | Missense mutation | p.Y104A+p.N110D+p.E175Q+p.S179A |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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]
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Drug Inactivation by Structure Modification (DISM) | ||||
Key Molecule: Metallo-beta-lactamase (VIM1) | [4] | |||
Molecule Alteration | Expression | Acquired |
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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]
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Drug Inactivation by Structure Modification (DISM) | ||||
Key Molecule: OXA-23 carbapenemase (BLA OXA-23) | [5] | |||
Molecule Alteration | Expression | Up-regulation |
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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]
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Drug Inactivation by Structure Modification (DISM) | ||||
Key Molecule: CAM-1 carbapenemase (CAM1) | [1] | |||
Molecule Alteration | Expression | Up-regulation |
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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
Pneumonia [ICD-11: CA40]
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Irregularity in Drug Uptake and Drug Efflux (IDUE) | ||||
Key Molecule: Bcr/CflA family efflux transporter (BCML) | [6] | |||
Molecule Alteration | Expression | Inherence |
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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 |
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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) | ||||
Key Molecule: Bcr/CflA family efflux transporter (BCML) | [6] | |||
Molecule Alteration | Expression | Antagonism |
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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 |
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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
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