Drug Information

Drug (ID: DG00184) and It's Reported Resistant Information

• Name: Cephaloridine
• Synonyms: Cephaloridine; cefaloridine; Cefaloridin; Cephaloridin; Cephaloridinum; Cepaloridin; Cefalorizin; Cephalomycine; Cefaloridinum; Cepalorin; Cefaloridina; Loridine; Ceflorin; 50-59-9; Kefloridin; Glaxoridin; Ceporin; Vioviantine; Intrasporin; Sefacin; Keflordin; Deflorin; Cilifor; Ceporan; Sasperin; Faredina; Ceporine; Keflodin; Verolgin; Lloncefal; Kefspor; Ampligram; Betaine cephaloridine; CHEBI:3537; UNII-LVZ1VC61HB; Cefaloridinum [INN-Latin]; Cefaloridina [INN-Spanish]; N-(7-(2'-Thienylacetamidoceph-3-ylmethyl))-pyridinium-2-carboxylate; SCH
• Indication:
  In total 1 Indication(s)
  Gram-positive bacterial infection [ICD-11: 1B74-1F40]; Withdrawn from market; [1], [2], [3]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [4]
  Pneumonia [ICD-11: CA40]; [5]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1], [2], [3]
• Formula: C19H17N3O4S2
• IsoSMILES: C1C(=C(N2[C@H](S1)[C@@H](C2=O)NC(=O)CC3=CC=CS3)C(=O)[O-])C[N+]4=CC=CC=C4
• InChI: 1S/C19H17N3O4S2/c23-14(9-13-5-4-8-27-13)20-15-17(24)22-16(19(25)26)12(11-28-18(15)22)10-21-6-2-1-3-7-21/h1-8,15,18H,9-11H2,(H-,20,23,25,26)/t15-,18-/m1/s1
• InChIKey: CZTQZXZIADLWOZ-CRAIPNDOSA-N
• PubChem CID: 5773
• ChEBI ID: CHEBI:3537
• TTD Drug ID: D0F8IO
• VARIDT ID: DR00612
• INTEDE ID: DR0285
• DrugBank ID: DB09008

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

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) [4]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• Experiment for Molecule Alteration: DNA sequencing and protein assay
• Experiment for Drug Resistance: Disk diffusion assay
• Mechanism Description: P. aeruginosa harbors two naturally encoded Beta-lactamase genes, one of which encodes an inducible cephalosporinase and the other of which encodes a constitutively expressed oxacillinase. AmpC is a kind of cephalosporinase which lead to drug resistance.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Outer membrane porin C (OMPC) [1], [2], [3]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli 1422; 562
• In Vitro Model: Escherichia coli 1437; 562
• In Vitro Model: Escherichia coli B1343; 562
• In Vitro Model: Escherichia coli B1350; 562
• In Vitro Model: Escherichia coli B1421; 562
• In Vitro Model: Escherichia coli pop1010; 562
• Experiment for Drug Resistance: Disk diffusion test assay
• Mechanism Description: Permeability of the outer membrane to lowmolecular-weight hydrophilic molecules is due to the presence of porin protein molecules such as OmpF and OmpC, which form pores in the outer membrane that allow small molecules to diffuse rapidly into the periplasmic space.The case of cephaloridine and cefazolin is remarkable because mutants lacking the OmpF or the OmpC proteins individually were as susceptible to cefaloridine and cefazolin as was the wild type, but mutants lacking both proteins were resistant to these Beta-lactams.

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) [5]

• 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
• In Vitro Model: Escherichia coli strain NCTC 50192; 562
• In Vitro Model: 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) [5]

• 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
• In Vitro Model: Escherichia coli strain NCTC 50192; 562
• In Vitro Model: 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) [5]

• 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
• In Vitro Model: Escherichia coli strain NCTC 50192; 562
• In Vitro Model: 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.

References

• Ref 1: Antibiotic stress, genetic response and altered permeability of E. coli. PLoS One. 2007 Apr 11;2(4):e365. doi: 10.1371/journal.pone.0000365.
• Ref 2: Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin Microbiol Rev. 2012 Oct;25(4):661-81. doi: 10.1128/CMR.00043-12.
• Ref 3: Role of porin proteins OmpF and OmpC in the permeation of beta-lactams. Antimicrob Agents Chemother. 1982 Dec;22(6):942-8. doi: 10.1128/AAC.22.6.942.
• Ref 4: Biochemical characterization of the naturally occurring oxacillinase OXA-50 of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2004 Jun;48(6):2043-8. doi: 10.1128/AAC.48.6.2043-2048.2004.
• Ref 5: 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.