Drug Information

Drug (ID: DG00080) and It's Reported Resistant Information

• Name: Meticillin
• Synonyms: Dimocillin; MII; Metacillin; Methicillin; Methicillinum; Methycillin; Meticilina; Meticillina; Meticilline; Meticillinum; Staphcillin; Methicillin [BAN]; Meticillin [INN]; Meticillina [DCIT]; BRL 1241; Methicillin Monohydrate, Monosodium Salt; Meticilina [INN-Spanish]; Meticilline [INN-French]; Meticillinum [INN-Latin]; Penicillin, Dimethoxyphenyl; (2,6-Dimethoxyphenyl)penicillin; (2S,5R,6R)-6-[(2,6-dimethoxybenzoyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2S,5R,6R)-6-{[(2,6-dimethoxyphenyl)carbonyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 6-(2,3-Dimethoxybenzamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid; 6-(2,6-Dimethoxybenzamido)penicillanic acid; 6beta-(2,6-dimethoxybenzamido)-2,2-dimethylpenam-3alpha-carboxylic acid; 6beta-(2,6-dimethoxybenzamido)penicillanic acid
• Indication:
  In total 2 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Approved; [1]
  Dissociative neurological symptom disorder [ICD-11: 6B60]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (5 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
  Methicillin resistant staphylococcus aureus infection [ICD-11: MG51]; [2]
  Osteomyelitis/osteitis [ICD-11: FB84]; [3]
  Pseudomonas aeruginosa infection [ICD-11: 1A0Y]; [4]
  Staphylococcus meningitis [ICD-11: 1B54]; [5]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [6]
• Target: Bacterial Penicillin binding protein (Bact PBP); NOUNIPROTAC; [1]
• Formula: C17H20N2O6S
• IsoSMILES: CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)NC(=O)C3=C(C=CC=C3OC)OC)C(=O)O)C
• InChI: 1S/C17H20N2O6S/c1-17(2)12(16(22)23)19-14(21)11(15(19)26-17)18-13(20)10-8(24-3)6-5-7-9(10)25-4/h5-7,11-12,15H,1-4H3,(H,18,20)(H,22,23)/t11-,12+,15-/m1/s1
• InChIKey: RJQXTJLFIWVMTO-TYNCELHUSA-N
• PubChem CID: 6087
• ChEBI ID: CHEBI:6827
• TTD Drug ID: D06TQZ
• DrugBank ID: DB01603

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  DISM: Drug Inactivation by Structure Modification

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

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Alternative penicillin-binding protein 2a (MECD) [1]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Macrococcus caseolyticus strains; 69966
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Mechanism Description: Methicillin-resistant Macrococcus caseolyticus strains from bovine and canine origins were found to carry a novel mecD gene conferring resistance to all classes of Beta-lactams including anti-MRSA cephalosporins. Association of Beta-lactam resistance with mecD was demonstrated by gene expression in S. aureus and deletion of the mecD-containing island in M. caseolyticus.

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [6]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Rhodobacter sphaeroides infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Rhodopseudomonas sphaeroides strain DSM 160(Y); 1063
• In Vitro Model: Rhodopseudomonas sphaeroides strain DSM158; 1063
• In Vitro Model: Rhodopseudomonas sphaeroides strain DSM159; 1063
• Experiment for Molecule Alteration: Sodium dodecyl sulfate-PAGE assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Thirteen strains of the gram-negative, facultative phototrophic bacterium Rhodobacter sphaeroides were examined fro susceptibility to beta-lactam antibiotics. All strains were sensitive to the semisynthetic penicillins ampicillin, carbenicillin, oxacillin, cloxacillin, and methicillin, but 10 of the 13 strains were resistant to penicillin G, as well as a number of cephalosporins, such as cephalothin, cephapirin, and cephalosporin C. A beta-lactamase (EC 3.5.2.6) with strong cephalosporinase activity was detected in all of the resistant strains of R. sphaeroides. With strain Y-1 as a model, it was shown that the beta-lactamase was inducible by penicillin G, cephalosporin C, cephalothin, and to some minor extent, cephapirin.

References

• Ref 1: Novel methicillin resistance gene mecD in clinical Macrococcus caseolyticus strains from bovine and canine sources. Sci Rep. 2017 Mar 8;7:43797. doi: 10.1038/srep43797.
• Ref 2: Prevalence and Therapies of Antibiotic-Resistance in Staphylococcus aureusFront Cell Infect Microbiol. 2020 Mar 17;10:107. doi: 10.3389/fcimb.2020.00107. eCollection 2020.
• Ref 3: Paediatric Osteomyelitis and Septic Arthritis Pathogen Distribution and Antimicrobial Resistance in a Single Centre: A 15-Year Retrospective AnalysisJ Trop Pediatr. 2022 Apr 5;68(3):fmac038. doi: 10.1093/tropej/fmac038.
• Ref 4: Clinico-bacteriological and antibiotic drug resistance profile of chronic suppurative otitis media at a tertiary care hospital in Western RajasthanJ Family Med Prim Care. 2021 Jul;10(7):2572-2579. doi: 10.4103/jfmpc.jfmpc_2480_20. Epub 2021 Jul 30.
• Ref 5: A Panton-Valentine leucocidin (PVL)-positive community-acquired methicillin-resistant Staphylococcus aureus (MRSA) strain, another such strain carrying a multiple-drug resistance plasmid, and other more-typical PVL-negative MRSA strains found in Japan .J Clin Microbiol. 2005 Jul;43(7):3356-63. doi: 10.1128/JCM.43.7.3356-3363.2005. 10.1128/JCM.43.7.3356-3363.2005
• Ref 6: Susceptibility of Rhodobacter sphaeroides to beta-lactam antibiotics: isolation and characterization of a periplasmic beta-lactamase (cephalosporinase). J Bacteriol. 1989 Jan;171(1):308-13. doi: 10.1128/jb.171.1.308-313.1989.