Drug Information

Drug (ID: DG00378) and It's Reported Resistant Information

• Name: Florfenicol
• Synonyms: Florfenicol; 73231-34-2; Nuflor; (-)-Florfenicol; Sch-25298; 76639-94-6; Sch 25298; Aquafen; Nuflor gold; C12H14Cl2FNO4S; UNII-9J97307Y1H; 2,2-dichloro-N-[(1R,2S)-3-fluoro-1-hydroxy-1-(4-methylsulfonylphenyl)propan-2-yl]acetamide; CHEBI:87185; MFCD00864834; D-threo-2,2-Dichloro-N-(alpha-(fluoromethyl)-beta-hydroxy-p-(methylsulfonyl)phenethyl)acetamide; 9J97307Y1H; Acetamide, 2,2-dichloro-N-((1S,2R)-1-(fluoromethyl)-2-hydroxy-2-(4-(methylsulfonyl)phenyl)ethyl)-; 2,2-dichloro-N-[(1R,2S)-3-fluoro-1-hydroxy-1-(4-methanesulfonylphenyl)propan-2-yl]acetamide; 2,2-Dichloro-N-[(1R,2S)-3-fluoro-1-hydroxy-1-(4-methylsulfonylphenyl)-2-propyl]acetamide; DSSTox_CID_25500; DSSTox_RID_80918; DSSTox_GSID_45500; 2,2-Dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(methylsulfonyl)phenyl)propan-2-yl)acetamide; Florfenicol [USAN:INN:BAN]; 2,2-Dichloro-N-(1-(fluoromethyl)-2-hydroxy-2-(4-(methylsulfonyl)phenyl)ethyl)acetamide; NCGC00016922-01; CAS-73231-34-2; Nuflor (TN); Prestwick0_000955; Prestwick1_000955; Prestwick2_000955; Prestwick3_000955; Florfenicol (USAN/INN); SCHEMBL49425; BSPBio_000950; MLS002154071; SPBio_003099; BPBio1_001046; CHEMBL1241590; DTXSID9045500; SCHEMBL21835523; (-)-Florfenicol;SCH-25298; D-(-)-threo-2-Dichloroacetamido-3-fluoro-1-(4-methylsulfonylphenyl)-1-propanol; HMS1570P12; HMS2090I10; HMS2097P12; HMS2230K18; HMS3714P12; ZINC537733; ACT06682; HY-B1374; Aquafen; ; ; Nuflor; ; ; SCH-25298; Tox21_110683; s4201; AKOS015889457; Tox21_110683_1; AC-4340; CCG-220955; CS-4857; DB11413; KS-5028; NSC 759287; 2,2-dichloro-N-[(1S,2R)-1-(fluoromethyl)-2-hydroxy-2-(4-methylsulfonylphenyl)ethyl]acetamide; NCGC00179366-01; NCGC00179366-03; NCGC00179366-04; [R-(R*,S*)]-2,2-Dichloro-N-[1-(fluoromethyl)-2-hydroxy-2-[4-(methylsulfonyl)phenyl]ethyl]acetamide; 2,2-Dichloro-N-((alphaS,betaR)-alpha-(fluoromethyl)-beta-hydroxy-p-(methylsulfonyl)phenethyl)acetamide; 2,2-Dichloro-N-[(1S,2R)-1-(fluoromethyl)-2-hydroxy-2-[4-(methylsulfonyl)phenyl]ethyl]acetamide; Acetamide, 2,2-dichloro-N-(1-(fluoromethyl)-2-hydroxy-2-(4-(methylsulfonyl)phenyl)ethyl)-, (R-(R*,S*))-; Benzenesulfonic acid, 4-(2-((dichloroacetyl)amino)-3-fluoro-1-hydroxypropyl)-, methyl ester, (R-(R*,S*))-; BF166386; SMR001233384; AB0008500; (methylsulfonyl)phenyl)propan-2-yl)acetamide; AB00513976; F0811; SW197224-3; D04194; J10454; T72886; AB00513976_09; 231F342; A838774; Q408400; Florfenicol, analytical standard, for drug analysis; BRD-K11298197-001-03-9; 2,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-; (1R,2S)-2-DICHLOROACETAMIDO-3-FLUORO-1-[4-(METHYLSULFONYL) PHENYL]-1-PROPANOL; (1R,2S)-2-dichloroacetamido-3-fluoro-1-[4-(methylsulfonyl)phenyl]-1-propanol; 2,2-Dichlor-N-((1R,2S)-3-fluor-1-hydroxy- 1-(4-(methylsulfonyl)-phenyl)-propan-2-yl)-ethanamide; 2,2-dichloro-N-[(1R,2R)-3-fluoro-1-hydroxy-1-(4-methylsulfonylphenyl)propan-2-yl]acetamide; 2,2-dichloro-N-{(1R,2S)-3-fluoro-1-hydroxy-1-[4-(methanesulfonyl)phenyl]propan-2-yl}acetamide
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (7 diseases)
  Bacteremia [ICD-11: MA15]; [1]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [2]
  Infective endocarditis [ICD-11: BB40]; [1]
  Non-tuberculous mycobacteria infection [ICD-11: 1B21]; [1]
  Serious necrotizing pneumonia [ICD-11: CA43]; [1]
  Surgical wound infection [ICD-11: NE81]; [1]
  Toxic shock syndrome [ICD-11: 1C45]; [1]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (3 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [3]
  Gram-negative bacterial infection [ICD-11: 1B74-1G40]; [4]
  Pasteurellosis [ICD-11: 1B99]; [5]
• Formula: C12H14Cl2FNO4S
• IsoSMILES: CS(=O)(=O)C1=CC=C(C=C1)[C@H]([C@@H](CF)NC(=O)C(Cl)Cl)O
• InChI: 1S/C12H14Cl2FNO4S/c1-21(19,20)8-4-2-7(3-5-8)10(17)9(6-15)16-12(18)11(13)14/h2-5,9-11,17H,6H2,1H3,(H,16,18)/t9-,10-/m1/s1
• InChIKey: AYIRNRDRBQJXIF-NXEZZACHSA-N
• PubChem CID: 114811
• DrugBank ID: DB11413

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

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: Carboxymethylenebutenolidase (CLCD) [6]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli AS19; 562
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The Cfr RNA methyltransferase causes multiple resistances to peptidyl transferase inhibitors by methylation of A2503 23S rRNA.clcD codes the same enzyme.

Key Molecule: Ribosomal RNA large subunit methyltransferase (CFR ) [7]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli AS19; 562
• In Vitro Model: Escherichia coli TOP10; 83333
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Cfr confers resistance to antibiotics binding to the peptidyl transferase center on the ribosome.The primary product of the Cfr-mediated methylation is 8-methyladenosine (m8A), a new natural RNA modification that has so far not been seen at sites other than A2503 in 23S rRNA.

Key Molecule: 23S rRNA (Adenine(2503)-C(8))-methyltransferase ClbA (CIBA) [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli AS19; 562
• In Vitro Model: Escherichia coli JW2501-1; 562
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The cfr gene encodes the Cfr methyltransferase that methylates a single adenine in the peptidyl transferase region of bacterial ribosomes.Expression of the genes was induced in Escherichia coli, and MICs for selected antibiotics indicate that the cfr-like genes confer resistance to PhLOPSa (phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A) antibiotics in the same way as the cfr gene.The Cfr-like proteins ClbA, ClbC, and ClbB confer a resistance pattern similar to that of the Cfr methyltransferase.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ARE-ABC-F family resistance factor PoxtA (POXTA) [8]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus RN4220; 1280
• In Vitro Model: Enterococcus faecalis JH2-2; 1351
• In Vitro Model: Escherichia coli Mach1 T1R; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth dilution test assay
• Mechanism Description: The poxtA gene encodes a protein that is 32% identical to OptrA and exhibits structural features typical of the F lineage of the ATP-binding cassette (ABC) protein superfamily that cause antibiotic resistance by ribosomal protection.

Key Molecule: Protein pexA (PEXA) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli; 668369
• Experiment for Molecule Alteration: Nucleotide sequence assay
• Experiment for Drug Resistance: Broth microdilution assay
• Mechanism Description: In its natural host, pexA could provide protection against chloramphenicol and florfenicol excreted by Streptomyces spp.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Colibactin polyketide synthase ClbC (CLBC) [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli AS19; 562
• In Vitro Model: Escherichia coli JW2501-1; 562
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The cfr gene encodes the Cfr methyltransferase that methylates a single adenine in the peptidyl transferase region of bacterial ribosomes.Expression of the genes was induced in Escherichia coli, and MICs for selected antibiotics indicate that the cfr-like genes confer resistance to PhLOPSa (phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A) antibiotics in the same way as the cfr gene.The Cfr-like proteins ClbA, ClbC, and ClbB confer a resistance pattern similar to that of the Cfr methyltransferase.

Non-tuberculous mycobacteria infection [ICD-11: 1B21]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Superficial skin infection by Staphylococcus aureus infection [ICD-11: 1B21.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• In Vitro Model: Staphylococcus aureus OM505; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: LmrS is a multidrug efflux pump of the major facilitator superfamily from staphylococcus aureus.

Gram-negative bacterial infection [ICD-11: 1B74-1G40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Ribosomal RNA large subunit methyltransferase N (CFRC) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Gram-negative bacterial infection [ICD-11: 1B74-1G40]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Clostridioides difficile T10; 1215084
• In Vitro Model: Clostridium bolteae 90B3; 997895
• In Vitro Model: Escherichia coli TG1; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Disk diffusion methods assay; agar dilution methods assay
• Mechanism Description: The cfr gene encodes a 23S rRNA methyltransferase, which causes C-8 modification in A2503 located in the peptidyl transferase region of bacterial ribosome.This mechanism confers PhLOPSA (phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A) resistance.

Pasteurellosis [ICD-11: 1B99]

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: Pasteurella multocida infection [ICD-11: 1B99.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Pasteurella multocida 36950; 1075089
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The analysis of one representative P. multocida isolate identified an 82 kb integrative and conjugative element (ICE) integrated into the chromosomal DNA. This ICE, designated ICEPmu1, harboured 11 resistance genes, which confer resistance to streptomycin/spectinomycin (aadA25), streptomycin (strA and strB), gentamicin (aadB), kanamycin/neomycin (aphA1), tetracycline [tetR-tet(H)], chloramphenicol/florfenicol (floR), sulphonamides (sul2), tilmicosin/clindamycin [erm(42)] or tilmicosin/tulathromycin [msr(E)-mph(E)].

Toxic shock syndrome [ICD-11: 1C45]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• In Vitro Model: Staphylococcus aureus OM505; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: LmrS is a multidrug efflux pump of the major facilitator superfamily from staphylococcus aureus.

ICD-11: Circulatory system diseases

Infective endocarditis [ICD-11: BB40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• In Vitro Model: Staphylococcus aureus OM505; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: LmrS is a multidrug efflux pump of the major facilitator superfamily from staphylococcus aureus.

ICD-12: Respiratory system diseases

Serious necrotizing pneumonia [ICD-11: CA43]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• In Vitro Model: Staphylococcus aureus OM505; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: LmrS is a multidrug efflux pump of the major facilitator superfamily from staphylococcus aureus.

ICD-21: Symptoms/clinical signs/unclassified clinical findings

Bacteremia [ICD-11: MA15]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• In Vitro Model: Staphylococcus aureus OM505; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: LmrS is a multidrug efflux pump of the major facilitator superfamily from staphylococcus aureus.

ICD-22: Injury/poisoning/certain external causes consequences

Surgical wound infection [ICD-11: NE81]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• In Vitro Model: Staphylococcus aureus OM505; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: LmrS is a multidrug efflux pump of the major facilitator superfamily from staphylococcus aureus.

References

• Ref 1: LmrS is a multidrug efflux pump of the major facilitator superfamily from Staphylococcus aureus. Antimicrob Agents Chemother. 2010 Dec;54(12):5406-12. doi: 10.1128/AAC.00580-10. Epub 2010 Sep 20.
• Ref 2: The order Bacillales hosts functional homologs of the worrisome cfr antibiotic resistance gene. Antimicrob Agents Chemother. 2012 Jul;56(7):3563-7. doi: 10.1128/AAC.00673-12. Epub 2012 Apr 30.
• Ref 3: Novel florfenicol and chloramphenicol resistance gene discovered in Alaskan soil by using functional metagenomics. Appl Environ Microbiol. 2010 Aug;76(15):5321-6. doi: 10.1128/AEM.00323-10. Epub 2010 Jun 11.
• Ref 4: A cfr-like gene cfr(C) conferring linezolid resistance is common in Clostridium difficile. Int J Antimicrob Agents. 2017 Sep;50(3):496-500. doi: 10.1016/j.ijantimicag.2017.03.013. Epub 2017 Jun 27.
• Ref 5: ICEPmu1, an integrative conjugative element (ICE) of Pasteurella multocida: analysis of the regions that comprise 12 antimicrobial resistance genes. J Antimicrob Chemother. 2012 Jan;67(1):84-90. doi: 10.1093/jac/dkr406. Epub 2011 Oct 14.
• Ref 6: A cfr-like gene from Clostridium difficile confers multiple antibiotic resistance by the same mechanism as the cfr gene. Antimicrob Agents Chemother. 2015 Sep;59(9):5841-3. doi: 10.1128/AAC.01274-15. Epub 2015 Jul 6.
• Ref 7: Distinction between the Cfr methyltransferase conferring antibiotic resistance and the housekeeping RlmN methyltransferase. Antimicrob Agents Chemother. 2013 Aug;57(8):4019-26. doi: 10.1128/AAC.00448-13. Epub 2013 Jun 10.
• Ref 8: Characterization of poxtA, a novel phenicol-oxazolidinone-tetracycline resistance gene from an MRSA of clinical origin. J Antimicrob Chemother. 2018 Jul 1;73(7):1763-1769. doi: 10.1093/jac/dky088.