Disease Information

General Information of the Disease (ID: DIS00018)

• Name: Non-tuberculous mycobacteria infection
• ICD: ICD-11: 1B21

Type(s) of Resistant Mechanism of This Disease

  DISM: Drug Inactivation by Structure Modification

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 24 drug(s) in total

Amikacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Amikacin
• Molecule Alteration: Expression; Up-regulation
• 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.

Ampicillin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Ampicillin
• Molecule Alteration: Expression; Up-regulation
• 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.

Cefazolin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Cefazolin
• Molecule Alteration: Expression; Up-regulation
• 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.

Cefepime

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Cefepime
• Molecule Alteration: Expression; Up-regulation
• 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.

Cefotaxime

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Cefotaxime
• Molecule Alteration: Expression; Up-regulation
• 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.

Cefozopran

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Cefozopran
• Molecule Alteration: Expression; Up-regulation
• 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.

Chloramphenicol

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Chloramphenicol
• Molecule Alteration: Expression; Up-regulation
• 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.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [2]

• Resistant Disease: Superficial skin infection by Staphylococcus aureus infection [ICD-11: 1B21.3]
• Resistant Drug: Chloramphenicol
• Molecule Alteration: Expression; Up-regulation
• 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.

Ciprofloxacin XR

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Expression; Up-regulation
• 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.

Clindamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [3]

• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Resistant Drug: Clindamycin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

Co-trimoxazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Co-trimoxazole
• Molecule Alteration: Expression; Up-regulation
• 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.

Dalfopristin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [3]

• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Resistant Drug: Dalfopristin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

Daptomycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cardiolipin synthase 2 (CLS2) [4]

• Resistant Disease: Complicated skin infection Staphylococcus aureus infection [ICD-11: 1B21.1]
• Resistant Drug: Daptomycin
• Molecule Alteration: Missense mutation; p.A23V+p.T33N+p.L52F+p.F60S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Staphylococcus aureus MRSA32 [A5948]; 553567
• In Vitro Model: Staphylococcus aureus RN6607 [A8115]; 553573
• In Vitro Model: Staphylococcus aureus RN9120 [A8117]; 553574
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Mutation in each of these genes act similarly to reduce the net-negative charge of the cell membrane leading to electrorepulsion of daptomycin. They may act in isolation or in concert with each other, particularly for mutations in mprF and cls2.

Key Molecule: Phosphatidylglycerophosphate synthase (PGSA) [4]

• Resistant Disease: Complicated skin infection Staphylococcus aureus infection [ICD-11: 1B21.1]
• Resistant Drug: Daptomycin
• Molecule Alteration: Missense mutation; p.V59D+p.A64V+p.K75N+p.Ins.G76;Q77+p.S177F
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Staphylococcus aureus MRSA32 [A5948]; 553567
• In Vitro Model: Staphylococcus aureus RN6607 [A8115]; 553573
• In Vitro Model: Staphylococcus aureus RN9120 [A8117]; 553574
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Mutation in each of these genes act similarly to reduce the net-negative charge of the cell membrane leading to electrorepulsion of daptomycin. They may act in isolation or in concert with each other, particularly for mutations in mprF and cls2.

Erythromycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [2]

• Resistant Disease: Superficial skin infection by Staphylococcus aureus infection [ICD-11: 1B21.3]
• Resistant Drug: Erythromycin
• Molecule Alteration: Expression; Up-regulation
• 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.

Florfenicol

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [2]

• Resistant Disease: Superficial skin infection by Staphylococcus aureus infection [ICD-11: 1B21.3]
• Resistant Drug: Florfenicol
• Molecule Alteration: Expression; Up-regulation
• 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.

Gentamicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Gentamicin
• Molecule Alteration: Expression; Up-regulation
• 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.

Kanamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [2]

• Resistant Disease: Superficial skin infection by Staphylococcus aureus infection [ICD-11: 1B21.3]
• Resistant Drug: Kanamycin
• Molecule Alteration: Expression; Up-regulation
• 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.

Levofloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Levofloxacin
• Molecule Alteration: Expression; Up-regulation
• 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.

Lincomycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [3]

• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Resistant Drug: Lincomycin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

Linezolid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [2]

• Resistant Disease: Superficial skin infection by Staphylococcus aureus infection [ICD-11: 1B21.3]
• Resistant Drug: Linezolid
• Molecule Alteration: Expression; Up-regulation
• 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.

Meropenem

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Meropenem
• Molecule Alteration: Expression; Up-regulation
• 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.

Piperacillin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Piperacillin
• Molecule Alteration: Expression; Up-regulation
• 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.

Streptomycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [2]

• Resistant Disease: Superficial skin infection by Staphylococcus aureus infection [ICD-11: 1B21.3]
• Resistant Drug: Streptomycin
• Molecule Alteration: Expression; Up-regulation
• 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.

Tiamulin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [3]

• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Resistant Drug: Tiamulin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

Trimethoprim

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [2]

• Resistant Disease: Superficial skin infection by Staphylococcus aureus infection [ICD-11: 1B21.3]
• Resistant Drug: Trimethoprim
• Molecule Alteration: Expression; Up-regulation
• 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.

Investigative Drug(s) 1 drug(s) in total

Flomoxef

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [1]

• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Resistant Drug: Flomoxef
• Molecule Alteration: Expression; Up-regulation
• 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.

References

• Ref 1: Daptomycin .J Antimicrob Chemother. 2018 Jan 1;73(1):1-11. doi: 10.1093/jac/dkx349. 10.1093/jac/dkx349
• Ref 2: 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 3: Cross-resistance to lincosamides, streptogramins A, and pleuromutilins due to the lsa(C) gene in Streptococcus agalactiae UCN70. Antimicrob Agents Chemother. 2011 Apr;55(4):1470-4. doi: 10.1128/AAC.01068-10. Epub 2011 Jan 18.
• Ref 4: Whole genome characterization of the mechanisms of daptomycin resistance in clinical and laboratory derived isolates of Staphylococcus aureus. PLoS One. 2012;7(1):e28316. doi: 10.1371/journal.pone.0028316. Epub 2012 Jan 6.