General Information of the Disease (ID: DIS00022)
Name
Tissue pyogenic bacterial infection
ICD
ICD-11: 1B7Y
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  IDUE: Irregularity in Drug Uptake and Drug Efflux
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
11 drug(s) in total
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Ampicillin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]
Resistant Disease Staphylococcus infection [ICD-11: 1B7Y.3]
Molecule Alteration Expression
Up-regulation
Resistant Drug Ampicillin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pseudomonas aeruginosa isolates 287
Staphylococcus aureus isolates 1280
Klebsiella pneumoniae isolates 573
Acinetobacter isolates 469
Enterobacter cloacae isolates 550
Experiment for
Drug Resistance
Disk diffusion method assay
Mechanism Description Up-regulation of P-glycoprotein led to ampicillin resistance in the staphylococcus infection.
Cefazolin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]
Resistant Disease Staphylococcus infection [ICD-11: 1B7Y.3]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cefazolin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pseudomonas aeruginosa isolates 287
Staphylococcus aureus isolates 1280
Klebsiella pneumoniae isolates 573
Acinetobacter isolates 469
Enterobacter cloacae isolates 550
Experiment for
Drug Resistance
Disk diffusion method assay
Mechanism Description Up-regulation of P-glycoprotein led to cefazolin resistance in the staphylococcus infection.
Cefotetan
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]
Resistant Disease Staphylococcus infection [ICD-11: 1B7Y.3]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cefotetan
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pseudomonas aeruginosa isolates 287
Staphylococcus aureus isolates 1280
Klebsiella pneumoniae isolates 573
Acinetobacter isolates 469
Enterobacter cloacae isolates 550
Experiment for
Drug Resistance
Disk diffusion method assay
Mechanism Description Up-regulation of P-glycoprotein led to ampicillin resistance in the staphylococcus infection.
Ciprofloxacin XR
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]
Resistant Disease Staphylococcus infection [ICD-11: 1B7Y.3]
Molecule Alteration Expression
Up-regulation
Resistant Drug Ciprofloxacin XR
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pseudomonas aeruginosa isolates 287
Staphylococcus aureus isolates 1280
Klebsiella pneumoniae isolates 573
Acinetobacter isolates 469
Enterobacter cloacae isolates 550
Experiment for
Drug Resistance
Disk diffusion method assay
Mechanism Description Up-regulation of P-glycoprotein led to ciprofloxacin resistance in the staphylococcus infection.
Clindamycin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ABC protein lsaC (lsaC-Unclear) [2]
Resistant Disease Streptococcus agalactiae infection [ICD-11: 1B21.2]
Molecule Alteration Expression
Up-regulation
Resistant Drug Clindamycin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Staphylococcus aureus ATCC 29213 1280
Streptococcus agalactiae UCN70 1311
Streptococcus agalactiae isolates 1311
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.
Dalfopristin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ABC protein lsaC (lsaC-Unclear) [2]
Resistant Disease Streptococcus agalactiae infection [ICD-11: 1B21.2]
Molecule Alteration Expression
Up-regulation
Resistant Drug Dalfopristin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Staphylococcus aureus ATCC 29213 1280
Streptococcus agalactiae UCN70 1311
Streptococcus agalactiae isolates 1311
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
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Cardiolipin synthase 2 (CLS2) [3]
Resistant Disease Complicated soft tissue infection [ICD-11: 1B7Y.0]
Molecule Alteration Missense mutation
p.A23V+p.T33N+p.L52F+p.F60S
Resistant Drug Daptomycin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Staphylococcus aureus isolates 1280
Staphylococcus aureus MRSA32 [A5948] 553567
Staphylococcus aureus RN6607 [A8115] 553573
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) [3]
Resistant Disease Complicated soft tissue infection [ICD-11: 1B7Y.0]
Molecule Alteration Missense mutation
p.V59D+p.A64V+p.K75N+p.Ins.G76;Q77+p.S177F
Resistant Drug Daptomycin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Staphylococcus aureus isolates 1280
Staphylococcus aureus MRSA32 [A5948] 553567
Staphylococcus aureus RN6607 [A8115] 553573
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.
Levofloxacin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]
Resistant Disease Staphylococcus infection [ICD-11: 1B7Y.3]
Molecule Alteration Expression
Up-regulation
Resistant Drug Levofloxacin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pseudomonas aeruginosa isolates 287
Staphylococcus aureus isolates 1280
Klebsiella pneumoniae isolates 573
Acinetobacter isolates 469
Enterobacter cloacae isolates 550
Experiment for
Drug Resistance
Disk diffusion method assay
Mechanism Description Up-regulation of P-glycoprotein led to levofloxacin resistance in the staphylococcus infection.
Lincomycin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ABC protein lsaC (lsaC-Unclear) [2]
Resistant Disease Streptococcus agalactiae infection [ICD-11: 1B21.2]
Molecule Alteration Expression
Up-regulation
Resistant Drug Lincomycin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Staphylococcus aureus ATCC 29213 1280
Streptococcus agalactiae UCN70 1311
Streptococcus agalactiae isolates 1311
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.
Nitrofurantoin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]
Resistant Disease Staphylococcus infection [ICD-11: 1B7Y.3]
Molecule Alteration Expression
Up-regulation
Resistant Drug Nitrofurantoin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pseudomonas aeruginosa isolates 287
Staphylococcus aureus isolates 1280
Klebsiella pneumoniae isolates 573
Acinetobacter isolates 469
Enterobacter cloacae isolates 550
Experiment for
Drug Resistance
Disk diffusion method assay
Mechanism Description Up-regulation of P-glycoprotein led to nitrofurantoin resistance in the staphylococcus infection.
Tiamulin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ABC protein lsaC (lsaC-Unclear) [2]
Resistant Disease Streptococcus agalactiae infection [ICD-11: 1B21.2]
Molecule Alteration Expression
Up-regulation
Resistant Drug Tiamulin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Staphylococcus aureus ATCC 29213 1280
Streptococcus agalactiae UCN70 1311
Streptococcus agalactiae isolates 1311
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.
Investigative Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Ampicillin-sulbactam
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]
Resistant Disease Staphylococcus infection [ICD-11: 1B7Y.3]
Molecule Alteration Expression
Up-regulation
Resistant Drug Ampicillin-sulbactam
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pseudomonas aeruginosa isolates 287
Staphylococcus aureus isolates 1280
Klebsiella pneumoniae isolates 573
Acinetobacter isolates 469
Enterobacter cloacae isolates 550
Experiment for
Drug Resistance
Disk diffusion method assay
Mechanism Description Up-regulation of P-glycoprotein led to ampicillin-sulbactam resistance in the staphylococcus infection.
References
Ref 1 Pathogen characteristics reveal novel antibacterial approaches for interstitial lung disease .Pulm Pharmacol Ther. 2014 Dec;29(2):250-4. doi: 10.1016/j.pupt.2014.03.005. Epub 2014 Apr 1. 10.1016/j.pupt.2014.03.005
Ref 2 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 3 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.

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