Impact of accessory gene regulator (<it>agr</it>) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant <it>Staphylococcus aureus</it>
<p>Abstract</p> <p>Background</p> <p>The accessory gene regulator (<it>agr</it>) is a quorum sensing cluster of genes which control colonization and virulence in <it>Staphylococcus aureus</it>. We evaluated <it>agr </it>function in co...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-05-01
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| Series: | Annals of Clinical Microbiology and Antimicrobials |
| Online Access: | http://www.ann-clinmicrob.com/content/10/1/20 |
| _version_ | 1818496491752259584 |
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| author | MacLean Robert D Tsuji Brian T Dresser Linda D McGavin Martin J Simor Andrew E |
| author_facet | MacLean Robert D Tsuji Brian T Dresser Linda D McGavin Martin J Simor Andrew E |
| author_sort | MacLean Robert D |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The accessory gene regulator (<it>agr</it>) is a quorum sensing cluster of genes which control colonization and virulence in <it>Staphylococcus aureus</it>. We evaluated <it>agr </it>function in community- (CA) and healthcare-associated (HA) MRSA, to compare the pharmacodynamics and bactericidal activity of vancomycin against <it>agr </it>functional and dysfunctional HA-MRSA and CA-MRSA.</p> <p>Methods</p> <p>40 clinical isolates of MRSA from the Canadian Nosocomial Infection Surveillance Program were evaluated for delta-haemolysin production, as a surrogate marker of <it>agr </it>function. Time kill experiments were performed for vancomycin at 0 to 64 times the MIC against an initial inoculum of 10<sup>6 </sup>and 10<sup>8 </sup>cfu/ml of <it>agr </it>functional and dysfunctional CA-MRSA and HA-MRSA and these data were fit to a hill-type pharmacodynamic model.</p> <p>Results</p> <p>15% isolates were <it>agr </it>dysfunctional, which was higher among HA-MRSA (26.3%) versus CA-MRSA (4.76%). Against a low initial inoculum of 10<sup>6 </sup>cfu/ml of CA-MRSA, vancomycin pharmacodynamics were similar among <it>agr </it>functional and dysfunctional strains. However, against a high initial inoculum of 10<sup>8 </sup>cfu/ml, killing activity was notably attenuated against <it>agr </it>dysfunctional CA-MRSA (USA400) and HA-MRSA (USA100). CA-MRSA displayed a 20.0 fold decrease in the maximal reduction in bacterial counts (Emax) which was 3.71 log<sub>10 </sub>CFU/ml for <it>agr </it>functional vs. 2.41 log<sub>10 </sub>CFU/ml for <it>agr </it>dysfunctional MRSA (p = 0.0007).</p> <p>Conclusions</p> <p>Dysfunction in <it>agr </it>was less common among CA-MRSA vs. HA-MRSA. <it>agr </it>dysfunction demonstrated an impact on vancomycin bactericidal activity and pharmacodynamics against a high initial inoculum of CA-MRSA and HA-MRSA, which may have implications for optimal antimicrobial therapy against persistent, difficult to treat MRSA infections.</p> |
| first_indexed | 2024-12-10T18:33:34Z |
| format | Article |
| id | doaj.art-584fc6eb16d3492c8361c7497ff005ef |
| institution | Directory Open Access Journal |
| issn | 1476-0711 |
| language | English |
| last_indexed | 2024-12-10T18:33:34Z |
| publishDate | 2011-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Annals of Clinical Microbiology and Antimicrobials |
| spelling | doaj.art-584fc6eb16d3492c8361c7497ff005ef2022-12-22T01:37:53ZengBMCAnnals of Clinical Microbiology and Antimicrobials1476-07112011-05-011012010.1186/1476-0711-10-20Impact of accessory gene regulator (<it>agr</it>) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant <it>Staphylococcus aureus</it>MacLean Robert DTsuji Brian TDresser Linda DMcGavin Martin JSimor Andrew E<p>Abstract</p> <p>Background</p> <p>The accessory gene regulator (<it>agr</it>) is a quorum sensing cluster of genes which control colonization and virulence in <it>Staphylococcus aureus</it>. We evaluated <it>agr </it>function in community- (CA) and healthcare-associated (HA) MRSA, to compare the pharmacodynamics and bactericidal activity of vancomycin against <it>agr </it>functional and dysfunctional HA-MRSA and CA-MRSA.</p> <p>Methods</p> <p>40 clinical isolates of MRSA from the Canadian Nosocomial Infection Surveillance Program were evaluated for delta-haemolysin production, as a surrogate marker of <it>agr </it>function. Time kill experiments were performed for vancomycin at 0 to 64 times the MIC against an initial inoculum of 10<sup>6 </sup>and 10<sup>8 </sup>cfu/ml of <it>agr </it>functional and dysfunctional CA-MRSA and HA-MRSA and these data were fit to a hill-type pharmacodynamic model.</p> <p>Results</p> <p>15% isolates were <it>agr </it>dysfunctional, which was higher among HA-MRSA (26.3%) versus CA-MRSA (4.76%). Against a low initial inoculum of 10<sup>6 </sup>cfu/ml of CA-MRSA, vancomycin pharmacodynamics were similar among <it>agr </it>functional and dysfunctional strains. However, against a high initial inoculum of 10<sup>8 </sup>cfu/ml, killing activity was notably attenuated against <it>agr </it>dysfunctional CA-MRSA (USA400) and HA-MRSA (USA100). CA-MRSA displayed a 20.0 fold decrease in the maximal reduction in bacterial counts (Emax) which was 3.71 log<sub>10 </sub>CFU/ml for <it>agr </it>functional vs. 2.41 log<sub>10 </sub>CFU/ml for <it>agr </it>dysfunctional MRSA (p = 0.0007).</p> <p>Conclusions</p> <p>Dysfunction in <it>agr </it>was less common among CA-MRSA vs. HA-MRSA. <it>agr </it>dysfunction demonstrated an impact on vancomycin bactericidal activity and pharmacodynamics against a high initial inoculum of CA-MRSA and HA-MRSA, which may have implications for optimal antimicrobial therapy against persistent, difficult to treat MRSA infections.</p>http://www.ann-clinmicrob.com/content/10/1/20 |
| spellingShingle | MacLean Robert D Tsuji Brian T Dresser Linda D McGavin Martin J Simor Andrew E Impact of accessory gene regulator (<it>agr</it>) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant <it>Staphylococcus aureus</it> Annals of Clinical Microbiology and Antimicrobials |
| title | Impact of accessory gene regulator (<it>agr</it>) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant <it>Staphylococcus aureus</it> |
| title_full | Impact of accessory gene regulator (<it>agr</it>) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant <it>Staphylococcus aureus</it> |
| title_fullStr | Impact of accessory gene regulator (<it>agr</it>) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant <it>Staphylococcus aureus</it> |
| title_full_unstemmed | Impact of accessory gene regulator (<it>agr</it>) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant <it>Staphylococcus aureus</it> |
| title_short | Impact of accessory gene regulator (<it>agr</it>) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant <it>Staphylococcus aureus</it> |
| title_sort | impact of accessory gene regulator it agr it dysfunction on vancomycin pharmacodynamics among canadian community and health care associated methicillin resistant it staphylococcus aureus it |
| url | http://www.ann-clinmicrob.com/content/10/1/20 |
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