Ability of Linezolid to Combat <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> Isolated from Polymicrobial Wound Infections

<b>Background/Objectives</b>: The optimal therapy for polymicrobial wound infections is poorly defined. We sought to characterize the ability of linezolid to combat mixed cultures of <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>. <b>Methods&...

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Main Authors: Samar A. Ahmed, Vy T. Luu, Teresa C. Oyono Nsuga, Steven E. Burgos, Eugene Kreys, Jered Arquiette, Justin R. Lenhard
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/6/597
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author Samar A. Ahmed
Vy T. Luu
Teresa C. Oyono Nsuga
Steven E. Burgos
Eugene Kreys
Jered Arquiette
Justin R. Lenhard
author_facet Samar A. Ahmed
Vy T. Luu
Teresa C. Oyono Nsuga
Steven E. Burgos
Eugene Kreys
Jered Arquiette
Justin R. Lenhard
author_sort Samar A. Ahmed
collection DOAJ
description <b>Background/Objectives</b>: The optimal therapy for polymicrobial wound infections is poorly defined. We sought to characterize the ability of linezolid to combat mixed cultures of <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>. <b>Methods</b>: The antistaphylococcal activity of linezolid was assessed in 24-h time-killing experiments that used <i>S. aureus</i> and <i>P. aeruginosa</i> isolated from polymicrobial wound infections. Clindamycin was also evaluated as a comparator. A Hill-type mathematical model was used to assess the maximum killing of <i>S. aureus</i> (E<sub>max</sub>). The ability of linezolid to potentiate the activity of host defense peptides against <i>P. aeruginosa</i> was evaluated using LL-37. <b>Results</b>: In the presence of <i>P. aeruginosa</i>, the E<sub>max</sub> of linezolid decreased in 5/9 co-culture experiments and increased in 4/9 co-culture experiments in comparison to linezolid against <i>S. aureus</i> alone. The potency of linezolid was not significantly impacted by the presence of <i>P. aeruginosa</i>. In comparison, the maximal <i>S. aureus</i> killing achieved by clindamycin decreased in eight out of nine experiments, and somewhat paradoxically, the potency increased in nine out of nine experiments. In the host defense peptide assay, the supratherapeutic linezolid concentration of 64 mg/L did not significantly enhance the killing of the LL-37 peptides (<i>p</i> ≥ 0.121), but the concentration of linezolid was significantly associated with the killing of one of three <i>P. aeruginosa</i> isolates (<i>p</i> = 0.005). <b>Conclusions</b>: <i>P. aeruginosa</i> had a minimal impact on the antistaphylococcal activity of linezolid in comparison to clindamycin. Linezolid did not exert a consistent ability to enhance the antipseudomonal activity of host defense peptides. These data may help inform antimicrobial selection during polymicrobial wound infections.
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spelling doaj-art-92ded19aea9b4d6481aaa9ffcf3c5e372025-08-20T03:32:28ZengMDPI AGAntibiotics2079-63822025-06-0114659710.3390/antibiotics14060597Ability of Linezolid to Combat <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> Isolated from Polymicrobial Wound InfectionsSamar A. Ahmed0Vy T. Luu1Teresa C. Oyono Nsuga2Steven E. Burgos3Eugene Kreys4Jered Arquiette5Justin R. Lenhard6Department of Clinical and Administrative Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USADepartment of Clinical and Administrative Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USADepartment of Clinical and Administrative Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USADepartment of Clinical and Administrative Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USADepartment of Clinical and Administrative Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USADepartment of Pharmacy, San Joaquin General Hospital, French Camp, CA 95231, USADepartment of Clinical and Administrative Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USA<b>Background/Objectives</b>: The optimal therapy for polymicrobial wound infections is poorly defined. We sought to characterize the ability of linezolid to combat mixed cultures of <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>. <b>Methods</b>: The antistaphylococcal activity of linezolid was assessed in 24-h time-killing experiments that used <i>S. aureus</i> and <i>P. aeruginosa</i> isolated from polymicrobial wound infections. Clindamycin was also evaluated as a comparator. A Hill-type mathematical model was used to assess the maximum killing of <i>S. aureus</i> (E<sub>max</sub>). The ability of linezolid to potentiate the activity of host defense peptides against <i>P. aeruginosa</i> was evaluated using LL-37. <b>Results</b>: In the presence of <i>P. aeruginosa</i>, the E<sub>max</sub> of linezolid decreased in 5/9 co-culture experiments and increased in 4/9 co-culture experiments in comparison to linezolid against <i>S. aureus</i> alone. The potency of linezolid was not significantly impacted by the presence of <i>P. aeruginosa</i>. In comparison, the maximal <i>S. aureus</i> killing achieved by clindamycin decreased in eight out of nine experiments, and somewhat paradoxically, the potency increased in nine out of nine experiments. In the host defense peptide assay, the supratherapeutic linezolid concentration of 64 mg/L did not significantly enhance the killing of the LL-37 peptides (<i>p</i> ≥ 0.121), but the concentration of linezolid was significantly associated with the killing of one of three <i>P. aeruginosa</i> isolates (<i>p</i> = 0.005). <b>Conclusions</b>: <i>P. aeruginosa</i> had a minimal impact on the antistaphylococcal activity of linezolid in comparison to clindamycin. Linezolid did not exert a consistent ability to enhance the antipseudomonal activity of host defense peptides. These data may help inform antimicrobial selection during polymicrobial wound infections.https://www.mdpi.com/2079-6382/14/6/597linezolid<i>Staphylococcus aureus</i><i>Pseudomonas aeruingosa</i>pharmacodynamicspolymicrobialclindamycin
spellingShingle Samar A. Ahmed
Vy T. Luu
Teresa C. Oyono Nsuga
Steven E. Burgos
Eugene Kreys
Jered Arquiette
Justin R. Lenhard
Ability of Linezolid to Combat <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> Isolated from Polymicrobial Wound Infections
Antibiotics
linezolid
<i>Staphylococcus aureus</i>
<i>Pseudomonas aeruingosa</i>
pharmacodynamics
polymicrobial
clindamycin
title Ability of Linezolid to Combat <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> Isolated from Polymicrobial Wound Infections
title_full Ability of Linezolid to Combat <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> Isolated from Polymicrobial Wound Infections
title_fullStr Ability of Linezolid to Combat <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> Isolated from Polymicrobial Wound Infections
title_full_unstemmed Ability of Linezolid to Combat <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> Isolated from Polymicrobial Wound Infections
title_short Ability of Linezolid to Combat <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> Isolated from Polymicrobial Wound Infections
title_sort ability of linezolid to combat i staphylococcus aureus i and i pseudomonas aeruginosa i isolated from polymicrobial wound infections
topic linezolid
<i>Staphylococcus aureus</i>
<i>Pseudomonas aeruingosa</i>
pharmacodynamics
polymicrobial
clindamycin
url https://www.mdpi.com/2079-6382/14/6/597
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