Collaterally Sensitive β-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant <i>Staphylococcus aureus</i> (MRSA) Biofilms
Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is among the leading causes of nosocomial infections and forms biofilms, which are difficult to eradicate because of their increasing resistance to antimicrobial agents. This is especially true for pre-existing biofilms. The curre...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/5/687 |
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| author | Hamna Batool Hashmi Muhammad Asad Farooq Muhammad Hashim Khan Abdulrahman Alshammari Alanoud T. Aljasham Sheikh Abdur Rashid Nauman Rahim Khan Irum Batool Hashmi Muhammad Badar Mohammad S. Mubarak |
| author_facet | Hamna Batool Hashmi Muhammad Asad Farooq Muhammad Hashim Khan Abdulrahman Alshammari Alanoud T. Aljasham Sheikh Abdur Rashid Nauman Rahim Khan Irum Batool Hashmi Muhammad Badar Mohammad S. Mubarak |
| author_sort | Hamna Batool Hashmi |
| collection | DOAJ |
| description | Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is among the leading causes of nosocomial infections and forms biofilms, which are difficult to eradicate because of their increasing resistance to antimicrobial agents. This is especially true for pre-existing biofilms. The current study focused on evaluating the efficacy of three β-lactam drugs, meropenem, piperacillin, and tazobactam, alone and in combination against the MRSA biofilms. When used individually, none of the drugs exhibited significant antibacterial activity against MRSA in a planktonic state. At the same time, the combination of meropenem, piperacillin, and tazobactam showed a 41.7 and 41.3% reduction in planktonic bacterial cell growth, respectively. These drugs were further assessed for biofilm inhibition and removal. The combination of meropenem, piperacillin, and tazobactam caused 44.3% biofilm inhibition, while the rest of the combinations did not show any significant effects. Results also revealed that piperacillin and tazobactam exhibited the best synergy against the pre-formed biofilm of MRSA, with 46% removal. However, adding meropenem to the piperacillin and tazobactam combination showed a slightly reduced activity towards the pre-formed biofilm of MRSA and removed 38.7% of it. Although the mechanism of synergism is not fully understood, our findings suggest that these three β-lactam drugs can be used in combination as very effective therapeutic agents for the treatment of pre-existing MRSA biofilms. The in vivo experiments on the antibiofilm activity of these drugs will pave the way for applying such synergistic combinations to clinics. |
| first_indexed | 2024-03-11T03:25:14Z |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T03:25:14Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-360b4b3126ec4fec9ed2848d1d0eaa6c2023-11-18T02:48:30ZengMDPI AGPharmaceuticals1424-82472023-05-0116568710.3390/ph16050687Collaterally Sensitive β-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant <i>Staphylococcus aureus</i> (MRSA) BiofilmsHamna Batool Hashmi0Muhammad Asad Farooq1Muhammad Hashim Khan2Abdulrahman Alshammari3Alanoud T. Aljasham4Sheikh Abdur Rashid5Nauman Rahim Khan6Irum Batool Hashmi7Muhammad Badar8Mohammad S. Mubarak9Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, PakistanShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200062, ChinaGomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, PakistanDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaNanocarriers Research Laboratory, Gomal Centre of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, PakistanDepartment of Pharmacy, Kohat University of Science and Technology, Kohat 26000, PakistanDepartment of Obstetrics and Gynecology, Gomal Medical College, Dera Ismail Khan 29050, PakistanGomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, PakistanDepartment of Chemistry, The University of Jordan, Amma 11942, JordanMethicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is among the leading causes of nosocomial infections and forms biofilms, which are difficult to eradicate because of their increasing resistance to antimicrobial agents. This is especially true for pre-existing biofilms. The current study focused on evaluating the efficacy of three β-lactam drugs, meropenem, piperacillin, and tazobactam, alone and in combination against the MRSA biofilms. When used individually, none of the drugs exhibited significant antibacterial activity against MRSA in a planktonic state. At the same time, the combination of meropenem, piperacillin, and tazobactam showed a 41.7 and 41.3% reduction in planktonic bacterial cell growth, respectively. These drugs were further assessed for biofilm inhibition and removal. The combination of meropenem, piperacillin, and tazobactam caused 44.3% biofilm inhibition, while the rest of the combinations did not show any significant effects. Results also revealed that piperacillin and tazobactam exhibited the best synergy against the pre-formed biofilm of MRSA, with 46% removal. However, adding meropenem to the piperacillin and tazobactam combination showed a slightly reduced activity towards the pre-formed biofilm of MRSA and removed 38.7% of it. Although the mechanism of synergism is not fully understood, our findings suggest that these three β-lactam drugs can be used in combination as very effective therapeutic agents for the treatment of pre-existing MRSA biofilms. The in vivo experiments on the antibiofilm activity of these drugs will pave the way for applying such synergistic combinations to clinics.https://www.mdpi.com/1424-8247/16/5/687methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)antibiotic resistanceβ-lactam antibioticsbiofilmsanti-bacterial activity |
| spellingShingle | Hamna Batool Hashmi Muhammad Asad Farooq Muhammad Hashim Khan Abdulrahman Alshammari Alanoud T. Aljasham Sheikh Abdur Rashid Nauman Rahim Khan Irum Batool Hashmi Muhammad Badar Mohammad S. Mubarak Collaterally Sensitive β-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant <i>Staphylococcus aureus</i> (MRSA) Biofilms Pharmaceuticals methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) antibiotic resistance β-lactam antibiotics biofilms anti-bacterial activity |
| title | Collaterally Sensitive β-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant <i>Staphylococcus aureus</i> (MRSA) Biofilms |
| title_full | Collaterally Sensitive β-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant <i>Staphylococcus aureus</i> (MRSA) Biofilms |
| title_fullStr | Collaterally Sensitive β-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant <i>Staphylococcus aureus</i> (MRSA) Biofilms |
| title_full_unstemmed | Collaterally Sensitive β-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant <i>Staphylococcus aureus</i> (MRSA) Biofilms |
| title_short | Collaterally Sensitive β-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant <i>Staphylococcus aureus</i> (MRSA) Biofilms |
| title_sort | collaterally sensitive β lactam drugs as an effective therapy against the pre existing methicillin resistant i staphylococcus aureus i mrsa biofilms |
| topic | methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) antibiotic resistance β-lactam antibiotics biofilms anti-bacterial activity |
| url | https://www.mdpi.com/1424-8247/16/5/687 |
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