Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria
Extensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. β-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs...
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| Format: | Article |
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MDPI AG
2023-10-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/10/1508 |
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| author | Sara Mahmoud Farhan Rehab Mahmoud Abd El-Baky Hala Rady Ahmed Zeinab Fathalla Ali Alamri Hamdy Abdelkader Adel Al Fatease |
| author_facet | Sara Mahmoud Farhan Rehab Mahmoud Abd El-Baky Hala Rady Ahmed Zeinab Fathalla Ali Alamri Hamdy Abdelkader Adel Al Fatease |
| author_sort | Sara Mahmoud Farhan |
| collection | DOAJ |
| description | Extensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. β-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs. This is because of the broad empiric coverage of the two drugs and their possession of different spectra of activity. Two cyclodextrins (β- and hydroxy propyl β-cyclodextrins) were utilized for inclusion complex formation with imipenem using the physical and kneading methods. In silico investigation using the molecular docking and Fourier-infrared spectroscopy (FTIR) were employed to estimate binding constant and confirm complex formation, respectively. The in vitro effects of amikacin and imipenem combination in comparison to the effect of imipenem-β- and hydroxy propyl β-cyclodextrin (CD) complexes against <i>Klebsiella</i> spp. and <i>Acinetobacter baumannii</i> were studied. The isolated microorganisms’ antimicrobial responsiveness to various antibiotics (19 antibiotics) was evaluated. It was found that piperacillin/tazobactam and gentamycin (resistance rates were 33.3% and 34%, respectively) were the most effective antimicrobials. The in vitro studies have been performed by the checkerboard technique and time-killing assay. The studied combination of amikacin and imipenem showed a substantial drop in bacterial count (<i>p</i> < 0.05). The in vitro studies demonstrated a synergism for the investigated combination. Conventional PCR was used in molecular studies to identify the resistance genes bla IMP and aac (6′)-Ib. The blaIMP and aac (6′)-Ib were recorded in 38.2% and 3.6% of the studied isolates, respectively. The in vitro studies showed synergistic effects among the tested antibiotics with FICIs of ≤0.5. Finally, the study compared the reduction in bacterial count between the tested antibiotic combinations and imipenem:CD physical and kneaded mixtures. Imipenem:CD inclusion complexes demonstrated a significant bacterial count reduction over the antibiotic combination. These results highlight the emerging role of CDs as safe biofunctional excipients in the combat against superbug bacterial resistance. |
| first_indexed | 2024-03-10T20:58:56Z |
| format | Article |
| id | doaj.art-a7068add8c71467586079ed9ed60edd9 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T20:58:56Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-a7068add8c71467586079ed9ed60edd92023-11-19T17:43:29ZengMDPI AGPharmaceuticals1424-82472023-10-011610150810.3390/ph16101508Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative BacteriaSara Mahmoud Farhan0Rehab Mahmoud Abd El-Baky1Hala Rady Ahmed2Zeinab Fathalla3Ali Alamri4Hamdy Abdelkader5Adel Al Fatease6Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University, Minia 11566, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Deraya University, Minia 11566, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia 61519, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, EgyptDepartment of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62223, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62223, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62223, Saudi ArabiaExtensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. β-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs. This is because of the broad empiric coverage of the two drugs and their possession of different spectra of activity. Two cyclodextrins (β- and hydroxy propyl β-cyclodextrins) were utilized for inclusion complex formation with imipenem using the physical and kneading methods. In silico investigation using the molecular docking and Fourier-infrared spectroscopy (FTIR) were employed to estimate binding constant and confirm complex formation, respectively. The in vitro effects of amikacin and imipenem combination in comparison to the effect of imipenem-β- and hydroxy propyl β-cyclodextrin (CD) complexes against <i>Klebsiella</i> spp. and <i>Acinetobacter baumannii</i> were studied. The isolated microorganisms’ antimicrobial responsiveness to various antibiotics (19 antibiotics) was evaluated. It was found that piperacillin/tazobactam and gentamycin (resistance rates were 33.3% and 34%, respectively) were the most effective antimicrobials. The in vitro studies have been performed by the checkerboard technique and time-killing assay. The studied combination of amikacin and imipenem showed a substantial drop in bacterial count (<i>p</i> < 0.05). The in vitro studies demonstrated a synergism for the investigated combination. Conventional PCR was used in molecular studies to identify the resistance genes bla IMP and aac (6′)-Ib. The blaIMP and aac (6′)-Ib were recorded in 38.2% and 3.6% of the studied isolates, respectively. The in vitro studies showed synergistic effects among the tested antibiotics with FICIs of ≤0.5. Finally, the study compared the reduction in bacterial count between the tested antibiotic combinations and imipenem:CD physical and kneaded mixtures. Imipenem:CD inclusion complexes demonstrated a significant bacterial count reduction over the antibiotic combination. These results highlight the emerging role of CDs as safe biofunctional excipients in the combat against superbug bacterial resistance.https://www.mdpi.com/1424-8247/16/10/1508proteusklebsiella<i>Acinetobacter baumannii</i>drug combinationimipenemamikacin |
| spellingShingle | Sara Mahmoud Farhan Rehab Mahmoud Abd El-Baky Hala Rady Ahmed Zeinab Fathalla Ali Alamri Hamdy Abdelkader Adel Al Fatease Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria Pharmaceuticals proteus klebsiella <i>Acinetobacter baumannii</i> drug combination imipenem amikacin |
| title | Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria |
| title_full | Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria |
| title_fullStr | Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria |
| title_full_unstemmed | Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria |
| title_short | Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria |
| title_sort | comparative investigation into the roles of imipenem cyclodextrin complexation and antibiotic combination in combatting antimicrobial resistance in gram negative bacteria |
| topic | proteus klebsiella <i>Acinetobacter baumannii</i> drug combination imipenem amikacin |
| url | https://www.mdpi.com/1424-8247/16/10/1508 |
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