In vitro synergy of antibiotic combinations against planktonic and biofilm Pseudomonas aeruginosa

Ghorbani, Hossein; Memar, Mohammad Yousef; Sefidan, Fatemeh Yeganeh; Yekani, Mina; Ghotaslou, Reza

doi:10.3205/dgkh000302

Cited by 14 publications

(8 citation statements)

References 25 publications

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“…Tob alone had an MIC value of 8 μg/ml, which is in agreement with the range commonly reported in the literature ( 13 , 51 ). When coupled with AgNPs either coincubated in solution (AgNP + Tob control) or coloaded into NCs 2a and 2b , an enhancement in antimicrobial activity was observed, with Tob MIC values decreasing to 2 μg/ml ( Fig.…”

Section: Resultssupporting

confidence: 91%

“…These drug combinations can function in parallel to target orthogonal mechanisms and prevent the evolution of resistance pathways. Combination therapeutics can also work together to enhance a singular pathway, such as by facilitating increased uptake of an antibiotic for improved efficacy ( 12 , 13 ). One particularly promising combination of antimicrobial therapeutics is Tob and silver nanoparticles (AgNPs).…”

Section: Introductionmentioning

confidence: 99%

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Codelivery of synergistic antimicrobials with polyelectrolyte nanocomplexes to treat bacterial biofilms and lung infections

et al. 2023

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Bacterial biofilm infections, particularly those of Pseudomonas aeruginosa (PA), have high rates of antimicrobial tolerance and are commonly found in chronic wound and cystic fibrosis lung infections. Combination therapeutics that act synergistically can overcome antimicrobial tolerance; however, the delivery of multiple therapeutics at relevant dosages remains a challenge. We therefore developed a nanoscale drug carrier for antimicrobial codelivery by combining approaches from polyelectrolyte nanocomplex (NC) formation and layer-by-layer electrostatic self-assembly. This strategy led to NC drug carriers loaded with tobramycin antibiotics and antimicrobial silver nanoparticles (AgTob-NCs). AgTob-NCs displayed synergistic enhancements in antimicrobial activity against both planktonic and biofilm PA cultures, with positively charged NCs outperforming negatively charged formulations. NCs were evaluated in mouse models of lung infection, leading to reduced bacterial burden and improved survival outcomes. This approach therefore shows promise for nanoscale therapeutic codelivery to treat recalcitrant bacterial infections.

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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Codelivery of synergistic antimicrobials with polyelectrolyte nanocomplexes to treat bacterial biofilms and lung infections

et al. 2023

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“…P. aeruginosa is widely regarded as the most dangerous and typical biofilm-forming pathogen in humans [ 19 ]. P. aeruginosa biofilms could seriously hinder its eradication during antibiotic therapy and stimulate recurrent infections [ 20 ]. Moreover, the increasing frequency of P. aeruginosa resistance to many antibiotics especially to carbapenems is another major challenge, where it negatively influences the antibiotic treatment efficiency either alone or in combination [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

“…Antimicrobial susceptibility usually evaluates the effectiveness of antibiotics against planktonic microorganisms; however, this is not always the current situation in case of infection with P. aeruginosa due to biofilm formation. Thus, the present study estimates the MBIC and MBBC along with the evaluation of the MIC and MBC, where the determination of the antibiotic’s MBIC is essential as it reflects its role in the treatment of biofilm-forming P. aeruginosa infections [ 20 ]. Also, the observed resistance to different antibiotics in the present study is an essential issue to highlight, where several antibiotic resistance mechanisms might be engaged in this resistance.…”

Section: Discussionmentioning

confidence: 99%

Mathematical pharmacodynamic modeling for antimicrobial assessment of ceftazidime/colistin versus gentamicin/meropenem combinations against carbapenem-resistant Pseudomonas aeruginosa biofilm

Badawy

Elkhatib

Shebl

2023

Ann Clin Microbiol Antimicrob

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Background Carbapenem-resistant Pseudomonas aeruginosa (CRPA) represents an escalating healthcare hazard with high mortality worldwide, especially in presence of biofilm. The current study aimed to evaluate the anti-biofilm potentials of ceftazidime, colistin, gentamicin, and meropenem alone and in combinations against biofilm-forming CRPA. Methods Biofilm killing and checkerboard assay were performed to detect the effectiveness of combined antibiotics against biofilms and planktonic cells, respectively. The bacterial bioburden retrieved from the established biofilms following treatment with combined antibiotics was utilized to construct a three-dimensional response surface plot. A sigmoidal maximum effect model was applied to determine the pharmacodynamic parameters (maximal effect, median effective concentration, and Hill factor) of each antibiotic to create a mathematical three-dimensional response surface plot. Results Data revealed statistically significant (p < 0.05) superior anti-biofilm potential in the case of colistin followed by a lower effect in the case of gentamicin and meropenem, while ceftazidime exhibited the least anti-biofilm activity. The fractional inhibitory concentration index (FICI ≤ 0.5) indicated synergism following treatment with the combined antibiotics. An elevated anti-biofilm activity was recorded in the case of gentamicin/meropenem compared to ceftazidime/colistin. Synergistic anti-biofilm potentials were also detected via the simulated pharmacodynamic modeling, with higher anti-biofilm activity in the case of the in vitro observation compared to the simulated anti-biofilm profile. Conclusions The present study highlighted the synergistic potentials of the tested antibiotic combinations against P. aeruginosa biofilms and the importance of the mathematical pharmacodynamic modeling in investigating the efficacy of antibiotics in combination as an effective strategy for successful antibiotic therapy to tackle the extensively growing resistance to the currently available antibiotics.

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“…Flagella consists of more than 20 different proteins, and it can participate in adhesion and invasion by promoting motility toward the host cells and adhering to them. Biofilm attachment to the biotic (such as mucus, intestine, connective tissue, epithelium, endothelium, cardiac valves, bone marrow, and the skin) and the abiotic surfaces (such as prostheses, stents, implants, and catheters) occurs through the presence of cell appendages such as flagella, pili, and fimbriae [ 131 , 133 , 164 ]. Therefore, this virulence factor has a significant role in colonization in the lung environment of CF patients [ 163 ].…”

Section: Pathogenesis Of P Aeruginosa In Cfmentioning

confidence: 99%

Bile effects on the Pseudomonas aeruginosa pathogenesis in cystic fibrosis patients with gastroesophageal reflux

Bayat,

Nahand,

Farsad-Akhatr

et al. 2023

Heliyon

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In vitro synergy of antibiotic combinations against planktonic and biofilm Pseudomonas aeruginosa

Cited by 14 publications

References 25 publications

Codelivery of synergistic antimicrobials with polyelectrolyte nanocomplexes to treat bacterial biofilms and lung infections

Codelivery of synergistic antimicrobials with polyelectrolyte nanocomplexes to treat bacterial biofilms and lung infections

Mathematical pharmacodynamic modeling for antimicrobial assessment of ceftazidime/colistin versus gentamicin/meropenem combinations against carbapenem-resistant Pseudomonas aeruginosa biofilm

Bile effects on the Pseudomonas aeruginosa pathogenesis in cystic fibrosis patients with gastroesophageal reflux

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