Evaluation of N-phenyl-2-aminothiazoles for treatment of multi-drug resistant and intracellular Staphylococcus aureus infections

Shahin, Inas G.; Abutaleb, Nader S.; Alhashimi, Marwa; Kassab, Asmaa E.; Mohamed, Khaled O.; Taher, Azza T.; Seleem, Mohamed N.; Mayhoub, Abdelrahman S.

doi:10.1016/j.ejmech.2020.112497

Cited by 26 publications

(14 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the studies reviewed, vancomycin was used at higher concentrations than can be expected in the bone but still showed a maximal inhibition effect of a 2-log reduction, independent of the cell type used. 17 , 74 , 125 , 141 , 144 , 162 , 163 It was possible to increase the effect in combination with other agents, such as ansamycins, 146 bacteriophages, 144 peptide-conjugated antimicrobial peptide TAT-KR12 164 or efflux pump inhibitors, 152 but not with liposomes or pegylated liposomes. 163 Interestingly, vancomycin showed increased antimicrobial potency when used after 7 days compared to that at an immediate treatment time.…”

Section: Resultsmentioning

confidence: 99%

“…Even though the variety of dosages of the antibiotics used gives a broader insight into the effectiveness of the treatment, using concentrations multiple times higher than can be expected to be achieved in the bone could render findings less meaningful. The different antibiotic concentrations used can be related to the experimental approach employed, with some studies based on the actual measured MIC in vitro, 54 , 74 , 125 , 142 , 152 , 162 while others chose the concentrations based on the maximum plasma/serum 17 , 74 , 75 or bone 53 , 135 , 153 concentrations observed in vivo. Ideally, both factors need to be considered.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies evaluated a treatment as being significantly effective when a certain percentage, e.g., 50% reduction, in the number of CFU was achieved, 55 , 57 , 58 , 142 , 153 , 157 , 165 , 178 while others considered the linear reduction in the CFU count, 126 , 141 , 156 , 163 , 179 logarithmic bacterial number reduction, 17 , 53 , 74 , 75 , 95 , 97 , 125 , 144 , 146 , 150 , 162 , 166 or only host-cell survival. 136 Since complete clearance is rarely achievable and a bacterial reduction of less than 1-log does not seem to be useful in an infection context, in this article, an effort was made to compare results at a logarithmic level.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics? A systematic review and narrative synthesis

et al. 2022

View full text Add to dashboard Cite

Approximately 40% of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence. Staphylococcus aureus, the predominant pathogen in human osteomyelitis, is known to persist by phenotypic adaptation as small-colony variants (SCVs) and by formation of intracellular reservoirs, including those in major bone cell types, reducing susceptibility to antibiotics. Intracellular infections with S. aureus are difficult to treat; however, there are no evidence-based clinical guidelines addressing these infections in osteomyelitis. We conducted a systematic review of the literature to determine the demonstrated efficacy of all antibiotics against intracellular S. aureus relevant to osteomyelitis, including protein biosynthesis inhibitors (lincosamides, streptogramins, macrolides, oxazolidines, tetracyclines, fusidic acid, and aminoglycosides), enzyme inhibitors (fluoroquinolones and ansamycines), and cell wall inhibitors (beta-lactam inhibitors, glycopeptides, fosfomycin, and lipopeptides). The PubMed and Embase databases were screened for articles related to intracellular S. aureus infections that compared the effectiveness of multiple antibiotics or a single antibiotic together with another treatment, which resulted in 34 full-text articles fitting the inclusion criteria. The combined findings of these studies were largely inconclusive, most likely due to the plethora of methodologies utilized. Therefore, the reported findings in the context of the models employed and possible solutions for improved understanding are explored here. While rifampicin, oritavancin, linezolid, moxifloxacin and oxacillin were identified as the most effective potential intracellular treatments, the scientific evidence for these is still relatively weak. We advocate for more standardized research on determining the intracellular effectiveness of antibiotics in S. aureus osteomyelitis to improve treatments and patient outcomes.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics? A systematic review and narrative synthesis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The PAE is important data that, in combination with in vivo pharmacokinetics, can inform the proper dosing regimen 80 , 81 . PAE was determined as previously described 72 , 73 , 82 . AZM displayed an observed PAE ranging from 2 to 4 h against N. gonorrhoeae strains tested while EZM exhibited a long PAE of at least 10 h against all the strains tested ( Table 4 ).…”

Section: Resultsmentioning

confidence: 99%

Repurposing FDA-approved sulphonamide carbonic anhydrase inhibitors for treatment of Neisseria gonorrhoeae

Abutaleb

Elhassanny

Nocentini

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Neisseria gonorrhoeae is a high-priority pathogen of concern due to the growing prevalence of resistance development against approved antibiotics. Herein, we report the anti-gonococcal activity of ethoxzolamide, the FDA-approved human carbonic anhydrase inhibitor. Ethoxzolamide displayed an MIC 50, against a panel of N. gonorrhoeae isolates, of 0.125 µg/mL, 16-fold more potent than acetazolamide, although both molecules exhibited almost similar potency against the gonococcal carbonic anhydrase enzyme (NgCA) in vitro . Acetazolamide displayed an inhibition constant ( K i ) versus NgCA of 74 nM, while Ethoxzolamide ’ s K i was estimated to 94 nM. Therefore, the increased anti-gonococcal potency of ethoxzolamide was attributed to its increased permeability in N. gonorrhoeae as compared to that of acetazolamide. Both drugs demonstrated bacteriostatic activity against N. gonorrhoeae , exhibited post-antibiotic effects up to 10 hours, and resistance was not observed against both. Taken together, these results indicate that acetazolamide and ethoxzolamide warrant further investigation for translation into effective anti- N. gonorrhoeae agents.

show abstract

“…S. aureus is a clinically important bacterial species, which is effectively treated using the antibiotic vancomycin ( Shahin et al, 2020 ; Simon et al, 2020 ). However, with the continuous use of antibiotics, vancomycin-resistant S. aureus strains are increasingly developing that can adapt to antibiotic environments and show strong phenotypic plasticity ( Bakri et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Functional Mapping of Phenotypic Plasticity of Staphylococcus aureus Under Vancomycin Pressure

et al. 2021

View full text Add to dashboard Cite

Phenotypic plasticity is the exhibition of various phenotypic traits produced by a single genotype in response to environmental changes, enabling organisms to adapt to environmental changes by maintaining growth and reproduction. Despite its significance in evolutionary studies, we still know little about the genetic control of phenotypic plasticity. In this study, we designed and conducted a genome-wide association study (GWAS) to reveal genetic architecture of how Staphylococcus aureus strains respond to increasing concentrations of vancomycin (0, 2, 4, and 6 μg/mL) in a time course. We implemented functional mapping, a dynamic model for genetic mapping using longitudinal data, to map specific loci that mediate the growth trajectories of abundance of vancomycin-exposed S. aureus strains. 78 significant single nucleotide polymorphisms were identified following analysis of the whole growth and development process, and seven genes might play a pivotal role in governing phenotypic plasticity to the pressure of vancomycin. These seven genes, SAOUHSC_00020 (walR), SAOUHSC_00176, SAOUHSC_00544 (sdrC), SAOUHSC_02998, SAOUHSC_00025, SAOUHSC_00169, and SAOUHSC_02023, were found to help S. aureus regulate antibiotic pressure. Our dynamic gene mapping technique provides a tool for dissecting the phenotypic plasticity mechanisms of S. aureus under vancomycin pressure, emphasizing the feasibility and potential of functional mapping in the study of bacterial phenotypic plasticity.

show abstract

Evaluation of N-phenyl-2-aminothiazoles for treatment of multi-drug resistant and intracellular Staphylococcus aureus infections

Cited by 26 publications

References 30 publications

Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics? A systematic review and narrative synthesis

Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics? A systematic review and narrative synthesis

Repurposing FDA-approved sulphonamide carbonic anhydrase inhibitors for treatment of Neisseria gonorrhoeae

Functional Mapping of Phenotypic Plasticity of Staphylococcus aureus Under Vancomycin Pressure

Contact Info

Product

Resources

About