scholarly journals Fluoroquinolone Metalloantibiotics: A Promising Approach against Methicillin-Resistant Staphylococcus aureus

Author(s):  
Mariana Ferreira ◽  
Lucinda J. Bessa ◽  
Carla F. Sousa ◽  
Peter Eaton ◽  
Dafne Bongiorno ◽  
...  

Fluoroquinolones (FQs) are antibiotics commonly used in clinical practice, although nowadays they are becoming ineffective due to the emergence of several mechanisms of resistance in most bacteria. The complexation of FQs with divalent metal ions and phenanthroline (phen) is a possible approach to circumvent antimicrobial resistance, since it forms very stable complexes known as metalloantibiotics. This work is aimed at determining the antimicrobial activity of metalloantibiotics of Cu(II)FQphen against a panel of multidrug-resistant (MDR) clinical isolates and to clarify their mechanism of action. Minimum inhibitory concentrations (MICs) were determined against MDR isolates of Escherichia coli, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). Metalloantibiotics showed improved antimicrobial activity against several clinical isolates, especially MRSA. Synergistic activity was evaluated in combination with ciprofloxacin and ampicillin by the disk diffusion and checkerboard methods. Synergistic and additive effects were shown against MRSA isolates. The mechanism of action was studied though enzymatic assays and atomic force microscopy (AFM) experiments. The results indicate a similar mechanism of action for FQs and metalloantibiotics. In summary, metalloantibiotics seem to be an effective alternative to pure FQs against MRSA. The results obtained in this work open the way to the screening of metalloantibiotics against other Gram-positive bacteria.

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1889
Author(s):  
Amal Alrashidi ◽  
Mohammed Jafar ◽  
Niamh Higgins ◽  
Ciara Mulligan ◽  
Carmine Varricchio ◽  
...  

There is a need for new antimicrobial systems due to increased global resistance to current antimicrobials. Pomegranate rind extract (PRE) and Zn (II) ions both possess a level of antimicrobial activity and work has previously shown that PRE/Zn (II) in combination possesses synergistic activity against Herpes simplex virus and Micrococcus luteus. Here, we determined whether such synergistic activity extended to other, more pathogenic, bacteria. Reference strains of methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa were cultured and subjected to challenge by PRE, Zn (II), or PRE + Zn (II), in time-kill assays. Data were obtained independently by two researchers using different PRE preparations. Statistically significant synergistic activity for PRE + Zn (II) was shown for all four bacterial strains tested compared to untreated controls, although the extent of efficacy and timescales varied. Zn (II) exerted activity and at 1 h, it was not possible to distinguish with PRE + Zn (II) combination treatment in all cases. PRE alone showed low activity against all four bacteria. Reproducible synergistic bactericidal activity involving PRE and Zn (II) has been confirmed. Potential mechanisms are discussed. The development of a therapeutic system that possesses demonstrable antimicrobial activity is supported which lends itself particularly to topical delivery applications, for example MRSA infections.


2021 ◽  
pp. 32-40
Author(s):  
S. D. Kugaperumal ◽  
R. D. De Silva ◽  
T. D. Karunarathne ◽  
C. P. Gunasekara ◽  
D. N. A. W. Samarakoon

Methicillin Resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumanii are known to cause delayed healing of infections in both acute and chronic wounds. Plants are a natural source of novel antimicrobials and many new drugs are derived from plants, as plants contain phytochemicals that have antimicrobial activity. Sri Lanka is a tropical country with a wide variety of plant species, many of which were identified as possessing medicinal qualities and have been used by traditional medicinal practitioners in the treatment of various diseases and ailments. Dressings made of Rhipsalis baccifera and Drymoglossum piloselloides have been used to treat wounds by Sri Lankan traditional medicine practitioners. This study determined the antibacterial activity of aqueous and methanol extracts of R. baccifera and D. piloselloides against MRSA and Multidrug-resistant A. baumanii. Aqueous and methanolic extractions of both plants were done by maceration. Their antibacterial properties were checked against MRSA and A. baumanii by the well diffusion method. The effectiveness of the extract was further tested against factors like temperature and storage time. R. baccifera (aqueous extract) exhibited antimicrobial properties against MRSA but no activity against A. baumanii. The antibiotic activity against MRSA was increased after two months of storage at 4°C. D. piloselloides exhibited no antibiotic activity against both MRSA and A. baumanii. The methanolic extracts did not demonstrate any antibacterial activity.


Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 952
Author(s):  
Lorenza Fagnani ◽  
Lisaurora Nazzicone ◽  
Fabrizia Brisdelli ◽  
Luisa Giansanti ◽  
Sara Battista ◽  
...  

The dramatic intensification of antimicrobial resistance occurrence in pathogenic bacteria concerns the global community. The revitalisation of inactive antibiotics is, at present, the only way to go through this health system crisis and the use of antimicrobial adjuvants is turning out the most promising approach. Due to their low toxicity, eco-friendly characteristics and antimicrobial activity, amphoteric surfactants are good candidates. This study investigated the adjuvant potentialities of commercial acyclic and newly cyclic N-oxide surfactants combined with therapeutically available antibiotics against MDR methicillin-resistant Staphylococcus aureus (MRSA). The safety profile of the new cyclic compounds, compared to commercial surfactants, was preliminarily assessed, evaluating the cytotoxicity on human peripheral mononuclear blood cells and the haemolysis in human red blood cells. The compounds show an efficacious antimicrobial activity strongly related to the length of the carbon atom chain. In drug–drug interaction assays, all surfactants act synergistically, restoring sensitivity to oxacillin in MRSA, with dodecyl acyclic and cyclic derivatives being the most effective. After evaluating the cytotoxicity and considering the antimicrobial action, the most promising compound is the L-prolinol amine-oxide C12NOX. These findings suggest that the combination of antibiotics with amphoteric surfactants is a valuable therapeutic option for topical infections sustained by multidrug-resistant S. aureus.


2019 ◽  
Vol 18 (24) ◽  
pp. 2116-2126 ◽  
Author(s):  
Eleonora Ciandrini ◽  
Gianluca Morroni ◽  
Daniela Arzeni ◽  
Wojciech Kamysz ◽  
Damian Neubauer ◽  
...  

Background: Antimicrobial research is being focused to look for more effective therapeutics against antibiotic-resistant infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In this direction, antimicrobial peptides (AMP) appear as promising tool. Objectives: This study evaluated the antimicrobial activity of different AMPs (Citropin 1.1, Temporin A, Pexiganan, CA(1–7)M(2–9)NH2, Pal-KGK-NH2, Pal-KKKK-NH2, LL-37) against human MRSA clinical isolates. Methods: The Minimum Inhibitory Concentration (MIC) was assessed for each AMP; then, the most active ones (Citropin 1.1, Temporin A, CA(1–7)M(2–9)NH2 and Pal-KGK-NH2) were tested against selected MRSA strains by time-kill studies. Results: The lowest MIC value was observed for Pal-KGK-NH2 (1 µg/ml), followed by Temporin A (4- 16 µg/ml), CA(1–7)M(2–9)NH2 (8-16 µg/ml) and Citropin 1.1 (16-64 µg/ml), while higher MICs were evidenced for LL-37, Pexiganan and Pal-KKKK-NH2 (> 128 µg/ml). In time-kill experiments, Citropin 1.1 and CA(1-7)M(2-9)NH2 showed a relatively high percentage of growth inhibition (>30 %) for all the tested MRSA clinical isolates, with a dose-dependent activity resulting in the highest percentage of bacterial growth inhibition (89.39%) at 2MIC concentration. Conclusion: Overall, our data demonstrated the potential of some AMPs against MRSA isolates, such as Citropin 1.1 and CA(1-7)M(2-9)NH2, that represents a promising area of development for different clinical applications.


2015 ◽  
Vol 59 (12) ◽  
pp. 7837-7841 ◽  
Author(s):  
I. J. Abbott ◽  
A. W. J. Jenney ◽  
C. J. Jeremiah ◽  
M. Mirčeta ◽  
J. P. Kandiah ◽  
...  

ABSTRACTA total of 421 methicillin-resistantStaphylococcus aureus(MRSA) clinical isolates were tested for ceftaroline susceptibility by Etest (bioMérieux). A multidrug resistant phenotype was found in 40.9%, and clonal complex 239 (CC239) was found in 33.5%. Ceftaroline nonsusceptibility (MIC, >1.0 μg/ml) was 16.9% overall. Nonsusceptibility was significantly higher in CC239 (41.1%, 58/141) and in isolates with a multidrug resistant phenotype (35.5%, 61/172) compared with comparators (P< 0.0001). Nonsusceptibility of common multidrug resistant MRSA clones limits the empirical use of ceftaroline for these infections.


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