scholarly journals Bactericidal Activity of a Self-Biodegradable Lysine-Containing Dendrimer against Clinical Isolates of Acinetobacter Genus

2021 ◽  
Vol 22 (14) ◽  
pp. 7274
Author(s):  
Silvana Alfei ◽  
Debora Caviglia ◽  
Gabriella Piatti ◽  
Guendalina Zuccari ◽  
Anna Maria Schito

The genus Acinetobacter consists of Gram-negative obligate aerobic pathogens, including clinically relevant species, such as A. baumannii, which frequently cause hospital infections, affecting debilitated patients. The growing resistance to antimicrobial therapies shown by A. baumannii is reaching unacceptable levels in clinical practice, and there is growing concern that the serious conditions it causes may soon become incurable. New therapeutic possibilities are, therefore, urgently needed to circumvent this important problem. Synthetic cationic macromolecules, such as cationic antimicrobial peptides (AMPs), which act as membrane disrupters, could find application in these conditions. A lysine-modified cationic polyester-based dendrimer (G5-PDK), capable of electrostatically interacting with bacterial surfaces as AMPs do, has been synthesized and characterized here. Given its chemical structure, similar to that of a fifth-generation lysine containing dendrimer (G5K) with a different core, and previously found inactive against Gram-positive bacterial species and Enterobacteriaceae, the new G5-PDK was also ineffective on the species mentioned above. In contrast, it showed minimum inhibitory concentration values (MICs) lower than reported for several AMPs and other synthetic cationic compounds on Acinetobacter genus (3.2–12.7 µM). Time-kill experiments on A. baumannii, A. pittii, and A. ursingii ascertained the rapid bactericidal effects of G5-PDK, while subsequent bacterial regrowth supported its self-biodegradability.

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Dayang Fredalina Basri ◽  
Vimashiinee Sandra

Canarium odontophyllum(CO) Miq. has been considered as one of the most sought-after plant species in Sarawak, Malaysia, due to its nutritional and pharmacological benefits. This study aimed to evaluate the pharmacodynamic interaction of crude methanol and acetone extracts from CO leaves in combination with oxacillin, vancomycin, and linezolid, respectively, against MRSA ATCC 33591 as preliminary study has reported its potential antistaphylococcal activity. The broth microdilution assay revealed that both methanol and acetone extracts were bactericidal with Minimum Inhibitory Concentration (MIC) of 312.5 μg/mL and 156.25 μg/mL and Minimum Bactericidal Concentration (MBC) of 625 μg/mL and 312.5 μg/mL, respectively. Fractional Inhibitory Concentration (FIC) indices were obtained via the chequerboard dilution assay where methanol extract-oxacillin, acetone extract-oxacillin, methanol extract-linezolid, and acetone extract-linezolid combinations exhibited synergism (FIC index ≤ 0.5). The synergistic action of the methanol extract-oxacillin combination was verified by time-kill analysis where bactericidal effect was observed at concentration of 1/8 × MIC of both compounds at 9.6 h compared to oxacillin alone. As such, these findings postulated that both extracts exert their anti-MRSA mechanism of action similar to that of vancomycin and provide evidence that the leaves ofC. odontophyllumhave the potential to be developed into antistaphylococcal agents.


1993 ◽  
Vol 21 (2) ◽  
pp. 151-155
Author(s):  
Gustaw Kerszman

The toxicity of the first ten MEIC chemicals to Escherichia coli and Bacillus subtilis was examined. Nine of the chemicals were toxic to the bacteria, with the minimal inhibitory concentration (MIC) ranging from 10-3 to 4.4M. The sensitivities of both organisms were similar, but the effect on E. coli was often bactericidal, while it was bacteriostatic for B. subtilis. Digoxin was not detectably toxic to either bacterial species. Amitriptyline and FeSO4 were relatively less toxic to the bacteria than to human cells. For seven chemicals, a highly significant linear regression was established between log MIC in bacteria and log of blood concentration, giving lethal and moderate/mild toxicity in humans, as well as with toxicity to human lymphocytes.


2021 ◽  
Vol 14 (6) ◽  
pp. 517
Author(s):  
Joseph Blondeau ◽  
Heleen DeCory

Background: Besifloxacin ophthalmic suspension 0.6% (w/v%) contains benzalkonium chloride (BAK) as a preservative. We evaluated the in vitro time-kill activity of besifloxacin, alone and in combination with BAK, against common bacteria implicated in ophthalmic infections. Methods: The activity of besifloxacin (100 µg/mL), BAK (10, 15, 20, and 100 µg/mL), and combinations of besifloxacin and BAK were evaluated against isolates of Staphylococcus epidermidis (n = 4), Staphylococcus aureus (n = 3), Haemophilus influenzae (n = 2), and Pseudomonas aeruginosa (n = 2) in time-kill experiments of 180 min duration. With the exception of one S. aureus isolate, all of the staphylococcal isolates were methicillin- and/or ciprofloxacin-resistant; one P. aeruginosa isolate was ciprofloxacin-resistant. The reductions in the viable colony counts (log10 CFU/mL) were plotted against time, and the differences among the time–kill curves were evaluated using an analysis of variance. Areas-under-the-killing-curve (AUKCs) were also computed. Results: Besifloxacin alone demonstrated ≥3-log killing of P. aeruginosa (<5 min) and H. influenzae (<120 min), and approached 3-log kills of S. aureus. BAK alone demonstrated concentration-dependent killing of S. epidermidis, S. aureus and H. influenzae, and at 100 µg/mL produced ≥3-log kills in <5 min against these species. The addition of BAK (10, 15, and 20 µg/mL) to besifloxacin increased the rate of killing compared to besifloxacin alone, with earlier 3-log kills of all species except P. aeruginosa and a variable impact on S. aureus. The greatest reductions in AUKC were observed among H. influenzae (8-fold) and S. epidermidis (≥5-fold). Similar results were found when the isolates were evaluated individually by their resistance phenotype. Conclusions: In addition to confirming the activity of 100 µg/mL BAK as a preservative in the bottle, these data suggest that BAK may help besifloxacin to achieve faster time-kills on-eye in the immediate timeframe post-instillation before extensive dilution against bacterial species implicated in ophthalmic infections, including drug-resistant S. epidermidis. Greater killing activity may help prevent resistance development and/or help treat resistant organisms.


Polymers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1375
Author(s):  
María J. Moreno-Vásquez ◽  
Maribel Plascencia-Jatomea ◽  
Saúl Sánchez-Valdes ◽  
Judith C. Tanori-Córdova ◽  
Francisco J. Castillo-Yañez ◽  
...  

Nanoparticles based on chitosan modified with epigallocatechin gallate (EGCG) were synthetized by nanoprecipitation (EGCG-g-chitosan-P). Chitosan was modified by free-radical-induced grafting, which was verified by Fourier transform infrared (FTIR). Furthermore, the morphology, particle size, polydispersity index, and zeta potential of the nanoparticles were investigated. The grafting degree of EGCG, reactive oxygen species (ROS) production, antibacterial and antioxidant activities of EGCG-g-chitosan-P were evaluated and compared with those of pure EGCG and chitosan nanoparticles (Chitosan-P). FTIR results confirmed the modification of the chitosan with EGCG. The EGCG-g-chitosan-P showed spherical shapes and smoother surfaces than those of Chitosan-P. EGCG content of the grafted chitosan nanoparticles was 330 μg/g. Minimal inhibitory concentration (MIC) of EGCG-g-chitosan-P (15.6 μg/mL) was lower than Chitosan-P (31.2 μg/mL) and EGCG (500 μg/mL) against Pseudomonas fluorescens (p < 0.05). Additionally, EGCG-g-chitosan-P and Chitosan-P presented higher Staphylococcus aureus growth inhibition (100%) than EGCG at the lowest concentration tested. The nanoparticles produced an increase of ROS (p < 0.05) in both bacterial species assayed. Furthermore, EGCG-g-chitosan-P exhibited higher antioxidant activity than that of Chitosan-P (p < 0.05) in 2,2′-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and ferric-reducing antioxidant power assays. Based on the above results, EGCG-g-chitosan-P shows the potential for food packaging and biomedical applications.


2017 ◽  
Vol 80 (1) ◽  
Author(s):  
Mohamad Khairil Radzali ◽  
Akmal Hayat Abdul Karim ◽  
Syahida Ahmad ◽  
Wan Zuhainis Saad

This study was undertaken to investigate the antibacterial properties and the mode of actions of crude extract of Aspergillus fumigatus SSH01. Antibacterial properties was observed against Gram-positive pathogens and showed inhibition against Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6538, methicillin-resistant S. aureus S547 (MRSA) and Listeria monocytogenes L10 with minimum inhibitory concentration (MIC, 0.097- 12.5 mg/ml) and minimum bactericidal concentration (MBC, 0.195 – 25 mg/ml). No surviving cells were detected after 15 h of treatment with the 2MIC of extracts for time-kill assay. Leakage of cellular contents of the treated test pathogens were identified and increased as the concentrations of the extracts increased. The study of morphological surface has shown the bacterial membrane was disrupted and caused loss of viability. This implies the antibacterial effects of A. fumigatus SSH01 extract may serve as the potential antibiotic. 


Author(s):  
Gautam Shiv Shankar ◽  
M Navneet ◽  
Kumar Sanjay ◽  
M Prabhat

The aim of present study was to evaluate the antibacterial potential of various extracts (petroleum ether, acetone, methanol and aqueous) of Nepeta ciliaris against selected respiratory tract pathogens. The extracts from the aerial parts of N. ciliaris at concentration of 200 mg/ml were screened against three gram-positive (Staphylococcus aureus MTCC 1144, Streptococcus pneumoniae MTCC 655 and Streptococcus pyogenes MTCC 442) and one gram-negative (Pseudomonas aeruginosa MTCC 2474) bacterial pathogens. The agar well diffusion method was adopted to examine antibacterial and minimum inhibitory concentration (MIC) values of most effective extracts against the susceptible bacteria. Erythromycin was used as positive control to determine the sensitivity of the strains. Out of the four bacterial species tested, S. pneumoniae was the most susceptible. The acetone extract exhibited maximum activity against all the tested microorganisms while methanol extract showed activity against P. aeruginosa. The MIC values ranged from 40 to 50 mg/ml for all the organisms. The N. ciliaris is potentially a good source of antimicrobial agents. DOI: http://dx.doi.org/10.3126/kuset.v8i1.6049 KUSET 2012; 8(1): 100-103


Polymers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1210
Author(s):  
L. Martinaga Pintarić ◽  
M. Somogi Škoc ◽  
V. Ljoljić Bilić ◽  
I. Pokrovac ◽  
I. Kosalec ◽  
...  

In this research, a textile surface was modified by the sol–gel methodology with a new antimicrobial coating containing nanoparticles active against bacteria resistant to antibiotics. The effect of ultrasonic irradiation power (40 to 90 kHz), the concentration of reagents (nanoparticles, precursor and acids) and time (15 to 72 min) were investigated in relation to the structure, morphology and antimicrobial activity of coatings with zinc oxide nanoparticles. The relationship between the sonocatalytic performance and structure of the resultant modification was established by using various techniques, such as FTIR spectroscopy (FTIR) and scanning electron microscopy with an EDX detector (SEM-EDX), thin-layer chromatography (TLC) and antimicrobial effects were determined on selected model microorganisms. The homogeneity of layers with ZnO nanoparticles on samples was increased by increasing the ultrasonic irradiation power and time. The ultrasonic irradiation unify did not only unify both the structure and the morphology of samples, it also prevented the agglomeration of the nanoparticles. Moreover, under optimal conditions, an antimicrobial coating with ZnO nanoparticles, active against bacterial species S. aureus and E. coli was efficiently prepared. Results of the Time-kill methodology revieled excellent results starting after 6 hours of exposal to antimicrobialy functionalized cellulose polymer.


1998 ◽  
Vol 42 (8) ◽  
pp. 2002-2005 ◽  
Author(s):  
Melissa A. Visalli ◽  
Michael R. Jacobs ◽  
Peter C. Appelbaum

The present study examined the activities of trovafloxacin, levofloxacin, and ciprofloxacin, alone and in combination with cefoperazone, ceftazidime, cefpirome, and gentamicin, against 100 strains of Stenotrophomonas maltophilia by the MIC determination method and by synergy testing of the combinations by the time-kill and checkerboard titration methods for 20 strains. The respective MICs at which 50% and 90% of isolates were inhibited for the drugs used alone were as follows: trovafloxacin, 0.5 and 2.0 μg/ml; levofloxacin, 2.0 and 4.0 μg/ml; ciprofloxacin, 4.0 and 16.0 μg/ml; cefoperazone, >128.0 and >128.0 μg/ml; ceftazidime, 32.0 and >128.0 μg/ml; cefpirome, >128.0 and >128.0 μg/ml; and gentamicin, 128.0 and >128.0 μg/ml. Synergistic fractional inhibitory concentration indices (≤0.5) were found for ≥50% of strains for trovafloxacin-cefoperazone, trovafloxacin-ceftazidime, levofloxacin-cefoperazone, levofloxacin-ceftazidime, ciprofloxacin-cefoperazone, and ciprofloxacin-ceftazidime, with other combinations affecting fewer strains. For 20 strains tested by the checkerboard titration and time-kill methods, synergy (≥100-fold drop in count compared to the count achieved with the more active compound) was more pronounced after 12 h due to regrowth after 24 h. At 12 h, trovafloxacin at 0.004 to 0.5 μg/ml showed synergy with cefoperazone for 90% of strains, with ceftazidime for 95% of strains with cefpirome for 95% of strains, and with gentamicin for 65% of strains. Levofloxacin at 0.03 to 0.5 μg/ml and ciprofloxacin at 0.5 to 2.0 μg/ml showed synergy with cefoperazone for 80% of strains, with ceftazidime for 90 and 85% of strains, respectively, with cefpirome for 85 and 75% of strains, respectively, and with gentamicin for 65 and 75% of strains, respectively. Time-kill assays were more discriminatory than checkerboard titration assays in demonstrating synergy for all combinations.


1996 ◽  
Vol 40 (9) ◽  
pp. 1973-1976 ◽  
Author(s):  
S Bajaksouzian ◽  
M A Visalli ◽  
M R Jacobs ◽  
P C Appelbaum

The checkerboard titration method was used to test the synergy of cefpirome and cefotaxime with teicoplanin or vancomycin against 35 penicillin-susceptible, 34 penicillin-intermediate, and 31 penicillin-resistant pneumococci. The MICs at which 50 and 90% of isolates are inhibited (MIC50s and MIC90s, respectively) of both cefpirome and cefotaxime were 0.016 and 0.06 microgram/ml, respectively, for penicillin-susceptible strains and 0.125 and 0.5 microgram/ml, respectively, for penicillin-intermediate strains. The MIC50s and MIC90s of cefotaxime for penicillin-resistant strains were 1.0 and 2.0 micrograms/ml, respectively, and those of cefpirome were 0.5 and 1.0 microgram/ml, respectively. All pneumococci were inhibited by cefpirome at MICs of < or = 1.0 microgram/ml. The MIC50s and MIC90s of vancomycin and teicoplanin (0.25 and 0.25 microgram/ml and 0.03 and 0.03 microgram/ml, respectively) did not differ for the three groups. Checkerboard synergy studies showed that cefpirome and vancomycin showed synergy for 31 strains (fractional inhibitory concentration [FIC] indices, < or = 0.5) cefpirome and teicoplanin showed synergy for 18 strains, cefotaxime and vancomycin showed synergy for 51 strains, and cefotaxime and teicoplanin showed synergy for 27 strains. Cefpirome and vancomycin had FIC indices indicating indifference (2.0) for two strains, and cefotaxime and vancomycin had FIC indices indicating indifference for one strain. All other FIC indices indicating indifference or additivity were > 0.5 to 1.0. No FIC indices indicating antagonism (> 4.0) were found. Synergy between beta-lactams and glycopeptides for three susceptible, three intermediate, and three resistant strains were tested by the time-kill assay, and all combinations were synergistic by this method. Synergy between cephalosporins and glycopeptides can be demonstrated and may be useful for the treatment of pneumococcal infections, especially meningitis.


2006 ◽  
Vol 50 (11) ◽  
pp. 3622-3630 ◽  
Author(s):  
Bruno Périchon ◽  
Patrice Courvalin

ABSTRACT Vancomycin resistance of Staphylococcus aureus NY-VRSA and VRSA-5 is due to acquisition of a vanA operon located in a Tn1546-like element. The vanA gene cluster of NY-VRSA contained one copy of insertion sequences IS1251 and IS1216V relative to that of VRSA-5. As evidenced by the nature of the late peptidoglycan precursors and by quantification of d,d-peptidase activities, the vancomycin resistance genes were efficiently expressed in both strains. Study of the stability and inducibility of glycopeptide resistance suggested that low-level glycopeptide resistance of NY-VRSA was most probably due to plasmid instability combined with a long delay for resistance induction. The activity of combinations of vancomycin or teicoplanin with oxacillin against the four VanA-type S. aureus strains already reported was tested by single and double disk diffusion, E-test on agar alone or supplemented with antibiotics, the checkerboard technique, and by determining time-kill curves. A strong synergism against the four clinical isolates, with fractional inhibitory concentration indexes from 0.008 to 0.024, was reproducibly observed between the two antibiotics by all methods. These observations indicate that cell wall inhibitors of the β-lactam and glycopeptide classes exert strong and mutual antagonistic effects on resistance to each other against VanA-type methicillin-resistant S. aureus.


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