scholarly journals Potent Broad-Spectrum Antibacterial Activity of Amphiphilic Peptides against Multidrug-Resistant Bacteria

2020 ◽  
Vol 8 (9) ◽  
pp. 1398 ◽  
Author(s):  
Yuan Liu ◽  
Jingru Shi ◽  
Ziwen Tong ◽  
Yuqian Jia ◽  
Kangni Yang ◽  
...  

The emergence and prevalence of multidrug-resistant (MDR) bacteria particularly Gram-negative bacteria presents a global crisis for human health. Colistin and tigecycline were recognized as the last resort of defenses against MDR Gram-negative pathogens. However, the emergence and prevalence of MCR or Tet(X)-mediated acquired drug resistance drastically impaired their clinical efficacy. It has been suggested that antimicrobial peptides might act a crucial role in combating antibiotic resistant bacteria owing to their multiple modes of action and characteristics that are not prone to developing drug resistance. Herein, we report a safe and stable tryptophan-rich amphiphilic peptide termed WRK-12 with broad-spectrum antibacterial activity against various MDR bacteria, including MRSA, colistin and tigecycline-resistant Escherichia coli. Mechanistical studies showed that WRK-12 killed resistant E. coli through permeabilizing the bacterial membrane, dissipating membrane potential and triggering the production of reactive oxygen species (ROS). Meanwhile, WRK-12 significantly inhibited the formation of an E. coli biofilm in a dose-dependent manner. These findings revealed that amphiphilic peptide WRK-12 is a promising drug candidate in the fight against MDR bacteria.

2020 ◽  
Author(s):  
Xiaowei Yang ◽  
Runsheng Guo ◽  
Banglin Xie ◽  
Qi Lai ◽  
Jiaxiang Xu ◽  
...  

Abstract Background: Hospital-acquired infections (HAIs) are an emerging global problem that increases in-hospital mortality, length of stay, and cost. We performed a 6-year retrospective study to provide valuable insight into appropriate antibiotic use in HAI cases. We also aimed to understand how hospitals could reduce pathogen drug resistance in a population that overuses antibiotics.Methods: All data (2012–2017) were obtained from the Hospital Information Warehouse and Clinical Microbiology Laboratory.Results: We isolated 1392 pathogen strains from patients admitted to the orthopedics department during 2012–2017. Escherichia coli (14.7%, 204/1392), Enterobacter cloacae (13.9%, 193/1392), and Staphylococcus aureus (11.3%, 157/1392) were the most common pathogens causing nosocomial infections. The dominant Gram-negative bacterium was E. coli, with high resistance to ampicillin, levofloxacin, cotrimoxazole, gentamicin, and ciprofloxacin, in that order. E. coli was least resistant to amikacin, cefoperazone-sulbactam. The most dominant Gram-positive bacterium was S. aureus, highly resistant to penicillin and ampicillin, but not resistant to fluoroquinolones and cotrimoxazole. Analysis of risk factors related to multidrug-resistant bacteria showed that patients with open fractures were significantly more susceptible to methicillin-resistant S. aureus infections (p < 0.05). Additionally, extended-spectrum β-lactamase-producing E. coli infections occurred significantly more often in patients with degenerative diseases (p < 0.05). Elderly patients tended to be more susceptible to multidrug-resistant bacterial infections, but this outcome was not statistically significant.Conclusions:Antimicrobial resistance is a serious problem in orthopedics. To effectively control antimicrobial resistance among pathogens, we advocate extensive and dynamic monitoring of MDR bacteria, coupled with careful use of antibiotics.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3168 ◽  
Author(s):  
Diana Machado ◽  
Laura Fernandes ◽  
Sofia S. Costa ◽  
Rolando Cannalire ◽  
Giuseppe Manfroni ◽  
...  

Efflux pump inhibitors are of great interest since their use as adjuvants of bacterial chemotherapy can increase the intracellular concentrations of the antibiotics and assist in the battle against the rising of antibiotic-resistant bacteria. In this work, we have described the mode of action of the 2-phenylquinoline efflux inhibitor (4-(2-(piperazin-1-yl)ethoxy)-2-(4-propoxyphenyl) quinolone – PQQ4R), againstEscherichia coli,by studding its efflux inhibitory ability, its synergistic activity in combination with antibiotics, and compared its effects with the inhibitors phenyl-arginine-β-naphthylamide (PAβN) and chlorpromazine (CPZ). The results showed that PQQ4R acts synergistically, in a concentration dependent manner, with antibiotics known to be subject to efflux inE. colireducing their MIC in correlation with the inhibition of their efflux. Real-time fluorometry assays demonstrated that PQQ4R at sub-inhibitory concentrations promote the intracellular accumulation of ethidium bromide inhibiting its efflux similarly to PAβN or CPZ, well-known and described efflux pump inhibitors for Gram-negative bacteria and whose clinical usage is limited by their levels of toxicity at clinical and bacteriological effective concentrations. The time-kill studies showed that PQQ4R, at bactericidal concentrations, has a rapid antimicrobial activity associated with a fast decrease of the intracellular ATP levels. The results also indicated that the mode of action of PQQ4R involves the destabilization of theE. coliinner membrane potential and ATP production impairment, ultimately leading to efflux pump inhibition by interference with the energy required by the efflux systems. At bactericidal concentrations, membrane permeabilization increases and finally ATP is totally depleted leading to cell death. Since drug resistance mediated by the activity of efflux pumps depends largely on the proton motive force (PMF), dissipaters of PMF such as PQQ4R, can be regarded as future adjuvants of conventional therapy againstE. coliand other Gram-negative bacteria, especially their multidrug resistant forms. Their major limitation is the high toxicity for human cells at the concentrations needed to be effective against bacteria. Their future molecular optimization to improve the efflux inhibitory properties and reduce relative toxicity will optimize their potential for clinical usage against multi-drug resistant bacterial infections due to efflux.


2019 ◽  
Vol 61 (1) ◽  
Author(s):  
Edgarthe Priscilla Ngaiganam ◽  
Isabelle Pagnier ◽  
Wafaa Chaalal ◽  
Thongpan Leangapichart ◽  
Selma Chabou ◽  
...  

Abstract Background We investigate here the presence of multidrug-resistant bacteria isolated from stool samples of yellow-legged gulls and chickens (n = 136) in urban parks and beaches of Marseille, France. Bacterial isolation was performed on selective media, including MacConkey agar with ceftriaxone and LBJMR medium. Antibiotic resistance genes, including extended-spectrum β-lactamases (ESBL) (i.e. blaCTX-M, blaTEM and blaSHV), carbapenemases (blaKPC, blaVIM, blaNDM, blaOXA-23, blaOXA-24, blaOXA-48 and blaOXA-58) and colistin resistance genes (mcr-1 to mcr-5) were screened by real-time PCR and standard PCR and sequenced when found. Results Of the 136 stools samples collected, seven ESBL-producing Gram-negative bacteria (BGN) and 12 colistin-resistant Enterobacteriaceae were isolated. Among them, five ESBL-producing Escherichia coli and eight colistin-resistant Hafnia alvei strains were identified. Four blaTEM-1 genes were detected in yellow-legged gulls and chickens. Three CTX-M-15 genes were detected in yellow-legged gulls and pigeons, and one CTX-M-1 in a yellow-legged gull. No mcr-1 to mcr-5 gene were detected in colistin-resistant isolates. Genotyping of E. coli strains revealed four different sequence types already described in humans and animals and one new sequence type. Conclusions Urban birds, which are believed to have no contact with antibiotics appear as potential source of ESBL genes. Our findings highlight the important role of urban birds in the proliferation of multidrug-resistant bacteria and also the possible zoonotic transmission of such bacteria from wild birds to humans.


2020 ◽  
Author(s):  
Jixun Zhang ◽  
Rui Li ◽  
Zhenzhong Liu ◽  
Chao Wang

Abstract Objectives: Considering the dynamic changes of MDR, we did an up-to-date study and analyzed the impact of MDR on the outcome of patients. Design: Collected MDR isolated from hospitalized patients between June 2018 and May 2020 and performed retrospective analysis. Setting: This study was conducted in a public regional central hospital in China.Patients: 1156 patients with MDR infections.Results: Total 1291 MDRS were isolated, intensive care unit (ICU) accounted for 32.3% as the most. The main samples were sputum (75.1%) and 89.6% MDR were Gram-negative. The most common MDR were Acinetobacter baumannii, carbapenemase-producing K. pneumoniae, Pseudomonas aeruginosa, ESBL-producing E. coli. Methicillin-resistant Staphylococcus aureus (MRSA) and ESBL-producing K.pneumoniae. 35.6% were nosocomial infections and 64.4% were community-acquired infections. There was a statistically significant difference in mortality between patients infected with MDR and those with non-MDR (7.4% [32/432] vs 2.6% [17/655]; P = 0.001). The Acinetobacter baumannii and Klebsiella pneumoniae were mainly sensitive to tigecycline. The Pseudomonas aeruginosa was mainly sensitive to amikacin and levofloxacin. More than 80% of the Escherichia coli were sensitive to tigecycline and carbapenems. More than 90% of MRSA were sensitive to vancomycin, linezolid, and quinoprptin / daptoptin.Conclusions: The MDRS are mainly gram-negative bacteria. ICU contributes most MDR and pulmonary infection is the main origin of MDR. MDR infection is an independent risk factor for death. ESBL-producing Enterobacteriaceae, especially carbapenemase producing Enterobacteriaceae, should be paid more attention. This study is helpful to understand the distribution of MDR in hospital and the extent of antibiotic resistance.


2019 ◽  
Author(s):  
Bin Zhang ◽  
Xiaowei Yang ◽  
Runsheng Guo ◽  
Banglin Xie ◽  
Qi Lai ◽  
...  

Abstract Abstract Background Hospital-acquired infections (HAIs) are an emerging global problem that increases in-hospital mortality, length of stay, and cost. Orthopedics departments experience a particularly high infection rate, partially due to their heavy reliance on invasive medical devices. We performed a 6-year retrospective study to provide valuable insight into appropriate antibiotic use in HAI cases. We also aimed to understand how hospitals could reduce pathogen drug resistance in a population that overuses antibiotics. Methods All data (2012–2017) were obtained from the Hospital Information Warehouse and Clinical Microbiology Laboratory. Results We isolated 1392 pathogen strains from patients admitted to the orthopedics department during 2012–2017. Escherichia coli (14.7%, 204/1392), Enterobacter cloacae (13.9%, 193/1392), and Staphylococcus aureus (11.3%, 157/1392) were the most common pathogens causing nosocomial infections. The dominant gram-negative bacterium was E. coli, with high resistance to ampicillin, levofloxacin, cotrimoxazole, gentamicin, and ciprofloxacin, in that order. E. coli was least resistant to amikacin, cefoperazone-sulbactam, meropenem, imipenem, and piperacillin-tazobactam. The most dominant gram-positive bacterium was S. aureus, highly resistant to penicillin and ampicillin, but not resistant to fluoroquinolones and cotrimoxazole. We also did not observe isolate resistance to nitrofurantoin, linezolid, and vancomycin. Analysis of risk factors related to multidrug-resistant bacteria showed that patients with open fractures were significantly more susceptible to methicillin-resistant S. aureus infections (p < 0.05). Additionally, extended-spectrum β-lactamase-producing E. coli infections occurred significantly more often in patients with degenerative diseases (p < 0.05). Elderly patients tended to be more susceptible to multidrug-resistant bacterial infections, but this outcome was not statistically significant. Conclusions Antimicrobial resistance is a serious problem in orthopedics. To effectively control antimicrobial resistance among pathogens, we advocate extensive and dynamic monitoring of MDR bacteria, coupled with careful use of antibiotics. Key words: hospital acquired infections; orthopedics; drug resistance; multidrug resistance


Antibiotics ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 29 ◽  
Author(s):  
Larbi Zakaria Nabti ◽  
Farida Sahli ◽  
Hocine Laouar ◽  
Ahmed Olowo-okere ◽  
Joice Guileine Nkuimi Wandjou ◽  
...  

Antibiotics are becoming ineffective against resistant bacteria. The use of essential oils (EOs) may constitute an alternative solution to fight against multidrug-resistant bacteria. This study aims to determine the chemical composition of EOs from five populations of the endemic Algerian Origanum glandulosum Desf. and to investigate their potential antibacterial activity against multidrug-resistant uropathogenic E. coli strains. The EOs were obtained by hydrodistillation and their composition was investigated by gas chromatography/mass spectrometry (GC/MS). The antibacterial activity was evaluated by the disc diffusion method against eight E. coli strains (six uropathogenic resistant and two referenced susceptible strains). Minimum inhibitory and bactericidal concentrations (MIC/MBC) were obtained by the broth microdilution method. The main EO components were thymol (15.2–56.4%), carvacrol (2.8–59.6%), γ-terpinene (9.9–21.8%) and p-cymene (8.5–13.9%). The antibacterial tests showed that all the EOs were active against all the strains, including the multidrug-resistant strains. The EO from the Bordj location, which contained the highest amount of carvacrol (59.6%), showed the highest antibacterial activity (inhibition diameters from 12 to 24.5 mm at a dilution of 1/10). To our knowledge, this is the first description of the activity of O. glandulosum EOs against resistant uropathogenic strains. Our study suggests that O. glandulosum EO could be used in some clinical situations to treat or prevent infections (e.g., urinary tract infections) with multidrug-resistant strains.


2020 ◽  
Vol 11 ◽  
pp. 1119-1125
Author(s):  
Mohammad Jaber ◽  
Asim Mushtaq ◽  
Kebiao Zhang ◽  
Jindan Wu ◽  
Dandan Luo ◽  
...  

The control over contagious diseases caused by pathogenic organisms has become a serious health issue. The extensive usage of antibiotics has led to the development of multidrug-resistant bacterial strains. In this regard, metal-oxide-based antibacterial nanomaterials have received potential research interest due to the efficient prevention of microorganism growth. In this study, splat-shaped Ag–TiO2 nanocomposites (NCs) were synthesized on the gram scale and the enhanced antibacterial properties of TiO2 in the presence of silver were examined. The formation of Ag–TiO2 NCs was analyzed through various characterization techniques. The cell viability experimental results demonstrated that the Ag–TiO2 NCs have good biocompatibility. The antibacterial activity of the prepared Ag–TiO2 NCs was tested against the Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacterial strains. The Ag–TiO2 NCs exhibited promising and superior antibacterial properties compared to TiO2 nanospheres as confirmed by the bacterial growth and inhibition zone. The improvement in the antibacterial activity was attributed to the synergistic effect of the hybrid nature of TiO2 nanoparticles in the presence of Ag.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Antonio Sorlozano-Puerto ◽  
Maria Albertuz-Crespo ◽  
Isaac Lopez-Machado ◽  
Juan Jose Ariza-Romero ◽  
Alberto Baños-Arjona ◽  
...  

Background. The aim of this study was to compare the in vitro antibacterial activity of two compounds derived from Alliaceae, PTS (propyl-propane-thiosulfinate), and PTSO (propyl-propane-thiosulfonate), with that of other antibiotics commonly used against bacteria isolated from humans. Materials and Methods. A total of 212 gram-negative bacilli and 267 gram-positive cocci isolated from human clinical samples and resistant to at least one group of antibiotics were selected. In order to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) to various antibiotics as well as PTS and PTSO, all isolates underwent broth microdilution assay. Results. PTS showed moderate activity against Enterobacteriaceae with MIC50 (and MBC50) and MIC90 (and MBC90) values of 256-512 mg/L, while PTSO showed greater activity with MIC50 and MIC90 values of 64-128 mg/L and MBC50 and MBC90 values of 128-512 mg/L. These data show the bactericidal activity of both compounds and indicate that PTSO was more active than PTS against this group of bacteria. Both compounds showed lower activity against P. aeruginosa (MIC50 = 1024 mg/L, MIC90 = 2048 mg/L, MBC50 = 2048 mg/L, and MBC90 = 2048 mg/L, for PTS; MIC50 = 512 mg/L, MIC90 = 1024 mg/L, MBC50 = 512 mg/L, and MBC90 = 2048 mg/L, for PTSO) compared to those obtained in others nonfermenting gram-negative bacilli (MIC50 = 128 mg/L, MIC90 = 512 mg/L, MBC50 = 128 mg/L, and MBC90 = 512 mg/L, for PTS; MIC50 = 64 mg/L, MIC90 = 256 mg/L, MBC50 = 64 mg/L, and MBC90 = 256 mg/L, for PTSO) and also indicate the bactericidal activity of both compounds against these groups of bacteria. Finally, the activity against S. aureus, E. faecalis, and S. agalactiae was higher than that observed against enterobacteria, especially in the case of PTSO (MIC50 = 8 mg/L, MIC90 = 8 mg/L, MBC50 = 32 mg/L, and MBC90 = 64 mg/L, in S. aureus; MIC50 = 4 mg/L, MIC90 = 8 mg/L, MBC50 = 8 mg/L, and MBC90 = 16 mg/L, in E. faecalis and S. agalactiae). Conclusion. PTS and PTSO have a significant broad spectrum antibacterial activity against multiresistant bacteria isolated from human clinical samples. Preliminary results in present work provide basic and useful information for development and potential use of these compounds in the treatment of human infections.


2017 ◽  
Vol 66 (4) ◽  
pp. 533-536 ◽  
Author(s):  
Moreno Bondi ◽  
Anna Mazzini ◽  
Simona de Niederhäusern ◽  
Ramona Iseppi ◽  
Patrizia Messi

The authors studied the in vitro antibacterial activity of the photo-activated porphyrin meso-tri(N-methyl-pyridyl), mono(N-tetradecyl-pyridyl)porphine (C14) against four multidrug-resistant bacteria: Staphylococcus aureus, Enterococcus faecalis (Gram-positive), Escherichia coli, Pseudomonas aeruginosa (Gram-negative). Using 10 μg/ml of porphyrin and 60 sec irradiation we observed the remarkable susceptibility of S. aureus and E. faecalis to treatment while, under the same conditions, E. coli and P. aeruginosa showed very low susceptibility. In a later stage, suspensions of Gram-negative bacteria were processed with EDTA before photo-activation, obtaining a significant decrease in viable counts. In view of the results, if the combination of low porphyrin concentrations and short irradiation times will be effective in vivo also, this approach could be a possible alternative to antibiotics, in particular against localized infections due to multidrug-resistant microorganisms.


Author(s):  
Roshni Agarwal ◽  
Vaibhav Agarwal ◽  
Anjali Tewari ◽  
Parwati Upadhyay

Background: Every time an antibiotic is used, whether appropriately or not, the probability of the development and spread of antibiotic resistant bacteria is increased. Thus, multidrug resistant bacteria particularly ESBL (Extended spectrum β­lactamase), Amp C and carbapenemases producing gram negative bacilli have emerged as a major health problem all over the world. Considering new treatment options as a carbapenems sparing and resistance prevention modality, this study was aimed to know the in vitro susceptibility pattern of Cefepime/Tazobactam (CPM/TZ) in comparison to other β-Lactam/ β-Lactamase inhibitors (BL/BLI) and carbapenems against GNB.Methods: A prospective study was conducted on all clinical samples received for a period of about 1 year. Identification and susceptibility of all isolates was done by Vitek 2 Compact system. Susceptibility of CPM/ TZ was done by disc diffusion method on the basis of CLSI guidelines. Both fermenters (E. coli and Klebsiella pneumoniae) and non-fermenters (Acintobacter baumanii and Pseudomonas aeruginosa) were included in the study.Results: Out of 550 GNB isolates the most common was E. coli (61.8%), Acintobacter baumanii (16%), Klebsiella pneumoniae (14.9%) and Pseudomonas aeruginosa (7.3%). Cefepime/tazobactam had a much higher susceptibility of 68% compared to cefepime (28%). Among the BL/BLI combinations tested cefepime/tazobactam (68%) showed the maximum percentage of susceptibility followed by cefoperazone/sulbactam (61.5%) and piperacillin/tazobactam (57.6%). Amongst all GNB isolates cefepime/tazobactam (68%) sensitivity was very much comparable to imipenem (71.8%) and meropenem (69.6%).Conclusions: CPM/TZ exhibited the best in vitro activity in comparison to the other BL/BLI. This new combination of cefepime/tazobactam appears to be a promising alternative therapeutic option to carbapenems. Clinical studies are needed to confirm this in vitro study result.


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