scholarly journals Improved Antibiotic-Impregnated Catheters with Extended-Spectrum Activity against Resistant Bacteria and Fungi

2011 ◽  
Vol 56 (2) ◽  
pp. 935-941 ◽  
Author(s):  
Issam Raad ◽  
Jamal A. Mohamed ◽  
Ruth A. Reitzel ◽  
Ying Jiang ◽  
Sammy Raad ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
First Generation ◽  
Bloodstream Infections ◽  
Resistant Bacteria ◽  
Content Type ◽  
Fungal Organisms ◽  
Colonization Model ◽  
Spectrum Activity ◽  
Generation M ◽  
Bacteria And Fungi

ABSTRACTMinocycline-rifampin-impregnated central venous catheters (M/R CVCs) have been shown to be efficacious in reducing catheter-related bloodstream infections (CRBSI) and inhibiting the biofilm adherence of resistant Gram-positive and Gram-negative pathogens, with the exception ofPseudomonas aeruginosaandCandidaspp. To expand the spectrum of antimicrobial activity, a novel second-generation M/R catheter was developed by adding chlorhexidine (CHX-M/R). CVCs and peripherally inserted central catheters (PICCs) were impregnated with CHX-M/R and compared with first-generation M/R catheters, CHX-silver sulfadiazine-treated CVCs (CHX/SS-CVCs), chlorhexidine-treated PICCs, and uncoated catheters. A biofilm catheter colonization model was used to assess the efficacy of catheters against methicillin-resistantStaphylococcus aureus(MRSA), vancomycin-resistantEnterococcus faecium(VRE),P. aeruginosa,Candida albicans, andCandida glabrata. CHX-M/R-impregnated CVCs were the only antimicrobial catheters that completely inhibited the biofilm colonization of all resistant bacterial and fungal organisms tested at all time intervals, and they were significantly superior to uncoated catheters (allPvalues were ≤0.003). Furthermore, CHX-M/R-coated CVCs had a significantly more effective and prolonged (up to 3 weeks) antimicrobial activity against MRSA andP. aeruginosathan M/R, CHX/SS, and uncoated CVCs (P< 0.0001). Similarly, CHX-M/R-coated PICCs were also superior to M/R-coated and CHX-coated PICCs in preventing biofilms of MRSA, VRE,P. aeruginosa, andCandidaspecies (Pvalue = 0.003 for all). Our study shows that novel CHX-M/R-coated catheters have unique properties in completely inhibiting biofilm colonization of MRSA, VRE,P. aeruginosa, and fungi in a manner superior to that of M/R- and chlorhexidine-treated catheters.

scholarly journals Membrane Perturbation Action Mode and Structure-Activity Relationships of Protonectin, a Novel Antimicrobial Peptide from the Venom of the Neotropical Social Wasp Agelaia pallipes pallipes

2013 ◽  
Vol 57 (10) ◽  
pp. 4632-4639 ◽  
Author(s):  
Kairong Wang ◽  
Wen Dang ◽  
Jiexi Yan ◽  
Ru Chen ◽  
Xin Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Social Wasp ◽  
Multidrug Resistant ◽  
Structural Features ◽  
Helical Conformation ◽  
Resistant Bacteria ◽  
Content Type ◽  
Natural Analog ◽  
Action Mode

ABSTRACTWith the extensive use of antibiotics, multidrug-resistant bacteria emerge frequently. New antimicrobial agents with novel modes of action are urgently needed. It is now widely accepted that antimicrobial peptides (AMPs) could be promising alternatives to conventional antibiotics. In this study, we aimed to study the antimicrobial activity and mechanism of action of protonectin, a cationic peptide from the venom of the neotropical social waspAgelaia pallipes pallipes. We demonstrated that protonectin exhibits potent antimicrobial activity against a spectrum of bacteria, including multidrug-resistant strains. To further understand this mechanism, the structural features of protonectin and its analogs were studied by circular dichroism (CD). The CD spectra demonstrated that protonectin and its natural analog polybia-CP formed a typical α-helical conformation in the membrane-mimicking environment, while its proline-substituted analog had much lower or even no α-helix conformation. Molecular dynamics simulations indicated that the α-helical conformation in the membrane is required for the exhibition of antibacterial activity. In conclusion, protonectin exhibits potent antimicrobial activity by disruption of the integrity of the bacterial membrane, and its α-helical confirmation in the membrane is essential for this action.

scholarly journals In Vitro Study of Antimicrobial Percutaneous Nephrostomy Catheters for Prevention of Renal Infections

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Nylev Vargas-Cruz ◽  
Ruth A. Reitzel ◽  
Joel Rosenblatt ◽  
Mohamed Jamal ◽  
Ariel D. Szvalb ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Biofilm Formation ◽  
In Vitro Study ◽  
Percutaneous Nephrostomy ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Fungal Organisms

ABSTRACT Percutaneous nephrostomy (PCN) catheters are the primary method for draining ureters obstructed by malignancy and preventing a decline of renal function. However, PCN catheter-related infections, such as pyelonephritis and urosepsis, remain a significant concern. Currently, no antimicrobial PCN catheters are available for preventing infection complications. Vascular catheters impregnated with minocycline-rifampin (M/R) and M/R with chlorhexidine coating (M/R plus CHD) have previously demonstrated antimicrobial activity. Therefore, in this study, we examined whether these combinations could be applied to PCN catheters and effectively inhibit biofilm formation by common uropathogens. An in vitro biofilm colonization model was used to assess the antimicrobial efficacy of M/R and M/R-plus-CHD PCN catheters against nine common multidrug-resistant Gram-positive and Gram-negative uropathogens as well as Candida glabrata and Candida albicans. Experimental catheters were also assessed for durability of antimicrobial activity for up 3 weeks. PCN catheters coated with M/R plus CHD completely inhibited biofilm formation for up to 3 weeks for all the organisms tested. The reduction in colonization compared to uncoated PCN catheters was significant for all Gram-positive, Gram-negative, and fungal organisms (P < 0.05). M/R-plus-CHD PCN catheters also produced significant reductions in biofilm colonization relative to M/R PCN catheters for Enterobacter spp., Escherichia coli, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, C. glabrata, and C. albicans (P < 0.05). M/R-plus-CHD PCN catheters proved to be highly efficacious in preventing biofilm colonization when exposed to multidrug-resistant pathogens common in PCN catheter-associated pyelonephritis. M/R-plus-CHD PCN catheters warrant evaluation in a clinical setting to assess their ability to prevent clinically relevant nephrostomy infections.

scholarly journals Novel Group of Leaderless Multipeptide Bacteriocins from Gram-Positive Bacteria

2016 ◽  
Vol 82 (17) ◽  
pp. 5216-5224 ◽  
Author(s):  
Kirill V. Ovchinnikov ◽  
Hai Chi ◽  
Ibrahim Mehmeti ◽  
Helge Holo ◽  
Ingolf F. Nes ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antimicrobial Activity ◽  
Bacterial Resistance ◽  
Raw Milk ◽  
Peptide Sequencing ◽  
Homology Search ◽  
Resistant Bacteria ◽  
Content Type ◽  
New Antibiotics ◽  
Inhibitory Spectrum

ABSTRACTFrom raw milk we found 10Lactococcus garvieaeisolates that produce a new broad-spectrum bacteriocin. Though the isolates were obtained from different farms, they turned out to possess identical inhibitory spectra, fermentation profiles of sugars, and repetitive sequence-based PCR (rep-PCR) DNA patterns, indicating that they produce the same bacteriocin. One of the isolates (L. garvieaeKS1546) was chosen for further assessment. Purification and peptide sequencing combined with genome sequencing revealed that the antimicrobial activity was due to a bacteriocin unit composed of three similar peptides of 32 to 34 amino acids. The three peptides are produced without leader sequences, and their genes are located next to each other in an operon-like structure, adjacent to the genes normally involved in bacteriocin transport (ABC transporter) and self-immunity. The bacteriocin, termed garvicin KS (GarKS), showed sequence homology to four multipeptide bacteriocins in databases: the known staphylococcal aureocin A70, consisting of four peptides, and three unannotated putative multipeptide bacteriocins produced byBacillus cereus. All these multipeptide bacteriocin loci show conserved genetic organization, including being located adjacent to conserved genetic determinants (Cro/cI and integrase) which are normally associated with mobile genetic elements or genome rearrangements. The antimicrobial activity of all multipeptide bacteriocins was confirmed with synthetic peptides, and all were shown to have broad antimicrobial spectra, with GarKS being the most active of them. The inhibitory spectrum of GarKS includes important pathogens belonging to the generaStaphylococcus,Bacillus,Listeria, andEnterococcus.IMPORTANCEBacterial resistance to antibiotics is a very serious global problem. There are no new antibiotics with novel antimicrobial mechanisms in clinical trials. Bacteriocins use antimicrobial mechanisms different from those of antibiotics and can kill antibiotic-resistant bacteria, but the number of bacteriocins with very broad antimicrobial spectra is very small. In this study, we have found and purified a novel three-peptide bacteriocin, garvicin KS. By homology search, we were able to find one known and three novel sequence-related bacteriocins consisting of 3 or 4 peptides. None of the peptides has modified amino acids in its sequence. Thus, the activity of all bacteriocins was confirmed with chemically synthesized peptides. All of them, especially garvicin KS, have very broad antibacterial spectra, thus representing a great potential in antimicrobial applications in the food industry and medicine.

Validation of γ-irradiation in controlling microorganisms in fish

2014 ◽  
Vol 44 (3) ◽  
pp. 258-266 ◽  
Author(s):  
Mrityunjoy Acharjee ◽  
Estiak Ahmed ◽  
Saurab Kishore Munshi ◽  
Rashed Noor
Keyword(s):  
Drug Resistance ◽  
Pathogenic Bacteria ◽  
Fecal Coliforms ◽  
Resistant Bacteria ◽  
Biochemical Tests ◽  
Γ Irradiation ◽  
Content Type ◽  
Fish Samples ◽  
Bacteria And Fungi ◽  
Sea Fish

Purpose – With a previous throughput of sea fish contamination with microorganisms, the present study extended the array of such spoilage over four other fish samples including Pseudapocryptes elongates, Scomberomorus cavalla, Xenentodon cancila and Otolithoides pama, evaluated the reductive impact of irradiation, and further validated the irradiation methodology in controlling the microbial quality of the sea fish samples. The paper aims to discuss these issues. Design/methodology/approach – Twelve samples of each sea fish were collected from super shops in Dhaka city and a portion of each sample was subjected to γ-irradiation at a dose of 3 kilo gray (kGy). Then, both non-irradiated and irradiated samples were tested for the presence of pathogenic bacteria though culture on different specific media followed by biochemical identification. Drug resistance among the pathogens was also investigated. Findings – Most of the non-irradiated samples were observed to harbor huge bacteria and fungi (1.3×102-1.5×107 cfu/g or cfu/ml) including the fecal coliforms ranging up to 105 cfu/g or cfu/ml, leading to an elevated threat to public health. Besides, the isolates were found to be resistant against single or multiple antibiotics, which further brought treatment complications during the possible disease outbreaks. However, the pathogenic load was significantly reduced after applying 3 kGy dose of γ-irradiation on the samples in consistent to the previous work using different fish samples. Research limitations/implications – A similar type of work has already been published by the group using different samples this year in the Journal of Microbiology, Biotechnology and Food Sciences, Vol. 2 No. 4, pp. 2420-2430. However, even being an increment of the previous work, the present work deals with extended array of sea fish samples with an objective of controlling food safety. Practical implications – The present work further confirms and assists the knowledge of food protection and the identification of spoiling bacteria and fungi by applying replicable methods projects of the novelty and practical outcome of the work. Originality/value – The reduction of pathogenic load revealed the efficacy of γ-irradiation as a mean of preserving fish quality. Besides, the study quantified the contaminating microorganisms as well as identified the drug-resistant bacteria among sea fish samples. Traditional but standard cultural and biochemical tests, demonstration of drug resistance among the isolated microorganisms from fish samples and finally the microbial elimination by irradiation might contribute to the existing knowledge on major sea fish.

scholarly journals Characterizing the Mechanism of Action of an Ancient Antimicrobial, Manuka Honey, against Pseudomonas aeruginosa Using Modern Transcriptomics

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Daniel Bouzo ◽  
Nural N. Cokcetin ◽  
Liping Li ◽  
Giulia Ballerin ◽  
Amy L. Bottomley ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Mechanism Of Action ◽  
Broad Spectrum ◽  
Bacterial Resistance ◽  
Resistant Bacteria ◽  
Antibiotics Resistance ◽  
Manuka Honey ◽  
Content Type ◽  
Bacterial Membranes

ABSTRACT Manuka honey has broad-spectrum antimicrobial activity, and unlike traditional antibiotics, resistance to its killing effects has not been reported. However, its mechanism of action remains unclear. Here, we investigated the mechanism of action of manuka honey and its key antibacterial components using a transcriptomic approach in a model organism, Pseudomonas aeruginosa. We show that no single component of honey can account for its total antimicrobial action, and that honey affects the expression of genes in the SOS response, oxidative damage, and quorum sensing. Manuka honey uniquely affects genes involved in the explosive cell lysis process and in maintaining the electron transport chain, causing protons to leak across membranes and collapsing the proton motive force, and it induces membrane depolarization and permeabilization in P. aeruginosa. These data indicate that the activity of manuka honey comes from multiple mechanisms of action that do not engender bacterial resistance. IMPORTANCE The threat of antimicrobial resistance to human health has prompted interest in complex, natural products with antimicrobial activity. Honey has been an effective topical wound treatment throughout history, predominantly due to its broad-spectrum antimicrobial activity. Unlike traditional antibiotics, honey-resistant bacteria have not been reported; however, honey remains underutilized in the clinic in part due to a lack of understanding of its mechanism of action. Here, we demonstrate that honey affects multiple processes in bacteria, and this is not explained by its major antibacterial components. Honey also uniquely affects bacterial membranes, and this can be exploited for combination therapy with antibiotics that are otherwise ineffective on their own. We argue that honey should be included as part of the current array of wound treatments due to its effective antibacterial activity that does not promote resistance in bacteria.

scholarly journals In Vitro and In Vivo Activity of a Novel Catheter Lock Solution against Bacterial and Fungal Biofilms

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
J. Chandra ◽  
L. Long ◽  
N. Isham ◽  
P. K. Mukherjee ◽  
G. DiSciullo ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Bloodstream Infections ◽  
Central Line ◽  
Resistant Bacteria ◽  
Content Type ◽  
Lock Solution ◽  
Catheter Lock ◽  
Adhesion Phase

ABSTRACT Central-line-associated bloodstream infections are increasingly recognized to be associated with intraluminal microbial biofilms, and effective measures for the prevention and treatment of bloodstream infections remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL), containing trimethoprim (5 mg/ml), ethanol (25%), and calcium EDTA (Ca-EDTA) (3%), for activity against bacterial and fungal biofilms, using in vitro and in vivo (rabbit) catheter biofilm models. Biofilms were formed by bacterial (seven different species, including vancomycin-resistant Enterococcus [VRE]) or fungal (Candida albicans) species on catheter materials. Biofilm formation was evaluated by quantitative culture (CFU) and scanning electron microscopy (SEM). Treatment with ACL inhibited the growth of adhesion-phase biofilms in vitro after 60 min (VRE) or 15 min (all others), while mature biofilms were completely inhibited after exposure for 2 or 4 h, compared to control. Similar results were observed for drug-resistant bacteria. Compared to the heparinized saline controls, ACL lock therapy significantly reduced the catheter bacterial (3.49 ± 0.75 versus 0.03 ± 0.06 log CFU/catheter; P = 0.016) and fungal (2.48 ± 1.60 versus 0.55 ± 1.19 log CFU/catheter segment; P = 0.013) burdens in the catheterized rabbit model. SEM also demonstrated eradication of bacterial and fungal biofilms in vivo on catheters exposed to ACL, while vigorous biofilms were observed on untreated control catheters. Our results demonstrated that ACL was efficacious against both adhesion-phase and mature biofilms formed by bacteria and fungi in vitro and in vivo.

scholarly journals Therapeutic Effect and Mechanisms of the Novel Monosulfactam 0073

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Ying Sun ◽  
Xueyuan Liao ◽  
Zhigang Huang ◽  
Yaliu Xie ◽  
Yanbin Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Serial Passage ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Infection Model ◽  
The Novel ◽  
Gram Negative ◽  
Content Type

ABSTRACT This study aimed to evaluate the antimicrobial activity of the novel monosulfactam 0073 against multidrug-resistant Gram-negative bacteria in vitro and in vivo and to characterize the mechanisms underlying 0073 activity. The in vitro activities of 0073, aztreonam, and the combination with avibactam were assessed by MIC and time-kill assays. The safety of 0073 was evaluated using 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and acute toxicity assays. Murine thigh infection and pneumonia models were employed to define in vivo efficacy. A penicillin-binding protein (PBP) competition assay and confocal microscopy were conducted. The inhibitory action of 0073 against β-lactamases was evaluated by the half-maximal inhibitory concentration (IC50), and resistance development was evaluated via serial passage. The monosulfactam 0073 showed promising antimicrobial activity against Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii isolates producing metallo-β-lactamases (MBLs) and serine β-lactamases. In preliminary experiments, compound 0073 exhibited safety both in vitro and in vivo. In the murine thigh infection model and the pneumonia models in which infection was induced by P. aeruginosa and Klebsiella pneumoniae, 0073 significantly reduced the bacterial burden. Compound 0073 targeted several PBPs and exerted inhibitory effects against some serine β-lactamases. Finally, 0073 showed a reduced propensity for resistance selection compared with that of aztreonam. The novel monosulfactam 0073 exhibited increased activity against β-lactamase-producing Gram-negative organisms compared with the activity of aztreonam and showed good safety profiles both in vitro and in vivo. The underlying mechanisms may be attributed to the affinity of 0073 for several PBPs and its inhibitory activity against some serine β-lactamases. These data indicate that 0073 represents a potential treatment for infections caused by β-lactamase-producing multidrug-resistant bacteria.

scholarly journals Antimicrobial Activity of B-Lock against Bacterial and Candida spp. Causing Catheter-Related Bloodstream Infections

2011 ◽  
Vol 55 (9) ◽  
pp. 4430-4431 ◽  
Author(s):  
M. A. Ghannoum ◽  
N. Isham ◽  
M. R. Jacobs
Keyword(s):  
Antimicrobial Activity ◽  
Bloodstream Infections ◽  
Triple Combination ◽  
Bacterial Strains ◽  
Candida Spp ◽  
Content Type ◽  
Potential Value ◽  
Lock Solution ◽  
Prevention And Treatment ◽  
Intravascular Catheters

ABSTRACTThe triple combination trimethoprim, EDTA, and ethanol (B-Lock), is an antimicrobial lock solution for use in indwelling intravascular catheters to prevent and treat catheter-associated infections. B-Lock demonstrated MICs of ≤0.05% (percentage of solution) againstCandidaspp. (n= 125) and 0.003% to 25% against bacterial strains (n= 175). B-Lock was also fungicidal against the majority of theCandidastrains at 6% to 25%. B-Lock demonstrates potential value for the prevention and treatment of catheter-associated infections.

scholarly journals Genetic and Biochemical Characterization of OXA-405, an OXA-48-Type Extended-Spectrum β-Lactamase without Significant Carbapenemase Activity

2015 ◽  
Vol 59 (7) ◽  
pp. 3823-3828 ◽  
Author(s):  
Laurent Dortet ◽  
Saoussen Oueslati ◽  
Katy Jeannot ◽  
Didier Tandé ◽  
Thierry Naas ◽  
...  
Keyword(s):  
First Generation ◽  
Biochemical Characterization ◽  
Clinical Settings ◽  
Significant Activity ◽  
Content Type ◽  
Extended Spectrum ◽  
Spectrum Activity ◽  
Biochemical Detection ◽  
Type Gene

ABSTRACTThe epidemiology of carbapenemases worldwide is showing that OXA-48 variants are becoming the predominant carbapenemase type inEnterobacteriaceaein many countries. However, not all OXA-48 variants possess significant activity toward carbapenems (e.g., OXA-163). TwoSerratia marcescensisolates with resistance either to carbapenems or to extended-spectrum cephalosporins were successively recovered from the same patient. A genomic comparison using pulsed-field gel electrophoresis and automated Rep-PCR typing identified a 97.8% similarity between the two isolates. Both strains were resistant to penicillins and first-generation cephalosporins. The first isolate was susceptible to expanded-spectrum cephalosporins, was resistant to carbapenems, and had a significant carbapenemase activity (positive Carba NP test) related to the expression of OXA-48. The second isolate was resistant to expanded-spectrum cephalosporins, was susceptible to carbapenems, and did not express a significant imipenemase activity, (negative for the Carba NP test) despite possessing ablaOXA-48-type gene. Sequencing identified a novel OXA-48-type β-lactamase, OXA-405, with a four-amino-acid deletion compared to OXA-48. TheblaOXA-405gene was located on a ca. 46-kb plasmid identical to the prototype IncL/MblaOXA-48-carrying plasmid except for a ca. 16.4-kb deletion in thetraoperon, leading to the suppression of self-conjugation properties. Biochemical analysis showed that OXA-405 has clavulanic acid-inhibited activity toward expanded-spectrum activity without significant imipenemase activity. This is the first identification of a successive switch of catalytic activity in OXA-48-like β-lactamases, suggesting their plasticity. Therefore, this report suggests that the first-line screening of carbapenemase producers inEnterobacteriaceaemay be based on the biochemical detection of carbapenemase activity in clinical settings.

scholarly journals Antibacterial Activity of Eravacycline (TP-434), a Novel Fluorocycline, against Hospital and Community Pathogens

2013 ◽  
Vol 57 (11) ◽  
pp. 5548-5558 ◽  
Author(s):  
J. A. Sutcliffe ◽  
W. O'Brien ◽  
C. Fyfe ◽  
T. H. Grossman
Keyword(s):  
Antibacterial Activity ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Burkholderia Cenocepacia ◽  
Resistant Bacteria ◽  
Oral Antibiotic ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Protection Mechanisms ◽  
Spectrum Activity

ABSTRACTEravacycline (TP-434 or 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline) is a novel fluorocycline that was evaluated for antimicrobial activity against panels of recently isolated aerobic and anaerobic Gram-negative and Gram-positive bacteria. Eravacycline showed potent broad-spectrum activity against 90% of the isolates (MIC90) in each panel at concentrations ranging from ≤0.008 to 2 μg/ml for all species panels except those ofPseudomonas aeruginosaandBurkholderia cenocepacia(MIC90values of 32 μg/ml for both organisms). The antibacterial activity of eravacycline was minimally affected by expression of tetracycline-specific efflux and ribosomal protection mechanisms in clinical isolates. Furthermore, eravacycline was active against multidrug-resistant bacteria, including those expressing extended-spectrum β-lactamases and mechanisms conferring resistance to other classes of antibiotics, including carbapenem resistance. Eravacycline has the potential to be a promising new intravenous (i.v.)/oral antibiotic for the empirical treatment of complicated hospital/health care infections and moderate-to-severe community-acquired infections.

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