In Vitro and In Vivo Efficacy of Catheters Impregnated With Antiseptics or Antibiotics: Evaluation of the Risk of Bacterial Resistance to the Antimicrobials in the Catheters

2001 ◽  
Vol 22 (10) ◽  
pp. 640-646 ◽  
Author(s):  
Lester A. Sampath ◽  
Suhas M. Tambe ◽  
Shanta M. Modak
Keyword(s):  
Bacterial Resistance ◽  
Test Organism ◽  
Similar Efficacy ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
In Vivo Efficacy ◽  
Development Of Resistance ◽  
Zones Of Inhibition

AbstractObjective:To compare the efficacy of a new antiseptic catheter containing silver sulfadiazine and chlorhexidine on the external surface and chlorhexidine in the lumens to an antibiotic catheter impregnated with minocycline and rifampin on its external and luminal surfaces.Design:Experimental trial.Methods:Antimicrobial spectrum of catheters was determined by zones of inhibition. Resistance to luminal colonization was tested in vitro by locking catheter lumens withStaphylococcus epidermidisorStaphylococcus aureusculture after 7 days of perfusion. In vitro development of resistance to the antiseptic or antibiotic combination used in catheters was investigated. In vivo efficacy was tested (rat subcutaneous model) by challenge with sensitive or antibiotic-resistant bacteria.Results:Antiseptic and antibiotic catheters exhibited broad-spectrum action. However, antibiotic catheters were not effective againstCandidaspecies andPseudomonas aeruginosa.Both catheters prevented luminal colonization. Compared to controls, both test catheters resisted colonization when challenged withS aureus7 and 14 days' postimplant (P<.05).Repeated in vitro exposure ofS epidermidisculture to the antibiotic and antiseptic combinations led to small increases in the minimum inhibitory concentration (15 times and 2 times, respectively). Unlike the antibiotic catheter, the in vitro and in vivo activity of the antiseptic catheter was unaffected by the resistance profile of the test organism. Antiseptic catheters were more effective than antibiotic catheters in preventing colonization by rifampin-resistantS epidermidisin vivo (P<.05).Conclusions:Antiseptic and antibiotic catheters exhibit similar efficacy; however, when challenged with a rifampin-resistant strain, the antibiotic catheter appeared to be more susceptible to colonization than the antiseptic device.

scholarly journals Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs

Toxins ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 255 ◽  
Author(s):  
Clara Pérez-Peinado ◽  
Sira Defaus ◽  
David Andreu
Keyword(s):  
Therapeutic Potential ◽  
State Of The Art ◽  
Resistant Bacteria ◽  
Snake Venoms ◽  
Antibiotic Resistant ◽  
Anticancer Peptides ◽  
Therapeutic Development ◽  
Drug Leads

For decades, natural products in general and snake venoms (SV) in particular have been a rich source of bioactive compounds for drug discovery, and they remain a promising substrate for therapeutic development. Currently, a handful of SV-based drugs for diagnosis and treatment of various cardiovascular disorders and blood abnormalities are on the market. Likewise, far more SV compounds and their mimetics are under investigation today for diverse therapeutic applications, including antibiotic-resistant bacteria and cancer. In this review, we analyze the state of the art regarding SV-derived compounds with therapeutic potential, focusing on the development of antimicrobial and anticancer drugs. Specifically, information about SV peptides experimentally validated or predicted to act as antimicrobial and anticancer peptides (AMPs and ACPs, respectively) has been collected and analyzed. Their principal activities both in vitro and in vivo, structures, mechanisms of action, and attempts at sequence optimization are discussed in order to highlight their potential as drug leads.

The Activity of Alkanna Species in vitro Culture and Intact Plant Extracts Against Antibiotic Resistant Bacteria

2019 ◽  
Vol 25 (16) ◽  
pp. 1861-1865 ◽  
Author(s):  
Naira Sahakyan ◽  
Margarit Petrosyan ◽  
Armen Trchounian
Keyword(s):  
Antibiotic Resistance ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Resistant Bacteria ◽  
Plant Origin ◽  
Bacterial Strains ◽  
Biotechnological Production ◽  
Antibiotic Resistant

Overcoming the antibiotic resistance is nowadays a challenge. There is still no clear strategy to combat this problem. Therefore, the urgent need to find new sources of antibacterial agents exists. According to some literature, substances of plant origin are able to overcome bacterial resistance against antibiotics. Alkanna species plants are among the valuable producers of these metabolites. But there is a problem of obtaining the standardized product. So, this review is focused on the discussion of the possibilities of biotechnological production of antimicrobial agents from Alkanna genus species against some microorganisms including antibiotic resistant bacterial strains.

scholarly journals Phage steering of antibiotic-resistance evolution in the bacterial pathogen, Pseudomonas aeruginosa

2020 ◽  
Vol 2020 (1) ◽  
pp. 148-157 ◽  
Author(s):  
James Gurney ◽  
Léa Pradier ◽  
Joanne S Griffin ◽  
Claire Gougat-Barbera ◽  
Benjamin K Chan ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Bacterial Pathogen ◽  
Antibiotic Sensitivity ◽  
Resistant Bacteria ◽  
Phage Resistance ◽  
Antibiotic Resistant ◽  
Trade Off

Abstract Background and objectives Antimicrobial resistance is a growing global concern and has spurred increasing efforts to find alternative therapeutics. Bacteriophage therapy has seen near constant use in Eastern Europe since its discovery over a century ago. One promising approach is to use phages that not only reduce bacterial pathogen loads but also select for phage resistance mechanisms that trade-off with antibiotic resistance—so called ‘phage steering’. Methodology Recent work has shown that the phage OMKO1 can interact with efflux pumps and in so doing select for both phage resistance and antibiotic sensitivity of the pathogenic bacterium Pseudomonas aeruginosa. We tested the robustness of this approach to three different antibiotics in vitro (tetracycline, erythromycin and ciprofloxacin) and one in vivo (erythromycin). Results We show that in vitro OMKO1 can reduce antibiotic resistance of P. aeruginosa (Washington PAO1) even in the presence of antibiotics, an effect still detectable after ca.70 bacterial generations in continuous culture with phage. Our in vivo experiment showed that phage both increased the survival times of wax moth larvae (Galleria mellonella) and increased bacterial sensitivity to erythromycin. This increased antibiotic sensitivity occurred both in lines with and without the antibiotic. Conclusions and implications Our study supports a trade-off between antibiotic resistance and phage sensitivity. This trade-off was maintained over co-evolutionary time scales even under combined phage and antibiotic pressure. Similarly, OMKO1 maintained this trade-off in vivo, again under dual phage/antibiotic pressure. Our findings have implications for the future clinical use of steering in phage therapies. Lay Summary: Given the rise of antibiotic-resistant bacterial infection, new approaches to treatment are urgently needed. Bacteriophages (phages) are bacterial viruses. The use of such viruses to treat infections has been in near-continuous use in several countries since the early 1900s. Recent developments have shown that these viruses are not only effective against routine infections but can also target antibiotic resistant bacteria in a novel, unexpected way. Similar to other lytic phages, these so-called ‘steering phages’ kill the majority of bacteria directly. However, steering phages also leave behind bacterial variants that resist the phages, but are now sensitive to antibiotics. Treatment combinations of these phages and antibiotics can now be used to greater effect than either one independently. We evaluated the impact of steering using phage OMKO1 and a panel of three antibiotics on Pseudomonas aeruginosa, an important pathogen in hospital settings and in people with cystic fibrosis. Our findings indicate that OMKO1, either alone or in combination with antibiotics, maintains antibiotic sensitivity both in vitro and in vivo, giving hope that phage steering will be an effective treatment option against antibiotic-resistant bacteria.

scholarly journals In Vitro Effects of Vitamin and Mineral Supplements on Antibiotic Resistance Profile of Some ESKAPE Pathogens

2021 ◽  
pp. 37-46
Author(s):  
Osmond C. Ekwebelem ◽  
David C. Ekwe ◽  
Emmanuel A. Eze
Keyword(s):  
Vitamin A ◽  
Vitamin C ◽  
Nalidixic Acid ◽  
Resistant Bacteria ◽  
Mineral Supplements ◽  
Zones Of Inhibition ◽  
In Vitro Effects ◽  
Eskape Pathogens

Background: Antibiotics once seen as miracle drugs are now becoming inefficient in treating various bacterial diseases. This study aimed to evaluate the effects of vitamin and mineral supplements on the antibiogram profile of some of the multidrug-resistant bacteria, which the Infectious Diseases Society of America (IDSA) has dubbed ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter spp, Pseudomonas aeruginosa, and Enterobacter spp), the predominant cause of hospital-acquired infections (HAIs). Methodology: The in vitro effects were evaluated using the disc diffusion (Kirby-Bauer) technique. All test bacteria were inoculated onto Mueller-Hinton agar (MHA), supplemented with varying concentrations (2.5, 5, 10, 20, and 25 mg/ml) of vitamin (A, C, or E) and mineral (calcium or iron). Agar without supplements served as the control. The effects of vitamin and mineral supplements were determined by measuring the zones of inhibition to the nearest millimeter as compared to the control. Result: Zones of inhibition for nalidixic acid and ampicillin on P. aeruginosa significantly increased from 5mm to 32mm and 0mm to 18mm respectively, with increasing concentration of vitamin C. Similarly, nalidixic acid and ampicillin zones of inhibition on P. aeruginosa increased from 5mm to 12mm and 0mm to 18mm respectively, with increasing concentration of vitamin A. Vitamin C resulted in significant decreases in all of the zones of inhibition for all antibiotics against E. coli, except reflacine and ciproflox. Varying concentrations of iron led to a sharp decrease in the zones of inhibition for all antibiotics against S. aureus and K. pneumonia. Significant changes were also observed in all zones of inhibitions for all antibiotics studied under varying concentrations of calcium. Conclusion: The effects of vitamin and mineral supplements appear to be important but concentration-dependent. However, there is a need to evaluate the in vivo effects of these vitamin and mineral supplements.

scholarly journals Detection of Quorum-Sensing Molecules for Pathogenic Molecules Using Cell-Based and Cell-Free Biosensors

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 259 ◽  
Author(s):  
Craig Miller ◽  
Jordon Gilmore
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Genetic Material ◽  
Treatment Strategies ◽  
Signaling Molecules ◽  
Resistant Bacteria ◽  
Acute Infections

Since the discovery and subsequent use of penicillin, antibiotics have been used to treat most bacterial infections in the U.S. Over time, the repeated prescription of many antibiotics has given rise to many antibiotic-resistant microbes. A bacterial strain becomes resistant by horizontal gene transfer, where surviving microbes acquire genetic material or DNA fragments from adjacent bacteria that encode for resistance. In order to avoid significant bacterial resistance, novel and target therapeutics are needed. Further advancement of diagnostic technologies could be used to develop novel treatment strategies. The use of biosensors to detect quorum-sensing signaling molecules has the potential to provide timely diagnostic information toward mitigating the multidrug-resistant bacteria epidemic. Resistance and pathogenesis are controlled by quorum-sensing (QS) circuits. QS systems secrete or passively release signaling molecules when the bacterial concentration reaches a certain threshold. Signaling molecules give an early indication of virulence. Detection of these compounds in vitro or in vivo can be used to identify the onset of infection. Whole-cell and cell-free biosensors have been developed to detect quorum-sensing signaling molecules. This review will give an overview of quorum networks in the most common pathogens found in chronic and acute infections. Additionally, the current state of research surrounding the detection of quorum-sensing molecules will be reviewed. Followed by a discussion of future works toward the advancement of technologies to quantify quorum signaling molecules in chronic and acute infections.

scholarly journals Multiple Mechanisms of the Synthesized Antimicrobial Peptide TS against Gram-Negative Bacteria for High Efficacy Antibacterial Action In Vivo

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 60
Author(s):  
Rui Zhang ◽  
Xiaobo Fan ◽  
Xinglu Jiang ◽  
Mingyuan Zou ◽  
Han Xiao ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Divalent Cations ◽  
Resistant Bacteria ◽  
Antibacterial Drug ◽  
Gram Negative Bacteria ◽  
Gram Negative

The emergence of drug-resistant bacteria emphasizes the urgent need for novel antibiotics. The antimicrobial peptide TS shows extensive antibacterial activity in vitro and in vivo, especially in gram-negative bacteria; however, its antibacterial mechanism is unclear. Here, we find that TS without hemolytic activity disrupts the integrity of the outer bacterial cell membrane by displacing divalent cations and competitively binding lipopolysaccharides. In addition, the antimicrobial peptide TS can inhibit and kill E. coli by disintegrating the bacteria from within by interacting with bacterial DNA. Thus, antimicrobial peptide TS’s multiple antibacterial mechanisms may not easily induce bacterial resistance, suggesting use as an antibacterial drug to be for combating bacterial infections in the future.

scholarly journals Effective antibacterial and anti-hemolysin activity of ellipticine hydrochloride against Streptococcus suis in mouse model

2021 ◽  
Author(s):  
Chenchen Wang ◽  
Hao Lu ◽  
Manli Liu ◽  
Gaoyan Wang ◽  
Xiaodan Li ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Hemolytic Activity ◽  
Bacterial Resistance ◽  
Bacterial Load ◽  
Streptococcus Suis ◽  
Resistant Bacteria ◽  
Inappropriate Use ◽  
Important Virulence Factor

Streptococcal toxic shock-like syndrome (STSLS) caused by the epidemic strain of Streptococcus suis leads to severe inflammation and high mortality. The life and health of humans and animals are also threatened by the increasingly severe antimicrobial resistance in Streptococcus suis (S. suis). To discover novel strategies for the treatment of S. suis is an urgent need. Suilysin (SLY) is considered to be an important virulence factor in the pathogenesis of S. suis. In this study, ellipticine hydrochloride (EH) was firstly reported as a compound to antagonize the hemolytic activity of SLY. In vitro, EH was found to effectively inhibit SLY-mediated hemolytic activity. Furthermore, EH and SLY had a strong affinity, thereby directly binding to SLY to interfere the hemolytic activity. Meanwhile, it was worth noting that EH was also found to have a significant antibacterial activity. In vivo, compared with traditional ampicillin, EH could not only significantly improve the survival rate of mice infected with S. suis 2 strain Sc19, but also relieve lung pathological damage. Furthermore, EH effectively decreased the levels of inflammatory cytokines (IL-6, TNF-α) and blood biochemistry (ALT, AST, CK) in Sc19-infected mice. Additionally, EH markedly reduced the bacterial load of tissues in Sc19-infected mice. In conclusion, our findings suggest that EH can be a potential compound for treating S. suis infection in view of its antibacterial and anti-hemolysin activity. Importance In recent years, the inappropriate use of antibiotics unnecessarily causes the continuous emergence of resistant bacteria. The antimicrobial resistance of Streptococcus suis (S. suis) becomes also an increasingly serious problem. Targeting virulence can reduce the selective pressure of bacteria on antibiotics, thereby alleviating the development of bacterial resistance to a certain extent. Meanwhile, the excessive inflammatory response caused by S. suis infection is considered the primary cause of acute death. Here, we found that ellipticine hydrochloride (EH) exhibited effective antibacterial and anti-hemolysin activity against S. suis in vitro. In vivo, compared with ampicillin, EH had a significant protective effect on S. suis 2 strain Sc19-infected mice. Our results indicated that EH with dual antibacterial and antivirulence effects will contribute to medicating S. suis infections and alleviating the antimicrobial resistance of S. suis to a certain extent. More importantly, EH may develop into a promising drug for the treatment of acute death caused by excessive inflammation.

scholarly journals Fosfomycin

2016 ◽  
Vol 29 (2) ◽  
pp. 321-347 ◽  
Author(s):  
Matthew E. Falagas ◽  
Evridiki K. Vouloumanou ◽  
George Samonis ◽  
Konstantinos Z. Vardakas
Keyword(s):  
Bacterial Infections ◽  
Clinical Effectiveness ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Development Of Resistance ◽  
Extensively Drug Resistant ◽  
New Antibiotics

SUMMARYThe treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, thein vitroactivity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.

Use of Germicides in the Home and the Healthcare Setting Is There a Relationship Between Germicide Use and Antibiotic Resistance?

2006 ◽  
Vol 27 (10) ◽  
pp. 1107-1119 ◽  
Author(s):  
David J. Weber ◽  
William A. Rutala
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Resistance ◽  
Scientific Literature ◽  
Test Organism ◽  
Healthcare Setting ◽  
Serum Levels ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Altered Level ◽  
Healthcare Facilities

Background.The spread of antibiotic-resistant pathogens represents an increasing threat in healthcare facilities. Concern has been expressed that the use of surface disinfectants and antiseptics may select for antibiotic-resistant pathogens.Objective.To review the scientific literature on whether there is a link between use of germicides (ie, disinfectants and antiseptics) and bacterial resistance to antibiotics. In addition, we will review whether antibiotic-resistant bacteria exhibit altered susceptibility to germicides that are recommended for use as disinfectants or antiseptics.Design.A review of the appropriate scientific literature.Results.In the laboratory, it has been possible to develop bacterial mutants with reduced susceptibility to disinfectants and antiseptics that also demonstrate decreased susceptibility to antibiotics. However, the antibiotic resistance described was not clinically relevant because the test organism was rarely a human pathogen, the altered level of antimicrobial susceptibility was within achievable serum levels for the antibiotic, or the antibiotic tested was not clinically used to treat the study pathogen. Similarly, wild-type strains with reduced susceptibility to disinfectants (principally, quaternary ammonium compounds) and antiseptics (principally, triclosan) have been reported. However, because the concentration of disinfectants used in the healthcare setting greatly exceeds the concentration required to kill strains with reduced susceptibility to disinfectants, the clinical relevance of these observations is questionable.Conclusion.To date, there is no evidence that using recommended antiseptics or disinfectants selects for antibiotic-resistant organisms in nature. Disinfectants and antiseptics should be used when there are scientific studies demonstrating benefit or when there is a strong theoretical rationale for using germicides.

scholarly journals Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo, and Clinical Application

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1497
Author(s):  
Katarzyna M. Danis-Wlodarczyk ◽  
Daniel J. Wozniak ◽  
Stephen T. Abedon
Keyword(s):  
Bacterial Infections ◽  
Bacterial Resistance ◽  
High Efficiency ◽  
Cross Resistance ◽  
Resistant Bacteria ◽  
Drug Classes ◽  
Peptidoglycan Hydrolases ◽  
Bacterial Peptidoglycan

Over the past few decades, we have witnessed a surge around the world in the emergence of antibiotic-resistant bacteria. This global health threat arose mainly due to the overuse and misuse of antibiotics as well as a relative lack of new drug classes in development pipelines. Innovative antibacterial therapeutics and strategies are, therefore, in grave need. For the last twenty years, antimicrobial enzymes encoded by bacteriophages, viruses that can lyse and kill bacteria, have gained tremendous interest. There are two classes of these phage-derived enzymes, referred to also as enzybiotics: peptidoglycan hydrolases (lysins), which degrade the bacterial peptidoglycan layer, and polysaccharide depolymerases, which target extracellular or surface polysaccharides, i.e., bacterial capsules, slime layers, biofilm matrix, or lipopolysaccharides. Their features include distinctive modes of action, high efficiency, pathogen specificity, diversity in structure and activity, low possibility of bacterial resistance development, and no observed cross-resistance with currently used antibiotics. Additionally, and unlike antibiotics, enzybiotics can target metabolically inactive persister cells. These phage-derived enzymes have been tested in various animal models to combat both Gram-positive and Gram-negative bacteria, and in recent years peptidoglycan hydrolases have entered clinical trials. Here, we review the testing and clinical use of these enzymes.

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