An Assay of Staphylococcus Epidermidis Biofilm Responses to Therapeutic Agents

1993 ◽  
Vol 16 (11) ◽  
pp. 777-787 ◽  
Author(s):  
G.K. Richards ◽  
R.F. Gagnon
Keyword(s):  
Staphylococcus Epidermidis ◽  
Antimicrobial Agents ◽  
Clinical Laboratory ◽  
Relative Rate ◽  
Fluid Phase ◽  
Therapeutic Agents ◽  
Triphenyltetrazolium Chloride ◽  
Implant Surface ◽  
Wide Range ◽  
The Impact

Implant-associated infections tend to become persistent, resisting host defences and antibiotic therapy. Routine clinical laboratory testing of bacterial isolates in the fluid phase for antibiotic susceptibility may not be predictive of therapeutic outcomes and therefore a number of antibiotic regimes have been formulated empirically. The resistance of implant-associated infections has been ascribed to the production by bacteria, when adherent to the implant surface, of a shielding matrix of polymerized carbohydrates protecting the enclosed bacteria from immune defences and antibiotics. This complex of surface, bacteria and matrix is termed a biofilm. We describe a technique to evaluate the efficacy of antimicrobial agents directed against biofilm-forming strains of Staphylococcus epidermidis (a major cause of implant infections) utilizing standardized biofilm preparations formed on glass. The impact of the antimicrobial agents was assessed quantally using the end-point of permanent cessation of metabolic activity (cell death) of the entire biofilm determined by the loss of ability to reduce 2,3,5-triphenyltetrazolium chloride to a visible red intracellular precipitate of formazan. The relative rate of action of differing antimicrobial agents could be determined by the minimum period of exposure of the biofilm to the agents that is required to bring about sterilization, the clinically relevant marker. A wide range of antimicrobial substances could be evaluated, including chemical disinfectants, immunoreactive substances, antibiotics; singly and in combination; and the modifying effects of interaction with non-antibacterial therapeutic agents and other environmental factors. The technique is simple, inexpensive, reproducible and readily adaptable to the clinical situation where evaluation of therapeutic regimes for individual cases of prosthetic device-associated infection is required routinely with despatch and ease of interpretation.

scholarly journals In VivoEfficacy of Anuran Trypsin Inhibitory Peptides against Staphylococcal Skin Infection and the Impact of Peptide Cyclization

2015 ◽  
Vol 59 (4) ◽  
pp. 2113-2121 ◽  
Author(s):  
U. Malik ◽  
O. N. Silva ◽  
I. C. M. Fensterseifer ◽  
L. Y. Chan ◽  
R. J. Clark ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Cyclic Peptide ◽  
Sequence Similarity ◽  
Infection Model ◽  
Content Type ◽  
Wide Range ◽  
Inhibitory Activities ◽  
The Impact

ABSTRACTStaphylococcus aureusis a virulent pathogen that is responsible for a wide range of superficial and invasive infections. Its resistance to existing antimicrobial drugs is a global problem, and the development of novel antimicrobial agents is crucial. Antimicrobial peptides from natural resources offer potential as new treatments against staphylococcal infections. In the current study, we have examined the antimicrobial properties of peptides isolated from anuran skin secretions and cyclized synthetic analogues of these peptides. The structures of the peptides were elucidated by nuclear magnetic resonance (NMR) spectroscopy, revealing high structural and sequence similarity with each other and with sunflower trypsin inhibitor 1 (SFTI-1). SFTI-1 is an ultrastable cyclic peptide isolated from sunflower seeds that has subnanomolar trypsin inhibitory activity, and this scaffold offers pharmaceutically relevant characteristics. The five anuran peptides were nonhemolytic and noncytotoxic and had trypsin inhibitory activities similar to that of SFTI-1. They demonstrated weakin vitroinhibitory activities againstS. aureus, but several had strong antibacterial activities againstS. aureusin anin vivomurine wound infection model. pYR, an immunomodulatory peptide fromRana sevosa, was the most potent, with complete bacterial clearance at 3 mg · kg−1. Cyclization of the peptides improved their stability but was associated with a concomitant decrease in antimicrobial activity. In summary, these anuran peptides are promising as novel therapeutic agents for treating infections from a clinically resistant pathogen.

scholarly journals Apotransferrin in Combination with Ciprofloxacin Slows Bacterial Replication, Prevents Resistance Amplification, and Increases Antimicrobial Regimen Effect

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Paul G. Ambrose ◽  
Brian D. VanScoy ◽  
Brian M. Luna ◽  
Jun Yan ◽  
Amber Ulhaq ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Bactericidal Effect ◽  
Bacterial Density ◽  
Infection Model ◽  
Time Curve ◽  
Content Type ◽  
Wide Range ◽  
Bacterial Replication ◽  
The Impact

ABSTRACT There has been renewed interest in combining traditional small-molecule antimicrobial agents with nontraditional therapies to potentiate antimicrobial effects. Apotransferrin, which decreases iron availability to microbes, is one such approach. We conducted a 48-h one-compartment in vitro infection model to explore the impact of apotransferrin on the bactericidal activity of ciprofloxacin. The challenge panel included four Klebsiella pneumoniae isolates with ciprofloxacin MIC values ranging from 0.08 to 32 mg/liter. Each challenge isolate was subjected to an ineffective ciprofloxacin monotherapy exposure (free-drug area under the concentration-time curve over 24 h divided by the MIC [AUC/MIC ratio] ranging from 0.19 to 96.6) with and without apotransferrin. As expected, the no-treatment and apotransferrin control arms showed unaltered prototypical logarithmic bacterial growth. We identified relationships between exposure and change in bacterial density for ciprofloxacin alone (R2 = 0.64) and ciprofloxacin in combination with apotransferrin (R2 = 0.84). Addition of apotransferrin to ciprofloxacin enabled a remarkable reduction in bacterial density across a wide range of ciprofloxacin exposures. For instance, at a ciprofloxacin AUC/MIC ratio of 20, ciprofloxacin monotherapy resulted in nearly 2 log10 CFU increase in bacterial density, while the combination of apotransferrin and ciprofloxacin resulted in 2 log10 CFU reduction in bacterial density. Furthermore, addition of apotransferrin significantly reduced the emergence of ciprofloxacin-resistant subpopulations compared to monotherapy. These data demonstrate that decreasing the rate of bacterial replication with apotransferrin in combination with antimicrobial therapy represents an opportunity to increase the magnitude of the bactericidal effect and to suppress the growth rate of drug-resistant subpopulations.

scholarly journals Establishment and Characterization of Bacterial Infection of Breast Implants in a Murine Model

2019 ◽  
Vol 40 (5) ◽  
pp. 516-528 ◽  
Author(s):  
Jennifer N Walker ◽  
Louis H Poppler ◽  
Chloe L Pinkner ◽  
Scott J Hultgren ◽  
Terence M Myckatyn
Keyword(s):  
Staphylococcus Epidermidis ◽  
Breast Implant ◽  
Breast Implants ◽  
Surface Characteristics ◽  
Implant Surface ◽  
Colony Forming Units ◽  
Common Causes ◽  
The Impact ◽  
Post Implantation

Abstract Background Staphylococcus epidermidis and Pseudomonas aeruginosa are the most common causes of Gram-positive and Gram-negative breast implant–associated infection. Little is known about how these bacteria infect breast implants as a function of implant surface characteristics and timing of infection. Objectives The aim of this work was to establish a mouse model for studying the impact of various conditions on breast implant infection. Methods Ninety-one mice were implanted with 273 breast implant shells and infected with S. epidermidis or P. aeruginosa. Smooth, microtextured, and macrotextured breast implant shells were implanted in each mouse. Bacterial inoculation occurred during implantation or 1 day later. Implants were retrieved 1 or 7 days later. Explanted breast implant shells were sonicated, cultured, and colony-forming units determined or analyzed with scanning electron microscopy. Results P. aeruginosa could be detected on all device surfaces at 1- and 7- days post infection (dpi), when mice were implanted and infected concurrently or when they were infected 1- day after implantation. However, P. aeruginosa infection was more robust on implant shells retrieved at 7 dpi and particularly on the macrotextured devices that were infected 1 day post implantation. S. epidermidis was mostly cleared from implants when mice were infected and implanted concurrently. Other the other hand, S. epidermidis could be detected on all device surfaces at 1 dpi and 2 days post implantation. However, S. epidermdis infection was suppressed by 7 dpi and 8 days post implantation. Conclusions S. epidermidis required higher inoculating doses to cause infection and was cleared within 7 days. P. aeruginosa infected at lower inoculating doses, with robust biofilms noted 7 days later.

scholarly journals Resolved and unresolved issues of cerebrovascular disease in diabetes mellitus

2021 ◽  
Vol 15 (3) ◽  
pp. 5-14
Author(s):  
Мarine М. Tanashyan ◽  
Kseniya V. Antonova ◽  
Оlga V. Lagoda ◽  
Аlla А. Shabalina
Keyword(s):  
Diabetes Mellitus ◽  
Cerebrovascular Disease ◽  
Vascular Tissue ◽  
Clinical Laboratory ◽  
Large Body ◽  
Blood Chemistry ◽  
Control Group ◽  
Functional Impairments ◽  
Wide Range ◽  
The Impact

Significant contribution of type 2 diabetes mellitus (T2DM) to the development and progression of cerebrovascular disease (CVD) has been confirmed over the past few decades. The aim of this article is to present the results of many years of research, summarizing generally resolved problems in CVD and T2DM comorbidity, as well as raising several issues that still need to be clarified. Materials and methods. The assessment results of 824 patients with CVD were selected from a large body of data for inclusion in the analysis. Ischaemic stroke was analysed in 250 patients: 128 patients with T2DM (aged 63 [54; 74] years) and 122 patients without T2DM (62 [52; 71] years). The group with chronic CVD consisted of 574 people: 300 patients with T2DM (62 [56; 69] years) and 274 patients without T2DM (63 [57; 68] years). The results of surgery for carotid artery stenosis were evaluated in 170 patients, including 72 patients with T2DM. The control group consisted of 86 persons without CVD (60 [54; 63] years). A wide range of clinical, laboratory and imaging assessments included physical and neurological examinations, neuropsychological tests, blood chemistry, haemorheological and haemostasis tests, as well as neuroimaging studies. Results. T2DM has a significant effect on neurological, neuropsychological, cognitive and functional impairments, as well as on the outcome of acute and chronic CVD, progression of intracranial atherosclerotic lesions, and changes in cerebral and vascular tissue. The impact of the quality of glycaemic control and duration of chronic hyperglycaemia on neurocognitive and structural brain changes has not been completely determined yet. The role of non-glycaemic changes, including influence of several mediators on the vascular and neurodegenerative mechanisms of cerebral tissue damage, warrants further study. Conclusion. The obtained results identify a wide range of unanswered questions and emphasize the need for both possible changes to several clinical algorithms and for ongoing in-depth studies of CVD associated with T2DM.

scholarly journals Choise of local antibacterial medications for prevention of sternal infection

2017 ◽  
Vol 8 (2) ◽  
pp. 89-93 ◽  
Author(s):  
Nazim N Shihverdiev ◽  
Gennadiy G Khubulava ◽  
Sergey P Marchenko ◽  
Vitaliy V Suvorov ◽  
Vladimir V Zaitsev ◽  
...  
Keyword(s):  
Wound Infection ◽  
Staphylococcus Epidermidis ◽  
Antimicrobial Agents ◽  
Local Antibiotics ◽  
Sternal Infection ◽  
Abdominal Organs ◽  
Time Period ◽  
Applied Dose ◽  
Duration Of Hospitalization ◽  
The Impact

Infection of wounds in surgery is one of the most frequent complications in the postoperative period. The development of this complication increases the duration of hospitalization, resulting in higher treatment costs, as well as the impact to the level of hospital mortality. There are many methods are exist to avoid this complication, which are allow to decontamination of pathogenic and conditionally pathogenic microorganisms including applying antimicrobial agents prior to surgery. One such method is intravenous antibiotic shortly before surgery. But there is evidence in the literature of successful local antibiotics in neurosurgery, traumatology and orthopedics, operations on the thorax and abdominal organs, including for prevention of sternal infection. For this purpose most often used vancomycin and gentamicin. This is often a causative agent of wound infection, which is a gram-positive flora: Staphylococcus aureus and Staphylococcus epidermidis. To increase the effectiveness of preventive measures to reduce the incidence of sternal infection intraoperatively topically applied antibiotics in various forms when closing the wound. For parenteral administration of antibiotics effective therapeutic dose is often not achieved, because it depend on the time period since the introduction of the substance until the start of the operation [3]. Local application of antibiotics to a reduction of frequency wound infection, as concentration of a substance is directly dependent on the applied dose.

Molecular Biology and the Clinician

1982 ◽  
Vol 27 (1) ◽  
pp. 20-28
Author(s):  
C. J. Bostock ◽  
N. G. L. Harding
Keyword(s):  
Molecular Biology ◽  
Information Flow ◽  
Medical Training ◽  
Therapeutic Agents ◽  
Current Medical ◽  
Molecular Probe ◽  
Medical Practitioners ◽  
Wide Range ◽  
Laboratory Workers ◽  
The Impact

Molecular biology has uncovered informational processes which broadly apply in medicine. The points of attack range from diagnosis at the most fundamental levels of information flow to the production of therapeutic agents. This is promoting movement from serendipitous strategies of advance to those of predictive rational clinical design. Specific examples show how three principal types of molecular probe are benefitting a wide range of clinical disciplines and thereby blurring interdisciplinary boundaries. There are signs that current medical training is not making the best use of contemporary molecular biology. The identification of areas in which molecular biology can be usefully applied to medicine requires medical practitioners to be aware of its diagnostic and prognostic potential. Equally, advances are delayed by gaps between laboratory workers and their clinical colleagues. The dilemma is that by creating a specialist discipline of clinical molecular biology we risk it becoming isolated and delay the impact of molecular biology in medicine as a whole. An alternative is to find a means for raising molecular consciousness throughout all disciplines in medicine.

A Mouse Model of Implant-Associated Infection

1993 ◽  
Vol 16 (11) ◽  
pp. 789-798 ◽  
Author(s):  
R.F. Gagnon ◽  
G.K. Richards
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Biofilm ◽  
Laboratory Model ◽  
Host Defenses ◽  
Implant Surface ◽  
Therapeutic Modalities ◽  
Selective Protection ◽  
Synthetic Materials ◽  
The Matrix ◽  
The Impact

Infections of implanted devices are of increasing frequency and importance, representing a significant limitation of many therapeutic modalities. There are puzzling features of implant-associated infection including the changes in microbial flora, the tendency to chronicity and impaired responses to conservative modes of treatment. The concept of the bacterial biofilm as a shielding mechanism generated by bacteria adherent to artificial surfaces has recently been proposed as an explanation for these features. The biofilm is a term applied to a complex comprising the implant surface, adherent bacteria and a specialized matrix enclosing the bacteria. The matrix of the biofilm is an electrostatically charged glue-like extracellular polymer derived by bacterial enzymes acting on tissue carbohydrates, formed by bacteria when adherent to surfaces. This matrix binds the bacteria to the surface providing a sequestration affording selective protection against harmful elements of the environment, especially mechanisms of host defenses and antimicrobial agents. These biological systems are complex to study because of the dynamic interaction of the microbial variables, host defenses, properties of synthetic materials and the biofilm matrix itself. There is a need for a laboratory model in which the variables can be controlled permitting the researcher to examine the outcomes of modifying one variable at a time in a planned and orderly manner. The practical way to attain this end is the conduct of studies in a stable reproducible animal model of localized biofilm-implant infection. Staphylococcus epidermidis is a representative of the class of microorganisms predominant in implant-associated infection. This paper describes the development of a model utilizing an implant-S. epidermidis-biofilm infection localized to the peritoneal cavity of the mouse. The natural history of the infection has been well documented and is stable in all respects for periods exceeding 3 months. This chronicity is especially advantageous in analyzing the impact of long-term therapeutic modalities and necessary periods of recovery and assessment. A representative example of an experimental use of this model to determine the relative efficacy of antibiotic therapeutic regimes is described, demonstrating its scope and efficacy.

scholarly journals COVID-19 pandemic and antimicrobial resistance in developing countries

Discoveries ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. e127
Author(s):  
Abdul Rehman Arshad ◽  
◽  
Farhat Ijaz ◽  
Mishal Shan Siddiqui ◽  
Saad Khalid ◽  
...  
Keyword(s):  
Developing Countries ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Developing World ◽  
Infection Prevention And Control ◽  
Middle Income ◽  
Middle Income Countries ◽  
Ability To Act ◽  
Wide Range ◽  
The Impact

A wide range of antimicrobial agents were touted as potential remedies during the COVID-19 pandemic. While both developed and developing countries have recorded an increase in the use of antimicrobial drugs, use and misuse have occurred to a far greater degree in developing countries. This can have deleterious consequences on antimicrobial resistance, especially when various developing countries have already reported the emergence of various drug-resistant organisms even before the pandemic. Telemedicine services, societal and cultural pressures, and bacterial co-infections can predispose to overwhelming antimicrobial prescriptions. The emergence of new multidrug resistance species is a major concern for the developing world especially since health services are already overburdened and lack the diagnostic capabilities and basic amenities for infection prevention and control. This can lead to outbreaks and the rampant spread of such microorganisms. Improper waste management and disposal from hospitals and communities establish freshwater runoffs as hubs of various microorganisms that can predispose to the rise of multidrug-resistant species. Microplastics' ability to act as vectors for antibioticresistant organisms is also particularly concerning for lower-middle-income countries. In this review, we aim to study the impact of antimicrobial use during the COVID-19 pandemic and antimicrobial resistance in lower middle-income countries, by understanding various determinants of resistance unique to the developing world and exploring solutions to combat the problem.

THE IMPACT OF LEADERSHIP PRACTICES TO TEAM MEMBERS’ SATISFACTION

2009 ◽  
Vol 8 (1) ◽  
Author(s):  
Chalimah .
Keyword(s):  
Conflict Resolution ◽  
Leadership Practices ◽  
Hotel Industry ◽  
Leader Behavior ◽  
Team Leader ◽  
Shop Floor ◽  
Team Members ◽  
Top Executives ◽  
Wide Range ◽  
The Impact

eamwork is becoming increasingly important to wide range of operations. It applies to all levels of the company. It is just as important for top executives as it is to middle management, supervisors and shop floor workers. Poor teamwork at any level or between levels can seriously damage organizational effectiveness. The focus of this paper was therefore to examine whether leadership practices consist of team leader behavior, conflict resolution style and openness in communication significantly influenced the team member’s satisfaction in hotel industry. Result indicates that team leader behavior and the conflict resolution style significantly influenced team member satisfaction. It was surprising that openness in communication did not affect significantly to the team members’ satisfaction.

Discovery of Antibacterial Agents Inhibiting the Energy-Coupling Factor (ECF) Transporters by Structure-Based Virtual Screening

2020 ◽  
Author(s):  
Eleonora Diamanti ◽  
Inda Setyawati ◽  
Spyridon Bousis ◽  
leticia mojas ◽  
lotteke Swier ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Energy Coupling ◽  
Coupling Factor ◽  
Design Synthesis ◽  
Screening Design ◽  
Starting Point ◽  
Wide Range ◽  
Vitamin Uptake

Here, we report on the virtual screening, design, synthesis and structure–activity relationships (SARs) of the first class of selective, antibacterial agents against the energy-coupling factor (ECF) transporters. The ECF transporters are a family of transmembrane proteins involved in the uptake of vitamins in a wide range of bacteria. Inhibition of the activity of these proteins could reduce the viability of pathogens that depend on vitamin uptake. Because of their central role in the metabolism of bacteria and their absence in humans, ECF transporters are novel potential antimicrobial targets to tackle infection. The hit compound’s metabolic and plasma stability, the potency (20, MIC Streptococcus pneumoniae = 2 µg/mL), the absence of cytotoxicity and a lack of resistance development under the conditions tested here suggest that this scaffold may represent a promising starting point for the development of novel antimicrobial agents with an unprecedented mechanism of action.<br>

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