IN VIVO STUDIES ON ANTISTAPHYLOCOCCAL PENICILLINASE SERUM

1964 ◽  
Vol 10 (4) ◽  
pp. 507-512
Author(s):  
M. Goldner ◽  
R. J. Wilson
Keyword(s):  
Staphylococcus Aureus ◽  
Combined Treatment ◽  
Rabbit Antiserum ◽  
Staphylococcal Infection ◽  
In Vivo Studies ◽  
Laboratory Animals ◽  
Single Strain ◽  
Lethal Doses ◽  
Observation Period

Several workers have shown that laboratory animals are protected from penicillin-resistant Staphylococcus aureus infections by antiserum to Bacillus cereus penicillinase in conjunction with benzylpenicillin. This paper shows that antiserum to staphylococcal penicillinase has the same effect. Concentrated penicillinase from a single strain of staphylococcus was used to prepare a rabbit antiserum. Groups of rabbits were injected intravenously with lethal doses of the same strain of staphylococcus. They were either given no treatment or were treated with penicillin only, antiserum only, or combined penicillin and antiserum. Antiserum was given in a single dose or in multiple doses. Throughout the 3-week observation period, the mortality in the group of rabbits receiving combined treatment was significantly less than in any other group. It was concluded that it might be possible to use antistaphylococcal penicillinase serum in the treatment of penicillin-resistant staphylococcal infection.

scholarly journals Evaluation of a bone filler scaffold for local antibiotic delivery to prevent Staphylococcus aureus infection in a contaminated bone defect

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karen E. Beenken ◽  
Mara J. Campbell ◽  
Aura M. Ramirez ◽  
Karrar Alghazali ◽  
Christopher M. Walker ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Defect ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Bovine Bone ◽  
Bone Filler ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Antibiotic Delivery

AbstractWe previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The current study was aimed at evaluating the use of this scaffold as a means of local antibiotic delivery to prevent infection in a bone defect contaminated with Staphylococcus aureus. We evaluated two scaffold formulations with the same component ratios but differing overall porosity and surface area. Studies with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity correlated with increased uptake and prolonged antibiotic release. We also demonstrate that vancomycin can be passively loaded into either formulation in sufficient concentration to prevent infection in a rabbit model of a contaminated segmental bone defect. Moreover, even in those few cases in which complete eradication was not achieved, the number of viable bacteria in the bone was significantly reduced by treatment and there was no radiographic evidence of osteomyelitis. Radiographs and microcomputed tomography (µCT) analysis from the in vivo studies also suggested that the addition of vancomycin did not have any significant effect on the scaffold itself. These results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery to prevent infection in contaminated bone defects.

Prevention of Panton-Valentine Toxin-Mediated Leucocyte Destruction Depending on the Ultra-Diluted Staphylococcinum Potency Gradient

2020 ◽  
Vol 33 (02) ◽  
pp. 099-103
Author(s):  
Pritam Goswami ◽  
Sayak Ghosh ◽  
Sk Swaif Ali ◽  
Anamika Basu ◽  
Joydeep Khanra ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Ecological Niche ◽  
Staphylococcal Infection ◽  
Buffy Coat ◽  
Preventive Action ◽  
Phagocytic Cells ◽  
Mortality And Morbidity ◽  
Aureus Infection ◽  
The Mean

Abstract Background Panton-Valentine toxin (PVT) is an important pathological marker of staphylococcal infection mediated by functional as well as morphological damage of the phagocytic cells. Human body being an ecological niche for the bacteria shows higher affinity toward staphylococcal infection. A steady escalation in mortality and morbidity associated with antibiotic resistance in gram-positive infections is an emerging threat all over the globe; thus, it is important to find out an alternative strategy that can diminish the virulence and pathogenicity of the bacteria. Staphylococcin is a colicin-type chemical secreted by Staphylococcus aureus helps to prevent growth of organisms other than its progenitor. In this study, we evaluated the efficacy of homoeopathic medicine Staphylococcinum against staphylococcal PVT at different potencies (6CH, 12CH, 30CH and 200CH). Materials and Methods Different potencies of Staphylococcinum were administered in a leucocyte buffy coat preparation infected with staphylococcal suspension (0.5 McFarland's standard) along with control with alcohol. They were kept in incubator for 2 hours and then centrifuged at 1200 rpm for 5 minutes. Smears prepared on slides with centrifuged deposits stained by Preston and Morrell's modified Gram's method of staining and evaluated under the microscope. Results It was observed that there was extensive destruction of leukocytes in control and 6CH potency, while the degree of destruction decreased markedly from 12CH to 200CH. At 200CH potency, leukocytes were almost normal, which clearly indicate the preventive action of Staphylococcinum against PVT. The mean percentages of intact leucocytes were 0.73, 0.93, 10.00, 27.67 and 65.00 in control, 6CH, 12CH, 30CH and 200CH potencies, respectively. Conclusion The finding may help in the use of this medicine in moribund patients in cases of disseminated S. aureus infection as there is no known side effect of the medicine. However, in vivo study is necessary before such use in those cases.

Cefotaxime and amikacin: results of in vitro and in vivo studies against Gram-negative bacteria and Staphylococcus aureus

1980 ◽  
Vol 6 (suppl A) ◽  
pp. 55-61 ◽  
Author(s):  
J. Klastersky ◽  
H. Gaya ◽  
S. H. Zinner ◽  
C. Bernard ◽  
J-C. Ryff ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
In Vivo Studies ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
And Staphylococcus Aureus

scholarly journals 204. Antagonistic Effect of Colistin on Vancomycin Activity Against Methicillin-Resistant Staphylococcus aureus in in vitro and in vivo Studies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S120-S121
Author(s):  
Sungim Choi ◽  
Taeeun Kim ◽  
Seongman Bae ◽  
Eunmi Yang ◽  
Su-Jin Park ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Antagonistic Effect ◽  
In Vivo Studies ◽  
Infection Model ◽  
Methicillin Resistant ◽  
Checkerboard Assay ◽  
Mrsa Strains ◽  
Time Kill

Abstract Background There is a concern that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concomitant colistin administered against multidrug-resistant gram-negative pathogen. Methods We confirmed the molecular genotypes of MRSA blood isolates collected in a tertiary hospital in Seoul, South Korea, and selected representative strains from the community-associated MRSA strains (CA-MRSA, ST72-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA, ST5-SCCmec II). USA CA-MRSA (USA300, ST8-SCCmec IV) and MRSA standard strain (ATCC 43300, ST39-SCCmec II) were also used for comparison with representative. We identified changes of the vancomycin MIC in MRSA by colistin exposure in a checkerboard assay and performed a time-kill assay to evaluate the combined effect of vancomycin and colistin on MRSA. In addition, we administered vancomycin, colistin, and combination of two antibiotics, respectively, to a neutropenic murine thigh infection model to evaluate the in vivo antagonistic effect of colistin on vancomycin treatment. Results In the checkerboard assay, all 4 MRSA strains showed a tendency for the vancomycin MIC to increase along with increasing concentrations of colistin. However, the time-kill assay showed the antagonism of vancomycin and colistin only against ST5-MRSA, when vancomycin concentration was 2 times the vancomycin MIC (Figure 1). No antagonism was observed in other strains. In the murine thigh infection model of ST5-MRSA, vancomycin monotherapy showed a significant log CFU reduction compared with a combination of vancomycin and colistin at 24 hours, demonstrating the antagonistic effect of vancomycin and colistin combination (Figure 2). Conclusion This study showed that exposure of colistin to certain MRSA strains may reduce the susceptibility to vancomycin. Combination therapy with vancomycin and colistin for MDR pathogens infections might result in treatment failure for concurrent MRSA infection. Disclosures All authors: No reported disclosures.

scholarly journals The purine biosynthesis regulator PurR moonlights as a virulence regulator in Staphylococcus aureus

2019 ◽  
Vol 116 (27) ◽  
pp. 13563-13572 ◽  
Author(s):  
William E. Sause ◽  
Divya Balasubramanian ◽  
Irnov Irnov ◽  
Richard Copin ◽  
Mitchell J. Sullivan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Ex Vivo ◽  
Purine Biosynthesis ◽  
In Vivo Studies ◽  
Human Neutrophils ◽  
Infection Models ◽  
Genes Encoding ◽  
Virulence Regulator

The pathogen Staphylococcus aureus colonizes and infects a variety of different sites within the human body. To adapt to these different environments, S. aureus relies on a complex and finely tuned regulatory network. While some of these networks have been well-elucidated, the functions of more than 50% of the transcriptional regulators in S. aureus remain unexplored. Here, we assess the contribution of the LacI family of metabolic regulators to staphylococcal virulence. We found that inactivating the purine biosynthesis regulator purR resulted in a strain that was acutely virulent in bloodstream infection models in mice and in ex vivo models using primary human neutrophils. Remarkably, these enhanced pathogenic traits are independent of purine biosynthesis, as the purR mutant was still highly virulent in the presence of mutations that disrupt PurR’s canonical role. Through the use of transcriptomics coupled with proteomics, we revealed that a number of virulence factors are differentially regulated in the absence of purR. Indeed, we demonstrate that PurR directly binds to the promoters of genes encoding virulence factors and to master regulators of virulence. These results guided us into further ex vivo and in vivo studies, where we discovered that S. aureus toxins drive the death of human phagocytes and mice, whereas the surface adhesin FnbA contributes to the increased bacterial burden observed in the purR mutant. Thus, S. aureus repurposes a metabolic regulator to directly control the expression of virulence factors, and by doing so, tempers its pathogenesis.

Modelling Staphylococcus aureus biofilms on infected chronic wounds

2020 ◽  
Author(s):  
Yanyan Cheng ◽  
Paul De Bank ◽  
Albert Bolhuis
Keyword(s):  
Staphylococcus Aureus ◽  
Dynamic Model ◽  
Chronic Wounds ◽  
Ex Vivo ◽  
Venous Pressure ◽  
Viable Count ◽  
Major Health Problem ◽  
Single Strain

<p>Chronic wounds, for instance venous, pressure, arterial and diabetic ulcers, are a major health problem throughout the world. Compared with normal wounds, those that take more than four weeks to heal are defined as chronic. Interestingly, the numbers of patients suffering from chronic wounds and the cost for treatment have been increasing during the past two decades. There is increasing evidence that suggests that bacteria infect those chronic wounds and there exist as a biofilm, which affects wound healing and success of treatment. To study biofilms in infected wounds, both in vitro and in vivo biofilm models are important to be developed.</p> <p> </p> <p>In this project, a dynamic ex vivo chronic wound biofilm model for Staphylococcus aureus using a 3D printed chamber and porcine skin was developed. This dynamic model then used to determine antibiotic treatment by using poly(ε‐caprolactone) (PCL) electrospun fibrous mats containing different antibiotics, e.g. tetracycline, gentamicin and fusidic acid. Furthermore, electrospun PCL/silk fibroin scaffolds were also used as carrier of gentamicin. The killing effect of mature S. aureus MRSA 252 growing in the wound model was tested by both viable count and qPCR.</p> <p> </p> <p>The results indicated that this newly designed dynamic model was successful in mimicking single-strain biofilm on infected chronic wounds. Compared with traditional biofilm assays, the flow system generates an air-liquid-solid interface, which more closely approaches to real conditions. Furthermore, results from using electrospun fibrous scaffolds provided strong evidence for their potential in clinical applications to treat infected skin.</p> <p> </p>

Zearalenone-induced changes in biochemical parameters, oxidative stress and apoptosis in cardiac tissue

2015 ◽  
Vol 35 (6) ◽  
pp. 623-634 ◽  
Author(s):  
I Ben Salem ◽  
M Boussabbeh ◽  
F Neffati ◽  
MF Najjar ◽  
S Abid-Essefi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Tissue ◽  
Fusarium Species ◽  
Combined Treatment ◽  
In Vivo Studies ◽  
Protein Carbonyls ◽  
Acute Administration ◽  
Dependent Manner ◽  
Immunological Parameters

Zearalenone (ZEN) is a mycotoxin from Fusarium species commonly found in food commodities and is known to cause reproductive disorders. Several in vivo studies have shown that ZEN is haematotoxic and hepatotoxic and causes several alterations of immunological parameters. Meantime, the available information on the cardiotoxic effects of ZEN is very much limited. In the present study, we investigated the toxic effects of ZEN in heart tissues of Balb/c mice. We demonstrated that ZEN (40 mg kg−1 body weight (b.w.)) increased creatine phosphokinase, lactate dehydrogenase, aspartate transaminase, alanine transaminase, total cholesterol and triglyceride levels and induced oxidative stress as monitored by measuring the malondialdehyde level, the generation of protein carbonyls, the catalase and superoxide dismutase activity and the expression of the heat shock proteins (Hsp 70). We also demonstrated that acute administration of ZEN triggers apoptosis in cardiac tissue. Furthermore, we aimed to evaluate the safety and efficacy of crocin (CRO), a natural carotenoid, to prevent ZEN-induced cardiotoxicity in mice. In fact, combined treatment of ZEN with different doses of CRO (50, 100, and 250 mg kg−1 b.w.) showed a significant reduction of ZEN-induced toxicity for all tested markers in a dose-dependent manner. It could be concluded that CRO was effective in the protection against ZEN-induced toxicity in cardiac tissue.

scholarly journals Antimicrobial photodynamic therapy with fulleropyrrolidine: photoinactivation mechanism of Staphylococcus aureus, in vitro and in vivo studies

2015 ◽  
Vol 99 (9) ◽  
pp. 4031-4043 ◽  
Author(s):  
Mariusz Grinholc ◽  
Joanna Nakonieczna ◽  
Grzegorz Fila ◽  
Aleksandra Taraszkiewicz ◽  
Anna Kawiak ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Photodynamic Therapy ◽  
In Vivo Studies ◽  
Antimicrobial Photodynamic Therapy

scholarly journals Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals

2016 ◽  
Vol 14 (3) ◽  
pp. 408-414 ◽  
Author(s):  
Jorge Mejia ◽  
Ana Claudia Camargo Miranda ◽  
Ana Claudia Ranucci Durante ◽  
Larissa Rolim de Oliveira ◽  
Marycel Rosa Felisa Figols de Barboza ◽  
...  
Keyword(s):  
Spatial Resolution ◽  
Gamma Camera ◽  
Large Scale ◽  
In Vivo Studies ◽  
Laboratory Animals ◽  
Operational Parameters ◽  
Combined System ◽  
Adult Rats ◽  
Tomographic Images

ABSTRACT Objective: To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images. Methods: An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein. The combined system was characterized, determining operational parameters, such as spatial resolution, magnification, maximum acceptable target size, number of projections, and acquisition and reconstruction times. Results: Images were obtained with 0.5mm spatial resolution, with acquisition and reconstruction times between 30 and 45 minutes, using iterative reconstruction with 10 to 20 iterations and 4 projection subsets. The system was validated acquiring in vivo tomographic images of the heart, kidneys and brain of normal animals (mice and adult rats), using the radiopharmaceuticals technetium-labeled hexakis-2-methoxy-isobutyl isonitrile (99mTc-Sestamibi), technetium-labeled dimercaptosuccinic acid (99mTc-DMSA) and technetium-labeled hexamethyl propyleneamine oxime (99mTc-HMPAO). Conclusion: This kind of application, which consists in the adaptation for an alternative objective of already existing instrumentation, resulted in a low-cost infrastructure option, allowing to carry out large scale in vivo studies with enhanced quality in several areas, such as neurology, nephrology, cardiology, among others.

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