scholarly journals Cathelicidin LL-37 in Severe Streptococcus pyogenes Soft Tissue Infections in Humans

2008 ◽  
Vol 76 (8) ◽  
pp. 3399-3404 ◽  
Author(s):  
Linda Johansson ◽  
Pontus Thulin ◽  
Parham Sendi ◽  
Erika Hertzén ◽  
Adam Linder ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Confocal Microscopy ◽  
Bacterial Resistance ◽  
Resistance Mechanism ◽  
Soft Tissue Infections ◽  
Bacterial Surface ◽  
Life Threatening ◽  
Severe Soft Tissue

ABSTRACT Severe soft tissue infections, such as necrotizing fasciitis and severe cellulitis, caused by group A streptococci (GAS) are rapidly progressing life-threatening infections characterized by massive bacterial loads in the tissue even late after the onset of infection. Antimicrobial peptides are important components of the innate host defense, and cathelicidins have been shown to protect against murine necrotic skin infections caused by GAS. However, it has been demonstrated that the streptococcal cysteine protease SpeB proteolytically inactivates the human cathelicidin LL-37 in vitro. Here we have investigated the expression of LL-37 and its interaction with GAS and SpeB during acute severe soft tissue infections by analyses of patient tissue biopsy specimens. The results showed large amounts of LL-37, both the proform (hCAP18) and the mature peptide, in the tissue. Confocal microscopy identified neutrophils as the main source of the peptide. A distinct colocalization between the bacteria and LL-37 could be noted, and bacterial loads showed positive correlation to the LL-37 levels. Areas with high LL-37 levels coincided with areas with large amounts of SpeB. Confocal microscopy confirmed strong colocalization of GAS, SpeB, and LL-37 at the bacterial surface. Taken together, the findings of this study provide in vivo support of the hypothesis that SpeB-mediated inactivation of LL-37 at the streptococcal surface represents a bacterial resistance mechanism at the infected tissue site in patients with severe GAS tissue infections.

scholarly journals Distribution and Antimicrobial Activity of Fosfomycin in the Interstitial Fluid of Human Soft Tissues

2000 ◽  
Vol 44 (10) ◽  
pp. 2728-2732 ◽  
Author(s):  
Martin Frossard ◽  
Christian Joukhadar ◽  
Boban M. Erovic ◽  
Peter Dittrich ◽  
Paulus E. Mrass ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissues ◽  
Pharmacokinetic Profile ◽  
Interstitial Space ◽  
Soft Tissue Infections ◽  
Time Curve ◽  
Tract Infections ◽  
High Degree

ABSTRACT Fosfomycin is a broad-spectrum antibiotic which is established as therapy for uncomplicated lower urinary tract infections. In addition, preliminary data indicate that fosfomycin has a potential role in the treatment of soft tissue infections. However, the use of fosfomycin has not been established for this condition, and it is unclear whether the level of fosfomycin penetration into human soft tissues is high enough to eradicate relevant pathogens. To better characterize the antibiotic potential of fosfomycin, we applied a combined in vivo pharmacokinetic-in vitro pharmacodynamic model to human volunteers. For this purpose fosfomycin concentrations in vivo in the fluid of the interstitial space of human soft tissues were measured by microdialysis following intravenous infusion of 4 or 8 g of fosfomycin (n = 6). Subsequently, bacterial isolates with relevance for soft tissue infections were exposed to concentrations according to the in vivo pharmacokinetic profile in the interstitial space fluid obtained by microdialysis. Our experiments indicated a high degree of soft tissue penetration for fosfomycin, with ratios of the area under the concentration-time curve from 0 to 8 h for muscle (AUC0–8muscle )/AUC0–8serum of 0.48 ± 0.08 and 0.53 ± 0.04 and ratios of AUC0–8adipose tissue /AUC0–8serum of 0.74 ± 0.12 and 0.71 ± 0.11 following administration of 4 and 8 g, respectively. In corresponding in vitro simulation experiments with selected isolates of Staphylococcus aureus,Enterobacter cloacae, and Serratia marcescensfor which MICs were 16 μg/ml, organisms were undetectable after a single dosing interval. Fosfomycin exhibits a strong ability to penetrate into the fluid of the interstitial space of soft tissues and reaches levels sufficient to substantially inhibit the growth of relevant bacteria at the target site. We therefore conclude that fosfomycin might qualify as an alternative candidate for the therapy of soft tissue infections.

scholarly journals Cefiderocol: An Overview of Its in-vitro and in-vivo Activity and Underlying Resistant Mechanisms

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiahui Yao ◽  
Jin Wang ◽  
Mengli Chen ◽  
Yun Cai
Keyword(s):  
Bacterial Resistance ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
New Delhi ◽  
Global Public Health ◽  
Gram Negative ◽  
First Line Therapy

Treatment of multidrug-resistant (MDR) Gram-negative bacteria (GNB) infections has led to a global public health challenging due to the bacterial resistance and limited choices of antibiotics. Cefiderocol (CFDC), a novel siderophore cephalosporin possessed unique drug delivery systems and stability to β-lactamases, has the potential to become first-line therapy for most aggressive MDR Gram-negative pathogens infection. However, there have been reports of drug resistance in the course of using CFDC. This study provides an overview of the in-vitro and in-vivo activity of CFDC and potential resistance mechanism was also summarized. In general, CFDC shows excellent activity against a broad range of MDR GNB pathogens including Enterobacteriaceae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. The expressions of metallo-β-lactamases such as inosine 5'-monophosphate (IMP), Verona integron-mediated metallo-β-lactamase (VIM), and New Delhi metallo-β-lactamase (NDM) are associated with a higher resistance rate of CFDC. Carbapenem-resistant phenotype has little effect on the resistance rate, although the acquisition of a particular carbapenemase may affect the susceptibility of the pathogens to CFDC. For potential resistance mechanism, mutations in β-lactamases and TonB-dependent receptors, which assist CFDC entering bacteria, would increase a minimum inhibitory concentration (MIC)90 value of CFDC against MDR pathogens. Since the development of CFDC, resistance during its utilization has been reported thus, prudent clinical applications are still necessary to preserve the activity of CFDC.

scholarly journals Effects of Local Application of Nano-silver on Osteomyelitis and Soft Tissue Infections: An Experimental Study in Rats

2018 ◽  
Vol 3 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Bahattin Kemah ◽  
Gökçer Uzer ◽  
Yalçın Turhan ◽  
Burak Özturan ◽  
Bülent Kılıç ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Surgical Debridement ◽  
Local Application ◽  
In Vivo Studies ◽  
Pathological Examination ◽  
X Rays ◽  
Soft Tissue Infections ◽  
Nano Silver

Abstract. Purpose: Bone and soft tissue infections are among the least desired complications after orthopaedic surgery. This study analysed the in vivo effects of the local application of nano-silver particles (AgNPs) [1nm = 1 billionth of a meter] in soft tissue infections.Materials-Method: An experimental osteomyelitis model was formed by inoculating both tibias of 24 rats with methicillin-resistant Staphylococcus aureus. The rats were followed without treatment for 21 days. Blood samples and tibial x-rays at day 21 confirmed the development of infection. Then, the rats were divided randomly into two groups. One group (12 rats) underwent surgical debridement and received 21 days of teicoplanin therapy. The second group had the same treatment, with the addition of local nano-silver. All of the rats were sacrificed at day 42. Blood and wound swab samples were taken and the culture results were analysed.Results: No differences were observed between the groups in healing values at pathological examination, or in changes in the number of colonies at days 21 and 42. No differences in white blood cell count (WBC) were observed between the groups before and after the treatment.Conclusion: Although in vitro studies suggest the effectiveness of AgNPs on pathogens, we found that the application of nano-silver did not make any difference when used in addition to the classical osteomyelitis treatment with antibiotics and local surgical debridement. We believe that additional in vivo studies using repeated nano-silver application could be beneficial.

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

scholarly journals Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 439
Author(s):  
Christopher G. Bunick ◽  
Jonette Keri ◽  
S. Ken Tanaka ◽  
Nika Furey ◽  
Giovanni Damiani ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Bacterial Resistance ◽  
Antibiotic Use ◽  
In Vivo Studies ◽  
Infection Model ◽  
Severe Acne ◽  
Rat Paw Edema ◽  
Infection And Inflammation

Prolonged broad-spectrum antibiotic use is more likely to induce bacterial resistance and dysbiosis of skin and gut microflora. First and second-generation tetracycline-class antibiotics have similar broad-spectrum antibacterial activity. Targeted tetracycline-class antibiotics are needed to limit antimicrobial resistance and improve patient outcomes. Sarecycline is a narrow-spectrum, third-generation tetracycline-class antibiotic Food and Drug Administration (FDA)-approved for treating moderate-to-severe acne. In vitro studies demonstrated activity against clinically relevant Gram-positive bacteria but reduced activity against Gram-negative bacteria. Recent studies have provided insight into how the structure of sarecycline, with a unique C7 moiety, interacts with bacterial ribosomes to block translation and prevent antibiotic resistance. Sarecycline reduces Staphylococcus aureus DNA and protein synthesis with limited effects on RNA, lipid, and bacterial wall synthesis. In agreement with in vitro data, sarecycline demonstrated narrower-spectrum in vivo activity in murine models of infection, exhibiting activity against S. aureus, but reduced efficacy against Escherichia coli compared to doxycycline and minocycline. In a murine neutropenic thigh wound infection model, sarecycline was as effective as doxycycline against S. aureus. The anti-inflammatory activity of sarecycline was comparable to doxycycline and minocycline in a rat paw edema model. Here, we review the antibacterial mechanisms of sarecycline and report results of in vivo studies of infection and inflammation.

scholarly journals Quinolones for the Treatment ofNeisseria GonorrhoeaeandChlamydia Trachomatis

1993 ◽  
Vol 1 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Sebastian Faro
Keyword(s):  
Urinary Tract ◽  
Soft Tissue ◽  
Chlamydia Trachomatis ◽  
Urinary Tract Infections ◽  
Single Agent ◽  
Moderate Activity ◽  
Sexually Transmitted ◽  
Tract Infections

The most commonly sexually transmitted bacteria areNeisseria gonorrhoeaeandChlamydia trachomatis.The quinolones ofloxacin and ciprofloxacin have been shown to have activity against both of these bacteria in vitro and in vivo. Ofloxacin is particularly well suited for the treatment ofN. gonorrhoeaeandC. trachomatiscervical infection, which can be considered the earliest manifestation of pelvic inflammatory disease (PID). Not only can ofloxacin be effectively used as a single agent, it is also useful in treating urinary tract infections caused by Enterobacteriaceae. Although it has moderate activity against anaerobes in general, ofloxacin does have activity against the anaerobes commonly isolated from female patients with soft tissue pelvic infections. Thus, ofloxacin has the potential for being utilized to treat early salpingitis.

scholarly journals A multi-center comparison of dual energy X-ray absorptiometers: In vivo and in vitro soft tissue measurement

1997 ◽  
Vol 51 (5) ◽  
pp. 312-317 ◽  
Author(s):  
CD Economos ◽  
ME Nelson ◽  
MA Fiatarone ◽  
GE Dallal ◽  
SB Heymsfield ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Dual Energy ◽  
X Ray

Skin and Soft Tissue Infections

2015 ◽  
Author(s):  
Daniel J. Pallin
Keyword(s):  
Soft Tissue ◽  
Necrotizing Fasciitis ◽  
Bacterial Infections ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Skin Infections ◽  
Soft Tissue Infections ◽  
Protective Mechanisms ◽  
Contact Precautions ◽  
Life Threatening ◽  
Plantar Warts

The skin is the largest organ of the human body, and has diverse functions including protection from infection, temperature regulation, sensation, and immunologic and hormonal functions. Skin infections occur when the skin’s protective mechanisms fail. Some infections may be life-threatening (eg, necrotizing fasciitis) or may require the patient to be placed on contact precautions; thus, the initial goals of assessment of patients with skin and soft tissue infections are to assess the patient’s stability and to determine whether precautions are necessary to protect others. This review covers the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes for a variety of skin and soft tissue infections. Figures show an algorithm for treatment of bacterial infections of the skin, and photographs of  various infections including necrotizing fasciitis, cellulitis, an abscess caused by methicillin-resistant Staphylococcus aureus, a furuncle, a carbuncle, nonbullous and bullous impetigo, echythma, folliculitis, anthrax lesion, tinea corporis, condyloma acuminatum, and plantar warts. Tables list cellulitis treatment with particular exposures, the dermatophytoses, and yeast infections of skin and mucous membranes. This review contains 16 highly rendered figures, 3 tables, and 32 references.

Irinotecan Resistance – In Search of New Markers in CRC.

2021 ◽  
Author(s):  
Jakub Kryczka ◽  
Joanna Boncela
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Expression Profiles ◽  
Resistance Mechanism ◽  
Interaction Network ◽  
In Vitro Study ◽  
Cancer Drug ◽  
New Genes

Abstract Colorectal cancer (CRC) is one of the most prominent causes of cancer death worldwide. Chemotherapeutic regimens consisting of different drugs combinations such as 5-fluorouracil, and oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) have been proven successful in the treatment of CRC. However, chemotherapy often leads to the acquisition of cancer drug resistance followed by metastasis and in the aftermath therapeutic failure. The molecular mechanism responsible for drug resistance is still unclear. The systemic search for new biomarkers of this phenomenon may identify new genes and pathways. To understand the drug resistance mechanism in CRC, the in vitro study based on the molecular analysis of drug-sensitive cells lines vs drug-resistant cells lines has been used. In our study to bridge the gap between in vitro and in vivo study, we compared the expression profiles of cell lines and patient samples from the publicly available database to select the new candidate genes for irinotecan resistance. Using The Gene Expression Omnibus (GEO) database of CRC cell lines (HT29, HTC116, LoVo, and their respective irinotecan-resistant variants) and patient samples (GSE42387, GSE62080, and GSE18105) we compared the changes in the mRNA expression profile of the main genes involved in irinotecan body’s processing, such as transport out of the cells and metabolism. Furthermore, using a protein-protein interaction network of differently expressed genes between FOLFIRI resistant and sensitive CRC patients, we have selected top networking proteins (upregulated: NDUFA2, SDHD, LSM5, DCAF4, and COX10, downregulated: RBM8A, TIMP1, QKI, TGOLN2, and PTGS2). Our analysis provided several potential irinotecan resistance markers, previously not described as such.

From local to global matrix organization by fibroblasts: a 4D laser-assisted bioprinting approach

2021 ◽  
Author(s):  
Camille Douillet ◽  
Marc Nicodeme ◽  
Loïc Hermant ◽  
Vanessa Bergeron ◽  
Fabien Guillemot ◽  
...  
Keyword(s):  
High Resolution ◽  
Soft Tissue ◽  
Dynamic Properties ◽  
Unmet Need ◽  
Specific Pattern ◽  
Matrix Remodeling ◽  
Collagen Gels ◽  
Lattice Contraction

Abstract Fibroblasts and myofibroblasts play a central role in skin homeostasis through dermal organization and maintenance. Nonetheless, the dynamic interactions between (myo)fibroblasts and the extracellular matrix (ECM) remain poorly exploited in skin repair strategies. Indeed, there is still an unmet need for soft tissue models allowing to study the spatial-temporal remodeling properties of (myo)fibroblasts. In vivo, wound healing studies in animals are limited by species specificity. In vitro, most models rely on collagen gels reorganized by randomly distributed fibroblasts. But biofabrication technologies have significantly evolved over the past ten years. High-resolution bioprinting now allows to investigate various cellular micropatterns and the emergent tissue organizations over time. In order to harness the full dynamic properties of cells and active biomaterials, it is essential to consider “time” as the 4th dimension in soft tissue design. Following this 4D bioprinting approach, we aimed to develop a novel model that could replicate fibroblast dynamic remodeling in vitro. For this purpose, (myo)fibroblasts were patterned on collagen gels with laser-assisted bioprinting (LAB) to study the generated matrix deformations and reorganizations. First, distinct populations, mainly composed of fibroblasts or myofibroblasts, were established in vitro to account for the variety of fibroblastic remodeling properties. Then, LAB was used to organize both populations on collagen gels in even isotropic patterns with high resolution, high density and high viability. With maturation, bioprinted patterns of fibroblasts and myofibroblasts reorganized into dispersed or aggregated cells, respectively. Stress-release contraction assays revealed that these phenotype-specific pattern maturations were associated with distinct lattice tension states. The two populations were then patterned in anisotropic rows in order to direct the cell-generated deformations and to orient global matrix remodeling. Only maturation of anisotropic fibroblast patterns, but not myofibroblasts, resulted in collagen anisotropic reorganizations both at tissue-scale, with lattice contraction, and at microscale, with embedded microbead displacements. Following a 4D bioprinting approach, LAB patterning enabled to elicit and orient the dynamic matrix remodeling mechanisms of distinct fibroblastic populations and organizations on collagen. For future studies, this method provides a new versatile tool to investigate in vitro dermal organizations and properties, processes of remodeling in healing, and new treatment opportunities.

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