scholarly journals Controlled and Local Delivery of Antibiotics by 3D Core/Shell Printed Hydrogel Scaffolds to Treat Soft Tissue Infections

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2151
Author(s):  
Ashwini Rahul Akkineni ◽  
Janina Spangenberg ◽  
Michael Geissler ◽  
Saskia Reichelt ◽  
Hubert Buechner ◽  
...  

Soft tissue infections in open fractures or burns are major cause for high morbidity in trauma patients. Sustained, long-term and localized delivery of antimicrobial agents is needed for early eradication of these infections. Traditional (topical or systemic) antibiotic delivery methods are associated with a variety of problems, including their long-term unavailability and possible low local concentration. Novel approaches for antibiotic delivery via wound coverage/healing scaffolds are constantly being developed. Many of these approaches are associated with burst release and thus seldom maintain long-term inhibitory concentrations. Using 3D core/shell extrusion printing, scaffolds consisting of antibiotic depot (in the core composed of low concentrated biomaterial ink 3% alginate) surrounded by a denser biomaterial ink (shell) were fabricated. Denser biomaterial ink (composed of alginate and methylcellulose or alginate, methylcellulose and Laponite) retained scaffold shape and modulated antibiotic release kinetics. Release of antibiotics was observed over seven days, indicating sustained release characteristics and maintenance of potency. Inclusion of Laponite in shell, significantly reduced burst release of antibiotics. Additionally, the effect of shell thickness on release kinetics was demonstrated. Amalgamation of such a modular delivery system with other biofabrication methods could potentially open new strategies to simultaneously treat soft tissue infections and aid wound regeneration.

2021 ◽  
Vol 1 ◽  
pp. 61
Author(s):  
Rashmi Sarkar ◽  
Sushil Tahiliani ◽  
Amit Madan ◽  
Anil Abraham ◽  
Anil Ganjoo ◽  
...  

Dermatologists often come across cases of skin and soft-tissue infections (SSTIs) which have diverse clinical presentations. Various local, systemic, and environmental risk factors predispose an individual to develop SSTIs. Topical antimicrobial agents are frequently used in superficial uncomplicated SSTIs, whereas systemic therapy is generally reserved for use in severe cases. However, emergence of resistance to these agents is becoming a common problem in clinical practice. This necessitates the use of other classes of antimicrobials for the effective treatment of SSTIs. Nadifloxacin, a potential drug belonging to the fluoroquinolone group, has various advantages such as binding to bacterial DNA gyrase and topoisomerase IV enzymes, inhibition of nor-A efflux pump, survival in acidic pH, anti-MRSA activity, and biofilms penetration. It has also shown least development of resistance since its introduction. Although its topical formulation has shown superior efficacy as an anti-acne agent, there are no specific guidelines for its appropriate use in SSTIs. Hence, a panel of experts was formed, under whose guidance an extensive literature search was performed in MEDLINE, Cochrane Library, and Science Direct databases. Using the modified Delphi technique, the available evidence was reviewed and corresponding recommendations were given for the use of topical Nadifloxacin as an empirical treatment in SSTIs.


2010 ◽  
Vol 44 (1) ◽  
pp. 97-106 ◽  
Author(s):  
loannis A Bliziotis ◽  
Eleni Plessa ◽  
George Peppas ◽  
Matthew E Falagas

2021 ◽  
pp. 000313482110517
Author(s):  
Maria G. Valadez ◽  
Neil Patel ◽  
Vince Chong ◽  
Brant A. Putnam ◽  
Ashkan Moazzez ◽  
...  

Introduction Necrotizing soft tissue infections (NSTIs) carry high morbidity and mortality. While early aggressive surgical debridement is well-accepted treatment for NSTIs, the optimum duration of adjunct antibiotic therapy is unclear. An increasing focus on safety and evidence-based antimicrobial stewardship suggests a value in addressing this knowledge gap. Objective To determine whether shorter antibiotic courses have similar outcomes compared to longer courses in patients with NSTI following adequate source control. Population 142 consecutive patients with surgically managed NSTI were identified on retrospective chart review between December 2014 and December 2018 at two academic medical centers. Results Patients were predominately male (74%) with a median age of 52 and similar baseline characteristics. The median number of debridements to definitive source control was 2 (IQR 1-3) with the short course group undergoing a greater number of debridements control 2.57 ± 1.8 vs 1.9 ± 1.2, ( P = .01). Of 142 patients, 34.5% received a short course and the remaining 65.5% received a longer course of antibiotics. There was no significant difference in the incidence of bacteremia or wound culture positivity between groups. There was also no significant difference in in-hospital mortality, 8% vs 6, ( P = .74), incidence of C. difficile infection, median length of stay, or 30-day readmission. Conclusion Provided adequate surgical debridement, similar outcomes in morbidity and mortality suggest antibiotic courses of 7 days or less are equally safe compared to longer courses.


2005 ◽  
Vol 52 (7) ◽  
pp. 143-148 ◽  
Author(s):  
S.M. Hunt ◽  
M.A. Hamilton ◽  
P.S. Stewart

A three-dimensional cellular automata model of biofilm dynamics was adapted to simulate the protection from killing by antimicrobial agents afforded to microorganisms in the biofilm state. The model incorporated diffusion and simultaneous utilization of a single substrate, growth and displacement of cells, detachment, and killing by an antimicrobial agent. The rate of killing was assumed to be directly proportional to the local concentration of substrate available to the microorganisms. Some of the features predicted by this model included development of dynamic, heterogeneous biofilm structures, gradients in substrate concentration leading to regions of substrate depletion in the interior of large cell clusters, variable killing by an antimicrobial agent from one simulation to the next, greater killing of cells at the periphery of cell clusters compared to those cells which were more deeply embedded, and reduced overall antimicrobial susceptibility of cells in the biofilm. These simulations show that substrate limitation can contribute to the protection from antimicrobial agents in biofilms but cannot explain the long-term persistence of biofilm viability that is often observed in practice.


2013 ◽  
Vol 79 (10) ◽  
pp. 1102-1105 ◽  
Author(s):  
Samuel Schwartz ◽  
Elizabeth Kightlinger ◽  
Christian De Virgilio ◽  
Michael De Virgilio ◽  
Amy Kaji ◽  
...  

Necrotizing soft tissue infections (NSTIs) require prompt diagnosis and treatment. Early identification of patients at greatest risk of limb amputation and death may help in targeting aggressive medical and surgical management. The aim of this study was to assess predictors of limb loss and mortality in patients with NSTI based on admission variables. We performed a retrospective review of two hospitals that care for a large volume of patients with NSTI. Univariate and multi-variable analyses were used to determine the association of admission biochemical markers to limb loss and mortality. Of 174 patients with NSTI, there were 19 deaths (10.9%) and 42 required amputations (24.1%). Multivariable logistic regression analysis revealed that only arterial lactate was predictive for both mortality (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1 to 2.0; P = 0.009) and limb loss (OR, 1.3; 95% CI, 1.0 to 1.7; P = 0.02). In patients with a suspected NSTI, an arterial lactate should be ordered early on to guide aggressive therapeutic interventions and to provide information with regard to long-term outcomes of amputation and death that is needed for early discussion with the patient and family.


2013 ◽  
Vol 1 (1) ◽  
pp. 4
Author(s):  
Chance Witt ◽  
Sharmila Dissanaike

Background: Necrotizing soft tissue infections (NSTI) are potentially severe infections that have a high morbidity and mortality even with modern medical care. This study examines factors associated with outcomes in patients with NSTI in an academic tertiary care hospital. Design: This is a retrospective cohort study of patients admitted with NSTI between 2003 and 2008. Baseline demographics and comorbid conditions, laboratory and clinical parameters, timing of surgery, and outcomes, including length of stay and mortality, were compared with univariate analysis; significant factors were then analyzed for their effects on mortality using binary logistic regression analysis. Results: Sixty-nine patients with NSTI were analyzed; 61% were men. Diabetes (39%) was the most common comorbid condition. Most infections (55%) were polymicrobial. The most common organism in monomicrobial infections was Staphylococcus aureus, and 50 % of these isolates were methicillin resistant. Nine patients (13%) required amputation. Mortality was 20%, and the most significant predictor of mortality was a higher respiratory rate on admission (p=0.02). Conclusion: Patients in this series frequently had diabetes, usually had polymicrobial infections, and had a 20% mortality rate.


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Scott C. Brakenridge ◽  
David A. Wilfret ◽  
Greg Maislin ◽  
Katherine E. Andrade ◽  
Valery Walker ◽  
...  

2014 ◽  
Vol 6 (01) ◽  
pp. 046-049 ◽  
Author(s):  
Madhuri Kulkarni ◽  
Vijay Kumar GS ◽  
Sowmya GS ◽  
Madhu CP ◽  
Ramya SR

ABSTRACTNecrotizing soft tissue infections (NSTI) can be rapidly progressive and polymicrobial in etiology. Establishing the element of necrotizing infection poses a clinical challenge. A 64-year-old diabetic patient presented to our hospital with a gangrenous patch on anterior abdominal wall, which progressed to an extensive necrotizing lesion within 1 week. Successive laboratory risk indicator for necrotizing softtissue infections (LRINEC) scores confirmed the necrotizing element. Cultures yielded Enterococci, Acinetobacter species and Apophysomyces elegans and the latter being considered as an emerging agent of Zygomycosis in immunocompromised hosts. Patient was managed with antibiotics, antifungal treatment and surgical debridement despite which he succumbed to the infection. NSTI’s require an early and aggressive management and LRINEC score can be applied to establish the element of necrotizing pathology. Isolation of multiple organisms becomes confusing to establish the etiological role. Apophysomyces elegans, which was isolated in our patient is being increasingly reported in cases of necrotizing infections and may be responsible for high morbidity and mortality. This scoring has been proposed as an adjunct tool to Microbiological diagnosis when NSTI’s need to be diagnosed early and managed promptly to decrease mortality and morbidity, which however may not come in handy in an immunocompromised host with polymicrobial aggressive infection.


2020 ◽  
Vol 19 (3) ◽  
pp. 236-241 ◽  
Author(s):  
Vasilios Petrakis ◽  
Periklis Panagopoulos ◽  
Nikolaos Papanas

New antimicrobial agents have been developed to treat infections caused by methicillin-resistant Staphylococcus aureus and other multidrug-resistant pathogens. Dalbavancin is a novel semisynthetic lipoglycopeptide antibiotic, particularly active against methicillin-resistant Staphylococcus aureus. Due to its unique pharmacological characteristics and longer half-life, it can be administered once-weekly or every 15 days and in outpatient setting. Currently, it is indicated for complicated skin and soft tissue infections, but accumulating evidence points to its off-label efficacy in osteomyelitis and endocarditis. Further experience is still needed to increase our knowledge on the role of dalbavancin in a wider range of Gram-positive infections requiring prolonged antimicrobial treatment.


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