minocycline and Burns

Topics: Acinetobacter baumannii; Acinetobacter Infections; Alginates; Animals; Anti-Bacterial Agents; Burns; Female; Gentamicins; Hydrogels; Microbial Sensitivity Tests; Minocycline; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Swine; Vancomycin; Wound Healing; Wound Infection

Bacterial infections of burn wounds are a significant problem that usually slows or stops the process of burn wounds healing. The use of topical antibiotics based on a novel drug delivery system could overcome the limitations of burn wound healing. In this work, the development of new wound dressings based on nanocomposite film of polyvinyl alcohol (PVA) and halloysite nanotubes (HNT) for the delivery of minocycline was investigated. These elastomeric nanocomposites were prepared based on HNT surface modification by APTES and then PVA coating by LbL strategy. The resulting nanocomposites were characterized by FT-IR, XRD, zeta potential, Tg analysis, FESEM, and antibacterial studies. The biodegradability and water uptake of the film were evaluated, the results of which revealed the absorption of scarring and non-degradation of the nanocomposite during treatment. Because minocycline decomposes by light, increasing photostability was another goal that was achieved. The release profile of the drug from the nanocomposite was studied, and it was found to be consistent with the Korsmeyer-Peppas model. In-vitro studies showed the antibacterial effect of nanocomposite on exposure to Gram-positive and Gram-negative bacteria. Due to the properties of the resulting nanocomposite film, it can be considered as a promising candidate for wound healing. In-vivo studies, cell culture, neuroprotective and anti-inflammatory effects may be investigated to develop this wound dressing in the future.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Bandages; Biocompatible Materials; Burns; Clay; Gram-Negative Bacteria; Gram-Positive Bacteria; Minocycline; Nanocomposites; Nanotubes; Neuroprotective Agents; Polyvinyl Alcohol; Spectroscopy, Fourier Transform Infrared; Wound Healing

The emergence of antibiotic-resistant pathogens has made the treatment of infected burn wounds even more problematical than the pre-antibiotic era. Phage therapy is now being considered a promising treatment options to fight against antibiotic resistant pathogens. Hence, we introduce a novel PVA-SA hydrogel based wound dressing system for topical delivery of bacteriophages and antibiotic to treat infected burn injuries. Hydrogel membrane provides wound healing environment while surface absorbed bacteriophages/antibiotic takes care of the local infection. Different blends of PVA and SA were crosslinked by boric acid and calcium ions to form the hydrogel membrane and assessed for ideal wound dressing properties. 1:2 blended PVA: SA membrane displayed highest swelling index, gel fraction, protein adsorption, hemocompatibility and best mechanical properties among the 3 blends studied in this study. The selected membrane was further characterised by FTIR, FESEM and TGA. Overall, self-adherent, antibacterial and biocompatible membrane was obtained as revealed by the in-vitro antibacterial assays, elution assays and cell cytotoxicity assays. The in-vivo potential was evaluated using MRSA-infected murine burn wound model revealing significant bacterial reduction, wound contraction and reduced inflammation in membrane treated groups in comparison to control group. The dual coated hydrogel membrane delivering both MR10 phage and minocycline proved to be better treatment strategy to treat the resistant burn wound infection rather than phage and antibiotic alone.

Topics: Administration, Topical; Adsorption; Alginates; Animals; Anti-Bacterial Agents; Bacteriophages; Bandages; Burns; Cell Line; Drug Delivery Systems; Female; Humans; Hydrogels; Male; Mice; Mice, Inbred BALB C; Minocycline; Polyvinyl Alcohol; RAW 264.7 Cells; Wound Healing; Wound Infection

Wound infections cause inflammation, tissue damage, and delayed healing that can lead to invasive infection and even death. The efficacy of systemic antibiotics is limited due to poor tissue penetration that is especially a problem in burn and blast wounds where the microcirculation is disrupted. Topical administration of antimicrobials is an attractive approach because it prevents infection and avoids systemic toxicity, while hydrogels are an appealing vehicle for topical drug delivery. They are easy to apply to the wound site by being injectable, the drug release properties can be controlled, and their many characteristics, such as biodegradation, mechanical strength, and chemical and biological response to stimuli can be tailored. Hydrogels also create a moist wound environment that is beneficial for healing. The purpose of this study was to formulate an agarose hydrogel that contains high concentrations of minocycline or gentamicin and study its characteristics. Subsequently, the minocycline agarose hydrogel was tested in a porcine burn model and its effect as a prophylactic treatment was studied. The results demonstrated that 0.5% agarose in water was the optimal concentration in terms of viscosity and pH. Bench testing at room temperature demonstrated that both antibiotics remained stable in the hydrogel for at least 7 days and both antibiotics demonstrated sustained release over the time of the experiment. The porcine burn experiment showed that prophylactic treatment with the agarose minocycline hydrogel decreased the burn depth and reduced the number of bacteria as efficiently as the commonly used silver sulfadiazine cream.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Burns; Drug Stability; Gentamicins; Hydrogels; Hydrogen-Ion Concentration; Minocycline; Models, Animal; Rheology; Sepharose; Swine; Wound Healing; Wound Infection

Injuries to the skin are often complicated by invasive infections. Standard treatment with intravenous antibiotics has limited tissue penetration and sometimes, major systemic toxicity. Traditional topical delivery of antimicrobials also has limited effectiveness and duration of action. We demonstrate the use of a new Platform Wound Device (PWD) for delivery of topical, ultrahigh concentrations of minocycline as well as lidocaine onto the burn eschar and on the surface of excisional wounds in a total of 56 burn wounds and 24 excisional wounds in a porcine model. Wounds were created on day 0, debrided on day 3, and pigs were killed on day 7. After 3 days of PWD with minocycline treatment, bacterial count was 5.44 log CFU/g in dorsal wound tissue inoculated with methicillin-resistant Staphylococcus aureus, less than that after treatment with silver sulfadiazine cream (7.64 log CFU/g). Pain was also relieved or eliminated in burn wounds and full-thickness excisional wounds when lidocaine was delivered by the PWD. The results demonstrate that ultrahigh concentrations of antibiotics can be delivered effectively by the PWD, and will accelerate wound bed preparation.

Topics: Administration, Topical; Anesthetics, Local; Animals; Anti-Bacterial Agents; Bacterial Load; Burns; Debridement; Disease Models, Animal; Female; Lidocaine; Methicillin-Resistant Staphylococcus aureus; Minocycline; Staphylococcal Infections; Swine; Wound Healing; Wound Infection

Burn and blast injuries are frequently complicated by invasive infections, which lead to poor wound healing, delay in treatment, disability, or death. Traditional approach centers on early debridement, fluid resuscitation, and adjunct intravenous antibiotics. These modalities often prove inadequate in burns, where compromised local vasculature limits the tissue penetration of systemic antibiotics. Here, we demonstrate the treatment of infected burns with topical delivery of ultrahigh concentrations of antibiotics. Standardized burns were inoculated with Staphylococcus aureus or Pseudomonas aeruginosa. After debridement, burns were treated with either gentamicin (2 mg/mL) or minocycline (1 mg/mL) at concentrations greater than 1,000 times the minimum inhibitory concentration. Amount of bacteria was quantified in tissue biopsies and wound fluid following treatment. After six days of gentamicin or minocycline treatment, S. aureus counts decreased from 4.2 to 0.31 and 0.72 log CFU/g in tissue, respectively. Similarly, P. aeruginosa counts decreased from 2.5 to 0.0 and 1.5 log CFU/g in tissue, respectively. Counts of both S. aureus and P. aeruginosa remained at a baseline of 0.0 log CFU/mL in wound fluid for both treatment groups. The findings here demonstrate that super-therapeutic concentrations of antibiotics delivered topically can rapidly reduce bacterial counts in infected full-thickness porcine burns. This treatment approach may aid wound bed preparation and accelerate time to grafting.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Burns; Debridement; Disease Models, Animal; Female; Gentamicins; Minocycline; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Swine; Wound Healing; Wound Infection

MRSA is the predominant pathogen responsible for fatal burn wound infection in patients. Antibiotic resistance and its ability to form biofilms on the surface of burn wounds limit the use of antibiotics to contain this pathogen. The results of present study have shown that single dose of combination therapy of endolysin MR-10 (50μg/s.c) and minocycline (50mg/kg/orally) resulted in 100% survival of group of mice with systemic MRSA infection. Maximum reduction in bacterial load in various organs was observed in the group that received combination therapy. In comparison to control, a significant reduction (p<0.01) of 4.82, 1.81, 1.51, 1.2 logs was observed in skin, blood, liver and spleen respectively, by 3rd day post infection. As a result of which, all organs became sterile thereby protecting mice from mortality. Histopathological analysis corroborated our findings showing no signs of inflammation and bacterial infection in the group that received combination therapy. Treatment of localized burn wound infection with combination therapy resulted in early resolution of infection followed by fast healing. The group that received combination therapy showed complete resolution of infection in less than 10days. Moreover, the skin samples obtained from animals treated with combination therapy showed no myeloperoxidase (MPO) activity on 10th day post treatment. In combination therapy group, ∼98% wound contraction was observed by 12th day followed by complete closure of wound within ∼14days. The histopathological analysis showed no signs of inflammation and infection. Collagen staining revealed early signs of re-epithelization of epidermis and signs of collagen regeneration in-group that received combination therapy. Hence, this study suggests that the combined therapy of endolysin MR-10 and minocycline is a better option in controlling burn wound infections.

Topics: Administration, Oral; Animal Structures; Animals; Anti-Bacterial Agents; Bacterial Load; Burns; Disease Models, Animal; Drug Therapy, Combination; Endopeptidases; Female; Histocytochemistry; Injections, Subcutaneous; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred BALB C; Minocycline; Sepsis; Staphylococcal Infections; Survival Analysis; Time Factors; Treatment Outcome; Wound Infection

The emergence and spread of carbapenems-resistant Klebsiella pneumoniae (CRKP) in burn ward is an important threat to burn management. CRKP isolates are resistant to almost all available antibiotics and are susceptible only to polymyxins and tigecycline. The mechanism of the drug resistance of CRKP is associated with the plasmid-encoded carbapenemase Klebsiella pneumoniae carbapenemase (KPC), a carbapenem-hydrolyzing β-lactamase. Antibiotics which can currently be used to treat CRKP infection include polymyxins, tigecycline, and some aminoglycosides. The efficacy of using antibiotics in combination is better than that of single-agent therapy for the treatment of CRKP infection in bloodstream. In order to control CRKP infection in burn patients, strategies for preventing CRKP dissemination in burn ward are strongly advocated.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Burns; Carbapenems; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Burns; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Humans; Male; Minocycline; Tigecycline; Treatment Outcome

The present study was carried out to understand the clonal relationship using enterobacteriaceae repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) among metallo-β-lactamase (MBL) producing multidrug resistant Pseudomonas aeruginosa isolates from burn victims and their susceptibility to commonly used anti-pseudomonal agents. In the present study 94 non-duplicate P. aeruginosa strains from the wound samples of burn patients were included. Identification of the isolates was done by biochemical methods and antibiotic sensitivity was done by disc diffusion method following CLSI (Clinical Laboratory Standard Institute) guidelines. By using imipenem (IPM)-EDTA disk diffusion/double disc synergy method carbapenem resistant organisms were tested for MBL. To define the clonal relationship ERIC-PCR was used. Of the 94 isolates, 18 (19.14%) were found resistant to IPM and MBL production was shown 11 (11.70%) by the IPM-EDTA disc diffusion method. From dendrogram of the ERIC-PCR profile four major clusters were obtained (A, B, C and D). Cluster B contained the majority of the isolates (6 strains 1, 4, 8, 9, 10 and 11). This study using ERIC-PCR of randomly collected isolates exhibits high genetic diversity which rules out cross contamination frequency.

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactamases; Burns; Ceftazidime; Ceftriaxone; Cilastatin; Clavulanic Acid; Colistin; Disk Diffusion Antimicrobial Tests; Drug Combinations; Drug Resistance, Multiple, Bacterial; Genetic Variation; Humans; Imipenem; Minocycline; Netilmicin; Ofloxacin; Phylogeny; Polymerase Chain Reaction; Pseudomonas aeruginosa; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Burns; Cefoperazone; Humans; Meropenem; Middle Aged; Minocycline; Retrospective Studies; Sulbactam; Thienamycins; Young Adult

We investigated the in vivo efficacy of tigecycline, a new glycylcycline (a tetracycline derivative), in the management of methicillin-resistant Staphylococcus aureus (MRSA)-infected experimental surgical wounds in rats. The main outcome measures were quantitative bacterial culture, histological examination and immunohistochemical expression of matrix metalloproteinase-9 (MMP-9) and collagen IV.. An animal model was used to compare the in vivo efficacy of teicoplanin and tigecycline in the treatment of burn wound infections by S. aureus. A copper bar, heated in boiling water, was placed on the paraspinal site of each rat, resulting in full thickness burns. A small gauze was placed over each burn and then inoculated with 5 × 10(7) cfu of S. aureus ATCC 43300. To mimic the clinical situation in burn patients, surgical debridement was performed 48 h after the injury. The wounds were left to heal by secondary intention. The study included an uninfected control group that did not receive any treatment, a contaminated group that did not receive any treatment, and two contaminated groups treated with intraperitoneal tigecycline (2 mg/kg) and teicoplanin (7 mg/kg), respectively.. All antibiotic treatments were significantly effective. Tigecycline showed the highest antimicrobial activity, with a better impact on histological results. Infected rats treated with tigecycline showed a significant decrease in MMP-9 expression both in epithelium and in dermis compared with rats treated with teicoplanin.. Tigecycline, besides its antimicrobial activity, exerts an important modulatory effect on MMP-9, accelerating wound healing in staphylococcal-infected burns.

Topics: Animals; Bacterial Load; Burns; Disease Models, Animal; Histocytochemistry; Immunohistochemistry; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Methicillin-Resistant Staphylococcus aureus; Minocycline; Rats; Rats, Wistar; Staphylococcal Infections; Teicoplanin; Tigecycline; Treatment Outcome; Wound Healing; Wound Infection

Burn injury induces severe pain that can be refractory to existing pharmacotherapies. The underlying mechanism of burn pain remains unclear. We previously established an animal model and reported that unilateral burn injury induces chronic and bilateral mechanical allodynia, which is associated with central sensitization and microglial activation in the spinal cord dorsal horn. Modulation of the activity of microglia and p38 mitogen-activated protein kinase (MAPK) has been shown to ameliorate neuropathic pain in several nerve-injury pain models. In the present study, we show in this rat model that daily treatment with the microglial inhibitor minocycline (10 mg/kg), administered at the time of burn injury and for 7 days thereafter, significantly attenuates ipsilateral and contralateral allodynia as assessed up to 1 month following burn injury. These sensory changes are paralleled by significant suppression of evoked hyperexcitability of dorsal-horn neurons and of the expression of phosphorylated p38 (phospho-p38) in OX42+ microglial cells within the dorsal horn. Our results suggest that modulation of inflammation at early times after burn injury may have long-lasting effects, attenuating central neuropathic mechanisms which contribute to pain after burn injury.. We demonstrate, in a rodent model of burn-associated pain, that the microglial inhibitor minocycline, delivered at the time of burn injury and for 1 week thereafter, has long-lasting effects, attenuating microglial activation and neuronal hyperresponsiveness in the dorsal horns, and ameliorating allodynia for at least 1 month.

Topics: Analgesics; Animals; Burns; Disease Models, Animal; Hyperalgesia; Inflammation Mediators; Male; Microglia; Minocycline; Pain, Intractable; Rats; Rats, Sprague-Dawley; Treatment Outcome

Tigecycline is a new semi-synthetic antibiotic from the glycylcycline class of antibiotics. In the Czech Republic this preparation is registered only primarily for complicated skin infections and infection of soft tissues, along with complicated intra-abdominal infections. In future its indications will perhaps widen to include respiratory tract infections, as is the case in the USA. So far we don't have sufficient data about the use of tigecycline in the treatment of critically ill patients, and in these patients it should not be the treatment of first choice. However, it remains to be seen whether increasing resistance and insufficient new types of antibiotics will force us to use tigecycline in these indications as well. Bacterial infections still present a huge threat to severely burned patients. Lately, in patients with burn trauma, as the source of infection complications have begun to dominate significantly multiresistant strains of bacteria. These bacteria originate from gram positive as well as gram negative spectrum. In severely burned patients the early and correct indication of antibiotic treatment, as well as the appropriate choice of antibiotics, forms one of the foundations of successful treatment. At the Department of Burns and Reconstructive Surgery we first used tigecycline on August 9th 2008 in the treatment of non-healing defects after autotransplant with dermo-epidermal grafts in the face, where the source of infection was identified as mixed bacterial microflora. The treatment was successful. Since then tigecycline has become a standard antibiotic at our workplace. In the observed period of 12 months we have used the antibiotic in 11 patients. Thanks to a wide antibacterial spectrum, monotherapy with tigecycline constitutes an interesting alternative to the frequently difficult combination of antibiotics used in other treatments. In this work we present our clinical experience, results, indications as well as difficulties in tigecycline treatment.

Topics: Adult; Aged; Anti-Bacterial Agents; Burns; Drug Resistance, Multiple; Female; Humans; Middle Aged; Minocycline; Tigecycline; Wound Infection; Young Adult

Infections in burn patients are usually caused by multidrug-resistant micro-organisms. Tigecycline, a derivative of glycylcyclines, is an effective antibiotic against the resistant strains. The aim of this study is to determine the in vitro activity of tigecycline against the multidrug-resistant bacteria isolated from burn patients. Fourty-seven bacteria isolated from 118 patients hospitalized in the burn unit during 2003-2006 were included in the study. Gram-negative bacteria that were resistant to at least six broad-spectrum antibiotics, methicillin-resistant staphylococci and ampicillin-resistant enterococci were studied. Minimal inhibitory concentration values of tigecycline against these bacteria were tested by E-test strips. Susceptibility breakpoints were determined according to the previous studies;

Topics: Acinetobacter; Anti-Bacterial Agents; Bacteriological Techniques; Burns; Drug Resistance, Multiple, Bacterial; Enterococcus; Gram-Negative Bacteria; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Staphylococcus aureus; Tigecycline

Novel wound dressings composed of chitosan (CH) film and minocycline hydrochloride (MH) were prepared using commercial polyurethane film (Tegaderm) as a backing. CHs with deacetylation degrees of 67%, 83% and 96% (mol/mol), named CH67, CH83 and CH96, respectively, were used. Wound dressing with a large piece of Tegaderm film (4 cm x 4 cm), named CH-MH-N, and wound dressing prepared by cutting CH-MH-N to the wound size, named CH-MH-A, were developed. As CH67-MH-N and CH83-MH-N showed the sustained release of minocycline in vitro, CH67 and CH83 were used as chitosan in the in vivo studies. Various formulations were applied to severe burn wounds in rats in the early stage, and the wound status and change in the wound surface area were examined. The use of 10mg of MH and complete sealing with Tegaderm had a negative effect. MH ointment was not effective, but Geben cream was fairly effective. However, CH83-MH-A containing 2mg of MH (CH83-MH2-A) and CH83 film showed an excellent effect. Considering the elimination of pus, CH83-MH2-A tended to be better than CH83 film. CH83-MH2-A is suggested as a useful formulation for the treatment of severe burn wounds.

Topics: Animals; Anti-Bacterial Agents; Bandages; Burns; Chitosan; Delayed-Action Preparations; Male; Minocycline; Polyurethanes; Rats; Technology, Pharmaceutical; Wound Healing

Topics: Adult; Aged; Burns; Escherichia coli; Female; Humans; Infusions, Parenteral; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Penicillins; Pneumonia; Tetracyclines; Urinary Tract Infections