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To test the therapeutic effect of recombinant fusion polypeptide hEGF-AWRK6 (EK) on burn infection of model mice. EK6 was expressed and purified with Escherichia coli expression system, and the Ⅱ degree burns and Pseudomonas aeruginosa infection model mouse were established. Experiment group was treated with EK (30 mg/L), and the control group was treated with PBS, gentamicin (30 mg/L), burn ointment (10 mg/L). The wound healing rate and colony count were calculated. Wound and surrounding skin were taken for HE staining and collagen western-blot analysis, and the wound pathological changes were observed after 10 days of drug delivery. The results showed that fusion peptide EK was successfully expressed and purified with significant antibacterial activities against Pseudomonas aeruginosa. Compared to the control group, the colony count (CFU) of the wound surface in EK mouse had a remarkable decrease (P<0.01) and healing rate had a significant increase in group EK6 (P<0.01). Pathological analysis result showed that compared to the control group, wound dermal cells in group EK arranged regularly, had more hair growth and a faster epithelization. These results indicated that the fusion peptide EK would be a good candidate for the drug development for the treatment of burning wounds.

Burn patients have a high risk of sepsis-related mortality even after surviving the initial injury. Immunosuppression increases the risk of sepsis after burn injury, as does the disruption of the intestinal epithelial barrier, which allows the translocation of bacteria and bacterial products into the circulation. The integrity of the intestinal epithelial barrier is largely maintained by the intestinal microbiota. Burn injury has been reported to result in significant changes in the intestinal microbiome composition. In this mouse study, we confirm these taxonomic differences in a full-thickness scald injury model using CF-1 mice. For the first time, we also address alterations in functional gene expression of the intestinal microbiota after burn injury to assess the microbiome's physiological capabilities for overgrowth and pathogenic invasion: 38 pathways were differentially abundant between the sham and burn injury mice, including bacterial invasion of epithelial cells and gap- and adherens junction pathways., Competing Interests: The authors have declared that no competing interests exist.

Background: Multidrug-resistant (MDR) bacteria are an emerging international concern in low- and middle-income countries that threaten recent public health gains. These challenges are exacerbated in immunocompromised hosts, such as those with burn injury. This study sought to describe the epidemiology and associated clinical outcomes of burn wound colonization in a Malawian tertiary burn center., Methods: This is a prospective analysis of burn patients presenting to Kamuzu Central Hospital in Lilongwe, Malawi, within 72 h of burn injury. A swab of each patient's primary wound was collected at admission and each subsequent week. The primary exposure was burn wound colonization with MDR bacteria, particularly Enterobacteriaceae. The primary outcome was in-hospital mortality. A log binomial model estimated the association between the exposure and outcome, adjusted for confounders., Results: Ninety-nine patients were enrolled with a median age of 4 years (IQR 2-12) and a male preponderance (54%). Median total body surface area burn (TBSA) was 14% (IQR 9-25), and crude in-hospital mortality was 19%. Enterobacteriaceae were the most common MDR bacteria with 36% of patients becoming colonized. Wound colonization with MDR Enterobacteriaceae was associated with increased in-hospital mortality with a risk ratio of 1.86 (95% CI 1.38, 2.50, p < 0.001) adjusted for TBSA, burn type (scald vs. flame), sex, age, length of stay, and methicillin-resistant Staphylococcus aureus colonization., Conclusion: MDR bacteria, especially Enterobacteriaceae, are common and are associated with worse burn injury outcomes. In resource-poor environments, a greater emphasis on prevention of MDR bacterial colonization, improved isolation precautions, affordable diagnostics, and antibiotic stewardship are imperative.

Considering the increased antibiotic resistance of Pseudomonas aeruginosa, the evaluation of immune response against the antigens of this bacterium seems necessary. In this study, the protective efficacy and immunological properties of P. aeruginosa recombinant PilQ (r-PilQ) and type b-flagellin (FLB) proteins was evaluated in the burn mouse model of infection. The inbred BALB/c mice were immunized with r-PilQ and FLB antigens. To investigate the type of induced immune response, sera were analyzed by ELISA for total IgG, IgG1, and IgG2a isotypes. After the final immunization, the IL-4, IFN-γ, and IL-17 cytokines level were examined in the spleen of non-challenged mice. Fifty days after lethal challenge, the survival rate and bacterial burden in the skin and other internal organs of experimental mice were assessed. The in vivo administration of r-PilQ, FLB and combined antigen resulted in a significant increase in the survival of mice (66%, 75%, and 83%, respectively) infected by the PAO1 strain of P. aeruginosa in the burn model of infection. Immunization of mice with r-PilQ and FLB mixture induced high titers of IL-4 and IL-17 cytokines compared to control groups (P < 0.05). The high titer of antisera raised against combined antigen was able to inhibit the systemic spread of the PAO1 strain from the site of infection to the internal organs. We concluded that the parallel role of IL-4 and IL-17 is necessary for elimination of the bacteria and promotion of survival in the immunized burn mice., (Copyright © 2018. Published by Elsevier Ltd.)

The authors summarize the medical history of a patient with impaired healing of a wound in the sole of foot. The 63-year-old male patient had a second-degree burn in the sole of the left foot as he stepped on the hot concrete after taking off his slipper. On admission to our department, local wound management had already been started, his wound showed no healing tendency. Bilateral X-ray was performed of his left leg, osteomyelitis was not confirmed, soft tissue drainage was applied, and bacterial culture from the wound confirmed methicillin-resistant Staphylococcus aureus infection. After soaking the leg in water, phlegmon developed on the dorsal part of the foot and the patient had septic fever. X-ray was repeated, and osteomyelitis was confirmed. Enucleation of the hallux of the left foot and metatarsal resection were performed. Wound dressing was exchanged and wound toilette was applied daily, insulin therapy was modified after consultation with a diabetologist. 7 months after the surgery, the wound was completely healed, carbohydrate metabolism of the patient was controlled. Our case draws attention to the importance of informing the patients of potential complications - in this case of the diabetic foot and its proper care. Treatment of ulcer of the lower leg requires multidisciplinary care, which means that the diabetologist and the surgeon has to cooperate in the care of these patients, carbohydrate metabolism should be balanced and regular wound care is necessary. Orv Hetil. 2018; 159(42): 1727-1730.

Purpose: Because infection can thwart burn healing, microorganisms, their susceptibility patterns, and the effect of tangential excision timing on outcomes of burn patients were examined., Methods: A prospective, observational study was conducted that involved 318 patients with deep second-degree burns from a gas explosion treated in Xinxiang, Henan, China between January 2009 and December 2016. Patient demographic data, culture and antimicrobial susceptibility test results, and outcome variables (resuscitation fluid volume, signs of shock, body temperature, heart rate, and time to wound healing) were analyzed. Outcomes were compared among patients who had early (<24 hours), middle (2 to 7 days), and late (> 7 days) post burn excision., Results: Bacterial culture and drug sensitivity data were available for 314 of the 318 persons with burns >10% of total body surface area (TBSA). Of the 486 bacterial isolates, 330 (67.9%) were gram-negative and 156 (32.1%) were gram-positive. The number of isolates and resistance to third-generation cephalosporins increased over time. Patients having early tangential excision had significantly lower heart rate (P <.05) and reduced time to healing (P <.01) than patients in the middle or late excision group., Conclusion: Early tangential excision was found to be safe and to facilitate healing.

Background: Pseudomonas aeruginosa is a major cause of hospital-acquired infection due to its high antibiotic resistance and biofilm formation ability. P. aeruginosa produces elastase lasB during biofilm formation, which can influence properties of biofilm. This study was carried out to evaluate the antibiotic resistance and distribution of the lasB gene among biofilm-producing P. aeruginosa strains isolated from burn patients., Methods: A total of 128 clinical samples were collected from burn patients. The P. aeruginosa isolates were identified using standard bacteriological procedures. Antibiotic susceptibility test was performed by the disk diffusion method. Biofilm formation was measured by microtiter plate assay. The presence of lasB gene was detected by PCR., Results: A total of 75 samples were positive for P. aeruginosa. A high rate of resistance was seen against ceftriaxone, cefotaxime, and piperacillin/tazobactam. Biofilm formation was seen in 57.3% of the isolates and the prevalence of the lasB gene was 85.3%. Biofilm formation in isolates without lasB was lower and these isolates were more sensitive to imipenem and piperacillin/tazobactam., Conclusions: In the present study, we did not find a statistically significant relationship among elastase gene (lasB) presence, antibiotic resistance, and biofilm formation in P. aeruginosa strains isolated from burn patients.

Introduction: Health care-associated infections caused by metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa are a significant growing concern in patients with burns worldwide. The aims of this study were to determine the antibiotic susceptibility of and detect the presence of MBLs among P. aeruginosa isolates and assess their clonal relationship using enterobacterial repetitive intergenic consensus (ERIC)-PCR., Methods: Non-duplicated clinical isolates (160) of P. aeruginosa were collected from patients with burns at the Motahari Hospital in Tehran, Iran. All isolates were identified using standard laboratory methods and further characterized for antimicrobial susceptibility. Any carbapenem-resistant isolates were then examined for MBL production by the E-test and MBL-encoding genes were detected by PCR. The clonal relatedness of MBL-producing isolates was assessed by ERIC-PCR., Results: For multidrug-resistant isolates, the highest rates of susceptibility were observed for colistin 160 (100%), polymyxin B 160 (100%), and ceftazidime 32 (20%). In total, 69 (43.7%) isolates were identified as MBL producers. Twenty-eight (17.5%) isolates were positive for the bla VIM-1 gene followed by the bla IMP-1 (15.6%) and bla SPM-1 (5.6%) genes. ERIC-PCR revealed three separate genotypes, where type A (76.8%) was the most prevalent, followed by B (20.3%), and then C (2.9%)., Conclusions: Our present study found that the bla IMP-1 and bla VIM-1 genes were present at a significant frequency and also detected the bla SPM-1 gene in P. aeruginosa isolates for the first time, highlighting the need for establishing suitable infection control measures to successfully treat patients and prevent further spread of these resistant organisms among patients with burns.

Mafenide acetate is an effective but costly antimicrobial solution used for burn wounds. The package insert instructs the user to discard unused solution within 48 hours of opening. The purpose of this study is to evaluate the antimicrobial activity of mafenide acetate beyond 48 hours after reconstitution, to possibly reduce cost by eliminating product waste. Staphylococcus aureus and Pseudomonas aeruginosa isolates were used to seed Mueller-Hinton agar plates. Filter paper disks were then saturated with 5% mafenide acetate at 0, 2, 7, 14, 30, and 60 days after reconstitution. Disks were then placed on the seeded agar plates and incubated. After incubation, the zone of inhibition around each plate was measured. A zone of inhibition of 2 mm or greater was indicative of susceptibility. Mafenide acetate remained efficacious, with a zone of inhibition of >2 mm to both organisms at 0, 2, 7, 14, 30, and 60 days after mafenide acetate reconstitution. This in vitro study demonstrates that the antimicrobial activity of mafenide acetate remains present for at least 60 days after reconstitution. Unused mafenide may not need to be discarded at 48 hours after opening. Reducing wasted product has the potential to translate into cost savings.

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.

Burn infections pose a serious obstacle to recovery. To investigate and analyze the antimicrobial resistance and distribution of pathogenic bacteria among hospitalized burn patients. A 3-year retrospective study was conducted in the southeast of China.The electronic medical records system was used to collect all clinical data on 1449 hospitalized patients from Fujian Medical University Union Hospital, the 180th Hospital of Chinese People's Liberation Army (PLA), the 92nd Hospital of PLA, and the First Hospital of Longyan City.A total of 1891 strains of pathogenic bacteria were detected from 3835 clinical specimens, and the total detection rate was 49.3% (1891/3835). The main pathogens were gram-negative bacteria (1089 strains; 57.6%), followed by gram-positive bacteria (689 strains; 36.4%), and fungi (113 strains; 6.0%). The predominant five bacteria were Staphylococcus aureus (19.0%), Acinetobacter baumannii (17.6%), Pseudomonas aeruginosa (16.7%), Klebsiella pneumoniae (7.4%), and Enterococcus faecalis (4.5%). Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 74.1% (265/359) of S aureus isolates. Staphylococcus epidermidis accounted for 40.6% (69/170) of coagulase-negative staphylococcal isolates, 72.5% (50/69) of which were methicillin-resistant Staphylococcus epidermidis (MRSE). Both MRSA and MRSE were 100% resistant to penicillin and ampicillin. A baumannii was the most commonly isolated strain of gram-negative bacteria with 100% resistance to ampicillin, amoxicillin, amoxicillin/clavulanic acid, and aztreonam. More than 80% of K pneumoniae isolates were resistant to ampicillin, amoxicillin and cefazolin. More than 80% of Escherichia coli isolates were resistant to ampicillin, piperacillin, cefazolin, amoxicillin, tetracycline, and sulfamethoxazole trimethoprim. The detection rates of extended-spectrum β-lactamases (ESBL) among K pneumoniae and E coli isolates were 44.6% (62/139) and 67.2% (41/61), respectively. Low-resistance antibiotics included teicoplanin, tigecycline, vancomycin, and linezolid.The pathogens presented high resistance to antimicrobial agents, especially MRSA and A baumannii. Monitoring of bacterial population dynamics should be established to inhibit the progression of bacterial resistance.

While physically crosslinked polycarbonate hydrogels are effective drug delivery platforms, their hydrophobic nature and lack of side chain functionality or affinity ligands for controlled release of hydrophilic drugs underscore the importance of their chemical compositions. This study evaluates an array of anionic hydrogel systems of phenylboronic acid functionalized triblock copolymers prepared via reversible physical interactions. Variation of key chemical functionalities while maintaining similar core structural features demonstrates the influence of the substitution position and protection of the boronic acid functionality on gel viscoelasticity and mechanical strength at physiological pH. The optimum gel systems obtained from the meta-substituted copolymers (m-PAP) are stable at physiological pH and nontoxic to mammalian dermal cells. The polymyxin B loaded m-PAP hydrogels demonstrate controlled in vitro drug release kinetics and in vitro antimicrobial activity against Pseudomonas aeruginosa over 48 h. In vivo antimicrobial efficacy of the drug loaded hydrogels further corroborates the in vitro results, demonstrating sustained antimicrobial activity against P. aeruginosa burn wound infections. The current strategy described in this study demonstrates a straightforward approach in designing physiologically relevant boronic acid hydrogel systems for controlled release of cationic antimicrobials for future clinical applications., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Infections are the most frequent complications in burn patients. Filamentous fungi have an uncertain place within the statistics, since in our media data regarding their prevalence, causal agents and outcome of those who suffer them remain scarce. The aim of this study was to evaluate the prevalence of fungal infection by filamentous fungi (IHF) in patients hospitalized in burn intensive care unit (BICU), and to review clinical, epidemiological, microbiological and evolutionary characteristics of these patients and to know the frequency and distribution of the isolated fungi., Materials and Methods: Retrospective and descriptive study. It includes all individuals admitted in burns intensive care unit (2012-2015), with positive culture for filamentous fungi in skin biopsies and bedsores., Results: A total of 168 patients were admitted in the BICU in a period of 3 years. 90% were major burned and 17% of them developed IHF (29/168). Aspergillus spp (24%), Fusarium sp (14%), Mucor spp (3%) and various black fungus genera (58%) were the main genera found in cultives. About 24% of the patients with IHF died and Fusarium spp was found in 50% of the cases. The cause of death was irreversible cardiogenic shock with multiorgan failure., Conclusions: Filamentous fungal infection was present in 17% of burned patients. The main isolatte fungi in samples were dematiaceous mould. Mortality among patients was 24%, with Fusarium being the fungus found in the highest number of deaths (50%).

Biofilm formation in wounds is considered a major barrier to successful treatment, and has been associated with the transition of wounds to a chronic non-healing state. Here, we present a novel laboratory model of wound biofilm formation using ex-vivo porcine skin and a custom burn wound array device. The model supports high-throughput studies of biofilm formation and is compatible with a range of established methods for monitoring bacterial growth, biofilm formation, and gene expression. We demonstrate the use of this model by evaluating the potential for bacteriophage to control biofilm formation by Staphylococcus aureus , and for population density dependant expression of S. aureus virulence factors (regulated by the Accessory Gene Regulator, agr ) to signal clinically relevant wound infection. Enumeration of colony forming units and metabolic activity using the XTT assay, confirmed growth of bacteria in wounds and showed a significant reduction in viable cells after phage treatment. Confocal laser scanning microscopy confirmed the growth of biofilms in wounds, and showed phage treatment could significantly reduce the formation of these communities. Evaluation of agr activity by qRT-PCR showed an increase in activity during growth in wound models for most strains. Activation of a prototype infection-responsive dressing designed to provide a visual signal of wound infection, was related to increased agr activity. In all assays, excellent reproducibility was observed between replicates using this model.

Colorimetric DNA detection is preferred over other methods for clinical molecular diagnosis because it does not require expensive equipment. In the present study, the colorimetric method based on gold nanoparticles (GNPs) and endonuclease enzyme was used for the detection of P. aeruginosa ETA gene. Firstly, the primers and probe for P. aeruginosa exotoxin A (ETA) gene were designed and checked for specificity by the PCR method. Then, GNPs were synthesized using the citrate reduction method and conjugated with the prepared probe to develop the new nano-biosensor. Next, the extracted target DNA of the bacteria was added to GNP-probe complex to check its efficacy for P. aeruginosa ETA gene diagnosis. A decrease in absorbance was seen when GNP-probe-target DNA cleaved into the small fragments of BamHI endonuclease due to the weakened electrostatic interaction between GNPs and the shortened DNA. The right shift of the absorbance peak from 530 to 562nm occurred after adding the endonuclease. It was measured using a UV-VIS absorption spectroscopy that indicates the existence of the P. aeruginosa ETA gene. Sensitivity was determined in the presence of different concentrations of target DNA of P. aeruginosa. The results obtained from the optimized conditions showed that the absorbance value has linear correlation with concentration of target DNA (R: 0.9850) in the range of 10-50ngmL -1 with the limit detection of 9.899ngmL -1 . Thus, the specificity of the new method for detection of P. aeruginosa was established in comparison with other bacteria. Additionally, the designed assay was quantitatively applied to detect the P. aeruginosa ETA gene from 10 3 to 10 8 CFUmL -1 in real samples with a detection limit of 320CFUmL -1 ., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Infections in burn patients are still the principal cause of complications in burn injuries. The aim of this study is to assess a new strategy for burn wound management in view of infection prevention and treatment in the experience of the Burn Treatment Center in Siemianowice Śląskie. The applied methodology involved the analysis of patient records describing the hospital's epidemiological situation between 2014 and 2016. The analysis also included the use and cost of antibiotics, silver-containing dressings, and other antiseptics relative to the number of sepsis cases, including those caused by Pseudomonas aeruginosa, as well as the mortality ratio. The total costs of prevention and treatment of infections were reduced, while the use of silver-containing dressings and antiseptics increased. The number of patients with sepsis decreased, including cases caused by P. aeruginosa, and the mortality ratio was reduced. Introducing a strategy for burn wound-oriented infection prevention and treatment in burn patients provides a number of benefits. It is also cost-effective. Using locally applied active dressings and antiseptics can be a welcome choice for often-unnecessary antibiotic therapy of a suspected or existing burn wound infection., (© 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Objectives: Pseudomonas aeruginosa is a frequent cause of infectious diseases, such as burn and wound infections, making it one of the most menacing opportunistic pathogens. The aim of this study was to investigate the antimicrobial resistance, biofilm-forming ability, and frequency of genes involved in biofilm formation and virulence of P. aeruginosa isolated from burn infections in Iran., Methods: Resistance of 90 P. aeruginosa isolates to 12 antimicrobial agents as well as production of extended-spectrum β-lactamase (ESBL) and metallo-β-lactamase (MBL) enzymes were assessed phenotypically according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Biofilm-forming capacity was assayed in a microtitre plate. The frequency of biofilm- and virulence-associated genes was investigated by PCR. Mutations in gyrA and parC in ciprofloxacin-resistant isolates were also determined by PCR., Results: In phenotypic assays, 72.2% (65/90) of P. aeruginosa isolates were multidrug-resistant (MDR), 55.5% (50/90) and 35.6% (32/90) were positive for ESBL and MBL production, respectively, and 67.8% (61/90) were positive for biofilm formation. Biofilm- and virulence-associated genes were identified in >50% of the P. aeruginosa isolates, with toxA and lasB being the most frequent. All of the virulence genes were more common in biofilm-forming and MDR phenotypes. Two point mutations in gyrA and one in parC in high-level ciprofloxacin-resistant isolates were identified., Conclusions: The results of this study indicate that there is a high frequency of multidrug resistance and a high percentage of virulence-associated genes present in clinical P. aeruginosa isolates in Iran., (Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Background: Acinetobacter baumannii causes difficult-to-treat nosocomial infections, which often lead to morbidity due to the development of antimicrobial drug resistance and expression of virulence genes. Data regarding the association of resistance to colistin, a last treatment option, and the virulence gene expression of A. baumannii is scarce., Methods: We evaluated the MLVA genotype, antimicrobial resistance, and biofilm formation of 100 A. baumannii isolates from burn patients, and further compared the in vitro and in vivo expression of four virulence genes among five colistin-resistant A. baumannii (Cst-R-AB) isolates. Five Cst-R-AB isolates were tested; one from the present study, and four isolated previously., Results: Our results showed that reduced expression of recA, along with increased in vivo expression of lpsB, dnaK, and blsA; are associated with colistin resistance among Cst-R-AB isolates. Differences in virulence gene expressions among Cst-R-AB isolates, may in part explain common discrepant in vitro vs. in vivo susceptibility data during treatment of infections caused by Cst-R-AB., Conclusions: Our findings highlight the intricate relationship between colistin-resistance and virulence among A. baumannii isolates, and underscore the importance of examining the interactions between virulence and antimicrobial resistance toward efforts to control the spread of multidrug-resistant A. baumannii (MDR-AB) isolates, and also to reduce disease severity in burn patients with MDR-AB infection.

Background: Burn injury induces immunosuppression and promotes infection with opportunistic pathogens. Pneumonia and sepsis are leading causes of post-burn morbidity and mortality. Fms-like tyrosine kinase-3 ligand (Flt3L) improves local and systemic resistance to P aeruginosa-associated burn wound infection. This study evaluates the effects of post-burn prophylactic Flt3L treatment on local and systemic infection and inflammation in a murine model of pneumonia and sepsis., Methods: Mice received a severe scald burn, were treated with Flt3L or vehicle (CTR) for 5 days, and inoculated trans-nasally with P aeruginosa. Lung, blood, and spleen were harvested at 24 and 48 h postinoculation (p.i.) to assess infection (bacterial burden, bacteremia, distant organ manifestation) and inflammation (interleukin-6 (IL-6) and myeloperoxidase (MPO) levels). Histology correlated infection and inflammation parameters with morphology. Survival at various bacterial concentrations was monitored for 14 days p.i., Results: Bacterial burden was significantly reduced in lung and spleen of Flt3L-treated mice. Flt3L treatment was associated with decreased signs of pulmonary inflammation (reduced wet weight and IL-6 levels), lower incidences of bacteremia and septic distant organ manifestation, and reduced systemic inflammation (IL-6 and MPO). Histologically, reduced alveolar and peribronchiolar neutrophil and lymphocyte infiltration indicated attenuated pulmonary inflammation after Flt3L treatment. Overall survival was comparable between groups for all doses of P aeruginosa, but mortality delayed in the Flt3L-treated group., Conclusion: Prophylactic treatment with Flt3L could augment antimicrobial therapy of post-burn pneumonia through improvement of the initial host response to challenge with P aeruginosa, attenuate local, and systemic inflammation as well as septic pathogen dissemination.

Aim: Nanoethosomal formulation containing silver sulfadiazine (SSD) was used to reduce bacterial burden and healing time in burn injuries., Materials & Methods: Ethosomal formulations were characterized for their size, ζ-potential, morphology, drug encapsulation efficiency and in vitro release kinetics of SSD., Results: The optimized nanoethosomal suspension with a size of 206.7 ± 1.18, and ζ-potential value of -67.3 ± 0.45 mV exhibited a high SSD encapsulation efficiency (92.03 ± 0.79%). Results of antimicrobial tests indicated SSD-loaded ethosome formulation led to a significant reduction of colony number. Histopathological results demonstrated a wound contraction rate of 96.83% for the group treated with SSD ethosomal gel while untreated group showed 59.41%., Conclusion: The SSD ethogels promotes the therapeutic effect of SSD for burn treatment.

Background: Raoultella planticola, a Gram-negative, aerobic bacillus commonly isolated from soil and water, rarely causes invasive infections in humans. Septic shock from R. planticola after burn injury has not been previously reported., Case Presentation: A 79-year-old male was admitted to the emergency intensive care unit after extensive flame burn injury. He accidently caught fire while burning trash and plunged into a nearby tank filled with contaminated rainwater to extinguish the fire. The patient developed septic shock on day 10. The blood culture detected R. planticola, which was identified using the VITEK-2 biochemical identification system. Although appropriate antibiotic treatment was continued, the patient died on day 12., Conclusions: Clinicians should be aware of fatal infections in patients with burn injury complicated by exposure to contaminated water.

As the development of new classes of antibiotics slows, bacterial resistance to existing antibiotics is becoming an increasing problem. A potential solution is to develop treatment strategies with an alternative mode of action. We consider one such strategy: anti-adhesion therapy. Whereas antibiotics act directly upon bacteria, either killing them or inhibiting their growth, anti-adhesion therapy impedes the binding of bacteria to host cells. This prevents bacteria from deploying their arsenal of virulence mechanisms, while simultaneously rendering them more susceptible to natural and artificial clearance. In this paper, we consider a particular form of anti-adhesion therapy, involving biomimetic multivalent adhesion molecule 7 coupled polystyrene microbeads, which competitively inhibit the binding of bacteria to host cells. We develop a mathematical model, formulated as a system of ordinary differential equations, to describe inhibitor treatment of a Pseudomonas aeruginosa burn wound infection in the rat. Benchmarking our model against in vivo data from an ongoing experimental programme, we use the model to explain bacteria population dynamics and to predict the efficacy of a range of treatment strategies, with the aim of improving treatment outcome. The model consists of two physical compartments: the host cells and the exudate. It is found that, when effective in reducing the bacterial burden, inhibitor treatment operates both by preventing bacteria from binding to the host cells and by reducing the flux of daughter cells from the host cells into the exudate. Our model predicts that inhibitor treatment cannot eliminate the bacterial burden when used in isolation; however, when combined with regular or continuous debridement of the exudate, elimination is theoretically possible. Lastly, we present ways to improve therapeutic efficacy, as predicted by our mathematical model.

The management of wounds and burns is becoming difficult using conventional therapeutics available due to resistance development by microbes. Therefore, there is an utmost need to develop therapeutic alternatives to these agents. Antimicrobial peptides have emerged as a novel class of agents for the effective management of wounds and burns due to their potent nature along with minimal chances of resistance development against them. This article focuses on highlighting the importance of these antimicrobial peptides among the various therapeutic alternatives for burns and wounds. Further, effective delivery strategies for these agents that are being employed and investigated are reported along with an overview of the importance of these agents in the coming years.

Background: The overexpression of efflux pumps and existence of class 1 integrons are the most important mechanisms that contribute to antimicrobial resistance in Pseudomonas aeruginosa especially in burn and Intensive Care Units (ICUs). The present study evaluated the role of MexAB-OprM and MexXY-OprM efflux pumps and class 1 integrons in resistance to antibiotics in burn and ICU isolates of P. aeruginosa., Methods: Fifteen burn and forty-two ICU isolates were obtained from four hospitals in Northwest Iran. The isolates were identified and evaluated by the disk diffusion and agar dilution methods for determining antibiotic resistances. The presence of class 1 integrons and associated resistance gene cassettes were detected by PCR and sequencing of the products. The expression levels of efflux pumps were evaluated by phenotypic and genotypic (Quantitative Real-time PCR) methods. The isolates were genotyped by Random Amplified Polymorphic DNA Typing (RAPD-PCR)., Results: All burn isolates were integron positive and Multi-drug resistant (MDR), while 78.5% and 69% of ICU isolates were found as MDR and integron positive, respectively. The aadB gene was the most prevalent gene cassette (63.6%) followed by aacA4 (47.7%). Thirty-nine (68.4%) and 43 (75.4%) isolates exhibited an overexpression of MexAB-OprM and MexXY-OprM. Among burn isolates, 80% and 86.6% of them were mexB and mexY overexpressed, while 64.2% and 71.4% of ICU isolates exhibited mexB and mexY overexpression, correspondingly. The isolates were genotyped as 24 different RAPD profiles and were grouped into 15 clusters., Conclusions: The data suggested that class 1 integron had a more significant role than efflux pumps in resistance to beta-lactams and aminoglycosides in burn and ICUs except for gentamicin in burn isolates. Based on our data, it is possible that efflux pumps were not the main cause of high-level resistance to antibiotics., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Biofilm forming drug-resistant Pseudomonas aeruginosa are responsible for major death in burn center of different hospitals across the globe., Objective: The aims of this study were to evaluate the effect of nano-silver (Ag), nano-copper (Cu), and two hospital disinfectants (deconex and benzalkonium chloride) on biofilm formation and expression of transcription regulatory quorum sensing gene rh1R in P. aeruginosa burn isolates., Methods: 28 multidrug-resistant P. aeruginosa (MDRPA) strains were isolated from patients hospitalized in the burn center of a referral hospital in Kerman, Iran. Sizes and purities of nanoparticles were checked by TEM and X-ray diffraction (XRD) analysis. The Minimal Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of the nanoparticles (NPs), deconex and benzalkonium chloride were determined by broth microdilution method. Antibiofilm activities of these compounds were measured by microtiter assay. Polymerase chain reaction (PCR) was used for detection of qacEΔ1, cepA, copA and rhlR genes. Quantification of rhlR gene expression in presence and absence of the above compounds was carried out by relative quantitative real-time PCR (qRT-PCR)., Results: Benzalkonium chloride had a potent antimicrobial activity and inhibited growth of all the isolates at MIC 0.06±0.2mg/mL, while nano-Ag was effective at MIC 20±0.2mg/mL. Furthermore, 28.5% of the isolates showed strong, 25% moderate, 14% weak and 32% demonstrated no biofilm activity. Ag NPs exerted highest antibiofilm activity, follow by deconex and benzalkonium chloride. The qacEΔ1 was absent in this study, whereas 17.8% and 60.8% of the isolates were positive for cepA and copA genes. Benzalkonium chloride, Ag NPs and deconex increased the expression of rhlR gene 64, 2 and 7 folds, respectively., Conclusion: Our results suggest that, there is direct relationship between decrease in antibiofilm activity and increase in expression of the rhlR gene in the presence of benzalkonium chloride. Absence of qacEΔ1 gene may be contributed in sensitivity of the isolates to the above agents., (Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.)

We isolated and identified yeasts from burn wounds and evaluated the ability of Candida parapsilosis isolates from burn wounds to penetrate an acellular dermal matrix (ADM). A prospective study was conducted with patients from the burn treatment center of North Paraná University Hospital in Londrina, Brazil from February 2015 to January 2016. Yeast cultures were obtained from the tissue of burn wounds that had been debrided and cleansed with 2% chlorhexidine. After identification and confirmation of the purity of the culture, the yeasts were placed on ADM fragments and incubated for three or seven days. During the study period, 273 patients were treated, and 36 of these patients fulfilled the inclusion criteria and provided samples for culture. Yeasts were isolated in 19.44% (n = 7) of the cultures, and the following species were identified: C. parapsilosis (57.1%), C. albicans (28.6%), and C. glabrata (14.3%). C. parapsilosis, the most frequent species, was chosen for the ADM tests. We demonstrated active penetration of the ADM by the yeast isolates from burn wounds. C. parapsilosis grew on ADM and penetrated the matrix, indicating that this yeast, which is common in skin and cutaneous wounds, has the potential to colonize and pass through ADM, a medical device that is frequently used to dress and regenerate burn wounds., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Bacterial pneumonia is a leading cause of death late after burn injury due to the severe immune dysfunction that follows this traumatic injury. The Mechanistic/Mammalian Target of Rapamycin (mTOR) pathway drives many effector functions of innate immune cells required for bacterial clearance. Studies have demonstrated alterations in multiple cellular processes in patients and animal models following burn injury in which mTOR is a central component. Goals of this study were to (1) investigate the importance of mTOR signaling in antimicrobial activity by neutrophils and (2) therapeutically target mTOR to promote normalization of the immune response. We utilized a murine model of 20% total body surface area burn and the mTOR-specific inhibitor rapamycin. Burn injury led to innate immune hyperresponsiveness in the lung including recruitment of neutrophils with greater ex vivo oxidative activity compared with neutrophils from sham-injured mice. Elevated oxidative function correlated with improved clearance of Pseudomonas aeruginosa, despite down-regulated expression of the bacterial-sensing TLR molecules. Rapamycin administration reversed the burn injury-induced lung innate immune hyperresponsiveness and inhibited enhanced bacterial clearance in burn mice compared with untreated burn mice, resulting in significantly higher mortality. Neutrophil ex vivo oxidative burst was decreased by rapamycin treatment. These data indicate that (1) neutrophil function within the lung is more important than recruitment for bacterial clearance following burn injury and (2) mTOR inhibition significantly impacts innate immune hyperresponsiveness, including neutrophil effector function, allowing normalization of the immune response late after burn injury., (©2018 Society for Leukocyte Biology.)

The efficacy of subcutaneously administered polymyxins against burn wound infections caused by Pseudomonas aeruginosa , Acinetobacter baumannii , and Klebsiella pneumoniae was examined in a murine infection model. Subcutaneously administered colistin and polymyxin B (30 mg/kg thrice daily) achieved a ≥2-log 10 reduction in the bacterial load for P. aeruginosa and A. baumannii infections, whereas wound infections by K. pneumoniae were less responsive (<1-log 10 reduction). This study highlights the potential therapeutic benefits of parenteral polymyxins for treating burn wound infections., (Copyright © 2018 American Society for Microbiology.)

Objective: The aim of this cross-sectional study is to assess the epidemiological profile and antibiotic susceptibility of bacteria isolates in burn patients hospitalized from 2007 to 2015 in a Moroccan hospital., Materials and Methods: Of 627 samples, 451 wounds, 126 blood cultures, and 50 catheter samples were analyzed. A total of 610 microorganisms were isolated from a total of 108 patients., Results: The most prevalent isolates were Pseudomonas aeruginosa (18.5%), Acinetobacter baumannii (14.7%), and Staphylococcus aureus (14.5%); a high prevalence (31.1%) of methicillin-resistant S aureus also was found. Imipenem followed by piperacillin/tazobactam performed best against P aeruginosa. A baumannii isolates showed a very high resistance to imipenem and all beta-lactams antibiotics but were sensitive to colistin., Conclusions: The profile of this bacterial ecology shows there are resistant species requiring frequent use of second-line antibiotics and strengthening of aseptic procedures in burn treatments.

Background/purpose: Bloodstream infection is a leading cause of mortality among burn patients. This study aimed to evaluate the risk factors, causative pathogens, and the relationship between bloodstream infections and other infections among burn patients from the Formosa Fun Coast Dust Explosion., Methods: This retrospective study evaluated the demographic and clinical characteristics, infection types, causative pathogen(s), and isolates' antibiotic susceptibilities from patients who were hospitalized between June 27 and September 31, 2015., Results: Fifty-eight patients were admitted during the study period (36 males, mean age: 22.6 years). The mean burned total body surface area (TBSA) was 40% for all patients. Eighteen (31%) patients with mean TBSA of 80% had 66 episodes of bloodstream infections caused by 92 isolates. Twelve (18.2%) episodes of bloodstream infections were polymicrobial. Acinetobacter baumannii (19, 20.7%), Ralstonia pickettii (17, 18.5%), and Chryseobacterium meningosepticum (13, 14.1%) were the most common pathogens causing bloodstream infections. A high concordance rate of wound cultures with blood cultures was seen in Staphylococcus aureus (3, 75%) and C. meningosepticum (8, 61.5%) infections. However, no Ralstonia isolate was found in burn wounds of patients with Ralstonia bacteremia. A high concordance rate of central venous catheter cultures with blood cultures was noted in Ralstonia mannitolilytica (5, 62.5%) and Chryseobacterium indologenes (3, 60%) infections. Approximately 21.1% of A. baumannii strains were resistant to carbapenem. All S. aureus isolates were susceptible to methicillin., Conclusions: Waterborne bacteria should be considered in patients of burns with possible water contact. Empirical broad-spectrum antibiotics should be considered for patients who were hospitalized for severe sepsis, or septic shock with a large burn. Antibiotic treatment should be administered based on the specific pathogens and their detection points., (Copyright © 2017. Published by Elsevier B.V.)

MicroRNA-199a (miR-199a) is a novel gene regulator with an important role in inflammation and lung injury. However, its role in the pathogenesis of sepsis-induced acute respiratory distress syndrome (ARDS) is currently unknown. Our study explored the role of miR-199a in sepsis-induced ARDS and its mechanism of action. First, we found that LPS could upregulate miR-199a in alveolar macrophages. Downregulation of miR-199a inhibited the upregulation of inflammatory cytokines in alveolar macrophages and induced the remission of histopathologic changes, the reduction of proinflammatory cytokines, and the upregulation of apoptosis protein expression in an ARDS lung, showing a protective role for miR-199a. We further identified sirtuin 1 (SIRT1) as a direct target of miR-199a in alveolar macrophages, and the expression of SIRT1 was negatively correlated with the level of miR-199a. The protective role of miR-199a downregulation in LPS-stimulated alveolar macrophages and sepsis-induced ARDS could be attenuated by SIRT1 inhibitor. Taken together, these results indicate that downregulation of miR-199a might protect lung tissue against sepsis-induced ARDS by upregulation of SIRT1 through the suppression of excessive inflammatory responses and the inhibition of cellular apoptosis in lung tissue, suggesting its potential therapeutic effects on sepsis-induced ARDS.

Background: Bupleurum chinense, a well-known Traditional Chinese Medicine, has been used for thousands of years in China. In this study, we would suggest that Bupleurum polysaccharides (BPS) could improve the prognosis of sepsis through its impact on redistribution of BMCs, which triggers immune reversal in late sepsis., Methods: BALB/c mice were divided into five groups: sham burn group, burn plus P aeruginosa group, burn plus P aeruginosa with BPS (40 mg/kg, 100 mg/kg, and 250 mg/kg) treatment group, and they were sacrificed at post-burn day (PBD) 0, 3, 5, and 7. BMCs, liver cells, and dendritic cells (DCs) were harvested. Flow cytometry was used to determine the change of phenotypes of DCs and isolate these cells. Cytometric beads array was utilized to analyze the level of inflammatory factors. Cell therapy of BMCs, liver cells, and DCs was administrated to explore the protective role of regional organ immunity., Results: BPS could decrease the lethality of burn sepsis in a dose-dependent fashion and increase both the percentage of CD11cCD45RB DCs in bone marrow (BM) and liver and the number of BMCs and liver cells significantly. Cell therapy of BMCs, liver cells, and CD11cCD45RB DCs at PBD7 could protect septic mice from sepsis., Conclusion: BPS has shown its potential in promoting the prognosis of post-burn sepsis through its effect on immune redistribution of BMCs, especially via differentiation of CD11cCD45RB DC cells in BM and nonimmune organs to induce immune reversal in late sepsis.

In recent decades, the prognosis for burn patients has improved considerably with the development of specialized care. The acellular dermal matrix (ADM) is a totally artificial acellular device that functions to control water loss, prevent penetration by bacteria and allow migration of endothelial cells and fibroblasts from patient tissues. However, little is known about its effectiveness against yeasts. The present study evaluated the capacity of colonization and migration of some human commensal yeasts. Three clinical isolates from skin scales, identified as Candida parapsilosis, Candida glabrata and Rhodotorula mucilaginosa, were used. Their ability to cross the ADM was evaluated. After three days, all isolates had crossed the ADM. C. parapsilosis showed the lowest growth, while R. mucilaginosa showed intermediate and C. glabrata the highest growth. In the plates incubated for seven days, the growth of C. parapsilosis and C. glabrata increased by 1 log over the third day. All isolates have the capacity to colonize and migrate through the matrix, increasing the potential risk to burn patients, who can develop severe and even fatal infections by invasive fungi., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: The aim of the current study was to investigate the therapeutic efficacy of cationic-charged bilayered nanoemulsion for topical delivery of fusidic acid in eradicating methicillin-resistant Staphylococcus aureus (MRSA) bacterial burn wound infection., Materials & Methods: The developed carriers were characterized for particle size, antibacterial activity, cell viability assay in HaCat cell lines, rheological profile, ex vivo and in vivo studies, namely, full thickness MRSA 33591 murine burn wound infection via topical route., Results: The developed cationic bilayered nanogel offered enhanced drug permeation, reduction in bacterial load and enhanced wound contraction along with faster re-epithelialization in burn wounds., Conclusion: The results encourage the exploration of the potential of cationic nanogel in treating resistant microorganisms such as MRSA, especially for application in burn wound infection.

Background: Bloodstream infections (BSI) are a major cause of mortality in burns patients. Knowledge of the microbiology is crucial to direct empirical therapy. We sought to determine the causative microorganisms and antibiotic resistance in burns patients with BSI., Methods: All consecutive BSI episodes in a tertiary hospital burns unit from 2000 to 2014 were included. The following three subperiods were compared: 2000-2004, 2005-2009 and 2010-2014. Changes in BSI occurring during early and late hospitalization periods were evaluated., Results: A total of 103 BSI episodes were included. The cumulative incidence was 2.4 episodes/1000 patient days. A positive trend in the frequency of Gram-negative BSI, especially in the upsurge of Pseudomonas aeruginosa and Klebsiella spp. BSI after 2004, was observed. The most common causative pathogens in early BSI were Gram-positive microorganisms. P. aeruginosa and Klebsiella spp. became the predominant aetiology in the fourth week of hospitalization and beyond. There was a progressive increase in imipenem-resistant P. aeruginosa over time (0%, 67%, 75% in 2000-2004, 2005-2009, 2010-2014, respectively) and during the hospital stay (50% vs. 85.7%, in <7 days-BSI vs. >30 days-BSI, respectively). A higher SOFA (Sepsis-related Organ Failure Assessment) score was associated with Gram-negative BSI versus non-Gram-negative BSI (median: 2.5 vs. 0; p = 0.041)., Conclusions: There is a changing trend in the types of pathogens causing BSI in burns patients over the 14-year period and during the course of hospitalization. The problematic increase in carbapenem-resistance highlights the need for new antimicrobial stewardship policies and antibiotic prescribing protocols.

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is considered a major cause of infection and mortality in burn patients, especially when nosocomially acquired. However, limited information is available on the prevalence of MRSA among burn patients in Iran., Methods: A systematic search was performed using different electronic databases including Medline (via PubMed), Embase, Web of Science and Iranian Database. A meta-analysis was performed using Comprehensive Meta-Analysis Software (BioStat v.2.2). Use of a fixed- or random-effects model was used based on a heterogeneity test, and publication bias was assessed using Begg rank correlation and Egger weighted regression methods., Results: Of 555 articles published from January 2000 to January 2016, 13 studies were included in this review. The meta-analyses showed that the prevalence of MRSA infection in burn patients was 77.9% (95% confidence interval 70.2-84.0%) among culture-positive cases., Conclusions: The results of this study indicate that the prevalence of MRSA among burn patients is very high in Iran. Thus, a comprehensive infection control strategy based on hand hygiene, education and training in antibiotic prescribing, environmental cleaning, contact precautions, good antibiotic stewardship and an active surveillance system on the basis of international criteria is urgently needed., (Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the clinical characteristics of burn patients infected with Stenotrophomonas maltophilia (SM) and antibiotic resistance of the strains. Methods: Clinical data of burn patients detected with SM, admitted to our unit from July 2011 to July 2017 were retrospectively analyzed. API 20NE bacteria identification panel or fully automated microbial identification instrument was used to identify pathogen. Minimal inhibitory concentration method was used in drug sensitivity test of levofloxacin, compound sulfamethoxazole, minocycline, and cefoperazone/sulbactam. Annual detection of SM, clinical characteristics and prognosis of patients infected with SM, sample source and detection time of SM, detection of the pathogens and antibiotics application of patients before their detection of SM, and drug resistance of SM to the above four antibiotics were analyzed. The results of drug sensitivity test were analyzed by software WHONET 5.5. Results: (1) There were totally 119 patients detected with SM, with 11, 12, 21, 22, 28, 13, and 12 cases from 2011 to 2017, respectively. (2) Among patients infected with SM, there were 86 (72.3%) males and 33 (27.7%) females. Patients aged more than or equal to 65 years accounted for 11.8% (14/119). Patients aged more than or equal to 18 years and less than 65 years accounted for 76.5% (91/119). Patients aged less than 18 years accounted for 11.8% (14/119). Patients with scald were the most common (totally 72 cases, accounted for 60.5%), and patients with total burn area less than or equal to 10% total body surface area were the most common (totally 35 cases, accounted for 29.4%), too. The proportion of patients with history of basic disease was 16.8% (20/119), with tracheotomy of 46.2% (55/119), with deep vein catheterization of 47.9% (57/119), with history of staying in intensive care unit (ICU) of 61.3% (73/119). Seventy-five (63.0%) patients were cured. Twenty-four (20.2%) patients were improved. Fourteen (11.8%) patients gave up treatment. Six (5.0%) patients died. (3) SM detected from wounds exudate of patients occupied the highest proportion (58.0%, 69/119), which was followed by samples of sputum (17.6%, 21/119), blood (14.3%, 17/119), wound tissue (4.2%, 5/119), catheter (4.2%, 5/119), and urine (1.7%, 2/119). The detection time of SM was 10 hours to 71 days post admission, with the average time of 12.7 days. (4) The proportion of patients detected with pathogens before detection of SM was 66.4% (79/119), and Acinetobacter baumannii and Staphylococcus aureus occupied high proportion among the strains. (5) The proportion of patients using antibiotics before detection of SM was 91.6% (109/119), and 44.0% (48/109) patients used 3 kinds of antibiotics or more. The antibiotics were applied for 271 times. The most frequently used antibiotics were glycopeptides antibiotics (63 times), followed by carbapenems antibiotics (61 times). (6) The total sensitivity rates of SM to levofloxacin and minocycline in 7 years were high (91.6% and 99.4%, respectively). The total sensitivity rate of SM to cefoperazone/sulbactam was low (52.5%). The total sensitivity rate of SM to compound sulfamethoxazole was high (77.6%), and the annual sensitivity rate was higher than 90.0% in recent 3 years. Conclusions: Burn patients infecting SM have high rates of tracheotomy and deep vein catheterization, and most of them stay in ICU and use broad-spectrum antibiotics. SM has high sensitivity to levofloxacin, minocycline, and compound sulfamethoxazole.

Objective: To investigate the acquired drug-resistant genes and strains relationship in 40 strains of Pseudomonas aeruginosa isolated from burn patients. Methods: Forty strains of Pseudomonas aeruginosa isolated from burn patients hospitalized in our burn department from January 2014 to December 2015 were selected, with 20 strains from each year. Kirby-Bauer paper disk diffusion method was used to detect sensitivity of the isolated Pseudomonas aeruginosa to 9 kinds of antibiotics of cefotaxime, ceftazidime, cefepime, imipenem, meropenem, gentamicin, amikacin, ciprofloxacin, and levofloxacin. Polymerase chain reaction was applied to detect 9 kinds of acquired β-lactamase antibiotics-resistant genes, outer membrane porin protein opr D2 genes, 12 kinds of acquired aminoglycosides antibiotics-resistant genes, and 6 kinds of acquired disinfectant-resistant genes and genetic marker genes of mobile genetic elements. Among the above genes, positive expression genes were verified by DNA sequencing and comparison. Sequences of twenty-eight acquired drug-resistant genes of the above 40 Pseudomonas aeruginosa strains were analyzed by unweighted pair-group method with arithmetic means cluster analysis. Results: Forty strains of Pseudomonas aeruginosa were resistant to the above 9 kinds of antibiotics. Two kinds of acquired β-lactamase antibiotics-resistant genes of bla (TEM), bla (CARB), 5 kinds of acquired aminoglycosides antibiotics-resistant genes of aac(6')-Ⅰb , aac(6')-Ⅱ , ant (2″)-Ⅰ , ant(3″)-Ⅰ , and rmt B, and 3 kinds of acquired disinfectant-resistant genes and genetic marker genes of mobile genetic elements of qac E△1- sul 1, mer A, and intⅠ1 were detected in 40 strains of Pseudomonas aeruginosa with opr D2 gene deficiency. Forty strains aggregated obviously, with a total of 7 gene modes and 3 clones. Drug-resistant gene sequences of strains of number 2 to 4, 6 to 9, 11, 14, and 17 to 39 were similar and with close relationship. Drug-resistant gene sequences of number 12 and 13 strains were similar and with close relationship. Drug-resistant sequences of number 10 and 16 strains were similar and with close relationship. Conclusions: Genes of bla (TEM), bla (CARB), aac(6')-Ⅰb , aac(6')-Ⅱ , ant(2″)-Ⅰ , rmt B, qac E△1- sul 1, mer A, and intⅠ1 were prevalent in these strains of Pseudomonas aeruginosa with opr D2 gene deficiency isolated from burn patients, which may play key roles in resistance of Pseudomonas aeruginosa to β-lactamase, aminoglycoside, and quinolone antibiotics, and the drug-resistant phenotypes were in good coincidence with genotypes. Pseudomonas aeruginosa strains isolated from burn patients were with similar acquired drug-resistant genes and close relationship.

Biofilm-infected wounds are clinically challenging. Vascular endothelial growth factor and host defence S100A8/A9 are crucial for wound healing but may be suppressed by biofilms. The natural course of Pseudomonas aeruginosa biofilm infection was compared in central and peripheral zones of burn-wounded, infection-susceptible BALB/c mice, which display delayed wound closure compared to C3H/HeN mice. Wounds were evaluated histopathologically 4, 7 or 10 days post-infection. Photoplanimetry evaluated necrotic areas. P. aeruginosa biofilm suppressed vascular endothelial growth factor levels centrally in BALB/c wounds but increased peripheral levels 4-7 days post-infection. Central zones of the burn wound displayed lower levels of central vascular endothelial growth factor as observed 4 and 7 days post-infection in BALB/c mice compared to their C3H/HeN counterparts. Biofilm suppressed early, centrally located S100A8/A9 in BALB/c and centrally and peripherally later on in C3H/HeN wounds as compared to uninfected mice. Peripheral polymorphonuclear-dominated inflammation and larger necrosis were observed in BALB/c wounds. In conclusion, P. aeruginosa biofilm modulates wounds by suppressing central, but inducing peripheral, vascular endothelial growth factor levels and reducing host response in wounds of BALB/c mice. This suppression is detrimental to the resolution of biofilm-infected necrosis., (© 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Multidrug resistant Pseudomonas aeruginosa has frequently been reported as the cause of nosocomial outbreaks of burn wound infections. The pathogenesis of P. aeruginosa is partly due to the production of several cell-associated and extracellular virulence factors. A total of 93 P. aeruginosa isolated from burn wound infections were investigated for antimicrobial susceptibility and distribution of virulence genes. All (100%) isolates were resistant to one or more antimicrobial agents. The most frequent resistance found against ampicillin (91.4%), co-trimoxazole (77.4%), gentamicin (68.8%), cefotaxime (50.5%), aztreonam and piperacillin (41.9%). A total of 88 (94.6%) isolates were resistant to at least three different classes of antimicrobial agents and considered as multidrug resistance MDR. All isolates carried at least two or more different virulence genes. The most prevalent virulence gene was toxA (97.8%), followed by plcH (96.7%), phzI (96.7%), exoY (93.1%) and phzII (90.3%). exoU was not detected in P. aeruginosa isolates. The frequency of pilB (17.2%), exoT (20.4%), pilA (24.7%) and phzS/phzH (27.9%) was lower than other virulence genes. Twenty nine (31.2%) isolates had simultaneously 8 virulence genes, 22 (23.7%) isolates had 6 virulence genes and 19 (20.4%) isolates had 7 virulence genes. All MDR isolates carried at least 5 virulence factors. These results indicate a high frequency and heterogeneity of virulence gene profiles among multidrug resistant P. aeruginosa isolates recovered from burn wound infections. Therefore, appropriate surveillance and control measures are essential to prevent the further spread of these isolates in hospitals., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Pseudomonas aeruginosa is an opportunistic pathogen involved in many infections. Carbapenem-resistant P.aeruginosa has emerged as an important cause of infection in different hospitals worldwide. We aimed to determine frequencies of the four main resistance mechanisms [metallo-beta lactamase (MBL) production (bla IMP , bla VIM , bla SPM and bla NDM ), overproduction of the MexAB-OprM and MexXY efflux pumps, overproduction of chromosome-encoded AmpC β-lactamase, and reduced OprD expression] in high-level carbapenem-resistant P.aeruginosa isolated from patients with burns., Methods: In a descriptive study, 107 P. aeruginosa isolates were collected from patients with burn injuries and tested for antibiotic susceptibility, by an E-test for carbapenems, an E-test for metallo-β-lactamase producer isolates, and PCR to detect MBL genes. Furthermore, high-level carbapenem-resistant isolates were tested by real-time PCR for the expression levels of the mexB, mexY, ampC, and oprD genes., Results: Amongst all P. aeruginosa isolates, 78.5%, 46.7%, and 15% were imipenem-, meropenem-, and doripenem-resistant, respectively; 72% of isolates were multidrug-resistant. The bla IMP and bla VIM genes were detected in 17.9% and 1.2% of isolates; respectively. The bla SPM and bla NDM genes were not observed. Among the resistant isolates, mexB overexpression (63.2%) was the most frequent mechanism, followed by mexY overexpression (52.6%), ampC overexpression (36.8%), and reduced oprD expression (21.1%)., Conclusion: Emerging antimicrobial resistance in burn wound bacterial pathogens is a serious therapeutic challenge for clinicians. In the present study, most of the isolates were MDR. This finding indicated an alarming spread of resistant isolates and suggested that infection control strategies should be considered. Resistance to carbapenems is influenced by several factors, not all of which were evaluated in our study; however, the results showed that production of MBLs and overexpression of the mexB gene were the most frequent mechanisms in carbapenem-resistant isolates., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Background: The early diagnosis of infection or sepsis in burns are important for patient care. Globally, a large number of burn centres advocate quantitative cultures of wound biopsies for patient management, since there is assumed to be a direct link between the bioburden of a burn wound and the risk of microbial invasion. Given the conflicting study findings in this area, a systematic review was warranted., Methods: Bibliographic databases were searched with no language restrictions to August 2015. Study selection, data extraction and risk of bias assessment were performed in duplicate using pre-defined criteria. Substantial heterogeneity precluded quantitative synthesis, and findings were described narratively, sub-grouped by clinical question., Results: Twenty six laboratory and/or clinical studies were included. Substantial heterogeneity hampered comparisons across studies and interpretation of findings. Limited evidence suggests that (i) more than one quantitative microbiology sample is required to obtain reliable estimates of bacterial load; (ii) biopsies are more sensitive than swabs in diagnosing or predicting sepsis; (iii) high bacterial loads may predict worse clinical outcomes, and (iv) both quantitative and semi-quantitative culture reports need to be interpreted with caution and in the context of other clinical risk factors., Conclusion: The evidence base for the utility and reliability of quantitative microbiology for diagnosing or predicting clinical outcomes in burns patients is limited and often poorly reported. Consequently future research is warranted., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Background: S.aureus is a predominant pathogen that causes infection in critically ill patients, but little information exists regarding the characterization of S. aureus from different sources in burn patients in southeastern China., Methods: We enrolled 125 patients with S. aureus infection in burns center between Jan 2014 and Dec 2015. S. aureus isolates were characterized by antimicrobial susceptibility test, toxin gene detection, and molecular typing with multilocus sequence type, staphylococcal protein A (spa) type, and staphylococcal cassette chromosome mec (SCCmec) type., Results: Sixty-eight MRSA were isolated from SSTI and 31 from non-SSTI patients, respectively. Overall, the drug-resistant ability of S. aureus isolated from SSTI was higher than that from non-SSTI groups. SCCmecIII-CC239-t030 was the most common clone (38 from SSTIs, and 8 from non-SSTIs). Seg was the most common enterotoxin gene (21 from SSTIs and 33 from non-SSTIs). Isolates from SSTIs was more likely to carry seb (P = 0.04), while those from non-SSTIs tended to carry sea and seg (P = 0.002 and 0.01, respectively). Although isolates carried four hemolysin genes, there was no significant difference between them (P > 0.05)., Conclusion: SCCmecIII-CC239-t030 was the most common clone in Jiangxi burns center, China. The molecular characterization of S. aureus was quite different between SSTI and non-SSTI groups.

Objective: The objective of this study was to determine the frequency of the antimicrobial resistance and genes encoding virulence factors of enterococci isolated in hospitalized burn patients in a major burn center in Ahvaz, southwest of Iran. A total of 340 bacterial isolates were collected from the burn center from February 2014 to February 2015. The antimicrobial susceptibility and MIC of vancomycin were determined using the disk diffusion and micro-agar dilution techniques. The genus and species-specific genes, potential virulence genes, and vanA and vanB genes were detected by polymerase chain reaction., Results: According to our results, out of the 340 bacterial isolates, 16.4% (n = 56) were identified as enterococci. Out of the 56 enterococcal isolates, 35 (62.5%) were Enterococcus faecalis and 21 (37.5%) were Enterococcus faecium. More than 20% (n = 5) of E. faecium demonstrated resistance to vancomycin. The gelE and asa genes were the most prevalent virulence genes in E. faecalis (48.5%) and E. faecium (43%) isolates. The emergence of vancomycin resistant E. faecium strains which have several virulence factors should be considered as a major cause of concern for burn centers. Control and management of infections induced by enterococci should be regarded as highly important in burn patients.

Enterococcus faecalis and Enterococcus faecium are among the main agents associated with nosocomial infections with high mortality in immunocompromised patients. Antibiotic resistance, especially against gentamicin and vancomycin among Enterococci , is a risk factor that could increase the morbidity and mortality rate. 179 Enterococci isolates from burn patients were included in this study. Antibiotic susceptibility testing was done using the disk diffusion test and minimum inhibitory concentration (MIC) was evaluated by agar microdilution. Vancomycin and gentamicin resistance associated genes including vanA , vanB , vanC , aac (6')-Ie aph(2''), aph(3')-IIIa and ant(4')-Ia were detected by PCR and their statistical relation with antibiotic resistance was evaluated. E. faecalis was the more prevalent strain among our local isolates and showed a higher antibiotic resistance in comparison to E. faecium . Vancomycin had a good antibacterial effect on the Enterococcus spp. isolates; however, resistance to this antibiotic and a high-level gentamicin resistance (HLGR) phenotype were observed. Among van operon genes, vanA was the most prevalent gene and among the gentamicin resistance genes, aph (3')-IIIa was more frequent. The HLGR Enterococci are a real challenge in nosocomial infections. Vancomycin is a key antibiotic to treat such infections but emergence of VRE in our region could be a real concern and, therefore, phenotypic and molecular surveillance must be considered., Enterococcus faecalis and Enterococcus faecium are among the main agents associated with nosocomial infections with high mortality in immunocompromised patients. Antibiotic resistance, especially against gentamicin and vancomycin among Enterococci , is a risk factor that could increase the morbidity and mortality rate. 179 Enterococci isolates from burn patients were included in this study. Antibiotic susceptibility testing was done using the disk diffusion test and minimum inhibitory concentration (MIC) was evaluated by agar microdilution. Vancomycin and gentamicin resistance associated genes including vanA , vanB , vanC , aac (6’)-Ie aph(2’’), aph(3’)-IIIa and ant(4’)-Ia were detected by PCR and their statistical relation with antibiotic resistance was evaluated. E. faecalis was the more prevalent strain among our local isolates and showed a higher antibiotic resistance in comparison to E. faecium . Vancomycin had a good antibacterial effect on the Enterococcus spp. isolates; however, resistance to this antibiotic and a high-level gentamicin resistance (HLGR) phenotype were observed. Among van operon genes, vanA was the most prevalent gene and among the gentamicin resistance genes, aph (3’)-IIIa was more frequent. The HLGR Enterococci are a real challenge in nosocomial infections. Vancomycin is a key antibiotic to treat such infections but emergence of VRE in our region could be a real concern and, therefore, phenotypic and molecular surveillance must be considered., (© 2018 Da Cheng Hao et al.)

Wound infection in burns is a relevant cause of morbidity and mortality in children. We aimed to determine the relationship between antibacterial chemotherapy and Gram-negative burn wound colonization and infection. All children admitted to the pediatric intensive care unit for burn trauma from June 1, 2005 to January 31, 2013 were included. We obtained 141 wound samples, of which 88 (65.7%) showed growth of Gram-positive bacteria. Treatment with antimicrobial chemotherapy was necessary in 23 (31.1%) patients. The proportion of Gram-negative isolates seems to increase linear from 12.5% (95% confidence interval (CI): 4.4%-28.7%) without antibacterial chemotherapy to 36.8% (95% CI: 25.5%-49.6%) with one to 48.9% (95% CI: 35.3%-62.8%) with 2 antimicrobial agents. The Odds ratio for a Gram-negative isolate, in comparison to patients without antibacterial chemotherapy, increased from 4.083 (95% CI: 1.140-15.961) for one administered substance to 6.708 (95% CI: 1.832-26.786) if 2 or more were used., Conclusion: We found that antibacterial chemotherapy seems to facilitate burn wound colonization and results in an increased number of gram-negative isolates from children with burn wounds., Competing Interests: Interessenkonflikt: Die Autoren erklären hiermit, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

The MolecuLight i:X Imaging Device is a portable, noninvasive, real-time camera used to visualize the bacterial load in a wound. It uses violet light illumination and a dual bandpass optical filter to capture the fluorescence of endogenous structures in the tissue matrix and harmful bacteria. The MolecuLight i:X captures images of wounds and highlights potentially detrimental levels of bacteria. This is an initial evaluation of using the MolecuLight i:X camera in the management of burns to demonstrate the following: the ability of the device to guide clinicians in their management of the burn (ie, detect, identify, and specify swabbing locations). Burn wounds were photographed under standard light and violet light illumination to compare presentations of obvious infection signs and symptoms. Microbiology swab samples were obtained to correlate any bacterial presence to the images. The fluorescence images were used to guide swabs to where the bacteria were congregating. Twenty patients were imaged. Four patients did not have bacterial contamination based on their images and swab results. Sixteen patients showed growth of Staphylococcus aureus, Pseudomonas aeruginosa, or other bacteria. Nine of the patients, by definition, had infections. These findings were correlated with the typical signs and symptoms of infection, the fluorescence images, and the microbiology results. The efficacy of the MolecuLight i:X is evident due to the microbiology results correlating to the images. Further research is being done to test the device in terms of being an early intervention tool. With these early results and guidance of swab samples, the MolecuLight i:X may be able to detect bacterial load before an infection and subsequent graft failure, thereby shortening lengths of hospital stay and improving overall healing.

Mucormycosis is an uncommon aggressive fungal infection usually seen in immunocompromised hosts or patients with burns and trauma. The common presentations include rhino-orbital-cerebral and pulmonary involvement. Osteoarticular involvement is a rare presentation of this disease. We present two cases of osteoarticular mucormycosis of pelvis and long bones of the lower limb, one in a patient with burn injury and other one in a patient with chronic granulomatous disease, hitherto a rarely reported association. Delayed diagnosis in a setting where tuberculosis is a common cause of chronic osteomyelitis, challenges in medical and surgical management of these patients are discussed in this report.