ALA-PDT shortens the course of antibiotic therapy for skin infection caused by Mycobacterium marinum.

BACKGROUND: Recently, the number of cases of Mycobacterium marinum infection has increased. Due to the nonspecific clinical manifestations and lack of standardized treatment guidelines, these infections are often misdiagnosed and are challenging to treat. METHODS: In this study, four patients had M. marinum skin infections accompanied by a high-risk exposure history and were diagnosed by bacterial culture and gene chip. Two patients were treated with antibiotic therapy alone, and the other two patients were treated with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with antibiotics. RESULTS: All four patients enrolled in the study were cured with 100 % efficacy. Two patients were cured after receiving two active antibiotics for 4 months. The other two patients, having considered the drug resistance and intolerance described above, were cured after receiving two active antibiotics for 1-1.5 months along with combination therapy with ALA-PDT. CONCLUSION: Combination therapy with ALA-PDT and antibiotics was chosen to shorten the duration of antibiotic treatment and reduce the occurrence of adverse reactions.

ALA-PDT regulates macrophage M1 polarization via ERK/MAPK-NLRP3 pathway to promote the early inflammatory response.

BACKGROUND: Photodynamic therapy (PDT) is a promising new approach to promote wound healing and its effectiveness has been demonstrated in both clinical and animal studies. Macrophages are the key cells in wound healing and inflammatory response. However, the mechanism of action of PDT on macrophages in promoting wound healing is still unclear. METHODS: In this study, RAW264.7 cells were used. We analyzed the expression levels of macrophage markers arginase 1 (Arg-1), CD206, iNOS, CD86, and inflammatory factors IL-6, TNF-α, and IL-1ß by reverse transcription-polymerase chain reaction and Western blot, Milliplex microtubule-associated protein multiplex assay was performed to analyze the expression of inflammatory factors in the supernatant. Live cell Imaging System to observe the dynamic process of macrophage phagocytosis. Western blot was performed to observe the activation of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) and NOD-like receptor protein 3 (NLRP3) inflammasome. RESULTS: 5-Aminolevulinic acid (ALA)-PDT increased the expression of M1 marker iNOS/CD86 and decreased the expression of Arg-1/CD206 in RAW264.7 cells, while, proinflammatory factors IL-6, TNF-α, and IL-1ß expression was enhanced and macrophage phagocytosis was increased. We also found that these phenomena were associated with activation of the ERK/MAPK-NLRP3 pathway. CONCLUSION: ALA-PDT promotes early inflammatory responses by regulating macrophage M1 polarization through the ERK/MAPK-NLRP3 pathway. It also promotes macrophage phagocytosis.

A new approach to the treatment of nontuberculous mycobacterium skin infections caused by iatrogenic manipulation: Photodynamic therapy combined with antibiotics: A pilot study.

BACKGROUND: Recently, the number of nontuberculous mycobacterium (NTM) infections caused by iatrogenic procedures, especially rapid NTM skin infections, has been increasing. Due to the nonspecific clinical manifestations and nonstandard treatment guidelines, these infections are often misdiagnosed and challenging to treat. METHODS: In this study, eight patients had NTM skin infections caused by iatrogenic procedures, and were diagnosed by bacterial culture and flight mass spectrometry tests. They were treated with 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) combined with antibiotic therapy. RESULTS: All eight patients enrolled in the study were cured with 100% efficacy after receiving combination therapy with ALA-PDT and antibiotics for 3-6 months. All patients experienced redness and pain during treatment but no other discomfort and were satisfified with the results of their treatments. CONCLUSION: Local ALA-PDT combined with antibiotics is a safe and effective method of treating NTM skin infections.

An unusual successful treatment with non-sulfonamides: primary cutaneous nocardiosis caused by Nocardia brasiliensis.

INTRODUCTION: Primary cutaneous nocardiosis is a rare suppurative or granulomatous inflammation disease caused by Nocardia infection. Because of nonspecific clinical findings, it is always misdiagnosed as common pyogenic infection. Sulfonamides have been the standard treatment for nocardiosis, but the outcome is always poor due to the high rates of misdiagnosis and refractoriness of the disease. CASES PRESENTATIONS: The presented cases are patients of acute suppurative cutaneous infection without involvement of other organs. We report four cases, of which two cases were localized cutaneous nocardiosis and the other two were lymphocutaneous type of nocardiosis. All cases were diagnosed with pus culture which turned out to be Nocardia brasiliensis. We report an improvement of primary cutaneous nocardiosis symptoms in the four patients treated with non-sulfonamides. All patients were cured and recovered without recurrence during follow-up. CONCLUSION: Our results suggest that non-sulfonamides are effective treatment for the patients with primary cutaneous nocardiosis who are resistant or intolerant to sulfonamides.

ALA-PDT combined with antibiotics for the treatment of atypical mycobacterial skin infections: Outcomes and safety.

BACKGROUND: Photodynamic therapy (PDT) has been shown to be a very successful therapy in clinical practice, and its usefulness as a treatment for bacterial infections has been gradually recognized by researchers, who believe it has very good clinical prospects. Atypical mycobacterial skin infections are a type of rare refractory infection. The aim of this study was to evaluate the efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with antibiotics for the treatment of atypical mycobacterial skin infections. METHODS: In this study, 4 patients with atypical mycobacterial skin infections were treated with ALA-PDT combined with antibiotic therapy. These patients were diagnosed with atypical mycobacterial skin infections by bacterial culture and microarray analysis, tests that were also useful for identifying the strains responsible for the infections. In addition to being treated with antibiotics, the skin was also treated locally with ALA-PDT (20% ALA was applied to the lesion and incubated in the dark, then, the lesion was irradiated with a red light with an energy density of 100J/cm2) every 10days for a total of 3-5 sessions. RESULTS: All four patients enrolled in the study were cured with 100% efficiency after receiving combination therapy with ALA-PDT and antibiotics for three months. All patients experienced redness and pain during treatment but did not experience any other forms of severe discomfort and were satisfied with the results of their treatments. CONCLUSION: Local ALA-PDT combined with antibiotics is a safe and effective method of treating atypical mycobacterial skin infections.

Burn Injury Leads to Increase in Relative Abundance of Opportunistic Pathogens in the Rat Gastrointestinal Microbiome.

The gastrointestinal microbiome is crucial in human health. With greater than 10 times the cell count of an individual, the gastrointestinal microbiome provides many benefits to the host. It plays an important role in chronic illnesses and immune diseases and also following burns and trauma. This study aimed to determine whether severe burns affect the gastrointestinal microbiome during the early stages of after burn injury and the extent to which the microbiome is disturbed by such burns. We used a rat burn model to investigate any changes occurring in the microbiome after the burn trauma using 16S rRNA sequencing and downstream α-diversity, ß-diversity, and taxonomy analysis. With 128631 and 143694 clean sequence reads, an average of 2287 and 2416 operational taxonomic units (OTUs) were recognized before and after the burn injury, respectively. Bacterial diversity within the pre- and post-burn groups was similar according to OTU richness, Chao 1 index, Shannon index and ACE index. However, the constituents of the gastrointestinal microbiota changed after the burn injury. Compared with the pre-burn samples, the post-burn samples showed a tendency to cluster together. The ratio of Firmicutes to Bacteroidetes decreased after the burn injury. Also, the abundance of some probiotic organisms (i.e., butyrate-producing bacteria and Lactobacillus) decreased after the burn injury. In contrast, opportunistic pathogenic bacteria, such as those of the genera Escherichia and Shigella and the phylum of Proteobacteria are more abundant post-burn. In conclusion, dysbiosis in the gastrointestinal microbiome was observed after the burn injury. Although the total number of species in the gastrointestinal microbiome did not differ significantly between the pre- and post-burn injury groups, the abundance of some bacterial components was affected to various extents.

Epidemiological characterization of Acinetobacter baumannii bloodstream isolates from a Chinese Burn Institute: A three-year study.

Acinetobacter baumannii infection is a serious threat to burn patients. Bacteremia due to A. baumannii is becoming the most common cause of mortality following burn. However, the epidemiology of A. baumannii causing burn-related bloodstream infections has rarely been reported. We retrospectively collected 81 A. baumannii isolates from the bloodstream of burn patients over a three-year period. Antibiotic susceptibility tests, the prevalence of antibiotic-resistant genes and sequence typing (ST) were conducted to characterize these strains. Most of the isolates showed an extensive drug-resistant phenotype. The resistance frequencies to imipenem and meropenem were 94% and 91%, respectively. The blaOXA-23-like gene, AmpC, IS-AmpC, PER and SIM are the five most prevalent resistant genes, and their prevalence rates are 93% (75/81), 86% (70/81), 73% (59/81), 73% (59/81) and 52% (42/81), respectively. The 81 isolates were grouped into 10 known and 18 unknown ST types, with ST368 (38%) being the most prevalent. Except for ST457 and four new types (STn2, STn6, STn11 and STn14), the remaining 23 ST types belonged to one clonal complex 92, which is most common among clinical isolate in China. The above results indicated that ST368 isolates possessing both the blaOXA-23-like gene and ampC gene were the main culprits of the increasing nosocomial A. baumannii infection in this study. More attention should be paid to monitoring the molecular epidemiology of A. baumannii isolates from burn patients to prevent further distribution. Such information may help clinicians with therapeutic decisions and infection control in the Burns Institute.

[Analysis on the prevalence of central venous catheter-related infection in burn patients and its risk factors].

OBJECTIVE: To investigate the prevalence of central venous catheter-related infection (CRI) in burn patients and its risk factors, so as to guide the clinical practice. METHODS: Clinical data of 5 026 days of 480 cases of central venous catheterization altogether in 228 burn patients admitted to our ward from June 2011 to December 2014, conforming to the study criteria, were retrospectively analyzed. (1) The incidence of CRI and that of catheter-related bloodstream infection (CRBSI) in patients (the infection rates per thousand days were calculated) and mortality due to them, and detection of concerning bacteria were recorded after each case of catheterization. (2) The incidence of CRI after each case of catheterization in patients was recorded according to the classification of their gender, age, total burn area, full-thickness burn area, cause of injury, severity of inhalation injury, location of catheterization, whether catheterization through wound or not, duration of catheterization, and the data were processed with chi-square test. Indexes with statistically significant differences were selected, and they were processed with multivariate logistic stepwise regression analysis to screen the independent risk factors of CRI. (3) To all cases of catheterization and cases with catheterization through wound, incidence of CRI after each case of catheterization in patients at each time period was recorded according to the sorting of duration of catheterization. Data were processed with chi-square test and Fisher's exact test, and the values of P were adjusted by Bonferroni. RESULTS: (1) Infection rate of CRI per thousand days was 50.14‰ (252/5 026), resulting in the mortality rate of 3.51% (8/228). Infection rate of CRBSI per thousand days was 18.70‰ (94/5 026), resulting in the mortality rate of 2.19% (5/228). Respectively 319 and 105 strains of pathogens were detected in CRI and CRBSI, in which the top four bacteria detected were Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae, and the most common fungus found was smooth Candida. (2) There were no statistically significant differences in the incidence of CRI after each case of catheterization among patients with different gender, age, cause of injury, severity of inhalation injury, and location of catheterization (with χ(2) values from 0.427 to 6.991, P values above 0.05). There were statistically significant differences in the incidence of CRI after each case of catheterization among patients with different total burn area, full-thickness burn area, whether catheterization through wound or not, duration of catheterization (with χ(2) values from 7.202 to 14.246, P<0.05 or P<0.01). (3) Total burn area, whether catheterization through wound or not, and duration of catheterization were the independent risk factors of CRI (with odd ratios respectively 1.495, 1.670, 1.924, 95% confidence intervals respectively 1.096-2.040, 1.077-2.590, 1.303-2.841, P<0.05 or P<0.01). (4) In all cases enduring catheterization, the incidence of CRI in patients after each episode of catheterization was close between cases enduring catheterization shorter than or equal to 3 days and those longer than 3 days and shorter than or equal to 5 days (χ(2) <0.001, P>0.05); the incidence of CRI in patients after each episode of catheterization was significantly higher in cases enduring catheterization longer than 5 days and shorter than or equal to 7 days, longer than 7 days and shorter than or equal to 14 days, and longer than 14 days than the former two periods (with χ(2) values from 3.625 to 13.495, P values below 0.05). In the cases with catheterization through wound, the incidence of CRI of patients after each episode of catheterization was close between cases enduring catheterization shorter than 5 days and those longer than or equal to 5 days and shorter than 7 days (P>0.05); the incidence of CRI of patients after each episode of catheterization was significantly higher in cases enduring catheterization longer than or equal to 7 days and shorter than 14 days and longer than or equal to 14 days than those with longer than or equal to 5 days and shorter than 7 days (with χ(2) values respectively 6.828 and 4.940, P values below 0.05). CONCLUSIONS: The infection rate of CRI per thousand days in burn patients is relatively low, while that of CRBSI is relatively high, both resulting in relatively low mortality, and Acinetobacter baumannii is the main pathogen. Total burn area, whether catheterization through wound or not, and duration of catheterization are independent risk factors of CRI in burn patients, and with which its occurrence could be predicted. It is suggested that central venous catheterization should be removed within 5 days, and catheterization through wounds should be avoided as much as possible. If catheterization through wound is unavoidable, removal of the catheter within 7 days is recommended.

[Effects of early oral administration of mixed enteral nutritional agent on intestinal mucosal barrier of patients with severe burn injury].

OBJECTIVE: To explore the effects of oral administration of mixed enteral nutritional agent on intestinal mucosal barrier of patients with severe burn injury at early stage. METHODS: Twenty-four patients with severe burn injury admitted to our burn ward from August 2013 to September 2014, conforming to the study criteria, were divided into conventional therapy group (n = 12) and early enteral feeding group (n = 12) according to the random number table. Patients in conventional therapy group received conventional treatment immediately after admission, while those in early enteral feeding group were orally given 100 mL of a mixture of glutamine, probiotics, and prebiotics once a day besides conventional treatment for 7 days. Serum levels of diamine oxidase (DAO) and procalcitonin (PCT) and plasma level of LPS were determined by ELISA before treatment and on treatment day (TD) 1, 3, 7, 14, and 21. Wound secretion and blood samples were collected for bacterial culture within the 21 TD. The incidence of MODS within the 21 TD was observed. Data were processed with Fisher's exact test, rank sum test, analysis of variance for repeated measurement, and LSD-t test. RESULTS: (1) Serum levels of DAO in patients of early enteral feeding group on TD 7, 14, and 21 were respectively (14.9 ± 3.7), (12.4 ± 3.1), and (9.5 ± 0.7) ng/mL, which were significantly lower than those of conventional therapy group [(17.5 ± 4.0), (16.3 ± 3.3), and (13.0 ± 1.1) ng/mL, with t values from 2.913 to 15.304, P values below 0.01]. Serum levels of DAO at the other time points were close between the two groups (with t values from -0.598 to 0.139, P values above 0.05). (2) Compared with serum levels of PCT in patients of conventional therapy group [(11.7 ± 20.9) and (12.9 ± 23.9) ng/mL], those of early enteral feeding group were significantly lower on TD 7 and 14 [(2.7 ± 8.1) and (2.0 ± 5.6) ng/mL, with Z values respectively -2.919 and -2.139, P < 0.05 or P < 0.01]. Serum levels of PCT at the other time points were close between the two groups (with Z values from -1.833 to -0.346, P values above 0.05). (3) Plasma level of LPS in patients of early enteral feeding group on TD 7 was (33 ± 56) pg/mL, which was significantly lower than that of conventional therapy group [(102 ± 108) pg/mL, Z = -2.046, P < 0.05]. Plasma levels of LPS at the other time points between the two groups showed no significant difference (with Z values from -2.003~-0.526, P values above 0.05). (4) Positive results in bacterial culture of wound secretion were approximately the same between the two groups (P > 0.05). Bacterial culture of blood was positive in 7 patients of conventional therapy group and 1 patient of early enteral feeding group, showing significantly statistical difference (P < 0.05). MODS was observed in 1 patient of conventional therapy group, showing no significantly statistical difference with that of early enteral feeding group (no patient, P > 0.05). CONCLUSIONS: Early intestinal feeding of mixed enteral nutritional agent in addition to conventional therapy can effectively promote repair of the impairment of intestinal mucosal barrier, protect integrity of intestinal mucosa, reduce damage to intestines, and alleviate inflammatory response in patients suffering from severe burn injury.