Silver dressing in the treatment of diabetic foot: A protocol for systematic review and meta-analysis.

Background Roxithromycin (RXM), a macrolide antibiotic, exhibits anti-asthmatic effects, but its specific mechanism of action remains elusive. We evaluated the effects of RXM on airway inflammation, the expression of calprotectin, and the activity of the receptor of advanced glycation end products (RAGE) to determine whether RXM alleviates inflammation by regulating RAGE activation, and thereby calprotectin expression, in neutrophilic asthma. Methods Male Brown Norway rats were sensitized with ovalbumin (OVA) and Freund's complete adjuvant (FCA) mixture, followed by OVA challenge to induce neutrophilic asthma. RXM (30 mg/kg) or FPS-ZM1 (RAGE inhibitor, 1.5 mg/kg) was administered 30 min prior to each challenge. The infiltration of airway inflammatory cells and cytokines, as well as the expression of calprotectin and RAGE, was assessed. Results The expression of airway inflammatory cells and cytokines was found to be significantly elevated in OVA + FCA-induced rats. Increased expression of both calprotectin and RAGE was also detected in OVA + FCA-induced asthma [bronchoalveolar lavage fluid (BALF) calprotectin: 15.07±1.79 vs. 3.86±0.69 ng/mL; serum calprotectin: 20.47±1.64 vs. 9.29±1.31 ng/mL; lung tissue homogenates calprotectin: 28.82±1.01 vs. 12.02±1.38 ng/mg; BALF RAGE: 762.93±36.47 vs. 294.25±45.92 ng/mL; serum RAGE: 906.43±58.95 vs. 505.60±30.16 ng/mL; lung tissue homogenates RAGE: 1,585.24±177.59 vs. 461.53±63.40 ng/mg; all P<0.001]. However, all of these changes were interrupted by RXM and FPS-ZM1. Conclusions RXM exerted similar effects as the RAGE inhibitor FPS-ZM1 in terms of reducing airway inflammation and downregulating the expression of calprotectin and RAGE in a neutrophilic asthma model. Our findings provide novel insights into the mechanisms underlying the effect of RXM pretreatment on neutrophilic asthma. Furthermore, FPS-ZM1 may be useful as an intervention specific to the neutrophilic asthma phenotype.

/pdf/roxithromycin-attenuates-inflammation-via-modulation-of-rage-38kc9yicjz.pdf

Roxithromycin attenuates inflammation via modulation of RAGE-influenced calprotectin expression in a neutrophilic asthma model.

Calprotectin is regulated by IL-17A and induces steroid hyporesponsiveness in asthma

Background To investigate the distribution of microbes and drug susceptibility in patients with diabetic foot infections (DFI) and provide guidance for clinical empirical treatment and the rational selection of antibacterial drugs. Methods Retrospective analysis of the pathogenic bacterium distribution and antimicrobial susceptibility isolated from 581 DFI patients with different Wagner grades. Results The 534 positive samples included 473 cases (88.58%)) of monomicrobial infections and 61 cases (11.42%) of polymicrobial infections before antibiotic therapy. A total of 656 strains were cultivated, including 387 (58.99%) strains of gram-positive organisms (GPOs), 235 (35.82%) gram-negative bacilli (GNB), and 21 (3.20%) fungal strains. Polymicrobial infections mainly occurred in patients with Wagner grade 3-4 ulcers. GPOs were predominant in Wagner grades 1-3 (grade 1: 96.67%, grade 2: 76.52%, grade 3 62.81%), and the most common was Staphylococcus aureus (grade 1: 31.66%, grade 2: 33.04%, grade 3 35.53%). GNB were predominant in grades 4-5 (grade 4: 51.46%, grade 5:60%), and the most common GNB in Wagner grades 4-5 was Proteus (grade 4:27.88%, grade 5: 42.86%), while the most common GPO was Enterococcus (grade 4:34.48%, grade 5:25.00%). Staphylococcus (including MRSA) and Enterococcus were still highly sensitive to vancomycin, linezolid, and tigecycline. Most GNB were still highly sensitive to meropenem, tigecycline, ertapenem, and amikacin. Proteus was most sensitive to amikacin (97.14%), followed by meropenem (92%) and ertapenem (80%). Conclusion The distribution of microbes and antimicrobial susceptibility in DFI patients varied with different Wagner grades. The most appropriate antimicrobial therapy should be selected based on the pathogen culture and antimicrobial susceptibility.

/pdf/distribution-of-microbes-and-antimicrobial-susceptibility-in-35arsoct.pdf

Distribution of microbes and antimicrobial susceptibility in patients with diabetic foot infections in South China

Objective. To compare the efficacy of swabbing versus tissue biopsy for microbiological diagnosis of diabetic foot infection. Methods. This was a prospective trial. Fifty-six patients with diabetic foot infection were divided into the following 3 groups according to the PEDIS grading system: grade 2 (n = 10), grade 3 (n = 29), and grade 4 (n = 17). Two specimens were collected from each wound for microbial culturing after debridement, including a superficial swab and a deep tissue punch biopsy specimen. Results. Swab culturing identified all of the microorganisms isolated from the corresponding deep tissue specimens in 9/10 of grade 2 wounds (90.0%), and this proportion decreased to 12/29 (41.4%) and 7/17 (41.2%) for grades 3 and 4 wounds, respectively (p = 0.02). Moreover, the sensitivity for identifying Gram-negative bacteria, such as E. coli and Citrobacter, by swabbing was low (33.3%). In addition, some Gram-negative bacteria, such as Serratia and Ralstonia pickettii, were isolated from deep tissues but not from swabs. Conclusions. Swab culturing may be reliable for identification of pathogens in diabetic foot wounds classified as grade 2. However, it is advisable to culture deep tissue specimens for wounds of grade ≥3 because swab culturing is associated with a high risk of missing pathogens, especially Gram-negative bacteria.

/pdf/a-comparison-of-tissue-versus-swab-culturing-of-infected-3s57fht66h.pdf

A Comparison of Tissue versus Swab Culturing of Infected Diabetic Foot Wounds.

Objective
To explore the microbiological profiles and antibiotic susceptibility patterns of organisms isolated from diabetic foot ulcers so as to provide selection rationales of antibiotics.


Methods
A retrospective study was conducted on the microbiological profiles and antibiotic susceptibilities in 754 strains of pathogens isolated from 519 patients with diabetic foot ulcers at our hospital from January 2010 to August 2013. The inter-group data were compared by Chi-square test.


Results
There were 322 (62.0%) males and 197 (38.0%) females. Their mean age was (67.7±12.3) (30-93) years, duration of diabetes 10 (0-40) years, duration of lower-limb lesion 1.0 (0.0-72.0) months and HbA1c (9.09%±2.28%). Among 444 (85.5%) cases, a total of 754 strains of pathogens were isolated. Gram-positive aerobes were the most frequently isolated (47.3%, 357 strains) and followed by gram-negative aerobes and fungus (40.3% vs 12.3%, 304 vs 93 strains respectively). With rising Wagner′s grades, bacterial floras transformed from Gram-positive cocci to Gram-negative rods while fungus and composite infections increased. And 122 strains were of multi drug resistant organisms (MDRO). Among 357 strains of Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis were dominating floras. Staphylococcus was highly resistant to penicillin G, erythromycin, and oxacillin while vancomycin and linezolid were the most effective agents against gram-positive bacteria. Among 304 strains of gram-negative bacteria, enterobacteria were the most prevalent, including 48 strains of Escherichia coli, 34 strains of Proteus mirabilis and 31 strains of Proteus vulgaris. And there were 29 strains of Pseudomonas aeruginosa. Enterobacteria were highly resistant to ampicillin, followed by bactrim and furadantin while meropenem, imipenem, piperacillin/sulbactam, sulperazone and cefepime were the most effective agents. The predominant fungus was Blastomyces albicans.


Conclusions
In patients with severe diabetic foot ulcers, Gram-negative rods predominate while the prevalence of fungus and composite infections increases. Vancomycin and imipenem maintain highly antibacterial activity. It is essential to pay attention to pathogen survey and use antibiotics more rationally.


Key words: 
Diabetic foot; Infection; Microbial; Drug resistance

Clinical distribution and antimicrobial resistance analysis of 754 pathogenic bacteria in diabetic foot infection

Objective: To explore the role of S100A8, the receptor for advanced glycation endproducts (RAGE) and Caveolin-1 in neutrophilic asthmatic rats, and to further study the intervention of roxithromycin and the possible mechanisms. Methods: Male Brown Norway rats were randomly assigned to a control group, an asthma group and a Roxithromycin group. The asthmatic rat model was established by intraperitoneal injection of ovalbumin (OVA) and Freund's complete adjuvant (FCA) mixture, and aerosol inhalation of OVA. Rats in the Roxithromycin group were given roxithromycin injection 30 mg/kg 30 minutes before each challenge. Rats in the control and the asthma groups were replaced with equal volumes of saline, respectively. Bronchoalveolar lavage fluid (BALF) neutrophil percentage (Neu%) and pathological changes of pulmonary tissue (hematoxylin-eosin, HE staining) were measured to confirm the establishment of asthmatic models. The concentration of inflammatory cytokines and S100A8 were quantified by enzyme-linked immunosorbent assay (ELISA), and the expression of Caveolin-1 and RAGE at protein levels were detected by immunohistochemistry and Western blot. Results: Neu% in BALF of the asthma group was significantly higher than those of the control group, and Neu% in the Roxithromycin group was lower than the asthma group (all P<0.01). Pulmonary histology revealed that there were a large number of inflammatory cells infiltrated in the bronchial and perivascular, pulmonary interstitial and alveolar spaces, and the bronchial wall and smooth muscles were thickened obviously in the asthma group. Rats in the Roxithromycin group showed milder inflammation and airway remodeling change than the asthma group. There was no obvious pathological damage in the control group. The concentration of IL-6 and IL-17 in BALF and serum of rats in the asthma group were significantly higher than those in the control group (P<0.01), and Roxithromycin inhibited the high expression of these cytokines (P<0.05). The expression of S100A8 and RAGE in the asthma group were significantly higher than those in the control group [(20.6±4.4) vs (7.1±2.0) ng/L; (885±118) vs (462±102) ng/L; (14.2±1.7) vs (7.6±1.8) ng/L; (774±166) vs (406±69) ng/L, all P<0.05], and Roxithromycin inhibited the high expression of these proteins [(14.3±3.7) vs (20.6±4.4) ng/L; (650±53) vs (885±118) ng/L; (10.4±1.2) vs (14.2±1.7) ng/L; (560±64) vs (728±72) ng/L] (all P<0.05). Meanwhile, the expression of Caveolin-1 in the asthma group was significantly lower than that in the control group (P<0.01), and Roxithromycin up-regulated its expression (P<0.01). Correlation analysis showed that there was a significantly positive correlation between the expression of S100A8 and RAGE (r=0.706, P<0.01), while there was a significantly negative correlation between the expression of S100A8 and Caveolin-1 (r=-0.775, P<0.01), and between the expression of Caveolin-1 and RAGE (r=-0.919, P<0.01). Conclusion: S100A8 and Caveolin-1 may play an important role in neutrophilic asthma via RAGE, and Roxithromycin may exerts anti-inflammatory effects and inhibition of airway remodeling partly through this signaling pathway.

[The role of S100A8/RAGE and Caveolin-1 and the effect of roxithromycin on their expression in a rat model of neutrophilic asthma].

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Roxithromycin attenuates inflammation via modulation of RAGE-influenced calprotectin expression in a neutrophilic asthma model.

Clinical distribution and antimicrobial resistance analysis of 754 pathogenic bacteria in diabetic foot infection

[The role of S100A8/RAGE and Caveolin-1 and the effect of roxithromycin on their expression in a rat model of neutrophilic asthma].