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Introduction: Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia due to impaired insulin production or utilization, leading to severe health complications. Diabetic foot ulcers (DFUs) represent a major complication, often exacerbated by polymicrobial infections involving Staphylococcus aureus and Acinetobacter baumannii. These pathogens, notorious for their resistance to antibiotics, complicate treatment efforts, especially due to biofilm formation, which enhances bacterial survival and resistance. This study explores the synergistic effects of combining gentamicin, imipenem, and fucoidan, a sulfated polysaccharide with antimicrobial properties, against both planktonic and biofilm forms of S. aureus and A. baumannii., Methods: Isolates of S. aureus and A. baumannii were collected from DFUs and genetically confirmed. Methicillin resistance in S. aureus was identified through disk diffusion and PCR. Biofilm formation, including dual-species biofilms, was analyzed using the microtiter plate method. The antimicrobial efficacy of gentamicin, imipenem, and fucoidan was assessed by determining the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC). Synergistic interactions were evaluated using the fractional inhibitory concentration index (FICi) and fractional bactericidal concentration index (FBCi). The expression of biofilm-associated genes (icaA in S. aureus and bap in A. baumannii) was analyzed, and the cytotoxicity of fucoidan was assessed., Results: The study revealed that 77.4% of S. aureus and all A. baumannii isolates showed multidrug resistance. Among 837 tested conditions for dual-species biofilm formation, 72 resulted in strong biofilm formation and 67 in moderate biofilm formation. The geometric mean MIC values for gentamicin were 12.2 µg/mL for S. aureus, 22.62 µg/mL for A. baumannii, and 5.87 µg/mL for their co-culture; for imipenem, they were 19.84, 9.18, and 3.70 µg/mL, respectively, and for fucoidan, 48.50, 31.20, and 19.65 µg/mL, respectively. The MBC values for gentamicin were 119.42, 128, and 11.75 µg/mL; for imipenem, they were 48.50, 14.92, and 8 µg/mL; and for fucoidan, they were 88.37, 62.62, and 42.48 µg/mL. The MBIC values were 55.71, 119.42, and 18.66 µg/mL for gentamicin; 68.59, 48.50, and 25.39 µg/mL for imipenem; and 153.89, 101.49, and 53.53 µg/mL for fucoidan. The MBEC values were 315.17, 362.03, and 59.25 µg/mL for gentamicin; 207.93, 157.58, and 74.65 µg/mL for imipenem; and 353.55, 189.46, and 99.19 µg/mL for fucoidan. When cultured in planktonic form, the geometric mean FICi and FBCi values indicated additive effects, while co-culture showed FICi values of ≤ 0.5, suggesting a synergistic interaction. Treatment with gentamicin and fucoidan led to significant downregulation of the icaA and bap genes in both single-species and dual-species biofilms of S. aureus and A. baumannii. The reductions in gene expression were more pronounced in dual-species biofilms compared to single-species biofilms. Additionally, treatment with imipenem and fucoidan also resulted in significant downregulation of these genes in both biofilm types. Cytotoxicity assessments indicated that higher concentrations of fucoidan were toxic, yet no harmful effects were noted at the optimal synergistic concentrations used with antibiotics., Conclusion: In our investigation, we found that combining gentamicin, imipenem, and fucoidan had a synergistic effect on dual-species biofilms of S. aureus and A. baumannii, suggesting potential benefits for treating such infections effectively. This underscores the importance of understanding microbial interactions, antibiotic susceptibility, and biofilm formation in DFUs., Competing Interests: Declarations Ethics approval and consent to participate The Ethics Review Board of the Hamadan University of Medical Sciences, Hamadan, Iran approved the present study (Ethical approval code: IR.UMSHA.REC.1401.809). Ethical Review Board approved informed consent taken from all the participants, and all experiments were performed in accordance with relevant guidelines and regulations. We reported our findings according to the STROBE guidelines. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Skin microbiota plays an essential role in the development and function of the cutaneous immune system, in the maintenance of the skin barrier through the release of antimicrobial peptides, and in the metabolism of some natural products. With the aim of characterizing changes in the cutaneous microbiota specifically associated with wound healing in the diabetic condition, we performed a 16 S rRNA gene Next Generation Sequencing of skin swabs taken within the ulcer bed of ten diabetic patients before (t0) and after 20 days of therapy (t20) with a fluorescein-based galenic treatment. Considering the twenty most representative genera, we found at t20 an increase of Corynebacterium, Peptostreptococcus, and Streptococcus, and a decrease of Enterococcus, Finegoldia, and Peptoniphilus genera. However, differences were not significant due to the high variability among samples and the small patient cohort. S. aureus was the most abundant species at t0 and was reduced by therapy in four patients. Comparing the microbiome in the ulcer bed and in the perilesional tissue of the same patient at t0, no major differences were observed. Taken together, our data indicate that in the absence of antibiotic-based therapy the healing process of diabetic ulcers is accompanied by changes in the microbiome composition., Competing Interests: Declarations Competing interests Carlo Alessio Tenoglio is the legal representative of Blufarma S.r.l., the producer of the FluorexinTM galenic product used in clinical practice for diabetic ulcer treatment. All other authors declare no competing interests., (© 2024. The Author(s).)

Background: This study aimed to analyze the distribution of multidrug-resistant (MDR) organisms (MDROs) in patients with diabetic foot ulcers (DFUs) and to identify risk factors for MDRO infections., Methods: Patients hospitalized with DFUs were enrolled, and ulcer swabs were cultured for bacterial identification and antibiotic susceptibility testing. Hematology and blood biochemistry were also assessed., Results: A total of 228 patients hospitalized with DFUs were enrolled. Out of 150 patients with positive cultures, 123 (82%) were infected with single strains, whereas 27 (18%) had mixed infections. Out of the 177 bacterial strains isolated, 78 (44%) were MDROs. Among the top 5 most common bacteria, coagulase-negative Staphylococcus, Staphylococcus aureus, and Proteus exhibited MDR rates of 92%, 56%, and 55%, respectively. Pseudomonas aeruginosa and Enterobacter cloacae had low MDR rates of 5% and 8%, respectively. Single variable logistic regression analysis showed that neutrophil percent (NEU%), creatinine, C-reactive protein, and fasting plasma glucose (FPG) were risk factors for MDRO infection, whereas hemoglobin and albumin levels were protective factors. Multivariable logistic regression analysis revealed that NEU% and FPG were independent risk factors for MDRO infection., Conclusions: A high percentage of the infections in patients with DFUs were caused by MDROs. To reduce MDRO infections in high-risk patients, it is important to use antibiotics rationally, improve patients' FPG levels and nutritional status, and strengthen hospital sterilization processes.

Staphylococcus aureus (S. aureus) infection is the most prevalent and resistant bacterial infection, posing a worldwide health risk. Compared with healthy people, diabetes patients with weak immune function and abnormal metabolism are more vulnerable to bacterial infection, which aggravates the intensity of infection and causes a series of common and dangerous complications, such as diabetes foot ulcer (DFU). Due to metabolic abnormalities of diabetic patients, S. aureus on the skin surface of DFU transitions from a commensal to an invasive infection. During this process, S. aureus resists a series of unfavorable conditions for bacterial growth by altering energy utilization and metabolic patterns, and secretes various virulence factors, causing persistent infection. With the emergence of multiple super-resistant bacteria, antibiotic treatment is no longer the only treatment option, and developing new drugs and therapies is urgent. Regulating the metabolic signaling pathway of S. aureus plays a decisive role in regulating its virulence factors and impacts adjuvant therapy for DFU. This article focuses on studying the impact of regulating metabolic signals on the virulence of S. aureus from a metabolism perspective. It provides an outlook on the future direction of the novel development of antimicrobial therapy., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Dysbiosis and diabetic foot ulcers: a metabolism perspective of Staphylococcus aureus infection”., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The switch to alternate cell types by Staphylococcus aureus creates sub-populations even within an active population, that are highly resilient, tolerant to antibiotics and lack clinical symptoms of infection. These cells present a challenge for clinical treatment where even after initial intervention has seemingly cleared the infection, these alternate cell types persist within tissue to revert and cause disease. Small colony variants (SCV) are a cell type which facilitate persistent infection but clinically isolated SCVs are often unstable in laboratory conditions. We have isolated a pair of S. aureus isolates from an individual patient with osteomyelitis presenting with heterogenous phenotypes; a stable SCV (sSCV) and a SCV that reverts upon laboratory culturing to the usual, active and non-SCV cell type. Thus we are able use this pair to investigate and compare the genetic mechanisms that underlie the clinical variatons of SCV phenotype. The switch to the sSCV phenotype was associated with frameshift mutations in the enolase eno and the histidine kinase arlS. The phenoptye of the sSCV was an impeded growth dependent on amino acid catabolism and modulated biofilm. These mutations present potentially a new molecular mechanism which confer persistence within osteomyelitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To genetically diagnose the isolates of methicillin-resistant staphylococcus aureus taken from patients with severe diabetic foot infections, and to test the inhibitory effect of reuterin on the growth of these bacteria., Method: The experimental study was conducted from June to November 2021 at the Diabetes Unit of Al-Faihaa General Hospital, Basrah, Iraq, and comprised 62 foot ulcer swabs from the necrotic lesions of patients with type 2 diabetes. The swabs were cultivated first in brain heart infusion broth media, and then streaked on Mannitol salt agar and staphylococcus chromogeneic agar media for phenotypic and genetic analysis. The genetic identification of bacteria was confirmed by deoxyribonucleic acid extraction, and methicillin-resistant staphylococcus aureus was confirmed by the presence of plasmid mecA gene. The inhibition activity of reuterin towards methicillin-resistant staphylococcus aureus was determined using the minimum inhibitory concentration test. All data was analyzed with SPSS version 23., Results: A total of 62 swabs were taken from the necrotic lesions of type 2 diabetes mellitus (T2DM) patients with diabetic foot ulcers. Of the total isolates, 9(14.5%) gave mauve to purple colour on staphylococcus chromogeneic agar, which was then genetically confirmed as methicillin-resistant staphylococcus aureus. The minimum inhibitory concentration value of these bacteria was 10μl/ml at 16mm inhibition zone diameter. There was no cytotoxicity of reuterin to human red blood cells., Conclusions: Reuterin was found to be a natural antimicrobial substance suitable for use to disinfect diabetic foot wounds from bacterial contamination and infection, especially those caused by methicillin-resistant staphylococcus aureus.

The objective of the study was to compare outcomes in patients with complete surgical resection versus partial resection of diabetic foot osteomyelitis (OM). A post hoc analysis of 171 patients with OM was performed using data from two randomized clinical trials. OM was confirmed with bone culture or histopathology. Surgical culture specimens were obtained from resected bone and sent for histopathology and microbiology. Residual osteomyelitis (RO) was defined as a positive resected margin on culture or histopathology. No residual osteomyelitis (NRO) was defined as no growth from bone culture and no histopathological inflammation in the biopsy of the resection margin. Data from the 12-month follow-up were used to determine clinical outcomes. During the index hospitalization, NRO patients had significantly shorter duration of antibiotic therapy (NRO 21.0, 13.0-38.0 vs. RO 37.0, 20.8-50.0, p <0.01) and more amputations than patients with RO (NRO 89.9% vs. RO 60.9%, p <0.01). During the 12-month follow-up, patients with NRO also had significantly shorter duration of antibiotic therapy (NRO 42, 21.0-66.5 vs. RO 50.5, 35.0-75.0, p = 0.02). During the 12-month follow-up, there was no difference in ulceration at the same site (NRO 3.7%, RO 4.3% p = 0.85), hospitalization (NRO 32.6%, RO 34.8%, p = 0.76), total re-infections (NRO 25.3%, RO 29.3%, p = 0.56), re-infection with osteomyelitis (NRO 13.3% vs. 13.5%, p = 0.36), amputation (NRO 8.8%, RO 5.4%, p = 0.86) and time to wound healing in days (NRO 94, 41.0-365 vs. RO 106, 42.8-365, p = 0.77). Successful treatment of osteomyelitis was achieved by 86.7% and 86.5% of patients. During the index hospitalization, patients with no residual osteomyelitis had more amputations and were treated with antibiotics for a shorter duration. During the 12-month follow-up, patients with no residual osteomyelitis had shorter durations of antibiotics. There were no differences in re-infection, amputation, re-ulceration or hospitalization. Level of evidence: 1., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Superficial skin injuries especially burn injuries and unhealed diabetic foot open wounds remain troubling for public health. The healing process is often interrupted by the invasion of resistant pathogens that results in the failure of conventional procedures outside the clinical settings. Herein, we designed nanofibers dressing with intrinsic antibacterial potential of poly(vinyl-pyrrolidone)-iodine/ poly (vinyl)-alcohol by electrospinning with chitosan encapsulating ceftriaxone (CPC/NFs). The optimized electrospun CPC/NFs exhibited smooth surface morphology with average diameter of 165 ± 7.1 nm, drug entrapment and loading efficiencies of 76.97 ± 4.7 % and 8.32 ± 1.73 %, respectively. The results displayed smooth and uniformed fibers with adequate thermal stability and ensured chemical doping. The enhanced in vitro antibacterial efficacy of CPC/NFs against resistant E. coli isolates and biosafety studies encourage the use of designed nanofibers dressing for burn injuries and diabetic foot injuries. In vivo studies proved the healing power of dressing for burn wounds model and diabetic infected wounds model. Immunofluorescence investigation of the wound tissue also suggested promising healing ability of CPC/NFs. The designed approach would be helpful to treat these infected skin open wounds in the hospitals and outside the clinical settings., Competing Interests: Declaration of competing interest All the authors of this manuscript declared that they have no potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

SUMMARY Diabetic foot infections (DFI) are a public health problem worldwide. DFI are polymicrobial, biofilm-associated infections involving complex bacterial communities organized in functional equivalent pathogroups, all including anaerobes. Indeed, multiple pathophysiological factors favor the growth of anaerobes in this context. However, the prevalence, role, and contribution of anaerobes in wound evolution remain poorly characterized due to their challenging detection. Studies based on culture reviewed herein showed a weighted average of 17% of patients with anaerobes. Comparatively, the weighted average of patients with anaerobes identified by 16S rRNA gene sequencing was 83.8%. Culture largely underestimated not only the presence but also the diversity of anaerobes compared with cultivation-independent approaches but both methods showed that anaerobic Gram-negative bacilli and Gram-positive cocci were the most commonly identified in DFI. Anaerobes were more present in deeper lesions, and their detection was associated with fever, malodorous lesions, and ulcer depth and duration. More specifically, initial abundance of Peptoniphilus spp. was associated with ulcer-impaired healing, Fusobacterium spp. detection was significantly correlated with the duration of DFI, and the presence of Bacteroides spp. was significantly associated with amputation. Antimicrobial resistance of anaerobes in DFI remains slightly studied and warrants more consideration in the context of increasing resistance of the most frequently identified anaerobes in DFI. The high rate of patients with DFI-involving anaerobes, the increased knowledge on the species identified, their virulence factors, and their potential role in wound evolution support recommendations combining debridement and antibiotic therapy effective on anaerobes in moderate and severe DFI., Competing Interests: The authors declare no conflict of interest.

Type 2 diabetes mellitus (T2DM) is globally recognized as a significant health concern, with diabetic foot (DF) identified as a severe long-term complication that can lead to tissue death or amputation. The discovery of the impact of mycobiota, a diverse group of multicellular eukaryotes in the gut microbiome, on the onset of endocrine disorders holds great significance. Therefore, this research aimed to examine variations in fungal mycobiome and identify potential biomarkers for T2DM and T2DM-DF. Fecal and blood samples were collected from 33 individuals with T2DM, 32 individuals with T2DM-DF, and 32 healthy individuals without any health conditions (HC). Blood samples were used for laboratory parameters analysis, while total DNA was extracted from fecal samples and sequenced using Illumina 18s rRNA. Bioinformatics tools were employed to analyze fungal abundance and diversity, revealing differentially expressed fungal species and signature fungi that distinguished between T2DM, T2DM-DF, and HC groups. Firstly, significant alterations in some laboratory parameters were observed among the three groups, which also differed between T2DM and T2DM-DF. The diversity of gut fungi in T2DM and T2DM-DF significantly differed from that of the HC group; however, more pronounced changes were observed in T2DM-DF. Additionally, two significantly altered phyla, Ascomycota and Basidiomycota, were identified with higher Ascomycota abundance but lower Basidiomycota abundance in both the T2DM and T2DM-DF compared to the HC group. Furthermore, the top 15 fungi showing significant changes at the species level included a notable decrease in Rhodotorula&#95;mucilaginosa abundance in patients with T2DM compared to HC and a substantial increase in unclassified&#95;g&#95;Candida abundance specifically seen only among patients with T2DM-DF, but not among those diagnosed with T2DM or HC. Thirdly, KEGG was employed to analyze enzyme expression across the three groups, revealing a more pronounced alteration in gut fungal function within T2DM-DF compared to T2DM. Subsequently, to accurately identify signature fungi in each group, a random forest was utilized to rank the top 15 significant fungi. Notably, 11 fungi were identified as potential biomarkers for distinguishing T2DM or T2DM-DF from HC, while eight fungi could discriminate between T2DM and T2DM-DF. Furthermore, receiver operating characteristic curve (ROC) analysis demonstrated enhanced accuracy of predicted outcomes. These findings suggest that changes in fungal mycobiome are closely associated with the progression and complications of T2DM and DF, offering promising prospects for diagnosis and treatment., (© 2024. The Author(s).)

Background: Reamputations are frequent after minor amputations performed for diabetic foot osteomyelitis (DFO). Whether the type of amputation is associated with a particular outcome is unknown. The aim of this study was to evaluate whether amputations of the transarticular compared with the transosseous type have different rates of clinical and microbiological failure., Methods: We actively followed 284 patients with DFO (543 episodes of minor foot amputations: 203 transarticular and 340 transosseous) for 1 year. We assessed the long-term effect of transarticular compared with transosseous amputations on the rates of clinical and microbiological failure using comparative statistics, log-rank survival analyses, Kaplan-Meier curves, and multivariate Cox regressions., Results: In 122 episodes (22.5%) there was clinical failure that led to reamputation. The difference in the risk of clinical failure of transarticular versus transosseous amputations was nonsignificant (44 [21.7%] versus 78 [22.9%]; Pearson χ2 test: P = .73). Similarly, the difference in microbiological failure (32 episodes, 5.9% overall) between groups was nonsignificant (11 [5.4%] and 21 [6.2%], respectively; P = .72). The mean time between the index surgery and clinical failure was 2.2 months for transarticular and 3.2 months for transosseous amputations (Mann-Whitney U test; P = .39). Survival analyses showed similar evolutions for each group (log-rank test; P = .85). In the multivariate Cox regression analysis, the type of amputation did not significantly influence clinical or microbiological failures., Conclusions: In DFO, there is no significant difference between transarticular and transosseous amputations within 1 year in the incidence of clinical or microbiological failures.

To identify the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection, reinfection and clinical outcomes. Four hundred forty-six patients that were admitted to the hospital with moderate or severe foot infections were retrospectively reviewed. Tissue and bone cultures were obtained from the index hospital admission. Conversion was defined as methicillin susceptible Staphylococcus aureus in the first culture and subsequently MRSA when there was a reinfection. The incidence of MRSA was 7.8% (n = 35), with no significant difference between soft tissue infections (7.7%) and osteomyelitis (8.0%). MRSA incidence was 9.4 times higher in non-diabetics (23.8% vs. 3.2%, p = <0.01). The incidence of reinfection was 40.8% (n = 182). Conversion to MRSA was seen in 2.2% (n = 4) total, occurring in 5.4%. Non-diabetics were 20.1 times more likely to have MRSA reinfection than people with diabetes (28.6% vs. 1.9%, p < 0.001). MRSA patients had a higher proportion of healed wounds (82.4% vs. 69.3%, p = 0.02). There were no differences in other clinical outcomes in MRSA vs. other infections in reinfection (28.6% vs. 24.3%, p = 0.11), amputation (48.6% vs. 52.0%, p = 0.69) or hospitalization (28.6% vs. 42.6, p = 0.11). The incidence of MRSA for the first infection (7.8%), reinfection (6.0%) and conversion to MRSA (2.2%) was low. MRSA was 9.4 times more common in people without diabetes., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Diabetic foot infection imposes a significant burden and is the major cause of nontraumatic limb amputation. Adequate patient management with effective antibiotic therapy is crucial.This retrospective cohort study aimed to characterize the microbiology and resistance patterns of moderate to severe neuropathic diabetic foot infection in patients hospitalized at a tertiary referral hospital between January 2020 and June 2023. Deep tissue specimens from ulcers were collected for culture.Sixty inpatients were included (62% male, mean age 59.1 ± 11.5 years). Osteomyelitis was present in 90% of the patients. Among 102 microorganisms (average of 1.91 ± 1.25 pathogens per patient), 60.8% were gram-positive bacteria, 31.4% were gram-negative, 3.92% were anaerobic bacteria, and 3.92% were fungi. Staphylococcus aureus (19%) and Enterococcus faecium (17%) were the most common. Pseudomonas aeruginosa (8%) and bacteria of the Enterobacterales family (24%) accounted for all the isolated gram-negative bacteria. Sixteen percent of Staphylococcus aureus and 67% of coagulase-negative Staphylococci were resistant to methicillin. Resistance to ampicillin was found in 11% of Enterococci. All Pseudomonas aeruginosa isolates were sensitive to piperacillin-tazobactam, ceftazidime, or cefepime. Among the Enterobacterales, resistance rates were 35% for piperacillin-tazobactam, 38% for ceftazidime, 21% for cefepime, and 13% for carbapenems.Although the prevalence of methicillin-resistant staphylococci was lower than that in other studies, carbapenem resistance among gram-negative bacteria warrants attention. This study highlights the importance of understanding local epidemiology for effective diabetic foot infection management and resistance mitigation., (© 2024. The Author(s).)

Staphylococcus aureus (S. aureus) is considered as one of the challenging ulcer infections in diabetic patients especially those who have acquired antibiotic-resistant infections. Nanotechnology products have enormous potential to treat diseases including infectious diseases. As chitosan and zinc oxide (ZnO) nanoparticles (NPs) have harbored a high antimicrobial effect, this survey was aimed to synthesize chitosan, ZnO, and ZnO-Urtica. diocia (ZnO-U. diocia) NPs, and to assess their antimicrobial effects and their influence on virulence genes expression in S. aureus isolates from diabetic ulcers. The antibacterial effect of NPs was detected by microdilution method. The most frequently components in U. diocia aqueous extract were linalool,4-thujanol, camphor, carvacrol, propanedioic acid, and di(butyl) phthalate. More than 95% of clinical S. aureus isolates were resistant to several antibiotics including erythromycin, cefoxitin, clindamycin, and ciprofloxacin. The most resistant isolates were S. aureus ATDS 52, ATDS 53, F5232, and F91. The lowest MIC and MBC by the NPs on the isolates was detected as 0.128 g/mL and 0.178 g/mL, respectively. A significant decrease of 90% in the expression rates of lukED and RNAIII genes was reported for S. aureus isolates treated with the NPs. The synthetized ZnO-U. diocia and chitosan NPs can be proposed as a reliable and effective antimicrobial agent targeting diabetic ulcers infections caused by S. aureus because of its high effects on the bacterial growth and virulence genes expression., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The aim was to evaluate the effectiveness of a marine omega fatty acid-containing multimodal wound matrix (MWM) in reducing bacterial contamination and supporting wound area reduction (WAR) in patients with hard-to-heal wounds of varying aetiologies., Method: A prospective, single-site, pilot case series of patients with hard-to-heal wounds. All wounds were considered non-healing prior to inclusion as they had failed to achieve at least 50% WAR after at least four weeks of standard of care (SoC) treatments. Patients were seen once weekly for wound assessments, matrix application and dressing changes. Baseline and weekly fluorescence images, standard wound images and wound measurements were obtained., Results: A total of three patients, two with venous leg ulcers (VLUs) and one with a diabetic foot ulcer (DFU) were enrolled in this pilot study. The mean baseline wound age prior to study enrolment was 24 weeks, with a mean baseline wound size of 8.61cm 2 . The two VLUs went on to complete closure. The DFU displayed a total WAR of 53% by six weeks, when the patient was lost to follow-up due to a geographical relocation. The mean percentage area reduction of all wounds combined was 82% upon study completion., Conclusion: The use of MWM proved to be effective and safe in this patient cohort. The wounds included in this case series failed to enter a healing trajectory with SoC wound therapies. The MWM supported wound closure and reduced bacterial loads in this patient cohort.

The study determined the prevalence, antimicrobial resistant (AMR) determinants, and genetic characteristics of Escherichia coli and Klebsiella pneumoniae isolates from patients with diabetic foot infection (DFI) in a Tunisian hospital. A total of 26 Escherichia spp. and Klebsiella spp. isolates were recovered and identified by MALDI-TOF-MS. Antimicrobial susceptibility testing, the detection of AMR determinants and Shiga-like toxin genes, phylogenetic grouping, and molecular typing were performed. Twelve E. coli , 10 K. pneumoniae , 3 K. oxytoca , and 1 E. hermanii were isolated. A multidrug-resistant phenotype was detected in 65.4% of the isolates. About 30.8% of isolates were extended-spectrum β-lactamase (ESBL) producers and mainly carried bla CTX -M-15 and bla CTX -M-14 genes. One bla NDM -1 -producing K. pneumoniae- ST1 strain was identified. Class 1 integrons were detected in 11 isolates and 5 gene cassette arrangements were noted: dfrA1+aadA1 ( n = 1), dfrA12+aadA2 ( n = 3), and dfrA17+aadA5 ( n = 1). Other non-β-lactam resistance genes detected were as follows (number of isolates): aac(3')-II (3), aac(6')-Ib-cr (8), qnrB (2), qnrS (4), cmlA (2), floR (4), sul1 (11), sul2 (11), and sul3 (2). The phylogroup B1 was the most frequent (41.7%) among E. coli , and two ESBL-producing isolates corresponded to the ST131-B2 lineage. The ESBL- and carbapenemase-producing Enterobacteriaceae in DFIs are described for the first time in Tunisia.

Background: Severely infected diabetic ulcers of the big toe often necessitate surgical treatment. Depending on the wound stage and presence of osteomyelitis, conservative surgery and amputation are the main surgical treatments. Few articles reported the outcomes and complications of such procedures. This study is a preliminary comparative report on the early outcomes and complications of hallucal diabetic foot infection (DFI) treated with either conservative surgery or amputation., Methods: This is a retrospective comparative study comprising a continuous series of patients admitted at our hospital. Initially, all diabetic foot ulcer (DFU) were infected and at advanced stage (Wagner Grade 3 or 4). All clinically suspected cases of osteomyelitis were confirmed by bone pathology and microbiology culture. The study included 37 patients diagnosed with DFI. Infection profile was as follows: 23 DFU with osteomyelitis (Wagner Grade 3 or 4) and 14 infected DFU (Wagner Grade 2). Twenty-four conservative procedures and 13 amputation surgeries were performed initially. The primary outcome was defined as the frequency of subsequent surgery (deep infection recurrence treated with surgery). Statistical analysis was used to look for significant difference between both groups., Results: Ten patients (27%) required additional surgeries because of deep infection recurrence. Four recurrences (16.7%) were observed in the conservative group and 6 (46%) in the amputation group (P = 0.054). Amputation rate as a subsequent procedure was 8.3% for the conservative group and the reamputation rate for the amputation group was 23.1% (P = 0.2)., Conclusions: The study findings would indicate that the more severe is the initial hallucal infection severity (higher Wagner grade), the higher is the frequency of early surgical complications mainly after an index amputation procedure. Our assessment tools of initial infection extent seem to be underperforming. A more aggressive treatment in the form of a more proximal cut with regard to magnetic resonance imaging bone infection signal could be considered to minimize the risk of subsequent surgeries and reamputations., (Copyright © 2024. Published by Elsevier Inc.)

Skin and soft tissue infections (SSTIs), and particularly diabetic-related foot infections (DFI), present diagnostic and therapeutic complexities, often leading to severe complications. This study aims to evaluate the in vitro efficacy of cefditoren and amoxicillin/clavulanic acid against typical DFI pathogens. Clinical samples from 40 patients with mild SSTIs were analyzed, revealing a predominance of Staphylococcus spp. and Streptococcus spp. species. Cefditoren exhibited activity against 90% of isolates, with superior potency over amoxicillin/clavulanic acid. These findings underscore the utility of cefditoren in empirical treatment of DFI, although a larger sample size would be desirable for further validation., (©The Author 2024. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

The aim was to investigate methicillin-resistant Staphylococcus aureus (MRSA) incidence, conversion and outcomes in diabetic foot infections (DFIs). This is a pooled patient-level analysis of combined data sets from two randomised clinical trials including 219 patients admitted to the hospital with moderate or severe DFIs. Intraoperative bone and tissue cultures identified bacterial pathogens. We identified pathogens at index infections and subsequent re-infections. We identified MRSA conversion (MSSA to MRSA) in re-infections. MRSA incidence in index infections was 10.5%, with no difference between soft tissue infections (STIs) and osteomyelitis (OM). MRSA conversion occurred in 7.7% of the re-infections in patients who initially had MSSA in their cultures. Patients with re-infection were 2.2 times more likely to have MRSA compared to the first infection (10.5% vs. 25.8%, relative risk [RR] = 2.2, p = 0.001). Patients with MRSA had longer antibiotic treatment during the 1-year follow-up, compared to other pathogens (other 49.8 ± 34.7 days, MRSA 65.3 ± 41.5 days, p = 0.04). Furthermore, there were no differences in healing, time to heal, length of stay, re-infection, amputation, re-ulceration, re-admission, surgery after discharge and amputation after discharge compared to other pathogens. The incidence of MRSA at the index was 10.5% with no difference in STI and OM. MRSA incidence was 25.8% in re-infections. The RR of having MRSA was 2.2 times higher in re-infections. Patients with MRSA used more antibiotics during the 1-year follow-up. Furthermore, there were no differences in clinical outcomes compared to other bacterial pathogens., (© 2024 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Purpose: Investigating risk factors for amputation in patients with diabetic foot ulcer (DFU) and developing a nomogram prediction model., Methods: We gathered case data of DFU patients from five medical institutions in Anhui Province, China. Following eligibility criteria, a retrospective case-control study was performed on data from 526 patients., Results: Among the 526 patients (mean age: 63.32 ± 12.14), 179 were female, and 347 were male; 264 underwent amputation. Univariate analysis identified several predictors for amputation, including Blood type-B, Ambulation, history of amputation (Hx. Of amputation), Bacterial culture-positive, Wagner grade, peripheral arterial disease (PAD), and laboratory parameters (HbA1c, Hb, CRP, ALB, FIB, PLT, Protein). In the multivariate regression, six variables emerged as independent predictors: Blood type-B (OR = 2.332, 95%CI [1.488-3.657], p < 0.001), Hx. Of amputation (2.298 [1.348-3.917], p = 0.002), Bacterial culture-positive (2.490 [1.618-3.830], p <0.001), Wagner 3 (1.787 [1.049-3.046], p = 0.033), Wagner 4-5 (4.272 [2.444-7.468], p <0.001), PAD (1.554 [1.030-2.345], p = 0.036). We developed a nomogram prediction model utilizing the aforementioned independent risk factors. The model demonstrated a favorable predictive ability for amputation risk, as evidenced by its area under the receiver operating characteristics (ROC) curve of 0.756 and the well-fitted corrected nomogram calibration curve., Conclusion: Our findings underscore Blood type-B, Hx. Of amputation, Bacterial culture-positive, Wagner 3-5, and PAD as independent risk factors for amputation in DFU patients. The resultant nomogram exhibits substantial accuracy in predicting amputation occurrence. Timely identification of these risk factors can reduce DFU-related amputation rates., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background. Pseudomonas aeruginosa is an invasive organism that frequently causes severe tissue damage in diabetic foot ulcers. Gap statement. The characterisation of P. aeruginosa strains isolated from diabetic foot infections has not been carried out in Tunisia. Purpose. The aim was to determine the prevalence of P. aeruginosa isolated from patients with diabetic foot infections (DFIs) in Tunisia and to characterize their resistance, virulence and molecular typing. Methods. Patients with DFIs admitted to the diabetes department of the International Hospital Centre of Tunisia, from September 2019 to April 2021, were included in this prospective study. P. aeruginosa were obtained from the wound swabs, aspiration and soft tissue biopsies during routine clinical care and were confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing, serotyping, integron and OprD characterization, virulence, biofilm production, pigment quantification, elastase activity and molecular typing were analysed in all recovered P. aeruginosa isolates by phenotypic tests, specific PCRs, sequencing, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Results. Sixteen P. aeruginosa isolates (16.3 %) were recovered from 98 samples of 78 diabetic patients and were classified into 6 serotypes (O:11 the most frequent), 11 different PFGE patterns and 10 sequence types (three of them new ones). The high-risk clone ST235 was found in two isolates. The highest resistance percentages were observed to netilmicin (69 %) and cefepime (43.8 %). Four multidrug-resistant (MDR) isolates (25 %) were detected, three of them being carbapenem-resistant. The ST235-MDR strain harboured the In51 class 1 integron ( intI1 +aadA6+orfD+qacED1-sul1 ). According to the detection of 14 genes involved in virulence or quorum sensing, 5 virulotypes were observed, including 5 exoU -positive, 9 exoS -positive and 2 exoU/exoS -positive strains. The lasR gene was truncated by IS Ppu21 insertion sequence in one isolate, and a deletion of 64 bp in the rhlR gene was detected in the ST235-MDR strain. Low biofilm, pyoverdine and elastase production were detected in all P. aeruginosa ; however, the lasR -truncated strain showed a chronic infection phenotype characterized by loss of serotype-specific antigenicity, high production of phenazines and high biofilm formation. Conclusions. Our study demonstrated for the first time the prevalence and the molecular characterization of P. aeruginosa strains from DFIs in Tunisia, showing a high genetic diversity, moderate antimicrobial resistance, but a high number of virulence-related traits, highlighting their pathological importance.

Residual osteomyelitis is a frequent problem following surgical intervention for diabetic foot infection. The Infectious Disease Society of America guidelines recommend a prolonged course of antibiotics for treatment of residual osteomyelitis. Recent literature suggests oral antibiotic therapy is not inferior to IV therapy. The primary aim of this study was to evaluate treatment success in 128 patients receiving oral versus IV antibiotics for residual osteomyelitis in the diabetic foot after amputation at a Level 1 academic medical trauma center. Treatment success was defined as completion of at least 4 weeks of antibiotic therapy, complete surgical wound healing, and no residual infection requiring further debridement or amputation within 1 year of the initial surgery. Patients with peripheral arterial disease were excluded. A retrospective chart review was performed, and we found no statistically significant difference in treatment success between these two groups (p = .2766). The median time to healing for oral antibiotic treatment was 3.17 months compared to 4.06 months for IV treatment (p = .1045). Furthermore, there was no significant difference in group demographics or comorbidities, aside from more patients in the IV group having coronary artery disease (p = .0416). The type of closure and whether the infection was single or polymicrobial were also not associated with a difference in outcomes between the two treatment arms. The results of the present study suggest oral antibiotics for treatment of residual osteomyelitis are not inferior to IV therapy and may be more efficacious for certain patients regarding cost and ease of administration., (Copyright © 2024 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to compare outcomes of moderate and severe foot infections in people with and without diabetes mellitus (DM). We retrospectively evaluated 382 patients (77% with DM and 23% non-DM). We collected demographic data, co-morbidities and one-year outcomes including healing, surgical interventions, number of surgeries, length of stay, re-infection and re-hospitalisation. DM patients required more surgeries (2.3 ± 2.2 vs. 1.7 ± 1.3, p = 0.01), but did not have a longer hospital length of stay during the index hospitalisation (DM 10.9 days ±9.2 vs. non-DM = 8.8 days ±5.8, p = 0.43). After the index hospitalisation, DM patients had increased rates of re-hospitalisation for any reason (63.3% vs. 35.2%, CI 1.9-5.2, OR 3.2, p < 0.01), re-infection at the index wound infection site (48% vs. 30.7%, CI 1.3-3.5, OR 2.1, p < 0.01), re-hospitalisation for a foot pathology (47.3% vs. 29.5%, CI 1.3-3.6, OR 2.1, p < 0.01), and longer times to ulcer healing (151.8 days ±108.8 vs. 108.8 ± 90.6 days, p = 0.04). Patients with DM admitted to hospital with foot infections have worse clinical outcomes during the index hospitalisation and are more likely to have re-infection and re-admission to hospital in the next year., (© 2024 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Background: Diabetic foot ulcers in developing countries often become infected. The healthcare systems are often not equipped to conduct the culture and the sensitivity tests required for prescribing a targeted antibiotic treatment for diabetic foot infection (DFI)., Methods: We evaluate antibiotic stewardship programmes for DFIs, at every level of health care, with an emphasis on resource-poor settings such as in Africa., Results: The management of DFI very often is adapted to the financial and practical realities of the resource-poor regions. The application of the point-of-care Gram stain of deep tissue samples is efficient, rapid, low cost and ubiquitously available. Upon the identification of the predominant pathogen in the Gram stain, a semi-quantitative preemptive antibiotic treatment can be started in accordance with the World Health Organization Aware, Watch and Restrict Essential Medicine List. This list is catered to every country and is a powerful tool. However, some basic knowledge of the local microbiological epidemiology is necessary to choose the most appropriate agent. We report our experience on using the rapidly available Gram stain for narrowing the preemptive choice of listed antibiotic agents, as an economic tool for antibiotic stewardship in DFIs., Conclusions: In the practical and resource-saving management of DFI, the 'therapeutic' use of Gram stains is not common in resource-rich countries but should be added to the arsenal of the general efforts for antibiotic stewardship., (© 2024 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Chronic wounds are a common and costly complication of diabetes, where multifactorial defects contribute to dysregulated skin repair, inflammation, tissue damage, and infection. We previously showed that aspects of the diabetic foot ulcer microbiota were correlated with poor healing outcomes, but many microbial species recovered remain uninvestigated with respect to wound healing. Here, we focused on Alcaligenes faecalis , a Gram-negative bacterium that is frequently recovered from chronic wounds but rarely causes infection. Treatment of diabetic wounds with A. faecalis accelerated healing during early stages. We investigated the underlying mechanisms and found that A. faecalis treatment promotes reepithelialization of diabetic keratinocytes, a process that is necessary for healing but deficient in chronic wounds. Overexpression of matrix metalloproteinases in diabetes contributes to failed epithelialization, and we found that A. faecalis treatment balances this overexpression to allow proper healing. This work uncovers a mechanism of bacterial-driven wound repair and provides a foundation for the development of microbiota-based wound interventions.

Introduction: Pathogens causing diabetic foot infections (DFIs) vary by region globally; however, knowledge of the causative organism is essential for effective empirical treatment. We aimed to determine the incidence and antibiotic susceptibility of DFI pathogens worldwide, focusing on Asia and China., Methods: Through a comprehensive literature search, we identified published studies on organisms isolated from DFI wounds from January 2000 to December 2020., Results: Based on our inclusion criteria, we analyzed 245 studies that cumulatively reported 38,744 patients and 41,427 isolated microorganisms. DFI pathogens varied according to time and region. Over time, the incidence of Gram-positive and Gram-negative aerobic bacteria have decreased and increased, respectively. America and Asia have the highest (62.74%) and lowest (44.82%) incidence of Gram-negative bacteria, respectively. Africa has the highest incidence (26.90%) of methicillin-resistant Staphylococcus aureus. Asia has the highest incidence (49.36%) of Gram-negative aerobic bacteria with species infection rates as follows: Escherichia coli , 10.77%; Enterobacter spp. , 3.95%; and Pseudomonas aeruginosa , 11.08%, with higher local rates in China and Southeast Asia. Linezolid, vancomycin, and teicoplanin were the most active agents against Gram-positive aerobes, while imipenem and cefoperazone-sulbactam were the most active agents against Gram-negative aerobes., Discussion: This systematic review showed that over 20 years, the pathogens causing DFIs varied considerably over time and region. This data may inform local clinical guidelines on empirical antibiotic therapy for DFI in China and globally. Regular large-scale epidemiological studies are necessary to identify trends in DFI pathogenic bacteria., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023447645., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qu, Ou, Zhang, Li, Xia, Yang, Liu, Ma, Jiang, Wang, Chen, Yu, Qi and Xu.)

Objective: To evaluate the association of multidrug-resistant bacteria (MDRB) and adverse clinical outcomes in patients with diabetic foot infection (DFI) in a Peruvian hospital., Materials and Methods: This retrospective cohort study evaluated patients treated in the Diabetic Foot Unit of a General Hospital in Lima, Peru. MDRB was defined by resistance to more than two pharmacological groups across six clinically significant genera. The primary outcome was death due to DFI complications and/or major amputation. Other outcomes included minor amputation, hospitalization, and a hospital stay longer than 14 days. Relative risks were estimated using Poisson regression for all outcomes., Results: The study included 192 DFI patients with a mean age of 59.9 years; 74% were males. A total of 80.8% exhibited MDRB. The primary outcome had an incidence rate of 23.2% and 5.4% in patients with and without MDRB, respectively (p = 0.01). After adjusting for sex, age, bone involvement, severe infection, ischemia, diabetes duration, and glycosylated hemoglobin, MDRB showed no association with the primary outcome (RR 3.29; 95% CI, 0.77-13.9), but did with hospitalization longer than 14 days (RR 1.43; 95% CI, 1.04-1.98)., Conclusions: Our study found no association between MDRB and increased mortality and/or major amputation due to DFI complications, but did find a correlation with prolonged hospitalization. The high proportion of MDRB could limit the demonstration of the relationship. It is urgent to apply continuous evaluation of bacterial resistance, implement a rational plan for antibiotic use, and maintain biosafety to confront this threat., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yovera-Aldana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Diabetic foot ulcers (DFUs) often become infected and are treated with antimicrobials, with samples collected to inform care. Swab samples are easier than tissue sampling but report fewer organisms. Compared with culture and sensitivity (C&S) methods, molecular microbiology identifies more organisms. Clinician perspectives on sampling and processing are unknown. We explored clinician perspectives on DFU sampling-tissue samples/wound swabs-and on processing techniques, culture and sensitivity or molecular techniques. The latter provides information on organisms which have not survived transport to the laboratory for culture. We solicited feedback on molecular microbiology reports. Qualitative study using semi-structured interview, with analysis using a Framework approach. CODIFI2 clinicians from UK DFU clinics. Seven consultants agreed to take part. They reported, overall, a preference for tissue samples over swabbing. Clinicians were not confident replacing C&S with molecular microbiology as the approach to reporting was unfamiliar. The study was small and did not recruit any podiatrists or nurses, who may have discipline-specific attitudes or perspectives on DFU care. Both sampling approaches appear to be used by clinicians. Molecular microbiology reports would not be, at present, suitable for replacement of traditional culture and sensitivity., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

This study aimed to determine the most accurate microbiological test for the detection of micro-organisms in infected diabetic foot ulcerations in people living with type-2 Diabetes. For 20 eligible patients, a superficial tissue swab and a deep tissue sample were taken during a regular appointment at a Diabetes out-patient's Podiatry Clinic. Two specimens were collected from each wound for microbial culturing after debridement. Infected foot ulcerations were graded according to the Wagner's classification as per clinical protocol. This study found a significant difference [p = 0.028] between the two different samples. The deep tissue sample was found to be more accurate in identifying micro-organisms than the superficial swabs, although the latter is more widely used in clinical practice. Further studies are warranted to provide more evidence to clinicians on the best method to adopt when swabbing different types of diabetic foot ulcerations with different wound classification since, it is clearly still a matter of debate how to detect wound infection., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

It is necessary to know the resistance profile of Staphylococcus aureus to better control diabetic foot ulcer infections, to establish rational antibiotic therapy, and to avoid the development of resistant strains. This cross-sectional study evaluated the clinical parameters, virulence, and antimicrobial resistance profiles of S aureus in patients with diabetic foot disease admitted to a public hospital. S aureus strains were identified in patients with diabetes with amputation indication. Infected tissue samples were collected, microbes were isolated and identified. The microbial resistance profile was determined. Samples were also analyzed for biofilm formation and other virulence markers. The 34 individuals examined were mostly men, black, aged 60 years on average, and generally had a low income and education level. Most individuals had type 2 diabetes, and the mean time since diagnosis was 13.9 years. On an SF-36 (the Medical Outcomes Study 36-item short-form health survey) quality-of-life questionnaire, 75% of individuals obtained a score equal to 0 for physical impairment. S aureus specimens from 17 patients were isolated, corresponding to 50% of samples. Five isolates were classified as methicillin-resistant S aureus (MRSA). Molecular typing revealed that 20% of MRSA strains were SCC mec type V and 80% were type I. All isolates were sensitive to doxycycline; 61.5% were resistant to erythromycin, 38.5% to cefoxitin, 30.7% to clindamycin and ciprofloxacin, 23% to meropenem, 15.3% to gentamicin, 38.5% to oxacillin, and 7.7% (one strain) to vancomycin. Regarding biofilm production, 53% of samples were able to produce biofilms, and 84.6% had icaA and/or icaD genes . Additionally, the following enterotoxin genes were identified in the isolates: seb, sec, seg, and sei (5.9%, 5.9%, 11.8%, and 23.9%, respectively) and agr types 1 (5.9%) and 2 (11.8%). Genotypic evaluation made it possible to understand the pathogenicity of S aureus strains isolated from the diabetic foot; laboratory tests can assist in the monitoring of patients with systemic involvement., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Diabetic foot syndrome is defined as the presence of a diabetic foot ulcer (DFU) associated with neuropathy, peripheral artery disease and infection. While the use of antimicrobials in the treatment of DFU infection remains a mainstay, the choice of antimicrobial remains problematic owing to the presence of multidrug-resistant polymicrobial infections. In the South African public healthcare sector, the treatment of DFUs is based on the Standard Treatment Guidelines (STGs) and the Essential Drug List. These guidelines are developed using evidence-based medicine and are based on global susceptibility patterns rather than local susceptibility data, and may not provide the most appropriate treatment options., Objectives: To determine the antimicrobial susceptibility patterns of DFUs isolated from patients visiting selected Gauteng provincial public hospitals in order to determine a clinically effective treatment protocol for the management of these infections., Methods: Sample swabs were taken from 51 DFUs using the Levine method. Each sample swab was spread onto blood agar plates, and thereafter individual pathogens were isolated. The antimicrobial susceptibility patterns of all isolated pathogens were determined using zone of inhibition measurements. Pathogens were grouped according to macromorphological characteristics as well as susceptibility patterns, and a representative isolate from each group was then identified., Results: A total of 51 DFU ulcer swabs from 45 patients were included in the study. From the sample swabs, a total of 445 pathogens were isolated. The most effective antimicrobial was found to be gentamicin, followed by ciprofloxacin. Amoxicillin/clavulanic acid, the first-line treatment according to the STGs, was found to be ineffective for many of the isolated pathogens. The most commonly isolated pathogens were Proteus mirabilis, Enterococcus faecalis and Pseudomonas aeruginosa., Conclusion: These findings demonstrate the urgent need to reassess the STGs and base treatment plans on local epidemiological data. This study provides valuable data on common causative pathogens in DFU infections, as well as the resistance patterns of these pathogens, forming a baseline on which to base future DFU treatment plans.

The primary objective of this study was to isolate bacteria from diabetic foot ulcers and subsequently assess their antibiotic resistance capabilities. Seventy-five patients diagnosed with diabetic foot ulcers were investigated. A number of these patients (97.33%) had type 2 diabetes, with a significant proportion of them having been diagnosed for 1-5 years (29.33%). Notably, a substantial number of these individuals were on insulin usage (78.66%). Among the patients under examination, 49.33% reported having no use of tobacco products, alcohol, or betel leaf. The ulcers analyzed in this study were classified into grades 1-5 according to the Wagner scale. Wagner grade 2 diabetic foot ulcers had the highest number of culture-positive patients, at 33.33%. Pus samples collected from patients were cultured on selective media, and bacterial identity was confirmed by biochemical tests and polymerase chain reaction. A total of 141 isolates were isolated. Among the isolates, 82.97% gram-negative bacteria and 17.02% gram-positive bacteria were detected. Klebsiella pneumoniae was the most common isolate. Proteus spp., Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were also detected. Approximately 61.33% of the ulcers exhibited were polybacterial. In this study, it was observed that all bacterial isolates, except for Proteus spp., were primarily detected in patients classified under Wagner's grade 2. Moreover, antibiotic susceptibility was also tested on these 141 isolates. Among them, Escherichia coli showed the highest multidrug resistance, 81.81%. Most of the gram-negative bacteria were resistant to ampicillin. All of the gram-negative isolates exhibited high levels of susceptibility to piperacillin-tazobactam, and these levels were Klebsiella pneumoniae (97.56%), Pseudomonas aeruginosa (95.24%), Escherichia coli (81.82%), and Proteus spp. (80%). On the other hand, gram-positive Staphylococcus aureus mostly showed sensitivity towards vancomycin and norfloxacin (79.17%)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Baral et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Non-surgical chronic wounds, including diabetes-related foot diseases (DRFD), pressure injuries (PIs) and venous leg ulcers (VLU), are common hard-to-heal wounds. Wound evolution partly depends on microbial colonisation or infection, which is often confused by clinicians, thereby hampering proper management. Current routine microbiology investigation of these wounds is based on in vitro culture, focusing only on a limited panel of the most frequently isolated bacteria, leaving a large part of the wound microbiome undocumented., Methods: A literature search was conducted on original studies published through October 2022 reporting metagenomic next generation sequencing (mNGS) of chronic wound samples. Studies were eligible for inclusion if they applied 16 S rRNA metagenomics or shotgun metagenomics for microbiome analysis or diagnosis. Case reports, prospective, or retrospective studies were included. However, review articles, animal studies, in vitro model optimisation, benchmarking, treatment optimisation studies, and non-clinical studies were excluded. Articles were identified in PubMed, Google Scholar, Web of Science, Microsoft Academic, Crossref and Semantic Scholar databases., Results: Of the 3,202 articles found in the initial search, 2,336 articles were removed after deduplication and 834 articles following title and abstract screening. A further 14 were removed after full text reading, with 18 articles finally included. Data were provided for 3,628 patients, including 1,535 DRFDs, 956 VLUs, and 791 PIs, with 164 microbial genera and 116 species identified using mNGS approaches. A high microbial diversity was observed depending on the geographical location and wound evolution. Clinically infected wounds were the most diverse, possibly due to a widespread colonisation by pathogenic bacteria from body and environmental microbiota. mNGS data identified the presence of virus (EBV) and fungi (Candida and Aspergillus species), as well as Staphylococcus and Pseudomonas bacteriophages., Conclusion: This study highlighted the benefit of mNGS for time-effective pathogen genome detection. Despite the majority of the included studies investigating only 16 S rDNA, ignoring a part of viral, fungal and parasite colonisation, mNGS detected a large number of bacteria through the included studies. Such technology could be implemented in routine microbiology for hard-to-heal wound microbiota investigation and post-treatment wound colonisation surveillance., (© 2024. The Author(s).)

Introduction: Diabetic foot infection (DFI) is one of the complications of diabetes mellitus. Clindamycin (CLY) is one of the antibiotics recommended to treat DFI, but CLY given orally and intravenously still causes many side effects., Methods: In this study, we encapsulated CLY in a bacteria sensitive microparticle system (MP-CLY) using polycaprolactone (PCL) polymer. MP-CLY was then delivered in a separable effervescent microarray patch (MP-CLY-SEMAP), which has the ability to separate between the needle layer and separable layer due to the formation of air bubbles when interacting with interstitial fluid in the skin., Result: The characterization results of MP-CLY proved that CLY was encapsulated in large amounts as the amount of PCL polymer used increased, and there was no change in the chemical structure of CLY. In vitro release test results showed increased CLY release in media cultured with Staphylococcus aureus bacteria and showed controlled release. The characterization results of MPCLY-SEMAP showed that the developed formula has optimal mechanical and penetration capabilities and can separate in 56 ± 5.099 s. An ex vivo dermatokinetic test on a bacterially infected skin model showed an improvement of CLY dermatokinetic profile from MP-CLY SEMAP and a decrease in bacterial viability by 99.99%., Conclusion: This research offers proof of concept demonstrating the improved dermatokinetic profile of CLY encapsulated in a bacteria sensitive MP form and delivered via MP-CLY-SEMAP. The results of this research can be developed for future research by testing MP-CLY-SEMAP in vivo in appropriate animal models., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Onychomycosis is a fungal infection of the nail unit and one of the common nail diseases that occurs commonly in diabetic patients. It poses a threat of diabetic foot complications to diabetics and negatively affects the quality of life of the patients., Objectives: The overall aim of the study was to determine the prevalence and clinical features of onychomycosis in diabetics, as well as the spectrum of causative fungi in Nigeria as compared with age and sex-matched controls., Methodology: This was a hospital-based, comparative cross-sectional study. One hundred and fifty consecutive adult diabetics and 150 healthy controls (accompanied persons and staff) matched for age and sex were recruited from the Diabetic Clinics and the Dermatology Clinic of the University of Nigeria Teaching Hospital, Ituku-Ozalla. The participants were interviewed using a pre-tested structured questionnaire, nail scrapings were collected for fungal studies, and clippings for nail histopathology using Periodic Acid Schiff., Results: The prevalence of onychomycosis among DM subjects was 45.3% vs. 35.3% in controls, which was not statistically significant (P value 0.078). Distal-lateral subungual onychomycosis was the most common clinical type in both study groups and presented mainly with nail discolouration, onycholysis, and subungual hyperkeratosis. The most common fungi isolated were dermatophytes (Trichophyton soudanense), non-dermatophytes (Aspergillus spp.), and Candida species (Candida albicans)., Conclusion: Onychomycosis in diabetics is a very common nail disorder in the South-Eastern part of Nigeria with a high prevalence. The presence of foot ulcers was associated with onychomycosis in diabetics, and they were more likely to have non-dermatophytic onychomycosis., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Objective: To observe the expression of inflammatory factors and autophagy-related proteins in granulation tissue of diabetic foot ulcer (DFU) patients and analyze their relationship with infection., Methods: This is a retrospective cohort study. One hundred and fifty-two patients with DFU in our hospital from July 2020 to March 2022 were selected as the DFU group, including 98 cases in infection stage group and 54 cases in infection control group. The patients were further graded as the mild (51 cases), the moderate (65 cases), and the severe infection group (36 cases) according to the Wagner grading criteria. Sixty-seven patients with foot burns during the same period were selected as the control group. The distribution of pathogenic bacteria on the ulcer surface was examined using fully automated bacterial analyzer. The expression of inflammatory factors (procalcitonin [PCT], tumor necrosis factor-α [TNF-α], and interleukin-6 [IL-6]) was valued by real-time fluorescence quantitative PCR (qRT-PCR). Protein expression was measured by immunohistochemistry (IHC). The correlation was analyzed by Pearson., Results: The surface infection of DFU patients was mostly induced by gram-negative and gram-positive bacteria, with Pseudomonas aeruginosa predominating among the Gram-negative bacteria and Staphylococcus aureus among the gram-positive bacteria. The infection stage group had higher content of PCT, TNF-α, and IL-6 and lower content of Beclin-1 and LC3 than the infection control group (p < .001). The levels of PCT, TNF-α, and IL-6 in the DFU patients with cardiovascular events were higher than those in the nonoccurrence group (p < .001). Glycated hemoglobin in patients with DFU was positively correlated with PCT, TNF-α, and IL-6 levels (p < .05), and negatively correlated with Beclin-1 and LC3 levels (p < .001)., Conclusion: P. aeruginosa and S. aureus were predominant bacterial in DFU infections. Inflammatory factor and autophagy protein expression were closely correlated with the degree of infection., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Multidrug-resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried out a meta-analysis aimed at investigating the prevalence of MDR bacteria isolated from DFUs and analysing the risk factors for MDR bacterial infection in patients with DFUs. The PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases were searched for studies published up to November 2023 on the clinical outcomes of MDR bacteria in DFUs. The main outcome was the prevalence of MDR bacteria in DFUs. A total of 21 studies were included, representing 4885 patients from which 2633 MDR bacterial isolates were obtained. The prevalence of MDR bacteria in DFUs was 50.86% (95% confidence interval (CI): 41.92%-59.78%). The prevalence of MDR gram-positive bacteria (GPB) in DFUs was 19.81% (95% CI: 14.35%-25.91%), and the prevalence of MDR gram-negative bacteria (GNB) in DFUs was 32.84% (95% CI: 26.40%-39.62%). MDR Staphylococcus aureus (12.13% (95% CI: 8.79%-15.91%)) and MDR Enterococcus spp. (3.33% (95% CI: 1.92%-5.07%)) were the main MDR-GPB in DFUs. MDR Escherichia coli, MDR Pseudomonas aeruginosa, MDR Enterobacter spp., MDR Klebsiella pneumoniae, and MDR Proteus mirabilis were the main MDR-GNB in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%-8.95%), 6.01% (95% CI: 4.03%-8.33%), 3.59% (95% CI: 0.42%-9.30%), 3.50% (95% CI: 2.31%-4.91%), and 3.27% (95% CI: 1.74%-5.21%), respectively. The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non-MDR bacteria in the included studies were analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non-MDR bacterial group. We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR-GNB was greater than that of MDR-GPB in DFUs. MDR S. aureus was the main MDR-GPB in DFUs, and MDR E. coli was the main MDR-GNB in DFUs. Our study also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Diabetic foot ulcer (DFU) is one of the main chronic complications caused by diabetes, leading to amputation in severe cases. Bacterial infection affects the wound healing in DFU., Methods: DFU patients who met the criteria were selected, and the clinical data were recorded in detail. The pus exudate from the patient's foot wound and venous blood were collected for biochemical analysis. The distribution of bacterial flora in pus exudates of patients was analyzed by 16S rRNA sequencing, and the correlation between DFU and pathogenic variables, pyroptosis and immunity was analyzed by statistical analysis. Then, the effects of key bacteria on the inflammation, proliferation, apoptosis, and pyroptosis of polymorphonuclear leukocytes were investigated by ELISA, CCK-8, flow cytometry, RT-qPCR and western blot., Results: Clinical data analysis showed that Wagner score was positively correlated with the level of inflammatory factors, and there was high CD3 + , CD4 + , and low CD8 + levels in DFU patients with high Wagner score. Through alpha, beta diversity analysis and species composition analysis, Corynebacterium accounted for a large proportion in DFU. Logistics regression model and Person correlation analysis demonstrated that mixed bacterial infections could aggravate foot ulcer, and the number of bacteria was closely related to inflammatory factors PCT, PRT, immune cells CD8 + , and pyroptosis-related proteins GSDMD and NLRP3. Through in vitro experiments, Corynebacterium inhibited cell proliferation, promoted inflammation (TNF-α, PCT, CRP), apoptosis and pyroptosis (IL-1β, LDH, IL-18, GSDMD, NLRP3, and caspase-3)., Conclusion: Mixed bacterial infections exacerbate DFU progression with a high predominance of Corynebacterium, and Corynebacterium promotes inflammation, apoptosis and pyroptosis to inhibit DFU healing., (© 2024. The Author(s).)

Diabetic foot ulcers (DFUs) are the most common complications of diabetes resulting from hyperglycemia leading to ischemic hypoxic tissue and nerve damage. Staphylococcus aureus is the most frequently isolated bacteria from DFUs and causes severe necrotic infections leading to amputations with a poor 5-year survival rate. However, very little is known about the mechanisms by which S. aureus dominantly colonizes and causes severe disease in DFUs. Herein, we utilized a pressure wound model in diabetic TALLYHO/JngJ mice to reproduce ischemic hypoxic tissue damage seen in DFUs and demonstrated that anaerobic fermentative growth of S. aureus significantly increased the virulence and the severity of disease by activating two-component regulatory systems leading to expression of virulence factors. Our in vitro studies showed that supplementation of nitrate as a terminal electron acceptor promotes anaerobic respiration and suppresses the expression of S. aureus virulence factors through inactivation of two-component regulatory systems, suggesting potential therapeutic benefits by promoting anaerobic nitrate respiration. Our in vivo studies revealed that dietary supplementation of L-arginine (L-Arg) significantly attenuated the severity of disease caused by S. aureus in the pressure wound model by providing nitrate. Collectively, these findings highlight the importance of anaerobic fermentative growth in S. aureus pathogenesis and the potential of dietary L-Arg supplementation as a therapeutic to prevent severe S. aureus infection in DFUs.IMPORTANCE S. aureus is the most common cause of infection in DFUs, often resulting in lower-extremity amputation with a distressingly poor 5-year survival rate. Treatment for S. aureus infections has largely remained unchanged for decades and involves tissue debridement with antibiotic therapy. With high levels of conservative treatment failure, recurrence of ulcers, and antibiotic resistance, a new approach is necessary to prevent lower-extremity amputations. Nutritional aspects of DFU treatment have largely been overlooked as there has been contradictory clinical trial evidence, but very few in vitro and in vivo modelings of nutritional treatment studies have been performed. Here we demonstrate that dietary supplementation of L-Arg in a diabetic mouse model significantly reduced duration and severity of disease caused by S. aureus . These findings suggest that L-Arg supplementation could be useful as a potential preventive measure against severe S. aureus infections in DFUs., Competing Interests: The authors declare no conflict of interest.

Purpose: Diabetes mellitus (DM-II) is a metabolic disorder either due to reduced insulin production or reduced insulin sensitivity. Diabetic foot ulcer (DFU) is one of the most devastating complications of DM-II. This study was performed to assess commonly isolated micro-organisms and their anti-microbial sensitivity pattern in diabetic foot ulcers in a tertiary care centre in Western Maharashtra., Methods: Adult patients with a known case of DM-II with foot lesions, suspected to be a Diabetic Foot Infections (DFIs) at the tertiary care hospital from Aug 2022 to Sept 2022 were included in the study. After obtaining informed written consent, pus sample was collected with sterile swab from lesion's base and submitted to Microbiology Laboratory for aerobic culture and sensitivity., Results: Out of 56 enrolled patients, 47 (83.9%) patients tested positive for bacteriological growth and there was 'no growth' in 9 (16.07%) patients at the end of 48 h of aerobic incubation. There was male preponderance and patients were in age group of 35-85 years. The most commonly isolated micro-organisms were P. aeruginosa (17.8%), followed by S. aureus (14.2%), K. pneumonia and P. mirabilis (12.5% each). The resistance markers observed was ESBL producer, AmpC producer, MBL producer, Methicillin resistance and Inducible Clindamycin Resistance (ICR)., Conclusion: Due to the injudicious use of antibiotics, antibiotic resistance has been increased in all types of soft tissue infections. The empirical formula for the treatment of DFIs should be decided for given geographical reasons according to antimicrobial susceptibility profile from particular geographical area or health care institute., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Background: Securing an early accurate diagnosis of diabetic foot infections and assessment of their severity are of paramount importance since these infections can cause great morbidity and potential mortality and present formidable challenges in surgical and antimicrobial treatment., Methods: In June 2022, we searched the literature using PubMed and EMBASE for published studies on the diagnosis of diabetic foot infection (DFI). On the basis of pre-determined criteria, we reviewed prospective controlled, as well as non-controlled, studies in English. We then developed evidence statements based on the included papers., Results: We selected a total of 64 papers that met our inclusion criteria. The certainty of the majority of the evidence statements was low because of the weak methodology of nearly all of the studies. The available data suggest that diagnosing diabetic foot infections on the basis of clinical signs and symptoms and classified according to the International Working Group of the Diabetic Foot/Infectious Diseases Society of America scheme correlates with the patient's likelihood of the need for hospitalisation, lower extremity amputation, and risk of death. Elevated levels of selected serum inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein and procalcitonin are supportive, but not diagnostic, of soft tissue infection. Culturing tissue samples of soft tissues or bone, when care is taken to avoid contamination, provides more accurate microbiological information than culturing superficial (swab) samples. Although non-culture techniques, especially next-generation sequencing, are likely to identify more bacteria from tissue samples including bone than standard cultures, no studies have established a significant impact on the management of patients with DFIs. In patients with suspected diabetic foot osteomyelitis, the combination of a positive probe-to-bone test and elevated ESR supports this diagnosis. Plain X-ray remains the first-line imaging examination when there is suspicion of diabetic foot osteomyelitis (DFO), but advanced imaging methods including magnetic resonance imaging (MRI) and nuclear imaging when MRI is not feasible help in cases when either the diagnosis or the localisation of infection is uncertain. Intra-operative or non-per-wound percutaneous biopsy is the best method to accurately identify bone pathogens in case of a suspicion of a DFO. Bedside percutaneous biopsies are effective and safe and are an option to obtain bone culture data when conventional (i.e. surgical or radiological) procedures are not feasible., Conclusions: The results of this systematic review of the diagnosis of diabetic foot infections provide some guidance for clinicians, but there is still a need for more prospective controlled studies of high quality., (© 2023 John Wiley & Sons Ltd.)

This cross-sectional study assessed the risk factors for infection in 150 diabetic foot patients admitted to the Xiamen University Hospital between October 2020 and October 2022. Patients were categorised as infected (n = 80) or uninfected (n = 70) cohorts. The diabetic foot was evaluated using the American Diabetic Foot Grading system, whereas ulcers were categorised using Wagner's method. Analysed were patient-specific information, clinical data and risk factors including neuropathy, arterial disease and foot deformities. Our findings revealed no statistically significant differences between infected and uninfected cohorts concerning age, body mass index, gender, duration of diabetes or ankle-brachial index values (p > 0.05). However, infected group had a higher proportion of smokers and reduced socio-economic status (p < 0.05). Wagner grades indicated a greater severity in the infected group, with grade 3, grade 4 and grade 5 differing significantly (p < 0.05). Comparative analysis of ulcer characteristics revealed no statistically significant differences in ulcer surface area and depth, but the infected group had a higher prevalence of osteomyelitis and a greater number of ulcers (p > 0.05). Blood vessel complications, retinopathy, the presence of three or more ulcers, osteomyelitis and diabetic nephropathy were substantially more prevalent in the infected group, as determined by univariate analysis (p < 0.05). Subsequent multivariate logistic analysis revealed that patients with blood vessel complications, retinopathy, osteomyelitis, diabetic nephropathy and three or more ulcers were at increased risk for infection (p < 0.05). In addition, lifestyle factors, such as smoking, sedentary behaviour, inadequate foot hygiene, obesity and poor glycaemic control, were also associated with higher infection rates. A multivariate analysis of foot wound factors revealed that deeper, longer and recurrent lesions increased the likelihood of infection. Escherichia coli was the most frequently isolated bacterium from the infected group's bacterial culture, followed by Pseudomonas aeruginosa and Staphylococcus aureus. The study enhanced our comprehension of the multifactorial risk factors associated with infections in diabetic foot patients, highlighting the need for thorough clinical evaluation, lifestyle modification and vigilant infection control., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Introduction: Appropriate care and treatment of a wound is the need of the hour whether it is an infected or a non-infected wound. If wound healing is delayed for some reason, it leads to serious complications and further increases the hospital stay and cost of treatment. Herein, we describe a novel antimicrobial wound dressing formulation (VG111), with an objective to generate the preliminary data showing the distinct advantages in various types of wounds.

Method: This case series involved the treatment of acute cases of wounds or chronic wounds that did not respond well to conventional wound healing treatments with VG111 in patients with different etiologies. Thirteen cases of patients that included patients with diabetes, pressure ulcers, burns, trauma, and others treated with VG111 showed rapid wound healing in all the cases, even obviating the need for a graft when complete skin regeneration occurred.

Result: This was illustrated by clearing of the wound infections, reduction/disappearance of the exudate, appearance of intense granulation, epithelialization, and anti-biofilm activity followed by complete wound closure. This VG111 precludes the need for systemic antimicrobial agents in localized infections and therefore, this single agent is an attempt to address the limitations and the drawbacks of the available products.

Conclusion: Despite patients belonging to the old age group and having comorbidities like diabetes, still VG111 showed effective rapid wound healing, and that too without any scar formation in hardto- heal, infected, and non-infected wounds.

Background: The transition from colonization to invasion is critical in diabetic foot ulcer (DFU). Staphylococcus aureus can colonize DFU, or invade the underlying tissues, causing serious infections. The ROSA-like prophage has previously been implicated in strain colonization characteristics of S aureus isolates in uninfected ulcers., Methods: In this study, we investigated this prophage in the S aureus-colonizing strain using an in vitro chronic wound medium mimicking the chronic wound environment., Results: Chronic wound medium reduced bacterial growth and increased biofilm formation and virulence in a zebrafish model., Conclusions: The ROSA-like prophage promoted intracellular survival of S aureus-colonizing strain in macrophages, keratinocytes, and osteoblasts., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To retrospectively analyze the concordance of bacterial culture between bone tissue and deep soft tissue in diabetic foot osteomyelitis (DFO) patients and clinical characteristics of patients., Methods: This study collected samples from 155 patients with suspected DFO (who required amputation after clinical evaluation). Bacterial culture and drug susceptibility tests were performed on the patients' deep soft tissue and bone tissue, and the consistency between the two was compared. In addition, the differences among DFO patients with different degrees of infection were compared classified by the PEDIS classifications., Results: Among the 155 patients diagnosed with DFO, the positive rate of bone culture was 78.7% (122/155). This study cultured 162 strains, including 73 Gram-positive bacteria, 83 Gram-negative bacteria, and 6 fungi. Staphylococcus aureus (33 strains) was the most common bacteria. The overall agreement between bone culture and tissue culture was 42.8%, with Staphylococcus aureus and Enterobacteria having the best (64.3%) and least agreements (27.3%), respectively. The drug sensitivity results in bone culture showed that Staphylococcus aureus was the main Gram-positive bacteria. The bacteria were sensitive to linezolid and vancomycin. Proteus mirabilis was the main Gram-negative bacteria. These were more sensitive than biapenem and piperacillin/tazobactam. Fungi were more sensitive to voriconazole and itraconazole., Conclusion: The culture results of deep soft tissues near the bone cannot accurately represent the true pathogen of DFO. For DFO patients, bone culture should be taken as much as possible, and appropriate antibiotics should be selected according to the drug susceptibility results., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Foot infections are the most prevalent problem in persons with diabetes. The burden of multidrug resistant (MDR) microorganisms in diabetic foot infections (DFIs) is rising day by day. Given that, the present study aims to determine the variety of microorganisms isolated from the diabetic foot ulcers (DFUs), and their antibiotic sensitivity pattern. This prospective observational study was conducted for 1 year at Bharati Hospital and Research Centre, Pune, India. Clinically infected patients with DFU admitted to the surgery ward were included in this study. The specimen for microbiological studies is obtained from the wound swabs, soft tissue, and bone tissue as a part of routine clinical care. All demographic, clinical data, microbial culture results were collected, and evaluated for each case. Antimicrobial susceptibility testing to different agents was carried out using the VITEK-2 ® machine. A total of 110 microorganisms were isolated from 76 specimens, with an average of 1.4 organisms per lesion. Staphylococcus aureus (n = 27, 24.5%) and Escherichia coli (n = 17, 15.4%) were the most prevalent Gram-positive and Gram-negative organisms isolated, respectively. MDR organisms constituted up to 52 (47.2%), while 6 (5.4%) of the samples were extensively drug resistant (XDR). Methicillin-resistant S aureus (MRSA) accounted for up to 19 (70.3%) of the S aureus isolates, likewise extended-spectrum beta-lactamase producing microorganisms constituted 16 (14.5%) of total isolates in this study. Oxacillin and benzyl penicillin exhibited least susceptibility against Gram-positive bacteria, among Gram-negative organisms; cefuroxime, ceftriaxone, and ciprofloxacin were least sensitive. As most of the S aureus isolate in our study was MRSA, empirical antimicrobial therapy may include coverage for MRSA in a patient with risk factors associated with this pathogen. A crucial observation is the presence of XDR strains of Proteus mirabilis in DFIs, which is resistant to almost all the antimicrobials, tested. Appropriate antimicrobial selection may reduce the morbidity and the emergence of MDR organisms in DFIs., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Staphylococcus sp. is the most common bacterial genus in infections related to diabetic foot ulcers (DFUs). The emergence of multidrug-resistant bacteria places a serious burden on public health systems. Phage therapy is an alternative treatment to antibiotics, overcoming the issue of antibiotic resistance. In this study, six phages (SAVM01 to SAVM06) were isolated from effluents and were used against a panel of staphylococcal clinical samples isolated from DFUs. A genomic analysis revealed that the phages belonged to the Herelleviridae family, with sequences similar to those of the Kayvirus genus. No lysogeny-associated genes, known virulence or drug resistance genes were identified in the phage genomes. The phages displayed a strong lytic and antibiofilm activity against DFU clinical isolates, as well as against opportunistic pathogenic coagulase-negative staphylococci. The results presented here suggest that these phages could be effective biocontrol agents against staphylococcal clinical isolates from DFUs.

Diabetic foot ulcer (DFU) is a neurological and peripherical complication of diabetes with unknown etiology that is often associated with polymicrobial infections. The present study was conducted to investigate the contributing factors in 285 DFU patients, which included 200 patients with diabetic foot infections (DFI). Identification and characterization of infecting bacterial isolates were done followed by assessment of their pattern of susceptibility to commonly used antibiotics. Among the studied subjects, type 2 diabetes mellitus (T2DM), ulcer type, depth, grade, loss of sensation, infection type, affected foot, recurrence, smoking status, Body Mass Index (BMI), and obesity levels revealed significant disease risk association. Ulcer grades 1 and 2 were more common in males while grade 3 in females. Recurrent infections were significantly higher in females (P = 0.03). Diabetic duration, hyperglycemia, ulcer type, infection type and BMI were positively correlated with delayed wound healing. In DFI samples, 40.2% consisted of gram-negative bacteria, with Pseudomonas aeruginosa (37.5%) being the most common, while in the 60% gram-positive isolates Staphylococcus aureus (40.5%) was the predominant species. Staphylococcus epidermidis was found more frequently in females (P = 0.05). The isolated bacterial strains presented higher resistance against the tested antibiotics; however, ceftriaxone was effective against most of the pathogens. In the current study T2DM along with diabetes duration, obesity, ulcer severity with polymicrobial infection was found to play a strong role in DFI development, where gender predisposition was also observed in ulcer grade and infection. DFI was correlated with loss of sensation, infection type, affected foot, smoking status, BMI and obesity levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Identifying the microbiome within chronic diabetic foot ulcers is essential if effective antimicrobial therapies are to be administered. Using culture and 16S rRNA gene sequencing, the aim of this study was to compare the microbiome of paired tissue scraping samples with swab samples, collected from participants during attendance at a high-risk foot clinic. The mean richness of cultured swab and tissue scraping samples was consistent, with anaerobes infrequently isolated from both sample types. Comparing percentage frequencies of detection of selected genera of known and potential pathogens namely Staphylococcus, Streptococcus, Enterococcus, Corynebacterium, Enterobacteriaceae and Pseudomonas from cultured and sequenced swab and tissue scrapings indicated that both collection methods captured varying percentages of all the selected genera. The mean abundance of sequenced samples was not significantly different between swabs and tissue scrapings. The mean richness or number of distinct operational taxonomic units (OTUs) and Shannon's H diversity index were not significantly different between the two collection methods. The mean relative abundance of the selected genera of known and potential pathogens, including anaerobes Anaerococcus and Finegoldia, was higher in swabs compared with tissue scrapings and significantly so in Staphylococcus and Pseudomonas genera. Multivariate analyses confirmed no significant differences between the bacterial community compositions of the paired samples. These results suggest that tissue scrapings and swabs can effectively capture the microbiome of chronic DFUs using culture and 16S rRNA gene sequencing., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)