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2.
Curr Microbiol ; 81(7): 208, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38833191

RESUMEN

Diabetes mellitus (DM) leads to impaired innate and adaptive immune responses. This renders individuals with DM highly susceptible to microbial infections such as COVID-19, tuberculosis and melioidosis. Melioidosis is a tropical disease caused by the bacterial pathogen Burkholderia pseudomallei, where diabetes is consistently reported as the most significant risk factor associated with the disease. Type-2 diabetes is observed in 39% of melioidosis patients where the risk of infection is 13-fold higher than non-diabetic individuals. B. pseudomallei is found in the environment and is an opportunistic pathogen in humans, often exhibiting severe clinical manifestations in immunocompromised patients. The pathophysiology of diabetes significantly affects the host immune responses that play a critical role in fighting the infection, such as leukocyte and neutrophil impairment, macrophage and monocyte inhibition and natural killer cell dysfunction. These defects result in delayed recruitment as well as activation of immune cells to target the invading B. pseudomallei. This provides an advantage for the pathogen to survive and adapt within the immunocompromised diabetic patients. Nevertheless, knowledge gaps on diabetes-infectious disease comorbidity, in particular, melioidosis-diabetes comorbidity, need to be filled to fully understand the dysfunctional host immune responses and adaptation of the pathogen under diabetic conditions to guide therapeutic options.


Asunto(s)
Burkholderia pseudomallei , Melioidosis , Melioidosis/microbiología , Melioidosis/inmunología , Humanos , Burkholderia pseudomallei/inmunología , Complicaciones de la Diabetes/microbiología , Diabetes Mellitus/inmunología , Diabetes Mellitus/microbiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/microbiología , Huésped Inmunocomprometido
3.
Mycoses ; 67(6): e13753, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38877612

RESUMEN

Candida species, commensal residents of human skin, are recognized as the cause of cutaneous candidiasis across various body surfaces. Individuals with weakened immune systems, particularly those with immunosuppressive conditions, are significantly more susceptible to this infection. Diabetes mellitus, a major metabolic disorder, has emerged as a critical factor inducing immunosuppression, thereby facilitating Candida colonization and subsequent skin infections. This comprehensive review examines the prevalence of different types of Candida albicans-induced cutaneous candidiasis in diabetic patients. It explores the underlying mechanisms of pathogenicity and offers insights into recommended preventive measures and treatment strategies. Diabetes notably increases vulnerability to oral and oesophageal candidiasis. Additionally, it can precipitate vulvovaginal candidiasis in females, Candida balanitis in males, and diaper candidiasis in young children with diabetes. Diabetic individuals may also experience candidal infections on their nails, hands and feet. Notably, diabetes appears to be a risk factor for intertrigo syndrome in obese individuals and periodontal disorders in denture wearers. In conclusion, the intricate relationship between diabetes and cutaneous candidiasis necessitates a comprehensive understanding to strategize effective management planning. Further investigation and interdisciplinary collaborative efforts are crucial to address this multifaceted challenge and uncover novel approaches for the treatment, management and prevention of both health conditions, including the development of safer and more effective antifungal agents.


Asunto(s)
Antifúngicos , Candida albicans , Candidiasis Cutánea , Complicaciones de la Diabetes , Humanos , Candida albicans/patogenicidad , Complicaciones de la Diabetes/microbiología , Candidiasis Cutánea/microbiología , Candidiasis Cutánea/tratamiento farmacológico , Antifúngicos/uso terapéutico , Femenino , Masculino , Diabetes Mellitus/microbiología , Factores de Riesgo , Piel/microbiología , Piel/patología , Prevalencia
4.
Indian J Public Health ; 68(1): 137-139, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38847641

RESUMEN

SUMMARY: Invasive fungal sinusitis is a highly lethal infection in an immunocompromised population that can spread rapidly to involve the adjacent structures by direct invasion or through vascular invasion. Involvement of cerebral parenchyma by vascular invasion is a devastating complication in these patients which may lead to vasculitis, thrombus formation, cerebritis, or abscess formation. Here, we present a case of a young male with uncontrolled diabetes mellitus who initially presented with COVID-19 lung disease and later developed sinonasal mucormycosis complicated with left orbital cellulitis and pulmonary mucormycosis.


Asunto(s)
COVID-19 , Mucormicosis , Humanos , Mucormicosis/complicaciones , Masculino , COVID-19/complicaciones , SARS-CoV-2 , Enfermedades Pulmonares Fúngicas/complicaciones , Adulto , Complicaciones de la Diabetes/microbiología
5.
PLoS One ; 19(5): e0303557, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38771840

RESUMEN

BACKGROUND: Urinary tract infections (UTI) is a prevalent condition in those with diabetes, and in severe cases, it may escalate to sepsis. Therefore, it is important to analyze the risk variables associated with sepsis in diabetes individuals with UTI. METHODS: This research was a retrospective cross-sectional analysis. From January 2011 to June 2022, a group of individuals with diabetes were identified as having UTI at a tertiary hospital situated in Southeastern China. Patient data, including information on urine culture, was collected retrospectively from a clinical record database. The participants were categorized into the sepsis and non-sepsis groups. The risk variables were derived using both uni-and multiple- variable regression analysis. RESULTS: The research included 1919 patients, of whom 1106 cases (57.63%) had positive urine cultures. In total, 445 blood culture samples were tested, identifying 186 positive cases (41.80%). The prevalence of bacteria in urine and blood samples was highest for Escherichia coli and Klebsiella pneumoniae, respectively. Moreover, 268 individuals (13.97%) exhibited sepsis. The regression analysis indicated a positive correlation between sepsis and albumin (ALB)<34.35 g/L, C-reactive protein (CRP)>55.84 mg/L and white blood cell count (WBC) >8.485 X 109/L in diabetic cases with UTIs. By integrating the three aforementioned parameters, the area under the receiver operating characteristic curve was 0.809. CONCLUSIONS: The early detection of sepsis in diabetic individuals with UTI may be achieved using a comprehensive analysis of CRP, WBC, and ALB test findings.


Asunto(s)
Sepsis , Infecciones Urinarias , Humanos , Infecciones Urinarias/complicaciones , Infecciones Urinarias/microbiología , Infecciones Urinarias/epidemiología , Masculino , Femenino , Sepsis/complicaciones , Sepsis/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Estudios Transversales , Factores de Riesgo , China/epidemiología , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Diabetes Mellitus/epidemiología , Adulto , Klebsiella pneumoniae/aislamiento & purificación , Recuento de Leucocitos , Complicaciones de la Diabetes/microbiología , Complicaciones de la Diabetes/epidemiología
6.
Arch Dermatol Res ; 316(5): 144, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695894

RESUMEN

Hand infection is a rare complication in patients with diabetes. Its clinical outcomes depend on the severity of hand infection caused by bacteria, but the difference in bacterial species in the regional disparity is unknown. The purpose of this study was to explore the influence of tropical and nontropical regions on bacterial species and clinical outcomes for diabetic hand. A systematic literature review was conducted using PubMed, EMBASE, Web of Science, and Google Scholar. Moreover, the bacterial species and clinical outcomes were analyzed with respect to multicenter wound care in China (nontropical regions). Both mixed bacteria (31.2% vs. 16.6%, p = 0.014) and fungi (7.5% vs. 0.8%, p = 0.017) in the nontropical region were significantly more prevalent than those in the tropical region. Staphylococcus and Streptococcus spp. were dominant in gram-positive bacteria, and Klebsiella, Escherichia coli, Proteus and Pseudomonas in gram-negative bacteria occupied the next majority in the two regions. The rate of surgical treatment in the patients was 31.2% in the nontropical region, which was significantly higher than the 11.4% in the tropical region (p = 0.001). Although the overall mortality was not significantly different, there was a tendency to be increased in tropical regions (6.3%) compared with nontropical regions (0.9%). However, amputation (32.9% vs. 31.3%, p = 0.762) and disability (6.3% vs. 12.2%, p = 0.138) were not significantly different between the two regions. Similar numbers of cases were reported, and the most common bacteria were similar in tropical and nontropical regions in patients with diabetic hand. There were more species of bacteria in the nontropical region, and their distribution was basically similar, except for fungi, which had differences between the two regions. The present study also showed that surgical treatment and mortality were inversely correlated because delays in debridement and surgery can deteriorate deep infections, eventually leading to amputation and even death.


Asunto(s)
Bacterias , Infecciones Bacterianas , Mano , Humanos , Amputación Quirúrgica/estadística & datos numéricos , Bacterias/aislamiento & purificación , Bacterias/clasificación , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/terapia , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/mortalidad , China/epidemiología , Complicaciones de la Diabetes/microbiología , Complicaciones de la Diabetes/epidemiología , Mano/microbiología , Resultado del Tratamiento , Clima Tropical
7.
Diabetes Obes Metab ; 26(8): 3306-3317, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38751358

RESUMEN

AIM: To assess and verify the effect of the gut microbiome on the susceptibility and complications of type 1 diabetes (T1D). MATERIALS AND METHODS: To achieve this aim, a two-sample and reverse Mendelian randomization (MR) analysis was conducted. In addition, an external validation study was performed using individual microbiome data of patients with T1D from the gutMEGA datasets and the National Clinical Research Center for Metabolic Diseases. The circulating metabolites facilitated two-sample MR analysis, mediation and multivariable MR analysis to evaluate the direct relationship between the gut microbiome and T1D complications. RESULTS: The MR analysis results from the discovery and validation phases confirmed that Veillonellaceae can potentially reduce the susceptibility of T1D. In the gutMEGA dataset, the average relative abundance of Veillonellaceae in patients with T1D was 0.66%, compared with 1.09% in the controls. Furthermore, the external validation, which included 60 patients with T1D and 30 matched healthy controls, found that the median relative abundance of Veillonellaceae was also lower than controls at 1.10% (95% CI 0.50%-1.80%). Specifically, the Eubacterium coprostanoligenes group, known for its ability to regulate cholesterol, was significantly associated with a lower risk of developing renal, neurological and ophthalmic complications in T1D. Moreover, high cholesterol in small high-density lipoprotein and cholesteryl esters in high-density lipoprotein were associated with a reduced risk of T1D renal and ophthalmic complications. The mediation and multivariable MR analysis combining cholesterol indicated that the E. coprostanoligenes group is the most dominant factor influencing T1D complications. CONCLUSIONS: Our findings supported the potential causal effect of gut microbiota on the susceptibility and complications of T1D.


Asunto(s)
Diabetes Mellitus Tipo 1 , Microbioma Gastrointestinal , Análisis de la Aleatorización Mendeliana , Humanos , Diabetes Mellitus Tipo 1/microbiología , Diabetes Mellitus Tipo 1/complicaciones , Microbioma Gastrointestinal/fisiología , Masculino , Femenino , Adulto , Susceptibilidad a Enfermedades , Complicaciones de la Diabetes/microbiología
8.
Neurogastroenterol Motil ; 36(7): e14798, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38651669

RESUMEN

BACKGROUND: Although diabetic gastroenteropathy (DGE) is associated with small intestinal bacterial overgrowth (SIBO), most studies have evaluated SIBO with a hydrogen breath test, which may be affected by altered transit in DGE. The risk factors for the consequences of SIBO in DGE are poorly understood. We aimed to evaluate the prevalence of, risk factors for, and gastrointestinal symptoms associated with SIBO in patients with DGE. METHODS: In 75 patients with DGE and dyspepsia, we tested for SIBO (≥105 colony forming units /mL of aerobic and/or anaerobic bacteria in a duodenal aspirate) and assessed gastric emptying (GE) of solids, symptoms during a GE study and during an enteral lipid challenge (300 kcal/2 h), and daily symptoms with a Gastroparesis Cardinal Symptom Index diary for 2 weeks. Symptoms and GE were compared in patients with versus without SIBO. KEY RESULTS: Of 75 patients, 34 (45%) had SIBO, which was not associated with the use of proton pump inhibitors, daily symptoms, GE, or symptoms during a GE study. During enteral lipid challenge, severe nausea (p = 0.006), fullness (p = 0.02) and bloating (p = 0.009) were each associated with SIBO. Twenty patients (59%) with versus 13 (32%) without SIBO had at least one severe symptom during the lipid challenge (p = 0.006). CONCLUSIONS & INFERENCES: Among patients with DGE 45% had SIBO, which was associated with symptoms during enteral lipid challenge but not with delayed GE, symptoms during a GE study, or daily symptoms. Perhaps bacterial products and even fatty acids are recognized by and activate mast cells that drive the increased lipid sensitivity in SIBO.


Asunto(s)
Intestino Delgado , Humanos , Femenino , Masculino , Persona de Mediana Edad , Intestino Delgado/microbiología , Adulto , Anciano , Vaciamiento Gástrico/fisiología , Enfermedades Gastrointestinales/microbiología , Enfermedades Gastrointestinales/epidemiología , Síndrome del Asa Ciega/epidemiología , Síndrome del Asa Ciega/diagnóstico , Síndrome del Asa Ciega/complicaciones , Complicaciones de la Diabetes/microbiología , Pruebas Respiratorias , Factores de Riesgo
9.
Indian J Med Microbiol ; 48: 100524, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38158184

RESUMEN

Sphingomonas paucimobilis is a rare cause of bacteremia. It can affect both healthy and immunocompromised individuals. Community acquired infections of this organism are more common than nosocomial ones. We report two cases of community acquired S. paucimobilis bacteremia-one in a healthy patient and other in a diabetic patient. Both presented with multiple episodes of loose stools, pain abdomen, vomiting, decreased oral intake and myalgia. They responded well to Cefipime 1g and Sulbactam 500mg combination antibiotic and were discharged satisfactorily. In the absence of standardized guidelines, antibiotic sensitivity guided case-to-case therapy is warranted with prompt initiation to prevent complications.


Asunto(s)
Antibacterianos , Bacteriemia , Infecciones Comunitarias Adquiridas , Infecciones por Bacterias Gramnegativas , Sphingomonas , Humanos , Sphingomonas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/diagnóstico , Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/diagnóstico , Masculino , Bacteriemia/microbiología , Bacteriemia/tratamiento farmacológico , Bacteriemia/diagnóstico , Persona de Mediana Edad , Sulbactam/uso terapéutico , Resultado del Tratamiento , Femenino , Adulto , Complicaciones de la Diabetes/microbiología
10.
Yi Chuan ; 45(11): 1052-1061, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-38764270

RESUMEN

Invasive infection caused by hypervirulent Klebsiella pneumoniae (HvKP) has been reported worldwide. Most of the patients are community population, related to diabetes mellitus (DM), chronic liver disease and other basic diseases, which prone to systemic migratory infection. In this study, we collected 377 patients with community acquired Klebsiella pneumoniae liver abscess in our hospital from January 2013 to December 2018, 65.8% of whom were male, and 49.6% had DM. Patients with DM are prone to eye and central nervous system (CNS) infection, which need continuous local abscess drainage during treatment. Among them, patients with poor blood glucose control have a higher rate of blood stream infections (BSI). 219 strains of HvKP were obtained, with K1/K2 Serotype accounted for 81.7%. The incidence of BSI in K2 patients was higher than that in K1 patients. The PCR results indicate that the carrying rate of virulence genes (rmpA、areo、kfu、allS、iroN、magA、uge、wcaG) in K1/K2 type strains is significantly higher than that in non K1/K2 type strains. ST23 and ST65 are the most common multilocus sequence typing (MLST), which belong to K1 and K2 Serotype respectively. All of HvKP strains showed high sensitivity to commonly used clinical antibiotics other than ampicillin, with 54.3% of the strains exhibiting high viscosity characteristics. Meanwhile, 35 classic Klebsiella pneumoniae (cKP) strains were collected, and their serum typing is mainly non K1/K2. The carrying rate of virulence genes and viscosity degree in HvKP are significantly higher than those in cKP. Primary liver abscess caused by HvKP is prone to multiple tissue and organ infections, but it shows higher sensitivity to most commonly used antibiotics in clinical practice except for ampicillin. After effective treatment, the overall prognosis of patients is better. This study analyzes the pathogenic characteristics of HvKP and elaborates on the clinical characteristics of patients, which can provide reference for clinical and scientific research work.


Asunto(s)
Infecciones Comunitarias Adquiridas , Infecciones por Klebsiella , Klebsiella pneumoniae , Absceso Hepático , Humanos , Klebsiella pneumoniae/patogenicidad , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/epidemiología , Femenino , Persona de Mediana Edad , Absceso Hepático/microbiología , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/epidemiología , Anciano , Virulencia , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Adulto , Diabetes Mellitus/microbiología , Tipificación de Secuencias Multilocus , Complicaciones de la Diabetes/microbiología , Factores de Virulencia/genética , Pruebas de Sensibilidad Microbiana
11.
Elife ; 112022 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-35112667

RESUMEN

Infection is a major co-morbidity that contributes to impaired healing in diabetic wounds. Although impairments in diabetic neutrophils have been blamed for this co-morbidity, what causes these impairments and whether they can be overcome, remain largely unclear. Diabetic neutrophils, isolated from diabetic individuals, exhibit chemotaxis impairment but this peculiar functional impairment has been largely ignored because it appears to contradict the clinical findings which blame excessive neutrophil influx as a major impediment to healing in chronic diabetic ulcers. Here, we report that exposure to glucose in diabetic range results in impaired chemotaxis signaling through the formyl peptide receptor (FPR) in neutrophils, culminating in reduced chemotaxis and delayed neutrophil trafficking in the wound of Leprdb (db/db) type two diabetic mice, rendering diabetic wound vulnerable to infection. We further show that at least some auxiliary receptors remain functional under diabetic conditions and their engagement by the pro-inflammatory cytokine CCL3, overrides the requirement for FPR signaling and substantially improves infection control by jumpstarting the neutrophil trafficking toward infection, and stimulates healing in diabetic wound. We posit that CCL3 may have therapeutic potential for the treatment of diabetic foot ulcers if it is applied topically after the surgical debridement process which is intended to reset chronic ulcers into acute fresh wounds.


Asunto(s)
Quimiotaxis de Leucocito/inmunología , Diabetes Mellitus Experimental/inmunología , Neutrófilos/patología , Receptores de Formil Péptido/genética , Transducción de Señal/inmunología , Cicatrización de Heridas/inmunología , Infección de Heridas/microbiología , Animales , Quimiocina CCL3/inmunología , Complicaciones de la Diabetes/microbiología , Glucosa/administración & dosificación , Masculino , Ratones , Ratones Endogámicos C57BL , Neutrófilos/inmunología , Receptores de Formil Péptido/inmunología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/etiología
12.
Exp Eye Res ; 216: 108941, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35077754

RESUMEN

Fungal keratitis (FK) is one of the main causes of blindness in China. People with diabetes are susceptible to corneal epithelial disease, even fungal keratitis. At present, there are few studies on this disease. Resolvins (Rv) has been reported as a mediators that exert crucial anti-inflammatory and immune regulation roles in serval diseases. In order to investigate the roles and underlying mechanism of Resolvins D1 (RvD1) on the Aspergillus fumigatus (A. fumigatus) keratitis in diabetes, we established in vivo and in vitro models of A. fumigatus keratitis, which were then exposed to high glucose. The expression levels of RvD1, 5-lipoxygenase (5-LOX), and 15-lipoxygenase (15-LOX) in A. fumigatus keratitis patients with diabetes were determined through Enzyme Linked Immunosorbent Assay (ELISA), Western blot and immunohistochemistry. Reactive Oxygen Species (ROS) production, ELISA, flow cytometry, Hematoxylin-Eosin (HE) staining and fungal loading determination were conducted to evaluate the severity of A. fumigatus infection. Lymphangiogenesis and angiogenesis were examined by immunofluorescence assay. Western blot was applied to detect the proteins of the MAPK-NF-κB pathway. The results showed that RvD1 diminished the high glucose-induced oxidative stress and inflammatory response, as evidenced by the reduction of ROS production, Interleukin-6 (IL-6), Interleukin-8 (IL-8), Heme Oxygenase-1 (HMOX-1), and the elevation of Cyclooxygenase-2 (COX2), Superoxide Dismutase (SOD-1), and Glutathione Peroxidase-2 (GPX2) levels in A. fumigatus-infected Human Corneal Endothelial Cells (HCECs). Additionally, lymphangiogenesis and angiogenesis prominently decreased after intervention with RvD1. Furthermore, RvD1 significantly reduced the levels of p-MEK1/2 and p-ERK1/2, and restrained the NF-κB and GPR32 activation. The above results showed that RvD1 protects against A. fumigatus keratitis in diabetes by suppressing oxidative stress, inflammatory response, fungal growth, and immunoreaction via modulating MAPK-NF-κB pathway. RvD1 provides clues for the therapeutic targets of Fungal keratitis complicated with diabetes.


Asunto(s)
Aspergilosis/prevención & control , Úlcera de la Córnea/prevención & control , Complicaciones de la Diabetes/microbiología , Ácidos Docosahexaenoicos/fisiología , Infecciones Fúngicas del Ojo/prevención & control , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Animales , Araquidonato 15-Lipooxigenasa/metabolismo , Araquidonato 5-Lipooxigenasa/metabolismo , Aspergilosis/metabolismo , Aspergilosis/microbiología , Aspergillus fumigatus/fisiología , Western Blotting , Células Cultivadas , Úlcera de la Córnea/metabolismo , Úlcera de la Córnea/microbiología , Complicaciones de la Diabetes/metabolismo , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Epitelio Corneal/efectos de los fármacos , Epitelio Corneal/microbiología , Infecciones Fúngicas del Ojo/metabolismo , Infecciones Fúngicas del Ojo/microbiología , Citometría de Flujo , Glucosa/farmacología , Humanos , Inmunohistoquímica , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Oxidorreductasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo
13.
J Nanobiotechnology ; 19(1): 404, 2021 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-34865643

RESUMEN

BACKGROUND: Diabetic wound healing remains a challenge because of its susceptibility to drug-resistant bacterial infection and its persistent proinflammatory state. Switching from proinflammatory M1 macrophages (Mφs) to proregenerative M2 dominant Mφs in a timely manner accelerates wound healing by coordinating inflammatory, proliferative, and angiogenic processes. METHODS: We propose a sequential photothermal antibacterial and subsequent M2 Mφ polarization strategy based on nanofibers (NFs) consisting of polydopamine (PDA) coating on curcumin (Cur) nanocrystals to treat Methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds. RESULTS: The PDA/Cur NFs showed excellent photothermal conversion and antibacterial effects due to the PDA shell under laser irradiation, consequently resulting in the release of the inner Cur with the ability to promote cell proliferation and reinforce the M2 Mφ phenotype in vitro. In vivo studies on MRSA-infected diabetic wounds showed that PDA/Cur NFs not only inhibited MRSA infection but also accelerated the wound regeneration process. Furthermore, the NFs displayed the ability to promote the M2 Mφ phenotype with enhanced collagen deposition, angiogenesis, and cell proliferation. CONCLUSION: Overall, the NFs displayed great potential as promising therapeutics for healing infected diabetic wounds through a sequential photothermal antibacterial and M2 Mφ polarization strategy.


Asunto(s)
Antibacterianos , Complicaciones de la Diabetes , Nanofibras , Infecciones Estafilocócicas , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/microbiología , Humanos , Macrófagos/efectos de los fármacos , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Nanofibras/química , Nanofibras/uso terapéutico , Células RAW 264.7 , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología
14.
Cells ; 10(11)2021 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-34831057

RESUMEN

The increasing prevalence of diabetes and its complications, such as cardiovascular and kidney disease, remains a huge burden globally. Identification of biomarkers for the screening, diagnosis, and prognosis of diabetes and its complications and better understanding of the molecular pathways involved in the development and progression of diabetes can facilitate individualized prevention and treatment. With the advancement of analytical techniques, metabolomics can identify and quantify multiple biomarkers simultaneously in a high-throughput manner. Providing information on underlying metabolic pathways, metabolomics can further identify mechanisms of diabetes and its progression. The application of metabolomics in epidemiological studies have identified novel biomarkers for type 2 diabetes (T2D) and its complications, such as branched-chain amino acids, metabolites of phenylalanine, metabolites involved in energy metabolism, and lipid metabolism. Metabolomics have also been applied to explore the potential pathways modulated by medications. Investigating diabetes using a systems biology approach by integrating metabolomics with other omics data, such as genetics, transcriptomics, proteomics, and clinical data can present a comprehensive metabolic network and facilitate causal inference. In this regard, metabolomics can deepen the molecular understanding, help identify potential therapeutic targets, and improve the prevention and management of T2D and its complications. The current review focused on metabolomic biomarkers for kidney and cardiovascular disease in T2D identified from epidemiological studies, and will also provide a brief overview on metabolomic investigations for T2D.


Asunto(s)
Complicaciones de la Diabetes/epidemiología , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Metabolómica , Biomarcadores/metabolismo , Complicaciones de la Diabetes/microbiología , Diabetes Mellitus Tipo 2/microbiología , Microbioma Gastrointestinal , Humanos , Metaboloma , Biología de Sistemas
15.
PLoS Negl Trop Dis ; 15(11): e0009921, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34793455

RESUMEN

Coronavirus Disease 2019 (COVID-19), during the second wave in early 2021, has caused devastating chaos in India. As daily infection rates rise alarmingly, the number of severe cases has increased dramatically. The country has encountered health infrastructure inadequacy and excessive demand for hospital beds, drugs, vaccines, and oxygen. Adding more burden to such a challenging situation, mucormycosis, an invasive fungal infection, has seen a sudden surge in patients with COVID-19. The rhino-orbital-cerebral form is the most common type observed. In particular, approximately three-fourths of them had diabetes as predisposing comorbidity and received corticosteroids to treat COVID-19. Possible mechanisms may involve immune and inflammatory processes. Diabetes, when coupled with COVID-19-induced systemic immune change, tends to cause decreased immunity and an increased risk of secondary infections. Since comprehensive data on this fatal opportunistic infection are evolving against the backdrop of a major pandemic, prevention strategies primarily involve managing comorbid conditions in high-risk groups. The recommended treatment strategies primarily included surgical debridement and antifungal therapy using Amphotericin B and selected azoles. Several India-centric clinical guidelines have emerged to rightly diagnose the infection, characterise the clinical presentation, understand the pathogenesis involved, and track the disease course. Code Mucor is the most comprehensive one, which proposes a simple but reliable staging system for the rhino-orbital-cerebral form. A staging system has recently been proposed, and a dedicated registry has been started. In this critical review, we extensively analyse recent evidence and guidance on COVID-19-associated mucormycosis in India.


Asunto(s)
COVID-19/complicaciones , COVID-19/epidemiología , Mucormicosis/epidemiología , Mucormicosis/virología , Antifúngicos/uso terapéutico , COVID-19/microbiología , Coinfección/tratamiento farmacológico , Coinfección/microbiología , Comorbilidad , Complicaciones de la Diabetes/microbiología , Humanos , India/epidemiología , Mucormicosis/tratamiento farmacológico , Factores de Riesgo
16.
Microbiol Spectr ; 9(2): e0085721, 2021 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-34549996

RESUMEN

Diabetic foot ulcer (DFU) is the most common and costly sequela of diabetes mellitus, often leading to lower-extremity amputation with poor 5-year survival rates. Staphylococcus aureus is the most prevalent pathogen isolated from DFU, suggesting adaptation of S. aureus to the unique metabolic conditions of diabetes. Diabetes is a complex metabolic disorder with increases not only in serum glucose levels but also in levels of other sugars, including fructose, mannose, and glucose-6-phosphate (G6P). However, the effect of metabolism of these sugars on the pathogenesis of S. aureus is not fully understood. In this study, we demonstrated that metabolism of G6P, fructose, and mannose induced greater expression of staphylococcal virulence factors than did glucose metabolism, but only G6P effects were independent of glucose-mediated carbon catabolite repression, suggesting a physiologically relevant role in diabetes. Our in vivo studies further demonstrated that G6P was highly present in skin adipose tissues of diabetic TALLYHO/JngJ mice, and subcutaneous infection with S. aureus caused significantly greater tissue necrosis and bacterial burden, compared to nondiabetic SWR/J mice. Finally, enhanced pathogenesis of S. aureus in diabetic TALLYHO/JngJ mice was significantly attenuated by deletion of the hexose phosphate transport (HPT) system. These results suggest that G6P is an important metabolic signal for S. aureus, enhancing the virulence in diabetes. A better understanding of how G6P metabolism is linked to the virulence of S. aureus will lead to the development of novel alternative therapeutics. IMPORTANCE Sugars are essential nutrients for S. aureus to survive and proliferate within the host. Because elevated serum glucose levels are a hallmark of diabetes, most studies have focused on the effect of glucose metabolism, and very little is known regarding the effects of metabolism of other sugars on the pathogenesis of S. aureus in diabetes. In this study, we demonstrated that G6P, which is highly present in diabetes, can induce expression of staphylococcal virulence factors that cause severe tissue necrosis and bacterial burden in skin infections. Our results highlight the importance of nutritional control of blood sugar levels, not only glucose but also other highly metabolizable sugars such as G6P. A better understanding of how activation of the HPT system is linked to the virulence of S. aureus will guide development of novel alternative therapeutics.


Asunto(s)
Diabetes Mellitus/patología , Glucosa-6-Fosfato/metabolismo , Proteínas de Transporte de Monosacáridos/genética , Infecciones Estafilocócicas/patología , Staphylococcus aureus/patogenicidad , Tejido Adiposo Blanco/química , Animales , Glucemia/análisis , Complicaciones de la Diabetes/microbiología , Pie Diabético/microbiología , Pie Diabético/patología , Modelos Animales de Enfermedad , Fructosa/metabolismo , Glucosa/metabolismo , Humanos , Masculino , Manosa/metabolismo , Ratones , Ratones Transgénicos , Staphylococcus aureus/metabolismo , Úlcera/microbiología , Factores de Virulencia/metabolismo
17.
PLoS One ; 16(9): e0257004, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34534230

RESUMEN

AIM: To investigate the epidemiology of S. aureus and MRSA nasal carriage among people with diabetes at the Korle Bu Teaching Hospital in Accra, including the prevalence, predictors of carriage, and antibiotic resistance. METHODOLOGY: This study was cross-sectional, involving 300 diabetes patients and 106 non-diabetic individuals. Swab specimens of the nares were obtained from the participants and bacteriologically-cultured. Identification and characterization of S. aureus and MRSA were based on standard bacteriological methods; antimicrobial susceptibility testing was by the Kirby-Bauer method. RESULTS: The prevalence of staphylococcal carriage, the diabetes group relative to the non-diabetes group, were 31.0% and 10.4% (S. aureus), and 3.3% and 0.0% (MRSA). Presence of diabetes predisposed to S. aureus carriage, but not MRSA nor coagulase-negative staphylococci (CoNS) carriage (OR = 3.88; p < 0.0001). Colonization with CoNS was protective of S. aureus (OR = 0.039, p < 0.001) and MRSA (OR = 0.115, p = 0.043) colonization among the diabetics. The antimicrobial resistance patterns recorded among the S. aureus isolated from the diabetic individuals relative to the non-diabetics were as follows: penicillin (95% vs. 91%), tetracycline (37% vs. 27%), cotrimoxazole (30% vs. 36%), erythromycin (17% vs. 0%), norfloxacin (13% vs. 0%), clindamycin (12% vs. 0%), gentamicin (9% vs. 0%), fusidic acid (10% vs. 9%), linezolid (4% vs. 0%), and rifampicin (5% vs. 0%). The proportion of multidrug resistant S. aureus was 41% (n = 38) in the diabetes group and 0% in the non-diabetes group; this difference was statistically significant (p = 0.01). CONCLUSIONS: The presence of diabetes predisposed the participants to S. aureus carriage by almost four folds, but not MRSA carriage. Colonization with CoNS was protective of S. aureus and MRSA carriage in the diabetes group. Finally, linezolid remains a good therapeutic agent for anti-MRSA therapy.


Asunto(s)
Complicaciones de la Diabetes/microbiología , Diabetes Mellitus/microbiología , Farmacorresistencia Bacteriana Múltiple , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones Estafilocócicas/microbiología , Adolescente , Adulto , Antibacterianos/uso terapéutico , Portador Sano , Clindamicina/uso terapéutico , Estudios Transversales , Complicaciones de la Diabetes/diagnóstico , Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamiento farmacológico , Eritromicina/uso terapéutico , Femenino , Ácido Fusídico/uso terapéutico , Gentamicinas/uso terapéutico , Humanos , Linezolid/uso terapéutico , Masculino , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Cavidad Nasal/microbiología , Norfloxacino/uso terapéutico , Penicilinas/uso terapéutico , Rifampin/uso terapéutico , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Tetraciclina/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico
18.
JAMA Netw Open ; 4(9): e2126099, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34546370

RESUMEN

Importance: The risk of tuberculosis (TB) associated with diabetes status, considering impaired fasting glucose or duration of diabetes, has not been well established. Objective: To evaluate the association of diabetes status with the development of TB in the general population. Design, Setting, and Participants: This population-based cohort study used data from the Korean National Health Insurance System database. Adult participants without a history of TB who underwent a health screening in 2009 were included. Eligible participants were followed up for incident TB cases from 1 year after the day of health screening until December 31, 2018. Data analysis was performed from September 2019 to September 2020. Exposures: Five levels of diabetes status were evaluated: normal glucose, impaired fasting glucose (considered as without diabetes), new-onset diabetes, diabetes duration less than 5 years, and diabetes duration 5 years or longer (considered as having diabetes). Main Outcomes and Measures: Newly diagnosed TB. Results: Among 4 423 177 participants, the mean (SD) age was 46.5 (13.9) years, and there were 2 597 142 men (58.7%). A total of 26 458 participants (0.6%) received a diagnosis of TB within a median (interquartile range) of 8.3 (8.1-8.6) years of follow-up. An increased risk of TB was observed in participants with diabetes compared with those without diabetes (adjusted hazard ratio [aHR], 1.48; 95% CI, 1.42-1.53). Although participants with impaired fasting glucose did not show an increased risk of TB incidence (aHR, 0.97; 95% CI, 0.93-1.01), the risk of TB incidence increased with diabetes duration (new-onset diabetes, aHR, 1.32; 95% CI, 1.23-1.42; diabetes duration <5 years, aHR, 1.45; 95% CI, 1.36-1.54; diabetes duration ≥5 years, aHR, 1.57; 95% CI, 1.48-1.66). Among participants with new-onset diabetes, compared with those in the lowest decile (fasting plasma glucose [FPG] level ≥126 but <128 mg/dL), the risk of TB was significantly increased for those in the highest decile (FPG level ≥202 mg/dL, aHR, 1.79; 95% CI, 1.42-2.26). Conclusions and Relevance: These findings suggest that longer diabetes duration is associated with development of TB, showing a dose-response association. Among participants with new-onset diabetes, incident TB was more common among those with FPG levels greater than or equal to 202 mg/dL.


Asunto(s)
Glucemia/análisis , Complicaciones de la Diabetes/microbiología , Diabetes Mellitus/sangre , Tuberculosis/complicaciones , Tuberculosis/epidemiología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Factores de Riesgo
19.
Ann R Coll Surg Engl ; 103(10): e330-e334, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34414780

RESUMEN

In the postantibiotic era, prostatic abscesses (PAs) are rare, affecting primarily immunocompromised men and/or caused by atypical drug-resistant pathogens, raising both diagnostic and management challenges. PA caused by methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon condition and also a primary source of bacteremia. Nevertheless, the continued pattern of increase in reported cases, due especially to community-associated strains, is a growing concern regarding the significant morbidity and mortality. Besides proper antibiotics, drainage of a PA may be required, which is usually transrectal or transurethral. Herein, we describe the case of MRSA PA extending into the penis with concomitant MRSA bacteremia of unknown origin, whereupon diabetes mellitus was newly diagnosed in a previously healthy man residing in a community setting, and managed successfully by a transperineal drainage with good outcome. This case also highlights that individuals diagnosed with such rare deep-seated MRSA infections should be assessed for undiagnosed comorbidities. To the best of our knowledge, this is the first reported case of percutaneous drainage of a PA by using a double-lumen catheter.


Asunto(s)
Absceso/terapia , Complicaciones de la Diabetes/microbiología , Staphylococcus aureus Resistente a Meticilina , Enfermedades del Pene/microbiología , Enfermedades de la Próstata/microbiología , Infecciones Estafilocócicas/terapia , Absceso/complicaciones , Absceso/microbiología , Drenaje , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Pene/complicaciones , Enfermedades del Pene/terapia , Enfermedades de la Próstata/complicaciones , Enfermedades de la Próstata/terapia , Infecciones Estafilocócicas/complicaciones
20.
Mycoses ; 64(10): 1238-1252, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34096653

RESUMEN

PURPOSE: The aim of the study was to report clinical features, contributing factors and outcome of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). METHODS: A cross-sectional descriptive multicentre study was conducted on patients with biopsy-proven mucormycosis with RT-PCR-confirmed COVID-19 from April to September 2020. Demographics, the time interval between COVID-19 and mucormycosis, underlying systemic diseases, clinical features, course of disease and outcomes were collected and analysed. RESULTS: Fifteen patients with COVID-19 and rhino-orbital mucormycosis were observed. The median age of patients was 52 years (range 14-71), and 66% were male. The median interval time between COVID-19 disease and diagnosis of mucormycosis was seven (range: 1-37) days. Among all, 13 patients (86%) had diabetes mellitus, while 7 (46.6%) previously received intravenous corticosteroid therapy. Five patients (33%) underwent orbital exenteration, while seven (47%) patients died from mucormycosis. Six patients (40%) received combined antifungal therapy and none that received combined antifungal therapy died. CONCLUSION: Clinicians should be aware that mucormycosis may be complication of COVID-19 in high-risk patients. Poor control of diabetes mellitus is an important predisposing factor for CAM. Systematic surveillance for control of diabetes mellitus and educating physician about the early diagnosis of CAM are suggested.


Asunto(s)
Antifúngicos/uso terapéutico , COVID-19/complicaciones , Coinfección , Mucormicosis/tratamiento farmacológico , Mucormicosis/mortalidad , Síndrome de Dificultad Respiratoria/mortalidad , Adolescente , Adulto , Anciano , Anfotericina B/uso terapéutico , COVID-19/patología , Caspofungina/uso terapéutico , Comorbilidad , Estudios Transversales , Complicaciones de la Diabetes/microbiología , Complicaciones de la Diabetes/mortalidad , Diabetes Mellitus/patología , Quimioterapia Combinada , Femenino , Humanos , Irán , Masculino , Persona de Mediana Edad , Mucormicosis/patología , Síndrome de Dificultad Respiratoria/microbiología , Síndrome de Dificultad Respiratoria/patología , Triazoles/uso terapéutico , Adulto Joven , Tratamiento Farmacológico de COVID-19
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