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1.
Elife ; 112022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35112667

RESUMO

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.


Assuntos
Quimiotaxia de Leucócito/imunologia , Diabetes Mellitus Experimental/imunologia , Neutrófilos/patologia , Receptores de Formil Peptídeo/genética , Transdução de Sinais/imunologia , Cicatrização/imunologia , Infecção dos Ferimentos/microbiologia , Animais , Quimiocina CCL3/imunologia , Complicações do Diabetes/microbiologia , Glucose/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Receptores de Formil Peptídeo/imunologia , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/etiologia
2.
Exp Eye Res ; 216: 108941, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35077754

RESUMO

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.


Assuntos
Aspergilose/prevenção & controle , Úlcera da Córnea/prevenção & controle , Complicações do Diabetes/microbiologia , Ácidos Docosa-Hexaenoicos/fisiologia , Infecções Oculares Fúngicas/prevenção & controle , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Animais , Araquidonato 15-Lipoxigenase/metabolismo , Araquidonato 5-Lipoxigenase/metabolismo , Aspergilose/metabolismo , Aspergilose/microbiologia , Aspergillus fumigatus/fisiologia , Western Blotting , Células Cultivadas , Úlcera da Córnea/metabolismo , Úlcera da Córnea/microbiologia , Complicações do Diabetes/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/microbiologia , Infecções Oculares Fúngicas/metabolismo , Infecções Oculares Fúngicas/microbiologia , Citometria de Fluxo , Glucose/farmacologia , Humanos , Imuno-Histoquímica , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Espécies Reativas de Oxigênio/metabolismo
3.
J Nanobiotechnology ; 19(1): 404, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34865643

RESUMO

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.


Assuntos
Antibacterianos , Complicações do Diabetes , Nanofibras , Infecções Estafilocócicas , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/microbiologia , Humanos , Macrófagos/efeitos dos fármacos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Nanofibras/química , Nanofibras/uso terapêutico , Células RAW 264.7 , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
4.
PLoS Negl Trop Dis ; 15(11): e0009921, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34793455

RESUMO

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.


Assuntos
COVID-19/complicações , COVID-19/epidemiologia , Mucormicose/epidemiologia , Mucormicose/virologia , Antifúngicos/uso terapêutico , COVID-19/microbiologia , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Comorbidade , Complicações do Diabetes/microbiologia , Humanos , Índia/epidemiologia , Mucormicose/tratamento farmacológico , Fatores de Risco
5.
Cells ; 10(11)2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34831057

RESUMO

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.


Assuntos
Complicações do Diabetes/epidemiologia , Complicações do Diabetes/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Metabolômica , Biomarcadores/metabolismo , Complicações do Diabetes/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal , Humanos , Metaboloma , Biologia de Sistemas
6.
PLoS One ; 16(9): e0257004, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34534230

RESUMO

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.


Assuntos
Complicações do Diabetes/microbiologia , Diabetes Mellitus/microbiologia , Farmacorresistência Bacteriana Múltipla , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia , Adolescente , Adulto , Antibacterianos/uso terapêutico , Portador Sadio , Clindamicina/uso terapêutico , Estudos Transversais , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Eritromicina/uso terapêutico , Feminino , Ácido Fusídico/uso terapêutico , Gentamicinas/uso terapêutico , Humanos , Linezolida/uso terapêutico , Masculino , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Cavidade Nasal/microbiologia , Norfloxacino/uso terapêutico , Penicilinas/uso terapêutico , Rifampina/uso terapêutico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Tetraciclina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
7.
Microbiol Spectr ; 9(2): e0085721, 2021 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-34549996

RESUMO

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.


Assuntos
Diabetes Mellitus/patologia , Glucose-6-Fosfato/metabolismo , Proteínas de Transporte de Monossacarídeos/genética , Infecções Estafilocócicas/patologia , Staphylococcus aureus/patogenicidade , Tecido Adiposo Branco/química , Animais , Glicemia/análise , Complicações do Diabetes/microbiologia , Pé Diabético/microbiologia , Pé Diabético/patologia , Modelos Animais de Doenças , Frutose/metabolismo , Glucose/metabolismo , Humanos , Masculino , Manose/metabolismo , Camundongos , Camundongos Transgênicos , Staphylococcus aureus/metabolismo , Úlcera/microbiologia , Fatores de Virulência/metabolismo
8.
JAMA Netw Open ; 4(9): e2126099, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34546370

RESUMO

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.


Assuntos
Glicemia/análise , Complicações do Diabetes/microbiologia , Diabetes Mellitus/sangue , Tuberculose/complicações , Tuberculose/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco
9.
Ann R Coll Surg Engl ; 103(10): e330-e334, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34414780

RESUMO

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.


Assuntos
Abscesso/terapia , Complicações do Diabetes/microbiologia , Staphylococcus aureus Resistente à Meticilina , Doenças do Pênis/microbiologia , Doenças Prostáticas/microbiologia , Infecções Estafilocócicas/terapia , Abscesso/complicações , Abscesso/microbiologia , Drenagem , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Pênis/complicações , Doenças do Pênis/terapia , Doenças Prostáticas/complicações , Doenças Prostáticas/terapia , Infecções Estafilocócicas/complicações
11.
Mycoses ; 64(10): 1238-1252, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34096653

RESUMO

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.


Assuntos
Antifúngicos/uso terapêutico , COVID-19/complicações , Coinfecção , Mucormicose/tratamento farmacológico , Mucormicose/mortalidade , Síndrome do Desconforto Respiratório/mortalidade , Adolescente , Adulto , Idoso , Anfotericina B/uso terapêutico , COVID-19/patologia , Caspofungina/uso terapêutico , Comorbidade , Estudos Transversais , Complicações do Diabetes/microbiologia , Complicações do Diabetes/mortalidade , Diabetes Mellitus/patologia , Quimioterapia Combinada , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Mucormicose/patologia , Síndrome do Desconforto Respiratório/microbiologia , Síndrome do Desconforto Respiratório/patologia , Triazóis/uso terapêutico , Adulto Jovem , Tratamento Farmacológico da COVID-19
12.
Sci Rep ; 11(1): 6211, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737624

RESUMO

We aimed to determine whether puncture sites for blood sampling and topical disinfectants are associated with rates of contaminated blood cultures in the emergency department (ED) of a single institution. This single-center, prospective observational study of 249 consecutive patients aged ≥ 20 years proceeded in the ED of a university hospital in Japan during 6 months. Pairs of blood samples were collected for aerobic and anaerobic culture from all patients in the ED. Physicians selected puncture sites and topical disinfectants according to their personal preference. We found 50 (20.1%) patients with potentially contaminated blood cultures. Fifty-six (22.5%) patients were true bacteremia and 143 (57.4%) patients were true negatives. Multivariate analysis associated more frequent contamination when puncture sites were disinfected with povidone-iodine than with alcohol/chlorhexidine (adjusted risk difference, 12.9%; 95% confidence interval [CI] 8.8-16.9; P < 0.001). Sites of blood collection were also associated with contamination. Femoral and central venous with other sites were associated with contamination more frequently than venous sites (adjusted risk difference), 13.1% (95% CI 8.2-17.9; P < 0.001]) vs. 17.3% (95% CI 3.6-31.0; P = 0.013). Rates of contaminated blood cultures were significantly higher when blood was collected from femoral sites and when povidone-iodine was the topical antiseptic.


Assuntos
Bacteriemia/complicações , Hemocultura/métodos , Complicações do Diabetes/microbiologia , Hipertensão/complicações , Neoplasias/complicações , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Bacteriemia/patologia , Coleta de Amostras Sanguíneas/efeitos adversos , Clorexidina/efeitos adversos , Complicações do Diabetes/patologia , Diabetes Mellitus/microbiologia , Diabetes Mellitus/patologia , Desinfetantes/efeitos adversos , Serviço Hospitalar de Emergência , Etanol/efeitos adversos , Reações Falso-Positivas , Feminino , Veia Femoral , Hospitais Universitários , Humanos , Hipertensão/microbiologia , Hipertensão/patologia , Japão , Masculino , Pessoa de Meia-Idade , Neoplasias/microbiologia , Neoplasias/patologia , Povidona-Iodo/efeitos adversos , Estudos Prospectivos
13.
Curr Osteoporos Rep ; 19(4): 462-479, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33523423

RESUMO

PURPOSE OF REVIEW: Patients with diabetes mellitus (DM) are at increased risk of developing osteopathogenesis and skeletal fragility. The role of the gut microbiota in both DM and osteopathy is not fully explored and may be involved in the pathology of both diseases. RECENT FINDINGS: Gut microbiota alterations have been observed in DM and osteopathogenic disorders as compared with healthy controls, such as significantly lower abundance of Prevotella and higher abundance of Lactobacillus, with a diminished bacterial diversity. Other overlapping gastro-intestinal features include the loss of intestinal barrier function with translocation of bacterial metabolites to the blood stream, induction of immunological deficits and changes in hormonal and endocrinal signalling, which may lead to the development of diabetic osteopathy. Signalling pathways involved in both DM and osteopathy are affected by gut bacteria and their metabolites. Future studies should focus on gut microbiota involvement in both diseases.


Assuntos
Doenças Ósseas/microbiologia , Complicações do Diabetes/microbiologia , Microbioma Gastrointestinal , Humanos , Transdução de Sinais
14.
Int J Infect Dis ; 104: 677-679, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33540127

RESUMO

Necrotizing soft tissue infection, with or without myositis, is classified among the most dangerous infectious emergencies in clinical practice. The authors report a case of an older diabetic woman who presented to the orthopedic service with right elbow pain after a small trauma with skin abrasion and released with an analgesic prescription. After 48h, she presented to the emergency room with a history of developing bullous and necrotic lesions in the upper right limb, hypotension, and numbness, with rapid and fatal evolution despite adequate clinical and surgical therapeutic support. Muscle biopsy showed necrotizing myositis. Blood culture was positive for Panton-Valentine leukocidin producing (PVL-positive) methicillin-resistant S. aureus. Although PVL has a strong epidemiologic association with Community-Acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, it can also be found in CA-MSSA in the context of necrotizing pneumonia and skin and soft tissue infections. Although infrequent, CA-MRSA or CA-MSSA PVL+ infections should always be suspected in high-risk patients because they can rapidly evolve with severe, sometimes fatal complications.


Assuntos
Complicações do Diabetes/mortalidade , Piomiosite/etiologia , Piomiosite/mortalidade , Infecções Estafilocócicas/mortalidade , Complicações do Diabetes/microbiologia , Evolução Fatal , Feminino , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/fisiologia , Pessoa de Meia-Idade , Piomiosite/microbiologia , Infecções dos Tecidos Moles/microbiologia , Infecções dos Tecidos Moles/mortalidade , Infecções Estafilocócicas/microbiologia
15.
J Med Microbiol ; 70(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33528353

RESUMO

Introduction. Since mcr-1 was first reported in China, there have been ten variants of MCR appearing nationwide so far. Multidrug-resistant Enterobacteriaceae bacteria carrying both NDM and MCR have become a serious threat to global public health.Hypothesis/Gap Statement. The genetic structure of mcr-9 needs to be better understood in order to better prevent and control the transmission of drug-resistant genes.Aims. The aim of this study was to characterize the presence of two Enterobacter hormaechei isolates, which carries bla NDM-5 CME2 and the coexistence of mcr-9 and bla NDM-1 strain CMD2, which were isolated from a patient with diabetes in Sichuan, China.Methodology. The microbroth dilution method was used for antibiotic susceptibility. Conjugation experiment was used to investigate the transferability of bla NDM-1, bla NDM-5 and mcr-9. Whole-genome sequencing was performed on Illumina HiSeq platform. The ability of biofilm formation was detected by crystal-violet staining, the virulence of the bacteria was measured by Galleria mellonella killing assay.Results. bla NDM-5 carrier CME2 and CMD2 with bla NDM-1 and mcr-9 were resistant to carbapenems, ß-lactam, aminoglycoside, quinolone and tetracycline, while CMD2 was also resistant to colistin. Conjugation assay and plasmid replicon typing further demonstrated that both bla NDM-1 and bla NDM-5 were respectively present on the self-transferrable IncX3 plasmid, mcr-9 was located on the self-transferrable IncHI2 plasmid. Through the analysis of mcr-9 gene context, the structure was DUF4942-rcnR-rcnA-copS-IS903-mcr-9-wbuC-qseC-qseB-IS1R-ΔsilR-IS903, bla NDM-1 context was IS3000-ΔISAba125-IS5-bla NDM-1-ble-trpF-groS-groL-insE-ΔIS26 structure, bla NDM-5 structure was IS3000-bla NDM-5-ble-trpF-dsbC-ΔIS26-umuD-ISKox3-tnpR-parA. Biofilm formation of CME2 was stronger than CMD2. There was no significant difference in virulence between the two strains.Conclusion. This study reveals two multiple drug-resistant E. hormaechei isolates from diabetes patient samples. E. hormaechei carrying two NDM-resistant genes is already a serious threat, where MCR is an important cause of treatment failure in bacterial infections. This study is a reminder not only to prevent infection in patients with diabetes, but also to constantly monitor the epidemic and spread of the drug-resistant gene.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Coinfecção/microbiologia , Complicações do Diabetes/microbiologia , Enterobacter/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Enterobacter/efeitos dos fármacos , Enterobacter/genética , Genoma Bacteriano/genética , Humanos , Masculino , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Fatores de Virulência/genética , Adulto Jovem
16.
J Basic Microbiol ; 61(3): 212-218, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33448040

RESUMO

Patients with diabetes are considered a high-risk group involved with cerebral mucormycosis (CM). Due to the potential of Mucorales to invade sinuses and its rapid progression into orbit and retro-orbital areas and even brain, in most cases, CM is fatal in patients with diabetes. In the last few decades, mucormycosis and background conditions responsible for the development of its infections have received a great deal of attention. Dysfunction of innate and adaptive immune system, the increased amount of available nutrition, expression of host factors, and free iron level in plasma in diabetic ketoacidosis are among the topics that have been mostly taken into account so far. Therefore, it is important to clarify the molecular mechanisms that let the Mucorales to involve the patients with diabetes, which even at early stages of diagnosis and treatment, there is minimum chance to control the disease.


Assuntos
Diabetes Mellitus Tipo 1/patologia , Olho/microbiologia , Mucormicose/microbiologia , Mucormicose/patologia , Complicações do Diabetes/microbiologia , Cetoacidose Diabética/complicações , Olho/patologia , Humanos , Ferro/sangue , Mucorales/isolamento & purificação , Mucormicose/complicações , Rhizopus oryzae/isolamento & purificação
17.
Infect Genet Evol ; 87: 104679, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33326876

RESUMO

There have been few studies focused on the molecular characterization of invasive Staphylococcus aureus strains in patients with diabetes in Iran. In the present study, 20 invasive S. aureus strains recovered from the patients with diabetes characterized by the virulence and resistance analysis, biofilm formation, staphylocoagulase (SC) typing, S. aureus protein A locus (spa) typing staphylococcal cassette chromosome mec (SCCmec) typing, and multilocus sequence typing (MLST). Virulence gene detection indicated a high prevalence of strains encoding the pvl genes (50%), a low prevalence of the tst and seg gene (each of them was 5%) and a markedly high prevalence of fnbB (95%), fnbA (85%), icaD (75%), icaA (65%). A total of 3 coagulase types (III, 85%; II, 10%; V, 5%), 2 agr types (I, 90%; II 10%) and 2 SCCmec types (IV, 65%; III, 35%) and four different clones namely ST8-MRSA-IV/t008 (50%) (USA300), ST239-MRSA-III/t030 (35%), ST5-MRSA-IV/t002 (10%), and ST45-MRSA-IV/t038 (5%) were detected in this study. Eighty-five percent of the isolates were biofilm producers. All the 4 high-level mupirocin resistance (HLMUPR) strains belonged to CC/ST8-MRSA-IV/t008 clone and carried mupA gene. Fusidic acid-resistant isolate belonged to ST239-SCCmec III/t030 clone. One vancomycin-intermediate resistance isolates was detected in our study, which belonged to ST5-MRSA-IVt002. Circulating clone in MRSA strains (USA300) isolated from the patients with diabetes highlighting the possibility of transmission of these microorganisms' clones between hospital, community, and environments. However, further studies require providing critical insights into the importance of continued controlling and treatment of S. aureus infections in patients with diabetes.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/microbiologia , Diabetes Mellitus/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/tratamento farmacológico , Virulência/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Variação Genética , Genótipo , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Epidemiologia Molecular , Infecções Estafilocócicas/epidemiologia
18.
PLoS One ; 15(12): e0244306, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33378365

RESUMO

INTRODUCTION: Diabetic foot ulcers (DFU) and infection (DFI) are a major diabetes-related problem around the world due to the high prevalence of diabetes in the population. The aim of our study was to determine the microbiological profile of infected ulcers in patients attending Dasman Diabetes Institute (DDI) clinics in Kuwait and to analyze the distribution of microbial isolates according to wound grade, sex, age and diabetes control. METHODS: We collected and analyzed clinical data and samples from 513 diabetic patients with foot ulcers referred to our podiatry clinic at DDI from Jan 2011 till Dec 2017. RESULTS: We show a higher prevalence of DFU in men than in women, and a greater percentage of DFU occurred in men at an earlier age (p<0.05). Only about half of the DFU were clinically infected (49.3%) but 92% of DFU showed bacterial growth in the microbiological lab analysis. In addition, we isolated more monomicrobial (57.3%) than polymicrobial (34.8%) DFI and representing an average of 1.30 pathogens per patient. The presence of Gram-positive and Gram-negative strains was comparable between men and women regardless their age or glucose levels. Interestingly, more Gram-positive strains are present in ulcers without ischemia while more Gram-negative strains are present in ulcers with ischemia (p<0.05). While Staphylococcus aureus was common in infected ulcers without ischemia, Pseudomonas aeruginosa was predominant in ulcers with infection and ischemia, regardless of ulcer depth. Finally, a higher percentage of women has controlled HbA1c levels (19.41% versus 11.95% in men) and more women in this group displayed non-infected wounds (60.6% and 43.90% for women and men, respectively). CONCLUSION: Our results provide an updated picture of the DFI patterns and antibiotics resistance in patients attending Dasman Diabetes Institute (DDI) clinics in Kuwait which might help in adopting the appropriate treatment of infected foot and improving clinical outcomes.


Assuntos
Pé Diabético/epidemiologia , Pé Diabético/microbiologia , Fatores Etários , Idoso , Antibacterianos/farmacologia , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/microbiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/microbiologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Feminino , Pé/microbiologia , Úlcera do Pé/epidemiologia , Úlcera do Pé/microbiologia , Humanos , Kuweit/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Pseudomonas aeruginosa/efeitos dos fármacos , Fatores Sexuais , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos
19.
J Diabetes Res ; 2020: 7201379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062714

RESUMO

BACKGROUND: Studies suggest an association between H. pylori infection and extragastrointestinal disease. Limited studies provided conflicting results on the association between H. pylori infection and diabetes. The present study was aimed at examining the association between H. pylori infection and diabetes in a large health checkup population in China. METHODS: A cross-sectional study was conducted; participants who attended health checkups at Beijing MJ Health Screening Center during 2017-2018 were included. H. pylori infection was diagnosed by 13C-urea breath test. Multivariate logistic regression analysis was performed to evaluate the association between H. pylori infection and diabetes. RESULTS: The mean age of 13,397 participants was 43.8 ± 12 years. The prevalence of H. pylori infection and diabetes was 28.2% and 8.1%, respectively. The prevalence of diabetes was higher among H. pylori-positive participants compared with their counterparts (8.9% vs 7.8%, p = 0.05). After adjustment of age, sex, family history of diabetes, smoking, education, stroke, coronary heart disease, BMI, SBP, TG, HDL-C, and LDL-C, multivariate logistic regression analysis found no association between H. pylori infection and diabetes (OR 1.02, 95% CI 0.88-1.18). Additionally, subgroup analysis indicated that H. pylori infection was significantly associated with increased risk of diabetes in the female group (OR 1.09, 95% CI 1.08-1.09). CONCLUSIONS: No significant association was found between H. pylori infection and diabetes. However, the subgroup analysis suggested that H. pylori infection was possibly associated with increased risk of diabetes among females. Future cohort studies are needed to verify this association in females and to address possible implication in the prevention of diabetes.


Assuntos
Complicações do Diabetes/microbiologia , Diabetes Mellitus/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Adulto , Testes Respiratórios , Isótopos de Carbono , China/epidemiologia , Estudos Transversais , Diabetes Mellitus/epidemiologia , Feminino , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Resultado do Tratamento , Ureia
20.
Mycoses ; 63(12): 1264-1282, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32965744

RESUMO

BACKGROUND: Patients with diabetes are known as an important high-risk group for cerebral mucormycosis (CM). METHOD: We conducted a structured search using PubMed/MEDLINE to collect both case reports and case series case (ie including at least two patients) onto CM in diabetic patient published between 2000 and March 2020. RESULTS: Forty-five reports of individual cases and eighteen case series articles were included. India accounted for the largest share of reports with 37.7% and 38.8% of individual cases and case series, respectively. Mortality ranged from 0% to 100% in the case series. The overall mortality in the individual cases was 46.3%, and 64.2% of deaths were reported in patients with ketoacidosis diabetes. Facial swelling (53.3%), headache (44.4%), loss of vision (35.5%) and ophthalmoplegia (35.5%) were the most frequently reported clinical symptoms. In all patients except 4 (91.1%), CM was treated surgically; however, in many cases (42%), despite the use of surgery, death occurred. Amphotericin B deoxycholate (AMB) and lipid-based AMB (LAMB) were used as the first lines of treatment for all patients; however, posaconazole, echinocandins, hyperbaric oxygen therapy (HBOT) and deferasirox were used in combination for a number of patients. Posaconazole has been shown to have positive therapeutic effect; however, posaconazole, LAMB and HBOT are not commonly used in low-income and health-challenged countries. CONCLUSION: Cerebral mucormycosis is a rapidly progressive infection in diabetic patients and carries immense morbidity despite early diagnosis and treatment. Low-income countries have had the highest number of reports of the disease in recent years, indicating the need to control diabetes in these countries.


Assuntos
Encefalopatias/epidemiologia , Encefalopatias/microbiologia , Complicações do Diabetes/microbiologia , Mucormicose/diagnóstico , Mucormicose/epidemiologia , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Encefalopatias/diagnóstico , Encefalopatias/tratamento farmacológico , Ácido Desoxicólico/uso terapêutico , Diabetes Mellitus/epidemiologia , Combinação de Medicamentos , Humanos , Mucormicose/tratamento farmacológico , Fatores de Risco , Triazóis/uso terapêutico
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