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1.
Front Immunol ; 12: 618807, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679760

RESUMO

Type 2 inflammation is found in most forms of asthma, which may co-exist with recurrent viral infections, bacterial colonization, and host cell death. These processes drive the accumulation of intracellular cyclic-di-nucleotides such as cyclic-di-GMP (CDG). Group 2 innate lymphoid cells (ILC2s) are critical drivers of type 2 lung inflammation during fungal allergen exposure in mice; however, it is unclear how CDG regulates lung ILC responses during lung inflammation. Here, we show that intranasal CDG induced early airway type 1 interferon (IFN) production and dramatically suppressed CD127+ST2+ ILC2s and type 2 lung inflammation during Alternaria and IL-33 exposure. Further, CD127-ST2-Thy1.2+ lung ILCs, which showed a transcriptomic signature consistent with ILC1s, were expanded and activated by CDG combined with either Alternaria or IL-33. CDG-mediated suppression of type 2 inflammation occurred independent of IL-18R, IL-12, and STAT6 but required the stimulator of interferon genes (STING) and type 1 IFN signaling. Thus, CDG potently suppresses ILC2-driven lung inflammation and promotes ILC1 responses. These results suggest potential therapeutic modulation of STING to suppress type 2 inflammation and/or increase anti-viral responses during respiratory infections.


Assuntos
Alternaria/imunologia , Alternariose/imunologia , GMP Cíclico/análogos & derivados , Imunidade Inata , Pulmão/imunologia , Proteínas de Membrana/imunologia , Pneumonia/imunologia , Alternariose/genética , Alternariose/patologia , Animais , GMP Cíclico/genética , GMP Cíclico/imunologia , Citocinas/genética , Citocinas/imunologia , Inflamação/genética , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia , Pulmão/microbiologia , Pulmão/patologia , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Pneumonia/genética , Pneumonia/microbiologia , Pneumonia/patologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia
2.
Medicine (Baltimore) ; 100(4): e24524, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530280

RESUMO

ABSTRACT: This study aimed to evaluate the incidence of co-infection with different types of pathogens in patients with hypoxemic pneumonia due to coronavirus disease 2019 (COVID-19) in Reunion Island.This observational study using a prospectively collected database of hypoxemic pneumonia due to COVID-19 cases was conducted at Félix Guyon University Hospital in Reunion Island, France.Between 18 March 2020 and 15 April 2020, 156 patients were admitted to our hospital for COVID-19. A total of 36 patients had hypoxemic pneumonia (23.1%) due to COVID-19. Thirty of these cases (83.3%) were imported by travelers returning mainly from metropolitan France and Spain. Patients were screened for co-infection with other pathogens at admission: 31 (86.1%) by multiplex polymerase chain reaction (PCR) and 16 (44.4%) by cytobacteriological examination of sputum culture. Five patients (13.9%) were found to have co-infection: 1 with influenza virus A H1N1 (pdm09) associated with Branhamella catarrhalis, 1 with Streptococcus pneumoniae associated with Haemophilus influenzae, 1 with Human Coronavirus 229E, 1 with Rhinovirus, and 1 with methicillin-susceptible Staphylococcus aureus. Patients with co-infection had higher D-dimer levels than those without co-infection (1.36 [1.34-2.36] µg/mL vs 0.63 [0.51-1.12] µg/mL, P = .05).The incidence of co-infection in our cohort was higher than expected (13.9%). Three co-infections (with influenza virus A(H1N1) pdm09, Streptococcus pneumoniae, and Staphylococcus aureus) required specific treatment. Patients with hypoxemic pneumonia due to COVID-19 should be screened for co-infection using respiratory cultures or multiplex PCR. Whilst our study has a number of limitations, the results from our study suggest that in the absence of screening, patients should be commenced on treatment for co-infection in the presence of an elevated D-dimer.


Assuntos
/epidemiologia , Coinfecção/epidemiologia , Pneumonia/epidemiologia , Pneumonia/microbiologia , Adulto , Feminino , França/epidemiologia , Humanos , Hipóxia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Artigo em Inglês | MEDLINE | ID: mdl-33503151

RESUMO

Round pneumonia is an unusual radiological manifestation of a bacterial lung infection. We present the case of an elderly male patient who arrived at the emergency room with a productive cough and exertional dyspnea. His chest x-ray and CT showed a round opacity and air bronchograms in the right upper lobe. Taken together, the patient's symptoms and images strongly suggest a pulmonary infection. Empirical antibiotic therapy with ceftriaxone and clarithromycin was started. The sputum culture was positive for Enterobacter hormaechei and the bacterium was sensitive to levofloxacin; therefore, the antibiotic therapy was changed. Despite the treatment, the patient progressed to respiratory failure and septic shock, dying six days after admission. Although round pneumonia is uncommon, it is a potentially curable disease and clinicians should always consider it in their differential diagnosis.


Assuntos
Enterobacter/isolamento & purificação , Infecções por Enterobacteriaceae/diagnóstico , Pulmão/diagnóstico por imagem , Pneumonia/diagnóstico , Adulto , Idoso , Antibacterianos/uso terapêutico , Tosse , Dispneia , Infecções por Enterobacteriaceae/tratamento farmacológico , Humanos , Levofloxacino/uso terapêutico , Masculino , Pneumonia/microbiologia , Escarro/microbiologia , Resultado do Tratamento
4.
Nat Commun ; 11(1): 5778, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188196

RESUMO

Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets.


Assuntos
Plaquetas/patologia , Vasos Sanguíneos/patologia , Quimiotaxia , Inflamação/patologia , Pneumonia/sangue , Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Adulto , Animais , Movimento Celular , Microambiente Celular , Modelos Animais de Doenças , Fibrinogênio/metabolismo , Humanos , Lipopolissacarídeos , Lesão Pulmonar/microbiologia , Lesão Pulmonar/patologia , Staphylococcus aureus Resistente à Meticilina/fisiologia , Camundongos Endogâmicos C57BL , Microvasos/patologia , Pneumonia/microbiologia , Pseudópodes/metabolismo
5.
BMC Infect Dis ; 20(1): 821, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172398

RESUMO

BACKGROUND: Although Moraxella catarrhalis (M. catarrhalis) is a common cause of community-acquired pneumonia (CAP), studies investigating clinical manifestations of CAP due to M. catarrhalis (MC-CAP) in adults are limited. Since S. pneumoniae is the leading cause of CAP globally, it is important to distinguish between MC-CAP and CAP due to S. pneumoniae (SP-CAP) in clinical practice. However, no past study compared clinical characteristics of MC-CAP and SP-CAP by statistical analysis. We aimed to clarify the clinical characteristics of MC-CAP by comparing those of SP-CAP, as well as the utility of sputum Gram staining. METHODS: This retrospective study screened CAP patients aged over 20 years visiting or admitted to Okinawa Miyako Hospital between May 2013 and April 2018. Among these, we included patients whom either M. catarrhalis alone or S. pneumoniae alone was isolated from their sputum by bacterial cultures. RESULTS: We identified 134 MC-CAP and 130 SP-CAP patients. Although seasonality was not observed in SP-CAP, almost half of MC-CAP patients were admitted in the winter. Compared to those with SP-CAP, MC-CAP patients were older (p < 0.01) and more likely to have underlying pulmonary diseases such as asthma and bronchiectasis (p < 0.01). Approximately half of asthmatic MC-CAP and SP-CAP patients had asthma attacks. Although winter is an influenza season in Japan, co-infection with influenza virus was less common in MC-CAP compared to SP-CAP patients (3% vs. 15%, p < 0.01). Bronchopneumonia patterns on X-ray, as well as bronchial wall thickening, bilateral distribution, and segmental pattern on CT were more common in MC-CAP patients than in SP-CAP patients (p < 0.01). Sputum Gram stain was highly useful method for the diagnosis in both MC-CAP and SP-CAP (78.4% vs. 89.2%), and penicillins were most frequently chosen as an initial treatment for both pneumonias. CONCLUSIONS: This is the first study to show that MC-CAP occurred in older people compared to SP-CAP, influenza virus co-infection was less common in MC-CAP than SP-CAP, and that MC-CAP frequently caused asthma attacks. Gram stain contributed for the appropriate treatment, resulting in conserving broad-spectrum antibiotics such as cephalosporins and fluoroquinolones in both MC-CAP and SP-CAP patients.


Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Moraxella catarrhalis/isolamento & purificação , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Streptococcus pneumoniae/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Violeta Genciana , Hospitalização , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fenazinas , Pneumonia/microbiologia , Estudos Retrospectivos , Escarro/microbiologia , Coloração e Rotulagem , Resultado do Tratamento , Adulto Jovem
7.
Medicine (Baltimore) ; 99(43): e22924, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120846

RESUMO

RATIONALE: Polymyxin B has been used to treat extensively drug-resistant gram-negative bacteria and shown a better antibacterial effect in the clinic at present. Meanwhile, polymyxin B is associated with several adverse effects. However, there is a lack of awareness that polymyxin B can cause rhabdomyolysis. In this study, we firstly report a case of polymyxin B-induced rhabdomyolysis during antiinfection therapy. PATIENT CONCERNS: A 70-year-old woman suffering from rheumatic heart disease underwent aortic and mitral valve replacement at our institute. Subsequently, she developed bacteremia and pneumonia caused by extensively drug resistance-acinetobacter baumannii. Polymyxin B was administered for 5 days. During treatment, the patient complained of muscle pain and limb weakness, and her serum creatine phosphokinase and myoglobin levels rose. DIAGNOSIS: The clinical symptoms and laboratory examination confirmed rhabdomyolysis, and polymyxin B-induced rhabdomyolysis was considered. INTERVENTION: We ceased polymyxin B treatment and monitored the patient daily. OUTCOMES: Serum creatine phosphokinase levels returned to normal, myoglobin levels decreased, and muscle pain was significantly alleviated after cessation of polymyxin B. We identified this as a case of polymyxin B-induced rhabdomyolysis. LESSONS: Here, we report the first reported case of rhabdomyolysis induced by polymyxin B administration. The awareness of rare adverse reaction helps ensure the clinical safety of polymyxin B treatment.


Assuntos
Antibacterianos/efeitos adversos , Polimixina B/efeitos adversos , Rabdomiólise/induzido quimicamente , Acinetobacter baumannii/isolamento & purificação , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Conscientização , Bacteriemia/tratamento farmacológico , Creatina Quinase/sangue , Feminino , Humanos , Debilidade Muscular/etiologia , Mialgia/etiologia , Mioglobina/sangue , Pneumonia/tratamento farmacológico , Pneumonia/microbiologia , Polimixina B/administração & dosagem , Polimixina B/uso terapêutico , Rabdomiólise/diagnóstico , Suspensão de Tratamento
8.
PLoS One ; 15(8): e0237871, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817720

RESUMO

Streptococcus pneumoniae is a common cause of infectious diseases such as pneumonia and sepsis. Its colonization is thought to be the first step in the development of invasive pneumococcal diseases. This study aimed to investigate pneumococcal colonization patterns in early childhood. A longitudinal birth cohort study was conducted for investigating nasopharyngeal colonized pneumococci at 1, 6, 12, 18, 24, and 36 months of age, particularly focusing on the serotype distribution and antimicrobial susceptibilities. Pneumococcal conjugate vaccine (PCV) effect on nasopharyngeal colonization was also assessed. During 2013-2017, 855 infants were enrolled and a total of 107 isolates were recovered from 95 infants during the first three years of life. In this period, the prevalence of pneumococcal colonization increased, with values ranging from 0.2% (2/834) at 1 month of age to 5.9% (19/323) at 36 months of age. The investigation of serotype revealed that 81.1% (73/90) belonged to the non-PCV13 serotypes-23A, 15A, 15C, and 15B. Moreover, PCV13 serotypes significantly decreased during 2014-2015, when routine PCV13 vaccination was initiated in Taiwan. PCV13 introduction may lead to the reduction in the rates of pneumococcal isolates resistant (R) to penicillin. Under conditional PCV13 vaccination, pneumococcal isolates primarily belonged to non-PCV13 serotypes. This non-PCV13 serotype replacement exhibited lower rates of penicillin R isolates, suggesting that PCV13 administration may reduce the antibiotic-nonsusceptible pneumococcal disease burden and antibiotic use.


Assuntos
Doenças Nasofaríngeas/tratamento farmacológico , Nasofaringe/efeitos dos fármacos , Infecções Pneumocócicas/tratamento farmacológico , Streptococcus pneumoniae/efeitos dos fármacos , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Doenças Nasofaríngeas/imunologia , Doenças Nasofaríngeas/microbiologia , Doenças Nasofaríngeas/patologia , Nasofaringe/microbiologia , Penicilinas/administração & dosagem , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/patologia , Vacinas Pneumocócicas/administração & dosagem , Pneumonia/microbiologia , Pneumonia/prevenção & controle , Sepse/microbiologia , Sepse/prevenção & controle , Sorogrupo , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Taiwan , Vacinas Conjugadas/administração & dosagem
9.
Wilderness Environ Med ; 31(3): 324-326, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32739040

RESUMO

Exposure to and consumption of brackish water are associated with an elevated risk of infection, hypernatremia, and hypothermia. Minimal data exist to support the diagnosis and treatment of patients with long-term brackish water exposure. We present a case of a patient who spent 5 to 10 d semisubmerged in the Elizabeth River in coastal Virginia. A 55-y-old male presented via ambulance after 5 to 10 d of being "stuck in the mud." He was hypernatremic, with a sodium of 176 mEq·L-1, hypothermic to 34.5°C (94.1°F), and hypotensive at 88/50 mm Hg, with a sodium concentration of 176 mEq·L-1 and an osmolality of 412 mosm·kg-1. He developed pneumonia, with respiratory cultures growing Vibrio parahemolyticus, Klebsiella oxytoca, and Shewanella algae. He had pustules, which grew Aeromonas hydrophilia and Aeromonas caviae. A nasogastric tube was placed. Using suction, 500 mL of coarse sand and gravel was removed from his stomach. Antibiotics and intravenous fluids were given. The patient fully recovered after 3 wk and was discharged to rehabilitation. Exposure to brackish water can present a unique set of infectious and metabolic complications. Initial care should include treatment of metabolic derangements, such as hypovolemia, hypernatremia, and hypothermia, and treatment of infections with antibiotics based on knowledge of the most likely causative organisms.


Assuntos
Furunculose/diagnóstico , Imersão/efeitos adversos , Intubação Gastrointestinal , Pneumonia/diagnóstico , Águas Salinas/efeitos adversos , Furunculose/microbiologia , Humanos , Hipernatremia/etiologia , Imersão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pneumonia/microbiologia , Areia , Resultado do Tratamento , Virginia
10.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(8): 639-647, 2020 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-32727174

RESUMO

Patients with diabetes mellitus are prone to various infections owing to host immune impairment, especially pneumonia. In China, morbidity of pneumonia in patients with diabetes mellitus is high. And in case of pneumonia, patients with diabetes mellitus were of increased probability of opportunistic infections, low detection rate of pathogens, more severe pneumonia and high mortality, resulting in heavy medical and economic burdens. Therefore, it is urgent for multi-disciplinary experts to explore and formulate standards for diagnosis and treatment of pneumonia in patients with diabetes mellitus to improve the prognosis. Based on domestic and international literatures and clinical experiences of experts in respiratory and critical care medicine, endocrinology, microbiology and clinical pharmacy, a consensus was developed on the diagnosis and treatment of pneumonia in patients with diabetes mellitus.


Assuntos
Complicações do Diabetes , Diabetes Mellitus , Pneumonia/diagnóstico , Pneumonia/terapia , China , Consenso , Humanos , Infecções Oportunistas/microbiologia , Pneumonia/microbiologia , Prognóstico
11.
Medicine (Baltimore) ; 99(28): e21051, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664118

RESUMO

Acinetobacter baumannii (AB) is one of the major types of infection in hospitalized patients. The development of AB resistance is becoming a global clinical challenge. To assist in the clinical management of AB-induced pneumonia, we designed the present retrospective observational study to investigate the risk factors for antimicrobial drug-resistant/-sensitive AB infections.A total of 214 individuals were reviewed, in which 100 and 55 pneumonia patients were infected with drug-resistant and drug-sensitive AB, respectively. Fifty-nine pneumonia patients without AB infection served as a control group. Age, sex, duration of hospital stay, prior surgery history, the presence of coinfection and companion diseases, routine blood test results, and immunogenicity were recorded. Logistic regression was performed to identify risk factors of AB infections.Multivariate analysis revealed that long duration of hospital stay (odds ratio = 1.091 [95% CI: 1.010-1.178], P = .027) and the absence of coinfection (odds ratio = 0.507 [95% CI: 0.265-0.970], P = .040) were independent risk factors for AB infections. Same pattern of risk factors was identified for the drug-sensitive group (long duration of hospital stay: odds ratio = 1.119 [95% CI: 1.016-1.232], P = .022; absence of coinfection: odds ratio = 0.328 [95% CI: 0.135-0.797], P = .014), while high blood urea nitrogen (odds ratio: 1.382 [95% CI: 1.042-1.833], P = .025) was the only significant risk factor for drug-resistant AB infection.Long duration of hospital stay and the absence of coinfection might predict AB infections in hospitalized patients. Antimicrobial drug-resistant and drug-sensitive AB infections possess different risk factor profiles. A poor kidney function may be predictive of drug-resistant AB infection. Further prospective studies are required to validate our findings.


Assuntos
Infecções por Acinetobacter/epidemiologia , Antibacterianos/farmacologia , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana Múltipla , Pneumonia/epidemiologia , Acinetobacter baumannii , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Coinfecção , Infecção Hospitalar/microbiologia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pneumonia/microbiologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
12.
Nat Commun ; 11(1): 3184, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576824

RESUMO

Peptide antibiotics are an abundant and synthetically tractable source of molecular diversity, but they are often cationic and can be cytotoxic, nephrotoxic and/or ototoxic, which has limited their clinical development. Here we report structure-guided optimization of an amphipathic peptide, arenicin-3, originally isolated from the marine lugworm Arenicola marina. The peptide induces bacterial membrane permeability and ATP release, with serial passaging resulting in a mutation in mlaC, a phospholipid transport gene. Structure-based design led to AA139, an antibiotic with broad-spectrum in vitro activity against multidrug-resistant and extensively drug-resistant bacteria, including ESBL, carbapenem- and colistin-resistant clinical isolates. The antibiotic induces a 3-4 log reduction in bacterial burden in mouse models of peritonitis, pneumonia and urinary tract infection. Cytotoxicity and haemolysis of the progenitor peptide is ameliorated with AA139, and the 'no observable adverse effect level' (NOAEL) dose in mice is ~10-fold greater than the dose generally required for efficacy in the infection models.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Animais , Carbapenêmicos/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Colistina/farmacologia , Modelos Animais de Doenças , Descoberta de Drogas , Feminino , Proteínas de Helminto/química , Proteínas de Helminto/farmacologia , Humanos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Peritonite/tratamento farmacológico , Peritonite/microbiologia , Pneumonia/tratamento farmacológico , Pneumonia/microbiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
13.
Gastroenterology ; 159(4): 1302-1310.e5, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32598884

RESUMO

BACKGROUND & AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects intestinal cells, and might affect the intestinal microbiota. We investigated changes in the fecal fungal microbiomes (mycobiome) of patients with SARS-CoV-2 infection during hospitalization and on recovery. METHODS: We performed deep shotgun metagenomic sequencing analysis of fecal samples from 30 patients with coronavirus disease 2019 (COVID-19) in Hong Kong, from February 5 through May 12, 2020. Fecal samples were collected 2 to 3 times per week from time of hospitalization until discharge. We compared fecal mycobiome compositions of patients with COVID-19 with those from 9 subjects with community-acquired pneumonia and 30 healthy individuals (controls). We assessed fecal mycobiome profiles throughout time of hospitalization until clearance of SARS-CoV-2 from nasopharyngeal samples. RESULTS: Patients with COVID-19 had significant alterations in their fecal mycobiomes compared with controls, characterized by enrichment of Candia albicans and a highly heterogeneous mycobiome configuration, at time of hospitalization. Although fecal mycobiomes of 22 patients with COVID-19 did not differ significantly from those of controls during times of hospitalization, 8 of 30 patients with COVID-19 had continued significant differences in fecal mycobiome composition, through the last sample collected. The diversity of the fecal mycobiome of the last sample collected from patients with COVID-19 was 2.5-fold higher than that of controls (P < .05). Samples collected at all timepoints from patients with COVID-19 had increased proportions of opportunistic fungal pathogens, Candida albicans, Candida auris, and Aspergillus flavus compared with controls. Two respiratory-associated fungal pathogens, A. flavus and Aspergillus niger, were detected in fecal samples from a subset of patients with COVID-19, even after clearance of SARS-CoV-2 from nasopharyngeal samples and resolution of respiratory symptoms. CONCLUSIONS: In a pilot study, we found heterogeneous configurations of the fecal mycobiome, with enrichment of fungal pathogens from the genera Candida and Aspergillus, during hospitalization of 30 patients with COVID-19 compared with controls. Unstable gut mycobiomes and prolonged dysbiosis persisted in a subset of patients with COVID-19 up to 12 days after nasopharyngeal clearance of SARS-CoV-2. Studies are needed to determine whether alterations in intestinal fungi contribute to or result from SARS-CoV-2 infection, and the effects of these changes in disease progression.


Assuntos
Infecções por Coronavirus/microbiologia , Fezes/microbiologia , Fungos/isolamento & purificação , Microbioma Gastrointestinal , Micobioma , Pneumonia Viral/microbiologia , Adulto , Idoso , Aspergillus flavus/genética , Aspergillus flavus/isolamento & purificação , Aspergillus niger/genética , Aspergillus niger/isolamento & purificação , Betacoronavirus , Candida/genética , Candida/isolamento & purificação , Candida albicans/genética , Candida albicans/isolamento & purificação , Estudos de Casos e Controles , Infecções Comunitárias Adquiridas/microbiologia , DNA Fúngico/análise , Feminino , Fungos/genética , Humanos , Masculino , Metagenômica , Pessoa de Meia-Idade , Nasofaringe/virologia , Pandemias , Alta do Paciente , Pneumonia/microbiologia , Fatores de Tempo , Adulto Jovem
15.
J Vet Sci ; 21(3): e46, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32476320

RESUMO

BACKGROUND: High concentrations of particulate matter less than 2.5 µm in diameter (PM2.5) in poultry houses is an important cause of respiratory disease in animals and humans. Pseudomonas aeruginosa is an opportunistic pathogen that can induce severe respiratory disease in animals under stress or with abnormal immune functions. When excessively high concentrations of PM2.5 in poultry houses damage the respiratory system and impair host immunity, secondary infections with P. aeruginosa can occur and produce a more intense inflammatory response, resulting in more severe lung injury. OBJECTIVES: In this study, we focused on the synergistic induction of inflammatory injury in the respiratory system and the related molecular mechanisms induced by PM2.5 and P. aeruginosa in poultry houses. METHODS: High-throughput 16S rDNA sequence analysis was used for characterizing the bacterial diversity and relative abundance of the PM2.5 samples, and the effects of PM2.5 and P. aeruginosa stimulation on inflammation were detected by in vitro and in vivo. RESULTS: Sequencing results indicated that the PM2.5 in poultry houses contained a high abundance of potentially pathogenic genera, such as Pseudomonas (2.94%). The lung tissues of mice had more significant pathological damage when co-stimulated by PM2.5 and P. aeruginosa, and it can increase the expression levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α through nuclear factor (NF)-κB pathway in vivo and in vitro. CONCLUSIONS: The results confirmed that poultry house PM2.5 in combination with P. aeruginosa could aggravate the inflammatory response and cause more severe respiratory system injuries through a process closely related to the activation of the NF-κB pathway.


Assuntos
Material Particulado/efeitos adversos , Pneumonia/etiologia , Infecções por Pseudomonas/fisiopatologia , Pseudomonas aeruginosa/fisiologia , Animais , Peso Corporal , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Subunidade p50 de NF-kappa B/metabolismo , Material Particulado/classificação , Pneumonia/induzido quimicamente , Pneumonia/microbiologia , Organismos Livres de Patógenos Específicos , Fator de Necrose Tumoral alfa/metabolismo
16.
BMC Infect Dis ; 20(1): 374, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460697

RESUMO

BACKGROUND: Elevated Staphylococcus aureus and oral bacterial concentrations are known to correlate with pneumonia hospitalization in nursing home residents. However, the effects of a professional oral care intervention on these factors remain unclear. The aims of this quasi-experimental study were to compare bacterial concentrations in saliva and sputum, oral health status, distribution of Staphylococcus aureus, and pneumonia status before and after a professional oral care intervention. METHODS: A purposive sample of residents from two nursing homes was divided into an intervention group that received a weekly professional oral care intervention and a control group. Oral bacterial concentration was determined by real-time polymerase chain reaction. The Staphylococcus aureus distribution was determined by bacterial culture and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. After data collection, a statistical analysis was performed to evaluate the effect of the intervention. RESULTS: Most residents were unconscious (80%), and most had a history of pneumonia (76%). Baseline demographic data did not significantly differ between the two groups. After the intervention, the intervention group had significant improvements in plaque index (1.66 ± 0.78 vs. 0.94 ± 0.64, p <  0.01), gingival index (2.36 ± 0.76 vs. 1.65 ± 0.83, p <  0.01), tongue coating index (0.96 ± 1.10 vs. 0.16 ± 0.47, p <  0.01), distribution of Staphylococcus aureus in salivary samples (11.11 ± 14.47% vs. 1.74 ± 3.75%, p = 0.02), and salivary bacterial concentration ([4.27 ± 3.65] × 105 vs. [0.75 ± 1.20] × 105, p <  0.01). Sputum bacterial concentration did not significantly differ. The intervention group also had a significantly lower annual prevalence of pneumonia hospitalization (1.24 ± 1.51 vs. 0.48 ± 0.59, p = 0.01), especially in residents whose salivary bacterial concentration exceeded the median. However, the duration of pneumonia hospitalization did not significantly differ between the two groups. CONCLUSION: A professional oral care intervention in nursing home residents can improve oral health, reduce levels of salivary bacteria and Staphylococcus aureus, and decrease the annual prevalence of pneumonia hospitalization. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov, NCT03874962. Registered 12 March 2019 - Retrospectively registered.


Assuntos
Boca/microbiologia , Pneumonia/microbiologia , Saliva/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Feminino , Pneumonia Associada a Assistência à Saúde/microbiologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Casas de Saúde/estatística & dados numéricos , Saúde Bucal , Projetos Piloto , Pneumonia/epidemiologia , Escarro/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/genética , Taiwan
18.
J Card Surg ; 35(6): 1258-1266, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32340078

RESUMO

BACKGROUND: The development of postoperative pneumonia following cardiac surgery is associated with significant morbidity and mortality. However, seasonal variation as a risk factor for the development of postoperative pneumonia remains to be investigated. We sought to investigate whether patients undergoing coronary artery bypass grafting (CABG) during "flu season" (Fall and Winter months) at increased risk of postoperative pneumonia. MATERIALS AND METHODS: A retrospective cohort study of patients undergoing CABG in the National Inpatient Sample between 2005 and 2015 was completed. Concomitant diagnosis of pneumonia was defined as the primary outcome. Secondary outcomes were defined to include pneumonia secondary to several known pathogens. Outcomes with significant differences between Fall/Winter and Spring/Summer groups were further analyzed with additive time series decomposition. Odds ratios were generated and adjusted for age, sex, elective status, and 29 other Agency for Healthcare Research and Quality comorbidity measures. RESULTS: A total of 238 757 and 277 941 patients undergoing CABG during Fall/Winter and Spring/Summer, respectively, were identified. A significantly increased risk of postoperative pneumonia (adjusted odds ratio [aOR] = 1.15) and infection with influenza (aOR = 4.08), Haemophilus influenzae (aOR = 1.40), and Streptococcus pneumoniae (aOR = 1.47) was observed among patients receiving CABG in Q1 (January-March) compared to Q3 (July-September). CONCLUSIONS: There is a strong seasonality in the incidence of postoperative pneumonia after CABG which may persist across other cardiothoracic surgeries. In addition to optimizing infection control and perioperative care, cardiac surgeons should consider preoperative vaccination against seasonal influenza, H. influenzae, and S. pneumoniae to improve outcomes among high-risk patients.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estações do Ano , Idoso , Estudos de Coortes , Feminino , Humanos , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Pneumonia/microbiologia , Pneumonia/mortalidade , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
19.
Transplant Proc ; 52(4): 1178-1182, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32340747

RESUMO

BACKGROUND: Pneumonia caused by opportunistic fungi is a serious complication in immunocompromised patients. Hypercalcemia has been described in renal transplantation associated with Pneumocystis jirovecii (PJP) or Histoplasma capsulatum (HCP) pneumonia. METHODS: We describe 5 patients who underwent kidney transplant between 2014 and 2019 and developed hypercalcemia before the diagnosis of pulmonary fungal infection: 4 patients with PJP and 1 with HCP. We assessed calcium metabolism and kidney function by total and ionized calcium, phosphorus, intact parathormone (iPTH), 25-OH vitamin D, 1,25(OH)2 vitamin D, and serum creatinine levels. RESULTS: Mean albumin-corrected calcium and ionized calcium were 12.56 mg/dL (range, 10.8-13.8 mg/dL) and 1.57 mmol/L (range, 1.43-1.69 mmol/L). Patients were normocalcemic, at 10.12 mg/dL (range, 9.6-10.5 mg/dL), before diagnosis and resolved hypercalcemia after antifungal treatment, at 8.86 mg/dL (range, 8.0-9.5 mg/dL). All patients had low or normal iPTH values, at 29.1 pg/mL (range, <3-44 pg/mL), with higher PTH levels 3 months before diagnosis and after treatment, at 147.3 pg/mL (range, 28.1-479 pg/mL) and 117.5 pg/mL (range, 18.2-245 pg/mL), respectively. The mean value for 25-OH vitamin D was 30.8 ng/mL (range, 14.6-62.8 ng/mL). This supports a PTH-independent mechanism, and we postulated an extrarenal production of 1,25(OH)2 vitamin D. CONCLUSION: In kidney transplant patients, hypercalcemia independent of PTH and refractory to treatment should alert for the possibility of opportunistic fungal pneumonia.


Assuntos
Hipercalcemia/etiologia , Hospedeiro Imunocomprometido , Transplante de Rim , Micoses/imunologia , Infecções Oportunistas/complicações , Pneumonia/imunologia , Adulto , Feminino , Histoplasmose/sangue , Histoplasmose/imunologia , Humanos , Hipercalcemia/sangue , Hipercalcemia/imunologia , Masculino , Pessoa de Meia-Idade , Micoses/sangue , Micoses/complicações , Infecções Oportunistas/imunologia , Infecções Oportunistas/microbiologia , Pneumonia/complicações , Pneumonia/microbiologia , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/imunologia , Adulto Jovem
20.
PLoS One ; 15(4): e0229757, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32310961

RESUMO

INTRODUCTION: Even though use of antiretroviral therapy (HAART) decreases the incidence of opportunistic infections (OIs) they are continuing to be a major cause of morbidity and mortality. Studies concerning this problem are scarce in Eastern Africa. The aim of this study was to determine the incidence and predictors of OIs after initiation of HAART in Ethiopia. METHODS: A health facility based single centered cohort study using structured data extraction sheet was conducted. The study population was all HIV positive ART naive adolescents and adults who started HAART between January 2009 and May 2012. Simple random sampling technique was used to select 317 patients from the record. Multivariate binary logistic regression model was used to determine factors for the occurrence of OIs after initiation of HAART. RESULTS: The incidence of OIs after HAART was 7.5 cases/100person years. Tuberculosis, oral candidiasis, pneumonia and toxoplasmosis were the leading OIs after HAART. A bed ridden functional status at initiation of HAART, presence of OIs before HAART, non-adherence and low hemoglobin level were predictors for the occurrence of OIs after HAART. CONCLUSION: The incidence of OIs after HAART was higher than in previous studies. Patients with the identified risk factors need strict follow up to reduce the morbidity and mortality attributed to OIs. Earlier initiation of HAART before advanced immune suppression, better management of TB and extended baseline assessment could help to reduce opportunistic infections and mortality after the initiation of HAART in Ethiopian patients.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Candidíase/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Pneumonia/tratamento farmacológico , Tuberculose/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adolescente , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Candidíase/complicações , Candidíase/microbiologia , Candidíase/virologia , Estudos de Coortes , Etiópia/epidemiologia , Feminino , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/microbiologia , Pneumonia/virologia , Tuberculose/complicações , Tuberculose/microbiologia , Tuberculose/virologia , Adulto Jovem
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