PDIA iminosugar influence on subcutaneous Staphylococcus aureus and Pseudomonas aeruginosa infections in mice.

Introduction: Biofilm-associated infections persist as a therapeutic challenge in contemporary medicine. The efficacy of antibiotic therapies is ineffective in numerous instances, necessitating a heightened focus on exploring novel anti-biofilm medical strategies. Among these, iminosugars emerge as a distinctive class of compounds displaying promising biofilm inhibition properties. Methods: This study employs an in vivo wound infection mouse model to evaluate the effectiveness of PDIA in treating biofilm-associated skin wound infections caused by Staphylococcus aureus and Pseudomonas aeruginosa. Dermic wounds in mice were infected with biofilm-forming strains, specifically S. aureus 48 and P. aeruginosa 5, which were isolated from patients with diabetic foot, and are well-known for their strong biofilm formation. The subsequent analysis included clinical, microbiological, and histopathological parameters. Furthermore, an exploration into the susceptibility of the infectious strains to hydrogen peroxide was conducted, acknowledging its potential presence during induced inflammation in mouse dermal wounds within an in vivo model. Results: The findings revealed the efficacy of PDIA iminosugar against the S. aureus strain, evidenced by a reduction in bacterial numbers within the wound and the inflammatory focus. Discussion: This study suggests that PDIA iminosugar emerges as an active and potentially effective antibiofilm agent, positioning it as a viable treatment option for staphylococcal infections.

Corneal ulceration following periocular scorpion sting: a case report.

BACKGROUND: Scorpion envenomation, a prevalent medical emergency in rural areas, demands immediate attention due to its potential severity. While ocular manifestations are uncommon, they can lead to significant complications such as corneal ulceration. We present a unique case of corneal ulceration subsequent to a yellow scorpion (Hemiscorpius lepturus) sting near the eye, a scenario not previously documented. CASE PRESENTATION: A 34-year-old male sought medical care following a scorpion sting despite prior anti-venom treatment. Clinical examination revealed pronounced ocular inflammation, corneal stromal melting, and anterior chamber inflammation, with microbiological confirmation of Pseudomonas spp infection. Treatment comprised fortified ceftazidime and vancomycin eye drops, alongside topical corticosteroids, leading to visual and corneal healing. CONCLUSION: This case highlights the urgency of addressing scorpion envenomation and its potential for severe ocular complications, including corneal ulceration. Prompt diagnosis and targeted therapy with antibiotics and corticosteroids are crucial for favorable outcomes. A comprehensive understanding and timely intervention in scorpion sting-induced ocular manifestations are essential for optimal patient management and outcomes in such cases.

Use of topical colistin in bacterial keratitis caused by extensively drug-resistant Pseudomonas Aeruginosa: a case report / Uso de colistina tópica em ceratite bacteriana causada por Pseudomonas Aeruginosa extensivamente resistente a medicamentos: relato de caso

ABSTRACT Bacterial keratitis caused by multidrug-resistant strains of Pseudomonas aeruginosa is a therapeutic challenge due to a limited number of active antimicrobials and rapid progression to corneal necrosis and perforation. To report the use of topical colistin and surgical tarsorrhaphy in a case of keratitis caused by extensively drug-resistant Pseudomonas aeruginosa in a patient with severe coronavirus disease-2019 (COVID-19) pneumonia. A 56-year-old male was admitted to the intensive care unit with clinical symptoms of severe COVID-19 pneumonia. During his stay in the unit, he developed rapidly progressive keratitis with Pseudomonas aeruginosa resistant to all drugs except for colistin on culture. Due to incomplete lid closure, a temporary tarsorrhaphy was performed, and a regimen of descending-dose topical colistin was initiated. After five weeks, keratitis resolved completely. Extensively drug-resistant Pseudomonas aeruginosa is an unusual cause of bacterial keratitis. We describe the safe and effective use of topical colistin in a case with severe corneal involvement.

RESUMO A ceratite bacteriana causada por cepas multirresistentes de Pseudomonas aeruginosa é um desafio terapêutico, devido à disponibilidade limitada de antimicrobianos e à rápida progressão para necrose e perfuração da córnea. O objetivo deste artigo é relatar o uso de colistina tópica e tarsorrafia cirúrgica em um caso de ceratite por Pseudomonas aeruginosa amplamente resistente a medicamentos em um paciente com pneumonia grave por COVID19. Um homem de 56 anos foi internado em uma unidade de terapia intensiva com sintomas clínicos de pneumonia grave por COVID19. Durante sua permanência na unidade de terapia intensiva, o paciente desenvolveu uma ceratite rapidamente progressiva, cuja cultura foi positiva para Pseudomonas aeruginosa resistente a todos os antimicrobianos, exceto colistina. Devido ao fechamento incompleto da pálpebra, foi realizada uma tarsorrafia temporária e foi instituído um esquema de colistina tópica em doses decrescentes. Após cinco semanas, a resolução completa da ceratite foi alcançada. Pseudomonas aeruginosa amplamente resistente a medicamentos é uma causa incomum de ceratite bacteriana. Este relato descreve o uso seguro e eficaz da colistina tópica em um caso com comprometimento corneano grave.

Características clínicas y resultados de pacientes con fibrosis quística con enfermedad pulmonar avanzada: experiencia en 10 años del Instituto Nacional del Tórax / Clinical features and outcomes of cystic fibrosis patients with advanced lung disease: experience of 10 years at the Instituto Nacional del Tórax

La enfermedad pulmonar avanzada (EPAV) es la principal causa de morbimortalidad en pacientes con Fibrosis Quística (FQ). Objetivo: describir características clínicas de pacientes con FQ con EPAV y mortalidad en el seguimiento. Método: Estudio descriptivo, retrospectivo de pacientes con FQ y EPAV: VEF1 4 años de vida. Un 75% era portador de infección crónica por Pseudomonas. Un 68% era dependiente de oxígeno y un 18% de ventilación mecánica no invasiva. El 70 % tuvo 2 o más hospitalizaciones el último año de seguimiento. De 27 pacientes derivados a trasplante, 7 se trasplantaron, 3 fallecieron en lista para trasplante, 9 presentaron alguna contraindicación: 4 de ellos por desnutrición y 5 por mala adherencia y escasa red de apoyo. En el seguimiento un 32% (n = 14) falleció, 93% de causa respiratoria. Conclusión: Un 39% de los pacientes tenían EPAV cuyo diagnóstico de FQ en promedio fue a los 11,2 años (SD ± 13 a). Las barreras de ingreso a lista para trasplante fueron: desnutrición, mala adherencia y falta de red de apoyo. Esta es una población con una elevada mortalidad.

Advanced cystic fibrosis lung disease (ACFLD) is the leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Objective: to describe clinical characteristics of patients with CF with ACFLD and mortality during follow-up. Method: Descriptive, retrospective study of patients with CF and ACFLD: FEVi < 40%, oxygen dependent, and/or referred to a lung transplantprogram. Clinical, microbiological, functional, genetic and mortality characteristics were collected. Results: Of 111 controlled patients, 39% met criteria for ACFLD. 52% were men and the mean age was 29,8 years- old. The average BMI was 19.9 kg/m2, 72% had pancreatic insufficiency and 87% had a genetic study, being the DF508 mutation the most frequent (67%). The average age of diagnosis was 11.2 years (SD ± 13 years), being in 54,5% over the age of 4 years. 75% had chronic Pseudomonas infection. 68% were oxygen dependent and 18% on noninvasive mechanical ventilation. In the last year of follow-up 70% had 2 or more hospitalizations. Of 27 patients who have been referred for transplantation, 7 underwent lung transplantation, 3 died waiting on the transplant list, 9 had contraindications: 4 due to malnutrition and 5 to poor adherence and poor support network. 32% (n = 14) of the ACFLD patients died, 93% due to respiratory causes. Conclusion: 39% of the patients had ACFLD. The average age for CF diagnosis was 11.2 years (SD ± 13 years) Barriers to entering the transplant list are: malnutrition, poor adherence, and lack of a support network. This is a population with a high mortality.

First case of non-traumatic community-acquired Pseudomonas fulva infection.

Pseudomonas fulva is a rare human pathogen associated with invasive procedures and trauma. An 85-year-old female presented with macroscopic hematuria, dysuria, and lower abdominal discomfort. The symptoms disappeared within three days of empirical antibiotic treatment. A bacterial isolate from urine was identified by MALDI-TOF as P. â€‹fulva. Computed tomography, cystoscopy, and urinary bladder lavage cytology failed to identify any bleeding source or malignancy. Awareness of possible P. â€‹fulva infections also in the absence of trauma and invasive procedures is warranted. Intravenous broad-spectrum antibiotics is recommended for invasive or more severe cases of suspected or confirmed P. â€‹fulva infection.

The role of microRNAs in chronic pseudomonas lung infection in Cystic fibrosis.

BACKGROUND: Cystic Fibrosis (CF) is the most common life limiting genetic disorder, characterized by chronic respiratory failure secondary to inflammation and chronic bacterial lung infection. Pseudomonas aeruginosa lung infection is associated with more severe lung disease and rapid progression of respiratory failure when compared to Staphylococcus aureus infection. We hypothesized that a specific signature of epigenetic factors targeting specific gene transcripts contributes to the increased morbidity seen in CF patients with chronic Pseudomonas infection. METHODS: We collected exhaled breath condensate (EBC) from 27 subjects and evaluated miRNA signatures in these samples using commercial PCR array. We identified predicted mRNA targets and associated signaling pathways using Ingenuity Pathway Analysis. RESULTS: We found 11 differentially expressed miRNAs in EBC of patients infected with Pseudomonas aeruginosa compared to EBC from CF patients who were not chronically infected with Pseudomonas aeruginosa (p < 0.05). Six of these miRNAs (hsa-miRNA-1247, hsa-miRNA-1276, hsa-miRNA-449c, hsa-miRNA-3170, hsa-miRNA-432-5p and hsa-miR-548) were significantly different in the CF Pseudomonas positive group when compared to both the CF Pseudomonas negative group and healthy control group. Ingenuity pathway analysis (IPA) revealed organismal injury and abnormalities, reproductive system disease and cancer as the top diseases and bio functions associated with these miRNAs. IPA also detected RELA, JUN, TNF, IL-10, CTNNB1, IL-13, SERPINB8, CALM1, STARD3NL, SFI1, CD55, RPS6KA4, TTC36 and HIST1H3D as the top target genes for these miRNAs. CONCLUSION: Our study identified 6 miRNAs as epigenetic factors specifically associated with chronic Pseudomonas infection in patients with CF.

Urinary Bladder Matrix Protects Host in a Murine Model of Bacterial-Induced Lung Infection.

IMPACT STATEMENT: Lung infection is a leading cause of human life lost to morbidity and/or mortality. This problem is exacerbated by the alarming emergence of increasingly antibiotic-resistant (AR) microorganisms worldwide and the lack of effective antimicrobials to overcome the AR bacterial infection. Urinary bladder matrix (UBM) is a biologically derived scaffold material that has been used to promote site-appropriate tissue regeneration and remodeling in a variety of body systems. Our novel findings demonstrate that the preformulated UBM effectively protects the host from methicillin-resistant Staphylococcus aureus (MRSA)- and Pseudomonas aeruginosa-induced murine pneumonia and may provide a viable alternative/supplement for protection against respiratory AR bacterial infection.

In vitro data support the investigation of vinegar as an antimicrobial agent for PD-associated Pseudomonas exit site infections.

Peritoneal dialysis exit site infections caused by Pseudomonas spp. are difficult to treat and can lead to peritonitis and/or modality failure. Effective alternative or adjunct non-antibiotic antimicrobial agents could improve treatment as well as reduce the use of antibiotics and contribute to a reduction in antibiotic selection pressure and the further development of antibiotic resistance. Vinegar is popularly promoted as a topical antimicrobial agent and has been recommended as an adjunct treatment for Pseudomonas exit site infections in PD patients. Systematic empirical data on the susceptibility of pseudomonads to vinegar are lacking. This study aimed to determine the susceptibility to vinegar of 57 isolates of Pseudomonas. The MICs and MBCs of four vinegars were determined for clinical, environmental and/or reference isolates of P. aeruginosa (n = 34), P. fluorescens (n = 11) and P. putida (n = 12) using a broth microdilution method. The MIC90 and MBC90 were also determined for each species. The MIC90 of all four vinegars against P. aeruginosa was 2% (vol/vol). The MBC90 was 8%. The MIC90 s for P. fluorescens and P. putida were also 2%. The MIC90 s were 4%. Dilutions of vinegar recommended for the treatment of Pseudomonas exit site infections have in vitro activity against these notoriously resistant bacteria. In light of increasing rates of antibiotic resistance and the need to reduce antibiotic selection pressure as part of good antibiotic stewardship, the efficacy of vinegar, or its active constituent acetic acid, for the treatment of Pseudomonas exit site infections should be investigated further.

Eradication failure of newly acquired Pseudomonas aeruginosa isolates in cystic fibrosis.

Eradication of Pseudomonas aeruginosa (PA) is critical in cystic fibrosis (CF) patients. OBJECTIVES: To determine eradication success rate of newly acquired PA and to identify characteristics associated with eradication failure. METHODS: In an observational study, data from patients with newly acquired PA infection from 2007 to 2013 were collected. Clinical variables were compared in patients with and without successful eradication for ≥1year. RESULTS: Of 183 patients out of 740 (25%) from 7 CF Centers that had newly acquired PA, eradication succeeded in 72%. Patients with the highest risk of failure had multi-resistant PA, fewer sputum cultures taken, were older, and were diagnosed at a later age. The risk of eradication failure increased by 1.3% with each year of delayed CF diagnosis; successful eradication increased by 17% with each additional sputum culture taken. CONCLUSIONS: Delayed detection of PA infection leading to delayed treatment and growth of multi-resistant organisms is associated with eradication failure.

YKL-40 as marker of severe lung disease in cystic fibrosis patients.

BACKGROUND: YKL-40 is a chitinase-like protein present in serum of healthy subjects and its levels are increased in several human inflammatory diseases. The aim of this study was to evaluate the levels of both serum and sputum YKL-40 in cystic fibrosis (CF) patients. METHODS: Serum and sputum YKL-40 levels were measured in a cohort of twenty-eight patients with a diagnosis of CF and twenty healthy controls. RESULTS: Serum YKL-40 levels were significantly higher in CF patients (88.8±56.7 vs 18.6±2.9ng/ml, P<0.001), as well as sputum YKL-40 levels (138.5±132.7 vs 28.2±24.34, P<0.001) than in healthy controls. Serum YKL-40 levels were closely related to YKL-40 levels assessed in sputum samples (r=0.71; P<0.01). CONCLUSIONS: YKL-40 is elevated in CF patients and is further elevated during severe exacerbations. Longitudinal studies in infant are needed to establish its role in disease pathogenesis.

Zinc Supplementation for One Year Among Children with Cystic Fibrosis Does Not Decrease Pulmonary Infection.

BACKGROUND: Children with cystic fibrosis may have a deficiency of micronutrients, including zinc, which may affect their susceptibility to infections. There is a paucity of data on zinc supplementation among children with cystic fibrosis. We hypothesized that a pharmacologic dose of zinc administered daily for 12 months would reduce the need for antibiotics by 50%. METHODS: This double-blind randomized placebo-controlled trial was conducted among children with cystic fibrosis to assess the effect of zinc supplementation on the need for antibiotics and pulmonary function tests. The children, age 5-15 y, of either sex, received either 30-mg zinc tablets or similar looking placebo tablets daily in addition to standard care. They were followed up every month for a period of 12 months and whenever they had pulmonary exacerbations. Their serum zinc was estimated at baseline and at 12 months of enrollment. During each visit, the children underwent a pulmonary function test and sputum culture. RESULTS: Of a total of 43 children screened, 40 were enrolled, and of them, 37 completed the study. The median (interquartile range) number of days of the administration of antibiotics over 12 months of follow-up among the children receiving zinc was 42 (14-97) d. In the placebo group, it was 38 (15-70) d (P = .79). There were no significant differences in the percent-of-predicted FEV1 or change in FEV1 values at 12 months (P = .44). The number of children in whose respiratory specimens Pseudomonas was isolated was similar for the 2 groups at different time intervals. The adverse events reported were similar in the 2 groups. CONCLUSION: We did not find any significant difference in the need for antibiotics, pulmonary function tests, hospitalization, colonization with Pseudomonas, or the need for antibiotics for children with cystic fibrosis receiving zinc supplementation of 30 mg/d.

Acute pulmonary exacerbation and lung function decline in patients with cystic fibrosis: high-mobility group box 1 (HMGB1) between inflammation and infection.

Airway inflammation plays a central role in cystic fibrosis (CF) lung disease, and biomarkers of inflammation, such as high-mobility group box 1 (HMGB1) could be used to monitor disease activity. The main aim of this study was to confirm the role of HMGB1 in CF patients, correlating its serum and sputum levels with pulmonary function and inflammation. Serum and sputum HMGB1 were evaluated in a cohort of 31 CF patients and 30 non-smoking healthy subjects (HS group). Acute pulmonary exacerbation events and lung function decline have been also evaluated during a 3-year follow-up period. Serum HMGB1 levels were significantly higher than those measured in HS, such as sputum HMGB1. Kaplan-Meier survival curves revealed that patients with high HMGB1 values experienced a significantly faster evolution to decline of lung function. A multiple Cox regression analysis assessed that an increase of serum HMGB1 was associated with 5% increased risk of pulmonary disease progression, whereas elevated sputum HMGB1 was related to a 10% increased risk of lung function decline. In CF patients, HMGB1 closely reflects the entity of pulmonary impairment and represents a strong and independent risk marker for progression of lung function decline.

Response of CFTR-deficient mice to long-term chronic Pseudomonas aeruginosa infection and PTX3 therapy.

BACKGROUND: In cystic fibrosis (CF) patients, chronic lung infection and inflammation due to Pseudomonas aeruginosa contribute to the decline of lung function. The increased prevalence of multidrug resistance among bacteria and the adverse effects of antiinflammatory agents highlight the need for alternative therapeutic approaches that should be tested in a relevant animal model. METHODS: Gut-corrected CF and non-CF mice were chronically infected with a multidrug-resistant P. aeruginosa strain and treated with the long pentraxin PTX3. Body weight, bacterial count, inflammation, and lung pathology were evaluated after 12 days. PTX3 localization in CF sputum specimens was analyzed by immunofluorescence. RESULTS: Chronic P. aeruginosa infection developed similarly in CF and non-CF mice but differed in terms of the inflammatory response. Leukocyte recruitment in the airways, cytokine levels, and chemokine levels were significantly higher in CF mice, compared with non-CF mice. PTX3 treatment, which facilitates phagocytosis of pathogens, reduced P. aeruginosa colonization and restored airway inflammation in CF mice to levels observed in non-CF mice. The presence of PTX3 in CF sputum, in leukocytes, or bound to P. aeruginosa macrocolonies, as well as previous data on PTX3 polymorphisms in colonized CF patients, confirm the relevance of this molecule. CONCLUSIONS: These findings represent a step forward in demonstrating the therapeutic potential of PTX3 in CF.