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.

Staphylococcus Scalded Skin Syndrome-Induced Thrombosis Leading to Free Flap Complications: A Case Report and Review.

Staphylococcal scalded skin syndrome (SSSS) is a clinical term used for a spectrum of blistering skin conditions induced by the epidermolytic toxins of the Staphylococcus aureus bacteria. The complications of SSSS include thrombosis; however, the pathophysiology of this is still poorly understood. We present a case of free anterolateral thigh (ALT) flap failure in a patient as a result of widespread flap thrombosis associated with staphylococcal scalded skin syndrome (SSSS). This is the first reported case of free flap failure associated with SSSS. Free flap failure due to acquired prothrombotic conditions, such as infection, is a rare and potentially under-reported phenomenon. This article aims to further explore the role of both thrombophilias and provoked thrombotic events in free flap failure. A review of the literature will also be presented, and cases of free flap failure in patients with infection-induced vascular complications will be summarised.

The Diagnostic Conundrum of Glomerular Crescents With IgA Deposits.

Introduction: Glomerulonephritis (GN) with crescents and IgA deposits in kidney biopsy poses a frequent diagnostic and therapeutic dilemma because of multiple possibilities. Methods: Native kidney biopsies showing glomerular IgA deposition and crescents (excluding lupus nephritis) were identified from our biopsy archives between 2010 and 2021. Detailed clinicopathologic features were assessed. One-year clinical follow-up on a subset of cases was obtained. Results: A total of 285 cases were identified, and these clustered into IgA nephropathy (IgAN, n = 108), Staphylococcus or other infection-associated GN/infection-related GN (SAGN/IRGN, n = 43), and antineutrophil cytoplasmic antibody-associated GN (ANCA-GN, n = 26) based on a constellation of clinicopathologic features, but 101 cases (group X) could not be definitively differentiated. The reasons have been elucidated, most important being atypical combination of clinicopathologic features and lack of definitive evidence of active infection. Follow-up (on 72/101 cases) revealed that clinicians' working diagnosis was IgAN in 43%, SAGN/IRGN in 22%, ANCA-GN in 28%, and others in 7% of the cases, but treatment approach varied from supportive or antibiotics to immunosuppression in each subgroup. Comparing these cases as "received immunosuppression" versus "non-immunosuppression," only 2 features differed, namely C3-dominant staining, and possibility of recent infection (both higher in the no-immunosuppression group) (P < 0.05). Renal loss was higher in the non-immunosuppression subgroup, but not statistically significant (P = 0.11). Conclusion: Diagnostic overlap may remain unresolved in a substantial number of kidney biopsies with glomerular crescents and IgA deposits. A case-by-case approach, appropriate antibiotics if infection is ongoing, and consideration for cautious immunosuppressive treatment for progressive renal dysfunction may be needed for best chance of renal recovery.

May the force be with you: The role of hyper-mechanostability of the bone sialoprotein binding protein during early stages of Staphylococci infections.

The bone sialoprotein-binding protein (Bbp) is a mechanoactive MSCRAMM protein expressed on the surface of Staphylococcus aureus that mediates adherence of the bacterium to fibrinogen-α (Fgα), a component of the bone and dentine extracellular matrix of the host cell. Mechanoactive proteins like Bbp have key roles in several physiological and pathological processes. Particularly, the Bbp: Fgα interaction is important in the formation of biofilms, an important virulence factor of pathogenic bacteria. Here, we investigated the mechanostability of the Bbp: Fgα complex using in silico single-molecule force spectroscopy (SMFS), in an approach that combines results from all-atom and coarse-grained steered molecular dynamics (SMD) simulations. Our results show that Bbp is the most mechanostable MSCRAMM investigated thus far, reaching rupture forces beyond the 2 nN range in typical experimental SMFS pulling rates. Our results show that high force-loads, which are common during initial stages of bacterial infection, stabilize the interconnection between the protein's amino acids, making the protein more "rigid". Our data offer new insights that are crucial on the development of novel anti-adhesion strategies.

Protein structure prediction in the era of AI: Challenges and limitations when applying to in silico force spectroscopy.

Mechanoactive proteins are essential for a myriad of physiological and pathological processes. Guided by the advances in single-molecule force spectroscopy (SMFS), we have reached a molecular-level understanding of how mechanoactive proteins sense and respond to mechanical forces. However, even SMFS has its limitations, including the lack of detailed structural information during force-loading experiments. That is where molecular dynamics (MD) methods shine, bringing atomistic details with femtosecond time-resolution. However, MD heavily relies on the availability of high-resolution structural data, which is not available for most proteins. For instance, the Protein Data Bank currently has 192K structures deposited, against 231M protein sequences available on Uniprot. But many are betting that this gap might become much smaller soon. Over the past year, the AI-based AlphaFold created a buzz on the structural biology field by being able to predict near-native protein folds from their sequences. For some, AlphaFold is causing the merge of structural biology with bioinformatics. Here, using an in silico SMFS approach pioneered by our group, we investigate how reliable AlphaFold structure predictions are to investigate mechanical properties of Staphylococcus bacteria adhesins proteins. Our results show that AlphaFold produce extremally reliable protein folds, but in many cases is unable to predict high-resolution protein complexes accurately. Nonetheless, the results show that AlphaFold can revolutionize the investigation of these proteins, particularly by allowing high-throughput scanning of protein structures. Meanwhile, we show that the AlphaFold results need to be validated and should not be employed blindly, with the risk of obtaining an erroneous protein mechanism.

Staphylococcus aureus Infection-Related Glomerulonephritis with Dominant IgA Deposition.

Since 1995, when we reported the case of a patient with glomerulonephritis with IgA deposition that occurred after a methicillin-resistant Staphylococcus aureus (MRSA) infection, many reports of MRSA infection-associated glomerulonephritis have accumulated. This disease is being systematized as Staphylococcus infection-associated glomerulonephritis (SAGN) in light of the apparent cause of infection, and as immunoglobulin A-dominant deposition infection-related glomerulonephritis (IgA-IRGN) in light of its histopathology. This glomerulonephritis usually presents as rapidly progressive glomerulonephritis or acute kidney injury with various degrees of proteinuria and microscopic hematuria along with an ongoing infection. Its renal pathology has shown several types of mesangial and/or endocapillary proliferative glomerulonephritis with various degrees of crescent formation and tubulointerstitial nephritis. IgA, IgG, and C3 staining in the mesangium and along the glomerular capillary walls have been observed on immunofluorescence examinations. A marked activation of T cells, an increase in specific variable regions of the T-cell receptor ß-chain-positive cells, hypercytokinemia, and increased polyclonal immune complexes have also been observed in this glomerulonephritis. In the development of this disease, staphylococcal enterotoxin may be involved as a superantigen, but further investigations are needed to clarify the mechanisms underlying this disease. Here, we review 336 cases of IgA-IRGN and 218 cases of SAGN.

Cardiocutaneous fistula secondary to left ventricular pseudo-aneurysm rupture.

Cardiocutaneous fistula (CF) is a potentially serious and catastrophic complication. Infection the suture line after left ventricular aneurysm repair, presenting with the CF. We present an unusual case of CF due to staphylococcus infection 6 months after repair of a myocardial rupture secondary to dehiscence repair.

Incidence and Risk Factors for Acute Kidney Injury during the Treatment of Methicillin-Sensitive Staphylococcus aureus Infections with Cloxacillin Based Antibiotic Regimens: A French Retrospective Study.

BACKGROUND: Cloxacillin has been associated with the occurrence of acute kidney injury (AKI). The incidence of this complication in the literature is low (2.5-3.5%) and probably underestimated, since most studies were done by selecting the presence of AKI in discharge codes. OBJECTIVES: The primary goal was to define the incidence of AKI in patients with a methicillin-sensitive Staphylococcus aureus infection treated with cloxacillin based antibiotic regimens. The secondary goals were to identify the risk factors associated with this complication and to describe the characteristics of AKI. PATIENTS AND METHODS: We carried out a retrospective study. The inclusion criteria were adult patients hospitalized in a medical department at the Le Mans Hospital between 1 July 2012 and 1 July 2019 with a diagnosis of methicillin-sensitive Staphylococcus aureus infection treated with cloxacillin. RESULTS: One hundred twenty-three patients were included in the study. Forty-two patients (34.2%) developed AKI. In the multivariate analysis, age, the use of diuretics and the presence of endocarditis were independently associated with AKI. Age was associated with an OR of 4.38 (p = 0.002) for patients older than 75, being treated with diuretics was associated with an OR of 2.94 (p = 0.036) for loop diuretics and an OR of 3.05 (p = 0.027) for non-loop diuretics; type of infection was associated with an OR of 3.42 (p = 0.012) for endocarditis. CONCLUSIONS: The occurrence of AKI is frequent during cloxacillin based antibiotic regimens for methicillin-sensitive Staphylococcus aureus infections. Being older than 75, being treated with diuretics and the presence of endocarditis were the main risk factors for AKI in our population.

Dosificación empírica de vancomicina en neonatos: relación entre recomendación de dosis iniciales y relación área bajo la curva en 24 h/concentración inhibitoria mínima / Empiric vancomycin dosing in neonates: relationship between initial dose and 24 h area under the curve/minimum inhibitory concentration ratio

Resumen Introducción: Vancomicina es un antimicrobiano ampliamente utilizado para infecciones por Staphylococcus coagulasa negativa en neonatos; sin embargo, no existe claridad sobre la dosis empírica que asegure su eficacia terapéutica. Objetivo: Evaluar la relación entre las dosis iniciales de vancomicina utilizadas en una Unidad de Cuidado Intensivo Neonatal (UCIN) con la eventualidad de alcanzar el objetivo terapéutico de área bajo la curva sobre concentración inhibitoria mínima (ABC/CIM) mayor a 400 µg/h/mL. Materiales y Método: Estudio descriptivo y retrospectivo, realizado entre febrero 2016 y marzo 2018. Se incluyeron neonatos en tratamiento con vancomicina por sospecha/confirmación de infección por cocáceas grampositivas y medición de concentraciones plasmáticas de vancomicina al inicio del tratamiento. La probabilidad de alcanzar el objetivo terapéutico se evaluó mediante re-muestreo de valores de ABC y CIM. Resultados: Se incluyeron 38 pacientes con 49 concentraciones plasmáticas de vancomicina. Los aislados microbiológicos se confirmaron en 94,7% de los pacientes (n = 36). Los valores de ABC/CIM en dos grupos (según niveles valle de vancomicina < 10 µg/mL y ≥ 10 µg/mL), fueron de una mediana de 327 (IQ 25-75 = 174-395) y 494 (IQ 25-75 = 318-631), respectivamente (p = 0,035). Las dosis empíricas utilizadas logran logran un objetivo terapéutico (ABC/CIM > 400) de sólo 47,7% considerando CIMs en nuestra institución. Conclusiones: Teniendo en cuenta las sensibilidades institucionales, no es posible asegurar alcanzar ABC/CIM > 400 µg/h/mL. Se debe seguir investigando para replantear las actuales estrategias de dosificación y así determinar la más apropiada para neonatos.

Abstract Background: Vancomycin is used for treating coagulase-negative staphylococcus infections in neonates. However, concerns about the appropriate empirical dosing required for optimal efficacy, still remain. Aim: To assess the relationship between the initial doses of vancomycin used in a Neonatal Intensive Care Unit (NICU) with the possibility of achieving therapeutic target of AUC024h/MIC > 400 µg/h/mL. Methods: Retrospective and descriptive study carried out between February 2016 and March 2018. All neonates treated with vancomycin for suspected/proven Gram-positive infection and with at least one trough serum concentration level were included. Probability of target attainment (PTA) was evaluated through resampling of AUC and MIC values. Results: Final dataset included 38 patients and 49 trough vancomycin levels; 94.7% of these cases (n = 36) were confirmed Gram-positive infections. The median AUC/MIC values for the trough values vancomycin < 10 µg/mL group and for the ≥ 10 µg/mL group were 327 (IQR 174-395) and 494 (IQR 318-631) respectively (p = 0.035). Current empirical dosing strategy has a 47.7% PTA (AUC/MIC > 400) when taking institutional MICs into account. Conclusions: It is not possible to assure achieving a AUC/MIC > 400 µg/h/mL when considering institutional sensibilities. Current empiric dosing strategies should be reconsidered and further investigation needs to be done to help determine the appropriate empirical dosing required for optimal efficacy in neonates.

Absceso subpectoral como diagnóstico diferencial de hombro doloroso: reporte de un caso / Subpectoral abscess as a differential diagnosis of painful shoulder: a case report

Los síndromes dolorosos del hombro son relativamente comunes en la práctica clínica. Habitualmente son causados por un número limitado de patologías. Dentro de los diagnósticos diferenciales, el pinzamiento subacromial, las lesiones aisladas del manguito rotador, capsulitis adhesiva, tendinitis cálcica, patología degenerativa de las articulaciones glenohumeral y acromioclavicular, y la inestabilidad crónica del hombro, son causas comunes. Causas infrecuentes son la rotura del tendón del bíceps, neuralgias, patología infecciosa articular y tumores del hombro. Un absceso subpectoral sin sintomatología infecciosa clara es una causa extremadamente rara de hombro doloroso en el adulto. Presentamos el caso de un paciente de 60 años, que inicia con un cuadro de hombro doloroso cuya causa se identifica como un absceso subpectoral por staphylococcus aureus que se maneja con drenaje quirúrgico y tratamiento antibiótico endovenoso con buenos resultados.

Painful shoulder syndromes are commonly caused by a limited assortment of pathologies. Differential diagnosis include rotator cuff impingement syndrome, rotator cuff tears, adhesive capsulitis, calcific tendonitis, degenerative disease of the joint including acromio-clavicular and gleno-humeral joints and chronic instability. Less common causes are labral tears, biceps tendon rupture, soft tissue infection, neurologic disease, joint infection and shoulder tumors. A subpectoral abscess without infectious clinical features is a very rare cause of shoulder pain in adults. We present the case of a 52 years old male who develops a painful shoulder syndrome caused by a staphylococcus aureus subpectoral abscess, treated by surgical drainage and intravenous antibiotic therapy with good results.

Key-properties outlook of a levofloxacin-loaded acrylic bone cement with improved antibiotic delivery.

Antibiotic-loaded acrylic bone cements (ALABCs) are widely used to decrease the occurrence of bone infections in cemented arthroplasties and actually being considered as a more cost-effective procedure when compared to cementless implants. However, ALABCs have a major drawback, which is the incomplete release of the antibiotics and, as a result, pathogens that commonly are responsible for those infections are becoming resistant. Consequently, it is of most relevance to find new antibacterial agents to load into BC with an effective mechanism against those microorganisms. This research work intended to load levofloxacin, a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues, on lactose-modified commercial bone cement (BC). This modified BC matrix exhibited increased levofloxacin release and delayed Staphylococcus aureus biofilm formation. Further insights on material-drug interaction during BC setting were investigated by density functional theory calculations. The obtained results suggested that favorable covalent and non-covalent interactions could be established between levofloxacin and the BC. Moreover, BC mechanical and biocompatibility properties were maintained. These features justify the potential of levofloxacin-loaded modified-BC as a valuable approach for local antibiotic delivery in bone infections management.

Phlyctenular keratoconjunctivitis among children in the tertiary eye hospital of Kathmandu, Nepal.

BACKGROUND: This study was conducted to determine clinical profile and etiological factors for phlyctenular keratoconjunctivitis (PKC) in our patients. MATERIALS AND METHODS: In the descriptive study, 50 pediatric cases of PKC were enrolled into the study from outpatient department of BP Koirala Lions Center for Ophthalmic Studies between August 2011 and August 2012. The age, sex, exposure to tuberculosis, ocular symptoms, and systemic complaints were recorded. Morphological description of PKC such as number, type, location and scars HISTORY and number of recurrence was also noted. The conjunctival swab was taken from all patients and sent for microbiological examination. Report of systemic involvement, worm infestation was also noted. Mantoux testing for possibility of tuberculosis was also performed. RESULTS: PKC was detected in 59 eyes of 50 children having mean age of 8.0 ± 6.2 years including 54% males, unilateral involvement in 82%, the limbal involvement in 52% and multiple PKC in 34% children. Associated ocular disorder was blepharitis in 12 (24%) children. Conjunctival swab and culture revealed Staphylococcus infection in 10 (20%) children. Of eight recurrent cases, two had urinary tract infection managed with systemic antibiotics, three had parasitic infestation treated with antihelmentics, one had mantoux positive without having evidence of tuberculosis and two cases had blepharitis as a local factor. CONCLUSIONS: PKC is mostly presented as unilateral disorder of conjunctiva. PKC is associated with blepharitis, Staphylococcus infection, worm infestation and systemic infection.