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The original version of this Article contained an error in the spelling of the author Emilien Etienne, which was incorrectly given as Emilien Ettiene. These errors have now been corrected in both the PDF and HTML versions of the Article.

Mucormycosis is a life-threatening respiratory fungal infection predominantly caused by Rhizopus species. Mucormycosis has incompletely understood pathogenesis, particularly how abnormalities in iron metabolism compromise immune responses. Here we show how, as opposed to other filamentous fungi, Rhizopus spp. establish intracellular persistence inside alveolar macrophages (AMs). Mechanistically, lack of intracellular swelling of Rhizopus conidia results in surface retention of melanin, which induces phagosome maturation arrest through inhibition of LC3-associated phagocytosis. Intracellular inhibition of Rhizopus is an important effector mechanism, as infection of immunocompetent mice with swollen conidia, which evade phagocytosis, results in acute lethality. Concordantly, AM depletion markedly increases susceptibility to mucormycosis. Host and pathogen transcriptomics, iron supplementation studies, and genetic manipulation of iron assimilation of fungal pathways demonstrate that iron restriction inside macrophages regulates immunity against Rhizopus. Our findings shed light on the pathogenetic mechanisms of mucormycosis and reveal the role of macrophage-mediated nutritional immunity against filamentous fungi.

Cellulosimicrobium species (formerly known as Oerskovia) are Gram-positive filamentous bacteria in the family Promicromonosporaceae and are more commonly found in sewage and soil. The present study aimed to identify all the published cases of Cellulosimicrobium species infections in the literature, describe the epidemiological, clinical, and microbiological characteristics, and provide data regarding its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a PubMed and Scopus database search. In total, 38 studies provided data on 40 patients with infections by these species. The median age of patients was 52.5 years, and 55% were male. The most common infection types were bacteremia, infective endocarditis (IE), osteoarticular infections, peritoneal dialysis-associated peritonitis, and endophthalmitis. Antimicrobial resistance to vancomycin and the combination of trimethoprim and sulfamethoxazole was minimal, and vancomycin was the most commonly used antimicrobial for treating these infections. Overall mortality was minimal for all infections, except for bacteremia and IE, which carried high mortality rates. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-associated thrombosis (CAT) is a severe cause of mortality and morbidity in cancer patients, while active cancer is present in 20% of all patients with venous thromboembolism (VTE). CAT presents several peculiarities that distinguish this entity from other clinical settings associated with VTE. Management of thromboembolic events in CAT is extremely challenging because of the multifactorial pathophysiology of this clinical setting. The objective of this review is to enlighten the complicated pathophysiology of CAT, discuss the available biomarkers for early identification of high-risk patients, and summarize the current guidelines regarding the treatment and management of thrombotic events in cancer patients. Dysregulated hemostasis in cancer patients is associated with various clinical conditions, from thromboembolic complications to disseminated intravascular coagulation. Despite the well-established association between cancer and thromboembolic complications, the mechanisms involved are not completely elucidated. There are several predisposing factors in cancer for increased thrombus generation, such as immobilization and chemotherapy. The term cancer-associated thrombosis (CAT) has been introduced to describe the close bidirectional relationship between cancer and thromboembolic events. Conventional coagulation tests (PT/aPTT) are more accurate in detecting a hypocoagulable rather than a hypercoagulable state; thus, their contribution to CAT management is limited. Traditionally, D-dimer levels have been the most common laboratory study for the evaluation of thrombotic risk. However, D-dimer levels only display a snapshot of the coagulation cascade, and they cannot provide a dynamic evaluation of evolving clot formation. Non-conventional assays, such as viscoelastic methods and microparticle formation are promising tools for the identification of patients at risk for developing CAT. Recent guidelines from the American Society of Clinical Oncology counsel against the estimation of thrombotic risk through a single test and recommend the use of scoring systems that take into account several risk factors. The present review outlines the current insights into the pathophysiological mechanisms of CAT and provides a comprehensive review of the latest advances in the laboratory assessment of CAT and the recent guidelines for the management of patients at risk for developing thromboembolic complications. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii has emerged as a pressing challenge in clinical practice, mainly due to the development of resistance to multiple antibiotics, including colistin, one of the last-resort treatments. This review highlights all the possible mechanisms of colistin resistance and the genetic basis contributing to this resistance, such as modifications to lipopolysaccharide or lipid A structures, alterations in outer membrane permeability via porins and heteroresistance. In light of this escalating threat, the review also evaluates available treatment options. The development of new antibiotics (cefiderocol, sulbactam/durlobactam) although not available everywhere, and the use of various combinations and synergistic drug combinations (including two or more of the following: a polymyxin, ampicillin/sulbactam, carbapenems, fosfomycin, tigecycline/minocycline, a rifamycin, and aminoglycosides) are discussed in the context of overcoming colistin resistance of A. baumannii infections. Although most studied combinations are polymyxin-based combinations, non-polymyxin-based combinations have been emerging as promising options. However, clinical data remain limited and continued investigation is essential to determine optimal therapeutic strategies against colistin-resistant A. baumannii. [ABSTRACT FROM AUTHOR]

Extrapulmonary infections by Coccidioides spp., though rare, can occur via dissemination, affecting singular or multiple sites, including the skin and musculoskeletal system. Skeletal involvement often manifests as osteomyelitis, particularly in the axial skeleton. The present systematic review evaluates all documented cases of skeletal coccidioidomycosis to assess the diagnostic and treatment strategies alongside the outcomes, drawing insights from an analysis of 163 verified cases. A systematic review following PRISMA guidelines identified all studies reporting skeletal infections by Coccidioides spp. up to 2023 from the PubMed and Scopus databases. Eligible studies evaluated osteoarticular infections from Coccidioides spp. Data extraction included demographics, microbiological data, diagnostic methods, and treatment outcomes. Of the 501 initially identified records, a total of 163 patients from 69 studies met the inclusion criteria. Most cases were from the USA, predominantly males, while the median age of the population was 36 years. Diabetes mellitus was the common comorbidity (14.7%). C. immitis was the most prevalent pathogen. The spine and hand were common sites of infection (17.5% and 15.1%, respectively). Osteomyelitis by Coccidioides spp. was diagnosed, in most cases, by positive cultures (n = 68; 41.7%), while, in 49 (30.9%), both the histological examination and cultures yielded the fungus. Surgical debridement was performed in 80.9% of cases. A total of 118 (72.3%) patients were treated with monotherapy, while combination therapy with two or more antifungal agents was reported in 45 (17.7%). Amphotericin B (either liposomal or deoxycholate) was the most commonly given agent as monotherapy in 51 (31.2%) patients, while 30 (18.4%) patients received itraconazole as monotherapy. The rate of infection's resolution was higher in patients undergoing surgical debridement (79.5%), compared to those treated only with antifungal agents (51.6%, p = 0.003). Treatment outcomes showed complete resolution in 74.2% of patients, with a mortality rate of 9.2%. Coccidioidal osseous infections present diagnostic and therapeutic challenges. Surgical intervention is often necessary, complementing antifungal therapy. Vigilance for Coccidioides spp. infections, especially in regions with endemicity, is crucial, particularly when bacterial cultures yield negative results. [ABSTRACT FROM AUTHOR]

Purpose: Hippocrates, the ancient Greek physician, is considered the father of Medicine; however, his contributions to Orthopaedics and Traumatology have not been highlighted enough. The present historical review represents an effort to present and categorize his work, in this field, per clinical disorder and anatomical region. Methods: The "Hippocratic Corpus" original text was thoroughly studied to identify all Hippocrates' contributions in Orthopaedics and Traumatology. Volume III of his works, especially "On Fractures", "On Joints", and "Mochlicon" includes a plethora of information regarding the management of traumas, as well as other disorders and clinical entities of the musculoskeletal system. Results: In particular, Hippocrates describes reduction techniques for fractures, as well as joint dislocations, elaborates on the biology of the fractures' healing process and the basic principles of fracture management and fixation, presents the signs and symptoms of gangrene, teaches the treatment of osseous infections and offers valuable insight on the biomechanics and treatment of spinal diseases. Conclusions: Hippocrates' contributions in Orthopaedics and Traumatology are unprecedented, making him a true pioneer in this field, while the basic principles that he presented were further studied and confirmed in the 19th and 20th centuries. [ABSTRACT FROM AUTHOR]

Bacteria of the genus Clostridium are anaerobic Gram-positive spore-forming bacilli that include more than 200 species. Some of them are known to cause invasive infections and diseases caused by the production of toxins. Some of the diseases that are mediated by toxins are colitis in patients with specific risk factors, such as previous administration of antimicrobials or foodborne botulism. Invasive diseases include bacteremia, infective endocarditis (IE), clostridial myonecrosis (gas gangrene), and other diseases that involve the destruction of soft tissue due to the local production of toxins. The present study aimed to review all cases of IE by Clostridioides and Clostridium species and describe the epidemiology, clinical characteristics, treatment, and outcomes of these infections. A narrative review was performed based on a search in PubMed and Scopus for studies published until 11 September 2023, providing such data of IE caused by Clostridioides and Clostridium species in humans. A total of 20 studies containing data for 21 patients were included. A prosthetic valve was present in 5 patients (23.8%). The aortic valve was the most commonly involved, followed by the mitral valve. Fever, sepsis, and embolic phenomena were the most common clinical presentations. Beta-lactams and metronidazole were the most commonly used antimicrobials. Surgery was performed in nine patients (45%). Mortality reached 33.3%. IE in multiple valves was associated with increased mortality. Despite the heterogeneous genetic and molecular characteristics that necessitate the taxonomic change of some of this genus's previous members, the clinical syndrome of IE caused by these bacteria seems to have similar characteristics. [ABSTRACT FROM AUTHOR]

Postoperative infection following percutaneous balloon kyphoplasty (PBK) is a rare complication and delayed onset infection is very rare. We report the case of a 62-year-old male, who developed spondylodiscitis and psoas abscess 5 years after two-level, L2 and L3 PBK. He was initially treated with abscess aspiration and long term antimicrobial treatment. Eventually, due to failure of conservative treatment he underwent anterior decompression, radical debridement of the infected tissue and non-instrumented fusion with strut graft, with excellent results. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus bacteremia (SAB) is a severe infection frequently associated with significant morbidity and mortality. Recent studies have shown that SAB mortality has decreased during the last decades. However, about 25% of patients suffering from the disease will ultimately die. Hence, there is an urgent need for more timely and efficient treatment of patients with SAB. The aim of the present study was to retrospectively evaluate a cohort of SAB patients hospitalized in a tertiary hospital and to identify factors independently associated with mortality. All 256 SAB patients hospitalized from January 2005 to December 2021 in the University Hospital of Heraklion, Greece, were evaluated. Their median age was 72 years, while 101 (39.5%) were female. Most SAB patients were cared for in medical wards (80.5%). The infection was community-acquired in 49.5%. Among all strains 37.9% were methicillin-resistant S. aureus (MRSA), however, definite treatment with an antistaphylococcal penicillin was given only in 22% of patients. Only 14.4% of patients had a repeat blood culture after the initiation of antimicrobial treatment. Infective endocarditis was present in 8%. In-hospital mortality has reached 15.9%. Female gender, older age, higher McCabe score, previous antimicrobial use, presence of a central venous catheter, neutropenia, severe sepsis, septic shock, and MRSA SAB were positively associated with in-hospital mortality, while monomicrobial bacteremia was negatively associated. The multivariate logistic regression model identified only severe sepsis (p = 0.05, odds ratio = 12.294) and septic shock (p = 0.007, odds ratio 57.18) to be independently positively associated with in-hospital mortality. The evaluation revealed high rates of inappropriate empirical antimicrobial treatment and non-adherence to guidelines, as shown, by the lack of repeat blood cultures. These data underline the urgent need for interventions with antimicrobial stewardship, increased involvement of infectious diseases physicians, educational sessions, and creation and implementation of local guidelines for improvement of the necessary steps for timely and efficient SAB treatment. Optimization of diagnostic techniques is needed to overcome challenges such as heteroresistance that may affect treatment. Clinicians should be aware of the factors associated with mortality in patients with SAB to identify those who are at a higher risk and optimize medical management. [ABSTRACT FROM AUTHOR]