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.

Antimicrobial combinations are at the moment the only potential treatment option for pandrug-resistant A. baumannii. A systematic review was conducted in PubMed and Scopus for studies reporting the activity of antimicrobial combinations against A. baumannii resistant to all components of the combination. The clinical relevance of synergistic combinations was assessed based on concentrations achieving synergy and PK/PD models. Eighty-four studies were retrieved including 818 eligible isolates. A variety of combinations (n = 141 double, n = 9 triple) were tested, with a variety of methods. Polymyxin-based combinations were the most studied, either as double or triple combinations with cell-wall acting agents (including sulbactam, carbapenems, glycopeptides), rifamycins and fosfomycin. Non-polymyxin combinations were predominantly based on rifampicin, fosfomycin, sulbactam and avibactam. Several combinations were synergistic at clinically relevant concentrations, while triple combinations appeared more active than the double ones. However, no combination was consistently synergistic against all strains tested. Notably, several studies reported synergy but at concentrations unlikely to be clinically relevant, or the concentration that synergy was observed was unclear. Selecting the most appropriate combinations is likely strain-specific and should be guided by in vitro synergy evaluation. Furthermore, there is an urgent need for clinical studies on the efficacy and safety of such combinations.

Kocuria species are catalase-positive and coagulase-negative Gram-positive coccoid bacteria that belong to the family Micrococcaceae, order Actinomycetales, and class Actinobacteria. Even though they may be relatively rare, they have been increasingly reported as the causes of human infections lately. The present study aims to review all published cases of Kocuria spp. infections in humans reporting data on epidemiology, microbiology, antimicrobial susceptibility, antimicrobial treatment, and mortality. A narrative review was performed based on a search of Pubmed and Scopus databases in the literature. In total, 73 studies provided data on 102 patients with Kocuria spp. infections. The mean age of patients was 47 years, and 68.3% were male. The most common types of infection were bacteremia (36.3%), skin and soft tissue infection (18.6%), endophthalmitis (15.7%), infective endocarditis (13.7%), and peritonitis (11.8%), most commonly peritoneal–dialysis-associated. The most frequently isolated species was K. kristinae (46.1%), and antimicrobial resistance was lower for vancomycin (7%) and tetracyclines (6.7%). Vancomycin (47%), cephalosporins (39.6%), and quinolones (36.6%) were the most commonly used antimicrobials. The empirical antimicrobial treatment of Kocuria spp. infections should include vancomycin as long as antimicrobial susceptibility results are pending. The infection outcome mainly depends on the type of infection and is higher for infective endocarditis. Endophthalmitis is associated with increased rates of low visual acuity after treatment.

Long COVID-19 is a recognized entity that affects millions of people worldwide. Its broad clinical symptoms include thrombotic events, brain fog, myocarditis, shortness of breath, fatigue, muscle pains, and others. Due to the binding of the virus with ACE-2 receptors, expressed in many organs, it can potentially affect any system; however, it most often affects the cardiovascular, central nervous, respiratory, and immune systems. Age, high body mass index, female sex, previous hospitalization, and smoking are some of its risk factors. Despite great efforts to define its pathophysiology, gaps remain to be explained. The main mechanisms described in the literature involve viral persistence, hypercoagulopathy, immune dysregulation, autoimmunity, hyperinflammation, or a combination of these. The exact mechanisms may differ from system to system, but some share the same pathways. This review aims to describe the most prevalent pathophysiological pathways explaining this syndrome.