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.

Gram-negative bacteria were the predominantly isolated pathogens from patients with cancer in our population. The overall mortality remains high.

Mortality in cancer patients with P. aeruginosa infections was high. Infection due to XDR isolates was independently associated with mortality.

BackgroundThis study aimed to evaluate the epidemiology, clinical and microbiological features, treatment, and outcomes of infective endocarditis (IE) on the island of Crete, a region with high levels of antimicrobial resistance.Materials and MethodsMedical records of all hospitalized patients diagnosed with IE at the University Hospital of Heraklion, Crete, Greece, from 1995 to 2015, were retrospectively reviewed. Patients who met the modified Duke's criteria for definite or possible IE were included.ResultsA total of 82 IE patients (median age 67 [range 21–86] years) were included. Most patients suffered from left-sided IE (94%), while most cases of infection occurred in native valves (53.6%). Systemic inflammatory response syndrome criteria were lacking in almost half of the patient population. The leading causative microorganism was Staphylococcus aureus, isolated in 24 cases (29%), followed by Streptococcus spp. in 15 (18%) and Enterococcus spp. in 12 (14.5%). A number of rare and difficult to treat microorganisms had been identified, such as Gemella morbillorum in four cases (4.5%), Streptococcus lugdunensis in two (2.5%) and Streptococcus pneumoniae in one (1%). One patient was serologically positive for Coxiella burnetii (1%). All patients received empirical antimicrobial treatment, proven appropriate in 39 blood culture-positive patients (56.5%). Thirteen (16%) patients were classified as culture negative. Seven patients (8.5%) were surgically treated. In-hospital death occurred in 9 patients (11%).ConclusionChanges in IE profile requires continuous epidemiological updates. Staphylococcus and Streptococcus spp. remain the most common etiologic agents. However, the presence of uncommon and/or difficult to treat pathogens raise concerns on the appropriate prophylaxis as well as empirical treatment.