Fosfomycin is being increasingly prescribed for multidrug-resistant bacterial infections. In patients with systemic involvement, intravenous fosfomycin is usually administered as a partner drug, as part of an antibiotic regimen. Hence, the knowledge of fosfomycin pharmacodynamic interactions (synergistic, additive, indifferent and antagonistic effect) is fundamental for a proper clinical management of severe bacterial infections. We performed a systematic review to point out fosfomycin’s synergistic properties, when administered with other antibiotics, in order to help clinicians to maximize drug efficacy optimizing its use in clinical practice. Interactions were more frequently additive or indifferent (65.4%). Synergism accounted for 33.7% of total interactions, while antagonism occurred sporadically (0.9%). Clinically significant synergistic interactions were mostly distributed in combination with penicillins (51%), carbapenems (43%), chloramphenicol (39%) and cephalosporins (33%) in Enterobactaerales; with linezolid (74%), tetracyclines (72%) and daptomycin (56%) in Staphylococcus aureus; with chloramphenicol (53%), aminoglycosides (43%) and cephalosporins (36%) against Pseudomonas aeruginosa; with daptomycin (97%) in Enterococcus spp. and with sulbactam (75%) and penicillins (60%) and in Acinetobacter spp. fosfomycin-based antibiotic associations benefit from increase in the bactericidal effect and prevention of antimicrobial resistances. Taken together, the presence of synergistic interactions and the nearly total absence of antagonisms, make fosfomycin a good partner drug in clinical practice.

Acetylsalicylic acid (ASA) is one of the most commonly used drugs in the world. It derives from the extract of white willow bark, whose therapeutic potential was known in Egypt since 1534 BC. ASA’s pharmacological effects are historically considered secondary to its anti-inflammatory, platelet-inhibiting properties; however, human studies demonstrating a pro-inflammatory effect of ASA exist. It is likely that we are aware of only part of ASA’s mechanisms of action; moreover, the clinical effect is largely dependent on dosages. During the past few decades, evidence of the anti-infective properties of ASA has emerged. We performed a review of such research in order to provide a comprehensive overview of ASA and viral, bacterial, fungal and parasitic infections, as well as ASA’s antibiofilm properties.

Systemic or pulmonary reactivations of herpes simplex virus 1 (HSV-1) have been reported in critically ill patients with COVID-19, posing a dilemma for clinicians in terms of their diagnostic and clinical relevance. Prevalence of HSV-1 reactivation may be as high as [ 40% in this population, but with large heterogeneity across studies, likely reflecting the different samples and/or cut-offs for defining reactivation. There is frequently agreement on the clinical significance of HSV-1 reactivation in the presence of severe manifestations clearly attributable to the virus. However, the clinical implications of HSV-1 reactivations in the absence of manifest signs and symptoms remain controversial. Our review aims at providing immunological background and at reviewing clinical findings on HSV-1 reactivations in critically ill patients with COVID-19.

Nocardia is a genus of aerobic actinomycetes that are usually responsible for opportunistic infection in immunocompromised patients. Less frequently nocardiosis can interest immunocompetent population, causing especially primary cutaneous infections. Cutaneous involvement by Nocardia spp. may occur mostly as one of four clinical manifestations: superficial cellulitis or abscess, mycetoma, lymphocutaneous (also defined "sporotrichoid") infection and secondary cutaneous involvement from systemic disease. Infections usually present after minor local injury, especially in traumatic outdoor activities (e.g. gardeners, farmers, road accidents), with subsequent environmental contamination of the wound. In sporadic cases cutaneous infection follows an insect bite. Microbiological diagnosis is often difficult to obtain and N. brasiliensis is the species isolated in most cases (80%). We present the case of a 45-year-old female with fever and a painful and necrotizing lesion on her right leg with secondary ascending lesions occurred on the homolateral knee and SUMMARY consensual groin lymphadenopathy after insect sting (maybe a spider bite). Cultures on skin biopsy identified Nocardia brasiliensis. Infection was completely healed after 5 months of targeted antibiotic therapy. In addition, we performed a literature review of all cutaneous nocardiosis cases in immunocompetent individuals, finding that only in 22 cases the infection presented after insect bite; in most of these cases lymphocutaneous manifestation was seen and N. brasiliensis was the Nocardia species isolated. Our case, along with others in literature, reveals that the real burden of soft-tissues nocardiosis seems low but probably many cases might go undiagnosed because of difficulties in microbiology diagnosis. Primary cutaneous nocardiosis should be included in the diagnostic pathway in cases of cellulitis following insect bite or sting, especially when localized to extremities.

Bacterial colonization has been already demonstrated in heart valve tissues of patients without cardiovascular infections. However, the evidence of a valvular microbiome is still scarce. The next-generation sequencing method was carried out on 34 specimens of aortic (n = 20) and mitral valves (n = 14) explanted from 34 patients having neither evidence nor history of infectious diseases, particularly infective endocarditis. While no bacteria were demonstrated using standard culture methods, bacterial deoxyribonucleic acid (DNA) sequences were found using next-generation sequencing in 15/34 (44%) cases. Escherichia coli was present in 6 specimens and was the most frequently identified bacterium. There was a trend towards a higher rate of bacterial DNA positivity in specimens of calcific valves than in those of non-calcific valves (10/17 vs 5/17, P = 0.17). Based on a quantitative test, E. coli accounted for 0.7% ± 1% in calcific valvular tissue and 0.3% ± 0.3% in non-calcific valvular tissue (P = 0.2), and for 11% ± 27% in the valvular tissue of diabetic patients and 0.3% ± 1% in the valvular tissue of non-diabetic patients (P = 0.08). Detection of bacterial DNA in non-endocarditis valvular tissues could be a relatively common finding. There could be an association between the valvular microbiome and certain models of valve degeneration and common metabolic disorders.