This review takes into consideration the principal vaccines developed against the SARS-CoV-2 in this unprecedented period of Covid-19 pandemic. We evaluated the mechanism of action of each vaccine as well as the efficacy, the safety and the storage temperature. In addition, the problem of the dose units, the vaccinal strategy, the activity of alternative compounds such as the monoclonal antibodies and especially the issue of the virus variants were also described in detail. Four vaccines are currently used in Italy: Pfizer-BioNTech mRNA BNT162b2 (Comirnaty) (USA), Moderna mRNA 1273 (USA), Astra-Zeneca ChAdOx1-S (recombinant) viral vector adenovirus belonging to Oxford (UK) and Pomezia (Italy), Janssen (two recombinant viral vector adenoviruses) belonging to Johnson & Johnson (USA). The efficacy of Pfizer and Moderna for preventing disease or severe disease results 95– 87.5% and 94.5– 100%, respectively. The efficacy of Astra-Zeneca and Janssen is about 70% and 65%, respectively; in the case of Janssen, it depends on the geographical area ranging from 72% to 57%. The problem of the administrated doses (one dose, two doses from the same vaccine or from different vaccines, half dose) is also discussed. The vaccination strategy based on the age group remains the simplest, most transparent and fair criterion. This strategy is also based on accelerating the administration of the vaccines, so that as many subjects as possible can be vaccinated quickly for achieving the “herd immunity”. The monoclonal antibodies appeared to be a valid solution for the treatment of Covid-19 disease. Two antibodies (bamlanivimab and etesevimab) have just been approved by the FDA. They could also be used for the infection by virus variants which represent a big problem due to their higher transmissibility and virulence and to their lower response to the vaccines.

Nox2 is responsible for artery dysfunction via production of reactive oxidant species. RNA viruses may activate Nox2, but it is unknown if this occurs in coronavirus 2019(Covid-19). Nox2 activation by soluble Nox2-derived peptide(sNox2-dp) was measured in patients hospitalized for Covid-19 (n = 182) and controls (n = 91). sNox2-dp values were higher in Covid-19 patients versus controls and in severe versus non severe Covid-19. Patients with thrombotic events(n = 35,19%) had higher sNox2-dp than thrombotic event-free ones. A logistic regression analysis showed that sNox2 and coronary heart disease predicted thrombotic events. Oxidative stress by Nox2 activation is associated severe disease and thrombotic events in Covid-19 patients.

Biofilm is the trigger for the majority of infections caused by the ability of microorganisms to adhere to tissues and medical devices. Microbial cells embedded in the biofilm matrix are highly tolerant to antimicrobials and escape the host immune system. Thus, the refractory nature of biofilm-related infections (BRIs) still represents a great challenge for physicians and is a serious health threat worldwide. Despite its importance, the microbiological diagnosis of a BRI is still difficult and not routinely assessed in clinical microbiology. Moreover, biofilm bacteria are up to 100–1000 times less susceptible to antibiotics than their planktonic counterpart. Consequently, conventional antibiograms might not be representative of the bacterial drug susceptibility in vivo. The timely recognition of a BRI is a crucial step to directing the most appropriate biofilm-targeted antimicrobial strategy.

Increasing antimicrobial resistance reduces treatment options for implant-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the activity of fosfomycin alone and in combination with vancomycin, daptomycin, rifampin, and tigecycline against MRSA (ATCC 43300) in a foreign-body (implantable cage) infection model. The MICs of the individual agents were as follows: fosfomycin, 1 μg/ml; daptomycin, 0.125 μg/ml; vancomycin, 1 μg/ml; rifampin, 0.04 μg/ml; and tigecycline, 0.125 μg/ml. Microcalorimetry showed synergistic activity of fosfomycin and rifampin at subinhibitory concentrations against planktonic and biofilm MRSA. In time-kill curves, fosfomycin exhibited time-dependent activity against MRSA with a reduction of 2.5 log ₁₀ CFU/ml at 128 × the MIC. In the animal model, planktonic bacteria in cage fluid were reduced by 6.0 log ₁₀ with daptomycin-rifampin and fosfomycin-rifampin. Daptomycin-rifampin cured 67% of cage-associated infections and fosfomycin-rifampin cured 83%, whereas all single drugs (fosfomycin, daptomycin, and tigecycline) and rifampin-free fosfomycin combinations showed no cure of MRSA cage-associated infections. No emergence of fosfomycin resistance was observed in animals; however, a 4-fold increase in fosfomycin MIC (from 2 to 16 μg/ml) occurred in the fosfomycin-vancomycin group. In summary, the highest eradication of MRSA cage-associated infections was achieved with fosfomycin in combination with rifampin (83%). Fosfomycin may be used in combination with rifampin against MRSA implant-associated infections, but it cannot replace rifampin as an antibiofilm agent.

Background: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram−negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. Methods: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≥72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events. Results: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P. aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia (n = 20; 48.8%), primary bacteremia (n = 7; 17.1%), intra-abdominal infection (n = 4; 9.8%), and bone infection (n = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment (n = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population. Conclusions: Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE.