Hepatitis C virus infection affects over 58 million individuals and is responsible for 290,000 annual deaths. The infection spread in the past via blood transfusion and iatrogenic transmission due to the use of non-sterilized glass syringes mostly in developing countries (Cameroon, Central Africa Republic, Egypt) but even in Italy. High-income countries have achieved successful results in preventing certain modes of transmission, particularly in ensuring the safety of blood and blood products, and to a lesser extent, reducing iatrogenic exposure. Conversely, in low-income countries, unscreened blood transfusions and non-sterile injection practices continue to play major roles, highlighting the stark inequalities between these regions. Currently, injection drug use is a major worldwide risk factor, with a growing trend even in low- and middle-income countries (LMICs). Emerging high-risk groups include men who have sex with men (MSM), individuals exposed to tattoo practices, and newborns of HCV-infected pregnant women. The World Health Organization (WHO) has proposed direct-acting antiviral (DAA) therapy as a tool to eliminate infection by interrupting viral transmission from infected to susceptible individuals. However, the feasibility of this ambitious and overly optimistic program generates concern about the need for universal screening, diagnosis, linkage to care, and access to affordable DAA regimens. These goals are very hard to reach, especially in LMICs, due to the cost and availability of drugs, as well as the logistical complexities involved. Globally, only a small proportion of individuals infected with HCV have been tested, and an even smaller fraction of those have initiated DAA therapy. The absence of an effective vaccine is a major barrier to controlling HCV infection. Without a vaccine, the WHO project may remain merely an illusion.

Purpose: This review examines the pathogenic mechanisms of Staphylococcus aureus, emphasizing its toxin-driven virulence factors, including pore-forming toxins, exfoliative toxins, and superantigens. Methods: This paper was conducted using the available literature (PubMed/MEDLINE/Google Scholar and books written by experts in pharmacology and infectious diseases). Results: Toxins are crucial in promoting tissue invasion, immune system evasion, and the development of systemic diseases. Notably, the qualitative and quantitative expression of these toxins influences the clinical presentation and severity of S. aureus infections. The paper explores toxins’ role in S. aureus pathogenesis and clinical manifestations as well as current and emerging therapeutic strategies aimed at targeting these toxins, including antibiotics, monoclonal antibodies, and anti-inflammatory treatments. Additionally, it highlights the potential of novel inhibitors and vaccines to neutralize specific toxins and prevent toxin-mediated diseases. Conclusion: By combining antimicrobial therapies with approaches that neutralize toxins and modulate the immune response, clinicians can improve outcomes in patients affected by S. aureus infections.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the leading cause of hepatocellular carcinoma (HCC) worldwide. Currently, HBV-related HCC predominates in Sub-Saharan Africa and South-East-Asia, while HCV-related HCC predominates in northern Africa and in the western world. Liver cirrhosis is the underlying condition in most HBV cases and in nearly all HCV cases. Several cofactors, viral and non-viral, play a role in the progression toward HCC: dual HBV/HCV infection, HDV, HIV, alcohol intake, smoking, diabetes mellitus, obesity, and NAFLD/NASH. HBV vaccine is effective in preventing both infection and HCC; antiviral drugs may suppress HBV replication and eradicate HCV infection, halting progression to HCC. Inequalities exist between high- and low-income countries with respect to vaccine availability and access to antivirals. These factors represent barriers to the control of HCC incidence. Lack of an effective vaccine against HCV is also a serious barrier to HCV elimination and HCC prevention. The most crucial steps and knowledge that have arisen over time on the association between the two major hepatotropic viruses and HCC are discussed in this historical review.

This systematic review and meta-analysis aimed to examine the performance of polymerase chain reaction (PCR) assays for diagnosing mucormycosis. A standardised search was conducted from conception to December 3rd 2024 using PubMed, Embase, Global Health, and Cochrane library. Original studies that used PCR-based methods on any human specimen to diagnose mucormycosis were analysed for eligibility. Using a bivariate meta-analysis, the diagnostic performance of PCR was examined against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group Education and Research Consortium 2020 (EORTC-MSGERC) definitions of proven and probable invasive mould disease, which was modified to include all patients at risk of mucormycosis. The study protocol was registered on the PROSPERO database (CRD42023478667). Of 4855 articles, a total of 30 met inclusion criteria, including 5920 PCR reactions on 5147 non-duplicate specimens from 819 cases of proven/probable mucormycosis and 4266 patients who did not meet the EORTC-MSGERC 2020 criteria. According to specimen type, sensitivity of PCR varied (p < 0.001) whereas specificity was similar (p = 0.662). Bronchoalveolar lavage fluid offered the highest sensitivity of 97.5% (95% CI 83.7-99.7%), specificity of 95.8% (95% CI 89.6-98.4%), positive likelihood ratio (LR+) of 23.5, and negative likelihood ratio (LR-) of 0.03. Tissue provided sensitivity of 86.4% (95% CI 78.9-91.5%), specificity of 90.6% (95% CI 78.1-96.3%), LR+ of 9.2, and LR- of 0.15. Blood provided reduced sensitivity of 81.6% (95% CI 70.1-89.4%), specificity of 95.5% (95% CI 87.4-98.5%), DOR of 95, LR+ of 18.3, and LR- of 0.19. Formalin-fixed paraffin-embedded specimens yielded the lowest sensitivity of 73.0% (95% CI 61.0-82.3%), highest specificity of 96.4% (CI 95% 87.5-99.0%), LR+ of 20.2, and LR- of 0.28. The covariates best explaining heterogeneity of the overall analysis were specimen type, study design (cohort versus case-control) and disease prevalence while patient population (COVID-19 versus other) and PCR (conventional versus quantitative) had less impact on heterogeneity. This meta-analysis confirms the high performance of PCR for diagnosing mucormycosis and supports the instatement of PCR detection of free-DNA in blood, BALF and tissue into future updated definitions and diagnostic guidelines for mucormycosis. None.

Bacterial resistance mechanisms are continuously and rapidly evolving. This is particularly true for Gram-negative bacteria. Over the last decade, the strategy to develop new β-lactam/β-lactamase inhibitors (BLs/BLIs) combinations has paid off and results from phase 3 and real-world studies are becoming available for several compounds. Cefiderocol warrants a separate discussion for its peculiar mechanism of action. Considering the complexity of summarizing and integrating the emerging literature data of clinical outcomes, microbiological mechanisms, and pharmacokinetic/pharmacodynamic properties of the new BL/BLI and cefiderocol, we aimed to provide an overview of data on the following compounds: aztreonam/avibactam, cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, cefiderocol, ceftaroline/avibactam, ceftolozane/tazobactam, ceftazidime/avibactam, imipenem/relebactam, meropenem/nacubactam and meropenem/vaborbactam. Each compound is described in a dedicated section by experts in infectious diseases, microbiology, and pharmacology, with tables providing at-a-glance information.

Background: Biofilm-associated infections frequently span multiple body sites and represent a significant clinical challenge, often requiring a multidisciplinary approach involving surgery and antimicrobial therapy. These infections are commonly healthcare-associated and frequently related to internal or external medical devices. The formation of biofilms complicates treatment, as they create environments that are difficult for most antimicrobial agents to penetrate. Fluoroquinolones play a critical role in the eradication of biofilm-related infections. Numerous studies have investigated the synergistic potential of combining fluoroquinolones with other chemical agents to augment their efficacy while minimizing potential toxicity. Comparative research suggests that the antibiofilm activity of fluoroquinolones is superior to that of beta-lactams and glycopeptides. However, their activity remains less effective than that of minocycline and fosfomycin. Noteworthy combinations include fluoroquinolones with fosfomycin and aminoglycosides for enhanced activity against Gram-negative organisms and fluoroquinolones with minocycline and rifampin for more effective treatment of Gram-positive infections. Despite the limitations of fluoroquinolones due to the intrinsic characteristics of this antibiotic, they remain fundamental in this setting thanks to their bioavailability and synergisms with other drugs. Methods: A comprehensive literature search was conducted using online databases (PubMed/MEDLINE/Google Scholar) and books written by experts in microbiology and infectious diseases to identify relevant studies on fluoroquinolones and biofilm. Results: This review critically assesses the role of fluoroquinolones in managing biofilm-associated infections in various clinical settings while also exploring the potential benefits of combination therapy with these antibiotics. Conclusions: The literature predominantly consists of in vitro studies, with limited in vivo investigations. Although real world data are scarce, they are in accordance with fluoroquinolones’ effectiveness in managing early biofilm-associated infections. Also, future perspectives of newer treatment options to be placed alongside fluoroquinolones are discussed. This review underscores the role of fluoroquinolones in the setting of biofilm-associated infections, providing a comprehensive guide for physicians regarding the best use of this class of antibiotics while highlighting the existing critical issues.