Current Opinion in Infectious Diseases最新文献

Purpose of review: The purpose of this review is to report the available evidence regarding the use of combination regimens of antivirals and/or antibody-based therapy in the treatment of SARS-CoV-2 in immunocompromised patients.

Recent findings: Literature search identified 24 articles, excluding single case reports, which included mainly patients with hematological malignancies and/or B-cell depletion. Data were divided based on the timing and reason for administration of combination treatment, that is, early treatment to prevent progression to severe COVID-19 and treatment of prolonged or relapsed infection. We described the treated populations, treatment duration and composition of combination treatment. We briefly addressed new treatment options and we proposed an algorithm for the management of COVID-19 infection in patients affected by hematological malignancies.

Summary: Combination treatment seems an effective (73-100%) and well tolerated (<5% reported bradycardia, hepatotoxicity, neutropenia) strategy for treating prolonged/relapsed SARS-CoV-2 infections in the immunocompromised host, although its optimal composition and duration cannot be defined based on the currently available evidence. The role of combination treatment as an early treatment strategy for immunocompromised patients at a high risk of progression to severe disease/persistent shedding requires further evidence from comparison with monotherapy, even though high efficacy was reported for combinations of antivirals plus mAbs in case of previous viral variants.

Purpose of review: To discuss the therapeutic options available for the management of difficult-to-treat strains of Stenotrophomonas maltophilia ( Sma ), namely those resistant to trimethoprim-sulfamethoxazole and fluoroquinolones.

Recent findings: Recent pharmacological studies have highlighted the fact that current breakpoints for first-line antibiotics against Sma are too high. In light of these data, it is likely that the prevalence of difficult-to-treat (DTR) Sma is underestimated worldwide. Two promising alternatives for treating DTR strains are cefiderocol and the combination of aztreonam and an L2 inhibitor. However, clinical trials are currently very limited for these antibiotics and no comparative studies have been carried out to date. It is important to note that the clinical efficacy of cefiderocol appears to be inferior to that initially anticipated from in-vitro and animal studies. Consequently, minocycline and ceftazidime may remain viable options if they are used against strains with a low minimum inhibitory concentration. We advise against the use of intravenous polymyxins and tigecycline. Finally, recent literature does not support the systematic use of combination therapy or long-course treatments. In the coming years, phage therapy may become a promising approach against DTR Sma infections.

Summary: Overall, clinical comparative studies focused on DTR strains are required in order to provide more accurate and actionable information for therapeutic decisions.

Purpose of review: Cytomegalovirus (CMV) infection is associated with severe clinical disease and high morbidity in immunocompromised hosts. Letermovir and maribavir, are two recently developed antiviral drugs used in the prevention and treatment of resistant and refractory CMV. Following the publication of landmark randomized trials and increased use, both clinical trial data and real-world experience has reported the development of antiviral drug resistance. The aim of this review was to comprehensively review the published literature on letermovir and maribavir drug resistance and to describe the clinical scenarios in which they may emerge.

Recent findings: For letermovir, the most frequently detected resistance mutations occur in the UL56 gene (C325Y/W/F) and confer total resistance. Maribavir resistance mutations most often occur in the UL97 gene and resistance-associated variants (RAVs) T409M, H411Y, C480F have all been detected. The clinical context in which letermovir and maribavir resistance occurs include high viral loads at initiation, intensified immunosuppression, subtherapeutic drug exposure because of poor adherence, drug interactions, and inadequate central nervous system (CNS) penetration. Emergence of resistance mutations generally occurs within the first 3 months of initiation.

Summary: The detection of letermovir and maribavir resistance mutations highlights an ongoing clinical challenge in the management of CMV.

Purpose of review: Culturing preservation fluids of solid organs before transplantation is not a standardized procedure. In this review, we aim to describe the state-of-the-art of literature evidence in this debated setting with a special focus on Gram-negative bacteria (GNB).

Recent findings: Contamination of preservation fluids is frequent, but preservation fluids related infections are rare and most commonly caused by high-risk pathogens, including GNB. GNB preservation fluids related infections are characterized by high morbidity and mortality. Recent studies showed improved outcomes in solid organ transplant recipients receiving antibiotic therapy tailored according to preservation fluids cultures especially when multidrug-resistant GNB are found. A robust procurement network is needed to alert recipients' centers in cases of positivity and the support of transplant infectious diseases specialists is essential to choose the best therapy.

Summary: Culturing preservation fluids is a further step into preventing donor-derived infections. Interpreting and managing GNB positivity require a multidisciplinary team with specific skills. Standardized randomized trials are needed for insight into the real utility of preservation fluids cultures, the role of preservation fluids positivity, and the impact of antimicrobial therapy.

Purpose of review: This review aims to highlight the multifaceted nature of brucellosis, emphasizing the latest advancements in its diagnosis and management. Given the global prevalence and potential complications of brucellosis, understanding recent advancements in diagnostic techniques and treatment strategies is crucial for clinicians.

Recent findings: Recent literature reveals significant progress in diagnostic methods, including the application of fluorescence polarization immunoassay and time-resolved fluorescence resonance energy transfer technologies as well as the invention of artificial Brucella antigens, which offer enhanced sensitivity and specificity. Advances in molecular diagnostics and serological tests have improved early detection rates, however their interpretation remains challenging. Evolving treatment regimens such as the use of hydroxychloroquine as part of triple therapy and the use of nano-delivery systems in therapies have shown promise, in hopes of reducing relapse rates and managing chronic cases.

Summary: The findings underscore the necessity for clinicians to adopt a comprehensive approach to diagnosing and managing brucellosis. Integrating advanced diagnostic tools with tailored therapeutic strategies can significantly improve patient outcomes. Future research should focus on optimizing these diagnostic techniques and exploring novel therapeutic agents.

Purpose of review: To discuss novel antibiotics under clinical development, focusing on agents showing in-vitro activity against metallo-β-lactamases (MBL)-producing carbapenem-resistant Gram-negative bacteria (CR-GNB).

Recent findings: Currently, only a few approved agents show activity, alone or in synergistic combinations, against MBL-producing CR-GNB. If approved by regulatory agencies in case of favorable results from ongoing (and, for some agents, already completed) phase-3 studies, some novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations could become available in the next few years as additional important options for treating MBL-producing CR-GNB infections. Additional interesting agents that belong both to BL/BLI combinations and to antibiotic classes other than BL and BL/BLI combinations have also shown activity against MBL-producing CR-GNB, with most of them being in early phases of clinical development.

Summary: Improving the use of these novel agents through virtuous antimicrobial stewardship frameworks able to guarantee both the efficacious treatment of infections requiring their use and the avoidance of their use whenever not necessary remains a challenge of utmost importance that should not be overlooked.

Purpose of review: Arboviral infections caused by Dengue, Zika, and Chikungunya viruses continue to pose a significant global health threat, particularly in endemic regions. This review is timely because of the increasing prevalence of these infections, driven by factors such as urbanization and climate change. Dermatological manifestations of these viruses are crucial for early diagnosis, especially given the overlap in symptoms, which can complicate differential diagnosis.

Recent findings: Recent studies emphasize the importance of mucocutaneous symptoms in diagnosing arboviral infections. In Dengue, distinctive rashes like the 'islands of white in a sea of red' and hemorrhagic skin manifestations have been key diagnostic features. Zika is marked by a pruritic maculopapular rash and nonpurulent conjunctivitis, whereas Chikungunya often results in persistent rashes, desquamation, and hyperpigmentation, particularly on the face. Emerging research highlights the skin's role as both a primary infection site and an immune mediator in these viral diseases, offering new insights into their pathophysiology and potential therapeutic targets.

Summary: The unique dermatological profiles of Dengue, Zika, and Chikungunya are critical for guiding clinical diagnosis and treatment, especially in resource-limited settings. Understanding these cutaneous manifestations can improve early recognition, particularly in differentiating between these viruses in co-endemic areas. Future research may uncover novel therapeutic strategies by focusing on the interaction between these viruses and the skin's immune responses.

Purpose of review: The scope of this review is to understand the epidemiology and potential role of respiratory viral infections in children with cancer and febrile neutropenia, as well as in children, undergoing hematopoietic stem cell transplantation. Early detection of respiratory viral infections through molecular diagnostic techniques has allowed recent randomized clinical studies to advance the possibility of more rational use of antimicrobials in this susceptible population.

Recent findings: Progress has been made in the early detection of respiratory viruses in episodes of fever and neutropenia in children with cancer. In selected patients who meet specific clinical safety criteria and have negative bacterial cultures, it has been possible to safely and effectively discontinue antimicrobials. This has been validated in recent randomized clinical studies. However, more evidence is still needed for a similar indication in children, undergoing hematopoietic stem cell transplantation with viral respiratory infection episodes.

Summary: Understanding the role of respiratory viral infections in populations of immunocompromised children may contribute to a more rational use of antimicrobials and, in the near future, may help to decrease antimicrobial resistance in this susceptible population.

Purpose of review: This opinion piece aims to explore the transformative potential of integrating artificial intelligence with digital microscopy to enhance diagnostics for soil-transmitted helminthiasis (STH) and schistosomiasis (SCH), two pervasive neglected tropical diseases (NTDs). By aligning innovative artificial intelligence-driven solutions with WHO's strategic objectives and calls for better, more accessible, and more integrated diagnostics, we highlight the latest advancements that may support improved health outcomes in affected communities.

Recent findings: The review covers recent advancements in artificial intelligence-based diagnostic technologies, emphasizing automated egg detection and quantification. These technologies promise to mitigate challenges such as human error and the need for skilled technicians.

Summary: The findings have significant implications for public health, ethical considerations and regulatory pathways, particularly in resource-limited settings. The authors advocate for interdisciplinary collaboration and a strategic focus on meeting WHO target product profiles to ensure uptake, ultimately to support reaching WHO NTD targets.

Purpose of review: Malaria threatens pregnant women and their babies, particularly in Africa.

Recent findings: This century, the number of women at risk of malaria in pregnancy has decreased globally, apart from in Africa, where it has increased. Low and sub microscopic infections are increasingly documented but remain hard to diagnose with current point-of-care tests, and their contribution to morbidity and transmission are unclear. Artemether-lumefantrine has been endorsed for treatment in first trimester, but many women attend antenatal clinics later in pregnancy, and reaching high-risk young, first-time mothers is particularly difficult. Small-for-gestational-age babies frequently result from malaria, which affects the placenta's development and its functions such as nutrient transport. Resistance to continues to increase to sulphadoxine-pyrimethamine, the mainstay of intermittent preventive treatment in pregnancy. The alternative, dihydroartemisinin-piperaquine controls malaria better, but does not improve pregnancy outcomes, suggesting that sulphadoxine-pyrimethamine may have nonmalarial effects including improving gut function or reducing dangerous inflammation. Understanding of how the malaria parasite uses the VAR2CSA protein to bind to its placental receptor is increasing, informing the search for a vaccine to prevent pregnancy malaria.

Summary: Progress in several areas increases optimism that improved prevention and control of malaria in pregnancy is possible, but obstacles remain.