Non-tuberculous mycobacteria (NTM) infections are challenging to recognize, diagnose, and manage, particularly in lung transplant recipients. The aim of this review is to provide recommendations for diagnosis, treatment (including key drug-drug interactions of antimycobacterial agents and immunosuppressants), and long-term management of NTM infections in lung transplant recipients. Two systematic meta-analyses, both published in 2023, analyzed NTM infection in lung transplant recipients, and both found that NTM disease was associated with higher mortality after lung transplantation. These findings underscore the importance of future study in this field. Clinicians should be cognizant of novel effective antimycobacterial agents, such as omadacycline for rapid growing mycobacteria. NTM infections pose a significant threat to lung transplant recipients, but these infections can be managed effectively in medical centers with experience in treating mycobacteria. The key management points are to consider all potential drug-drug interactions, consider the limitations of in vitro susceptibility testing, consider utilization of new antimycobacterial agents, and to consider close monitoring of patient’s symptoms and culture results.
Staphylococcus aureus is a major public health concern due to its ability to cause severe and complicated infections across multiple organs. Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant global threat, as it readily acquires resistance to various antibiotic classes. Its strong biofilm-forming capacity further complicates treatment in clinical settings. This review aims to explore the therapeutic potential of bacteriophages (phages) against S. aureus infections, highlighting their advantages, limitations, and challenges. Phage therapy has re-emerged as a promising approach for combating bacterial pathogens, including S. aureus. Lytic bacteriophages have demonstrated potential in managing localized and systemic bacterial infections. Recent studies have provided insights into the efficacy of phage therapy, suggesting it could complement or replace traditional antibiotic treatments, especially for multidrug-resistant strains like MRSA. The increasing prevalence of antibiotic resistance in S. aureus necessitates innovative treatment strategies. Phage therapy offers a viable alternative with significant therapeutic promise. However, further research must focus on addressing challenges such as resistance development, regulatory hurdles, and optimization of therapeutic protocols.
Machine perfusion strategies reduce the duration of organ ischemia and minimize tissue damage, increasing use of organs previously considered unsuitable for transplant. This review outlines the basic principles of organ preservation and machine perfusion, describes the risk of microbial contamination and role of antimicrobials during machine-based preservation, and discussed opportunities to leverage machine perfusion to reduce the risk of disease transmission. Ex situ machine perfusion (ESMP), which involves circulating perfusate through an organ’s vasculature to maintain physiological function, introduces new infectious considerations tied to its inherent function and real-world applications. Antimicrobials are routinely added to the perfusate in normothermic machine perfusion to mitigate the risk of microbial growth at normothermia. Microbial growth in ESMP perfusate has been described, but cultures often contain low-virulence organisms that do not predict post-transplant infection. Manipulation of organs on ESMP has been evaluated as a method to reduce the risk of infection transmission, but ESMP is not currently used for this purpose. Current data do not suggest that ESMP systems confer a clinically significant infection risk over traditional preservation methods, but large, multicenter, prospective studies are needed to better understand infection risk. Universal treatment of recipients with antimicrobials targeting preservation fluid cultures is likely to be unnecessary, but the benefits of targeted treatment of certain potential pathogens could outweigh the risks. ESMP offers a potential platform for targeting donor-derived pathogens, but optimization of ex situ manipulation will be required for it to be an effective infection prevention approach.
Refractory post-transplant CMV, with or without genotypic resistance, remains a challenging issue. Antivirals traditionally used for refractory CMV include foscarnet and cidofovir, which have major toxicities and suboptimal efficacy. In 2021, maribavir became the first antiviral drug approved for treatment of refractory CMV with or without resistance defined by genetic mutations (resistant/refractory CMV or “R/R” CMV). However, much remains to be learned. This review presents an illustrative case and summarizes current literature on real-world outcomes of maribavir treatment, as well as other interventions for R/R CMV. Several post-marketing case series regarding real-world use of maribavir for R/R CMV have reported successful outcomes in 40–67
This review offers a comprehensive and up-to-date overview of mpox virus (MPXV) infection, highlighting its evolving epidemiology, virological features, transmission patterns, clinical presentation, and diagnostic methods. Particular attention is given to current treatment options and preventive strategies, including vaccination. The review emphasizes insights from recent outbreaks and advances in therapeutic development. Since 2022, MPXV has emerged as a global public health concern with sustained human-to-human transmission, primarily through sexual contact, especially among men who have sex with men and people living with HIV. New viral clades, including clades 1b and 2b, have been identified, exhibiting genetic adaptations that enhance human infectivity. Although tecovirimat remains the primary antiviral treatment, emerging resistance and limited clinical efficacy data raise concerns. Several vaccine platforms, particularly MVA-BN, are in use or under evaluation, though issues remain regarding long-term protection and global accessibility. Mpox has shifted from an endemic zoonosis to a sexually transmitted infection with global reach. While most cases are self-limited, severe disease can occur in immunocompromised individuals. The current therapeutic armamentarium is restricted, and tecovirimat’s utility may be limited by timing, resistance, and viral clade. Vaccination is effective, but not universally available or durable. Enhanced surveillance, improved diagnostics, novel antivirals, and equitable vaccine access are crucial for containment. A One Health approach is essential to address ongoing transmission risks and potential spillover events.
Blood cultures (BCx) are crucial for diagnosing bacteremia, but BCx contamination (BCC) can lead to false positives that prolong hospitalization and promote antibiotic use. The purpose of this review is to summarize evidence-based interventions to reduce BCC and improve patient outcomes. Diagnostic stewardship programs can optimize BCx use, ensuring BCx are obtained when diagnostically valuable. Proper BCx techniques, including correct timing, adequate volume, and paired samples, are essential. Thorough disinfection of the skin is important, but there is not a clear consensus on the superiority of one disinfectant over another. Bundled interventions using standardized kits and sterile technique have reduced BCC. Initial specimen diversion devices (ISDDs) have significantly reduced BCC. Although molecular-based rapid diagnostic testing shortens pathogen identification time, allowing quicker optimization of antibiotics, this has not been clearly shown to reduce the consequences of BCC. Education, surveillance, and feedback are effective, especially in coordination with phlebotomy teams, in reducing BCC rates, as demonstrated by multidisciplinary interventions. Antiseptic caps may reduce BCC from catheters, but whether ISDDs are useful in decreasing BCC in catheter drawn blood cultures is uncertain. To improve outcomes, hospitals should aim for BCC rates below 1
Antimicrobial resistance (AMR) poses a global health crisis, with ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) driving severe, multidrug-resistant infections. Bacteriophage therapy (PT) offers a targeted alternative; however, its clinical efficacy, safety, and potential outbreak mitigation remain underexplored. This narrative review synthesized evidence from 30 clinical studies to evaluate PT for ESKAPE infections. Complete bacterial clearance was achieved in 10 studies, primarily for P. aeruginosa and K. pneumoniae, with clinical improvement in 24 studies, including complex cases like osteomyelitis and cystic fibrosis-related pneumonia. PT was safe, with no serious adverse effects across 25 studies; mild, transient events (e.g., fever) were rare. Mortality, reported in nine studies, was unrelated to PT. One study demonstrated a reduction in nosocomial transmission of A. baumannii using environmental phages, suggesting a potential for outbreak control. PT shows promise as a safe, effective adjunct for MDR infections, but larger trials and standardized protocols are needed to address resistance, optimize dosing, and explore public health applications.
Respiratory syncytial virus (RSV) is a frequent seasonal respiratory virus that can cause severe disease in children, elderly and those with immunocompromising conditions. RSV disease can be particularly severe in hematopoietic stem cell transplant recipients, hematologic malignancy patients and lung transplant recipients. This review explores the role of ribavirin in the management of RSV infections in these high-risk groups, summarizing historical and recent evidence to guide clinical practice. Ribavirin has been used off-label for RSV treatment in immunocompromised patients for decades, mostly based on observational data. Aerosolized ribavirin, once the standard of care, has since been replaced by oral ribavirin due to ease of administration, comparable efficacy and cost. More recent meta-analyses suggest ribavirin use may reduce mortality in hematologic malignancy and hematopoietic stem cell recipients, though data in lung transplant recipients remains uncertain. The combination of ribavirin and intravenous immunoglobulin is commonly utilized to prevent progression of upper respiratory tract infection to lower respiratory tract infections. Robust randomized trial data remain lacking. Ribavirin continues to remain an important therapeutic option for vulnerable immunocompromised patients, mainly to prevent progression of disease to lower respiratory tract infections and reduce mortality. While newer agents remain under investigation, the current evidence supports use of oral or aerosolized ribavirin in high-risk populations, often in combination with intravenous immunoglobulin. Future studies are needed to refine treatment strategies in these patients.
Leishmaniasis, a neglected tropical disease caused by the protozoan parasite Leishmania, remains a significant global health concern, particularly in endemic regions. Developing liposomal formulations for anti-leishmanial drugs has emerged as a promising strategy to enhance treatment efficacy, improve drug stability, and minimize systemic toxicity. This review explores the formulation strategies of liposomal anti-leishmanial drugs, their advantages over conventional therapies, and the challenges associated with their implementation in clinical practice. Liposomal formulations offer a flexible drug delivery platform, enabling the encapsulation of a wide range of anti-leishmanial compounds. Preclinical and clinical studies have demonstrated the efficacy and safety of liposomal drugs, with notable successes such as liposomal amphotericin B and sodium stibogluconate. These formulations enhance drug bioavailability, enable targeted intracellular parasite elimination, and reduce adverse effects. However, challenges such as high manufacturing costs, scalability, and accessibility in resource-limited settings remain. Emerging advancements, including stimuli-responsive liposomes, personalized formulations, combination therapies, and liposomal vaccines, promise to overcome these barriers. Liposomal anti-leishmanial therapies present a transformative approach to combating leishmaniasis by improving treatment outcomes and patient adherence while reducing toxicity. Despite existing challenges, continued research and global collaboration are essential to making these therapies more accessible and cost-effective. Integrating innovative drug delivery technologies with healthcare infrastructure improvements can significantly reduce the disease burden and contribute to the eventual eradication of leishmaniasis.
Candida albicans is the most prevalent fungal species responsible for human infection, ranging from mild to severe systemic diseases. The rising incidence of drug resistance C. albicans infections, coupled with the limited efficacy and toxicity of conventional antifungal drugs, necessitate novel therapeutic approaches. Nanomedicine is a promising approach by enhancing drug efficacy, reducing toxicity, and improving targeted delivery. Nanocarriers such as liposomes, ethosomes, polymeric nanospheres, and metal-organic frameworks have advanced antifungal therapy. Liposomal antifungal amphotericin B lowers kidney toxicity while effectively treating biofilm infections. Ethosomes with farnesol enhance transdermal delivery, improving treatment. Polymeric nanospheres, including chitosan and PLGA, offer strong antifungal and antibiofilm effects with minimal side effects. Nanozyme-based therapy generates reactive oxygen species to combat resistant strains, while metal-organic frameworks enhance drug penetration and sustained release. Clinical studies confirm the effectiveness of these nanomedicine in treating candidiasis. Nanomedicine is revolutionizing antifungal therapy by tackling drug resistance and enhancing treatment outcomes. Future research should refine nanoparticle stability, ensure long-term safety, and accelerate clinical application. These advancements in nanotechnology hold great potential for improving Candida albicans treatment and overcoming antifungal resistance.
By the end of 2023, approximately 39.9 million people worldwide were living with HIV, including 1.2 million in the United States. Although treatment advancements have improved health outcomes, HIV continues to pose significant challenges, particularly among key populations like men who have sex with men (MSM), transgender women, and cisgender women. Pre-exposure prophylaxis (PrEP) has emerged as an effective strategy to lower the risk of HIV transmission, but daily oral regimens often face adherence difficulties. This narrative review aims to summarize the effectiveness and safety of Lenacapavir, the latest long-acting injectable PrEP currently under clinical trials. Lenacapavir, a novel long-acting injectable PrEP with bi-annual dosing, offers significant advantages in terms of adherence and privacy, potentially reducing the stigma associated with daily medication. This review summarizes the effectiveness in preventing HIV, safety profile and the strategies being explored to overcome barriers to access. Compared to traditional daily oral PrEP options, lenacapavir has shown remarkable efficacy in recent clinical trials, including two different Phase 3 studies where it achieved a 100
Conventional antimalarial therapies often encounter issues of drug resistance, low bioavailability, and systemic toxicity. However, recent advancements in nanotechnology have opened new avenues for revolutionizing malaria treatment through precise drug delivery systems. This review delves into the multifaceted life cycle of the malaria parasite, highlighting its various stages and the intricate interactions between the parasite, mosquito vector, and human host. Nanotechnology has proven to be the most suitable approach for delivering antimalarial drugs to the targeted site with enhanced safety and efficacy. The advent of nanotechnology has led to the development of novel drug delivery systems that offer unprecedented control over drug release, distribution, and targeting. Researchers can encapsulate antimalarial agents by harnessing nanoparticles, liposomes, and other nanocarriers, protecting them from degradation and ensuring their targeted delivery to infected cells. These nanoscale systems also enable the exploitation of unique physicochemical properties that enhance drug solubility, circulation time, and cellular uptake. The article overviews recent breakthroughs in nanotechnology-based strategies for combating malaria. From passive targeting exploiting the enhanced permeability and retention effect to active targeting using surface-functionalized nanoparticles that recognize specific receptors on infected cells, these innovations are poised to revolutionize malaria treatment. The potential of combining multiple therapeutic agents within a single nanocarrier for synergistic effects is also discussed. The main focus of this review is the different nanotechnologies that are available for the successful administration of antimalarial drugs. Various nanotechnologies can be used: liposomes, dendrimers, solid lipid nanoparticles, self-micro emulsifying drug delivery systems, ethosomes, niosomes, etc. In this review paper, we will detail the study of different nanotechnologies available for administering antimalarial drugs.
Rabies is a universally fatal viral disease predominantly transmitted through the bites and scratches of infected animals, with domestic dogs being the primary source of human cases. The highest incidence rates are reported in Asia and Africa. Despite its high mortality rate, rabies is often not prioritized as a major health concern, especially in Asian countries. This review emphasizes the critical importance of timely and accurate diagnosis and immediate medical intervention, which can significantly reduce the disease's severity, prevent fatal outcomes and accurately diagnose suspected patients. Emerging novel therapeutic and diagnostic approaches are crucial to effectively managing and preventing rabies. This review provides a thorough and detailed analysis of laboratory diagnostic methods and management strategies for human rabies, tracing the advancements from historical methodologies to current practices. This evaluation is based on an extensive literature review from the past 20 years, offering valuable insights into the evolution of rabies diagnostics and management strategies. It reflects ongoing efforts to enhance outcomes for affected individuals and underscores the importance of continued innovation in combating this deadly disease. Rabies is often not prioritized as a major health concern, especially in Asia and Africa. This review highlights the importance of timely diagnosis and intervention, explores novel therapeutic and diagnostic approaches, and provides a comprehensive analysis of rabies management strategies based on a literature review from the past 20 years.
For immunocompromised travelers, travel medicine plays a key role in reducing infection risk. We aim to provide an overview on how to approach pre-travel counseling, travel-related vaccines, antimicrobial prophylaxis, and the evaluation of symptomatic returning travelers. Pre-travel emphasis on vaccination, education, and antimicrobial prophylaxis remains important as immunocompromised travelers often have itineraries with exposure risks similar to their immunocompetent counterparts. Regional health agencies’ guidelines should always be consulted for country-specific recommendations. Special attention should be given to vaccines for seasonal influenza, coronavirus disease-2019 vaccines, and respiratory syncytial virus as mass transit augments exposure to respiratory viruses. The practice of travel medicine for immunocompromised patients focuses on targeted risk reduction strategies, vaccination, prophylaxis, and contingency planning. An individualized approach is necessary for each case, and clinicians are obligated to remain updated on emerging infectious risks.
To review the current literature on ventricular assist device (VAD) infections, with emphasis on epidemiology, treatment, and post-transplant outcomes. Clarification on VAD infections is an ongoing process, with the INTERMACS 2020 report differentiating between mechanical circulatory support (MCS) related infections and MCS unrelated infections, with patient-related factors as further categorization. New data indicates colonization with multidrug resistant organisms (MDR) correlates with development of VAD-associated infections. Exploration of bacteriophages use for treatment of VAD related infections is still ongoing. Additionally, patients with VAD related infections who undergo transplant have similar outcomes to VAD patients without infection. In the evolving landscape of MCS, VADs remain a cornerstone of management for those with advanced heart failure who may not qualify for transplant. VAD related infections are a common complication, with efforts to understand and mitigate risk ongoing. Once infected, management is dependent on the component of the VAD involved – with topical and local efforts the focus of recent research for drive line exit site infections. If transplant is an option for a patient with a VAD related infection, their outcomes are similar to other patients with VADs.
Monkeypox (Mpox) is a zoonotic disease caused by monkeypox virus (MPXV) was formerly restricted within western and central Africa, but a surge in the number of cases in 2022, 2023 and 2024 is seen in several nations across the globe. This review gives a comprehensive update on the epidemiology of Mpox, MPXV reservoirs, transmission characteristics, mutation, mechanisms of infection, clinical indications, laboratory diagnosis, ways of management, and potential vaccine candidates. WHO announced the Mpox outburst as a public health emergency of international concern (PHEIC) on 14th August 2024 as a new variant of Mpox is reported and cases are now being documented for the first time from nations like Kenya and Rwanda. Recent cases specify that inter-human transmission might result in frequent eruptions, particularly in men who are sexually active with men. The creation of antiviral medicines and vaccines for treating Mpox is immediately required, regardless of the specific beneficial effects of repurposed drugs. Mpox is a viral disease responsible for symptoms such as rash, critical lymphadenopathy, and fever. In this article, we discussed preventive approaches like immunization using smallpox vaccines, providing insights on proper understanding of MPXV and suggestions for the management, prevention, and control of MPXV.
Purpose of Review The Epstein-Barr virus (EBV) is a common virus around the globe with approximately 98% of adults testing positive against EBV. However, EBV infection typically begins early in the childhood. Owing to the ability to infect various body organ, EBV is linked to a broad spectrum of symptoms, diseases, and inflammatory conditions. Moreover, since EBV exists in both latent and replicating forms in most healthy individuals, any disruption in the balance between the virus and its host can lead to the development of different diseases, including autoimmune disorders and cancer. Given these circumstances, we draw attention to the crucial need for developing prophylactic measures and treatments for EBV and its associated diseases. Recent Findings We propose leveraging the advantages of nanomedicine, such as ferritin and iron oxide nanoparticles, for the creation of EBV vaccines. These advancements can also be applied to developing drugs to treat EBV-associated diseases, such as cancer, autoimmune disorders, and cytokine storm syndrome. Summary We emphasize the urgency of having accessible EBV vaccines, as well as effective treatments for EBV-related diseases, especially when early diagnosis is involved. This approach, which includes comprehensive cytokine profiling for patients, can significantly enhance the effectiveness of treatment programs.
Malaria and other parasitic infections pose serious health risks to millions of people worldwide each year. Oral medication is a crucial component in a multi-prolonged approach to effectively managing malaria. The use of oral antimalarial medications is essential for both treating and preventing malaria. They are essential because of their effectiveness in focusing on the different phases involved in the life cycle of malarial parasite which is taking place inside the human body. Oral drugs work against Plasmodium in many ways, from quickly eliminating active parasites to completely eliminating latent versions that are stored in the liver. While lowering the possibility of medication resistance, the introduction of combination medicines, such artemisinin-based combination medicines (ACTs), has greatly improved treatment efficacy. But there are still issues, such as drug-resistant forms of the malaria parasite emerging, which emphasizes the need for continued investigation and the creation of novel oral treatments. Furthermore, maintaining access to these drugs continues to be a major challenge in the fight against malaria, especially in areas with low resources. To sum up, oral therapy is an essential component involved in the treatment of parasitic diseases like malaria. In order to lessen the impact of these diseases worldwide and eventually move towards their eradication, it is imperative that technology continues to be innovative, accessible, and integrated into complete healthcare programmes. WHO advised in October 2021 that individuals in places with risk of malaria (Plasmodium falciparum) transmission should start receiving the different dosage of vaccine because of its great safety profile and high effect. By concentrating on the parasite’s sporozoite stage and blocking its ability to enter the liver, the RTS, S vaccine seeks to develop protection against P. falciparum. In general, vaccines are challenged by the possibility of resistant strains emerging, affecting their vaccination effectiveness if the parasite experiences genetic alterations that enable it to avoid the immunological response that the vaccine triggers. Malaria is efficiently managed with a multi-prolonged strategy that includes oral treatment. Because oral antimalarial drugs effectively target many stages of the malarial parasite life cycle inside the human body, their usage is crucial for treating and preventing malaria. In this study, we are going to discuss about the seminal delivery systems for drug which are in lab, market, and clinical trials for treatment of malaria. Also, we focused on the commercial and conventional drug delivery systems which can be more effective and the challenges behind their success.
Combined positron emission tomography and computer tomography with 2-deoxy-[fluorine-18]-flouro-D-glucose ([18F]FDG-PET/CT) is increasingly used in suspected infection and inflammation. Evidence is mounting within several areas. We believe [18F]FDG-PET/CT is a key modality in infection and inflammation and this overview outlines the diagnostic values in most common uses within this domain. [18F]FDG-PET/CT is considered helpful in establishing the underlying disease in 50–60
Adenovirus (AdV) is a relatively common cause of viral infection in the general population, especially in childhood. In patients undergoing hematopoietic stem cell transplantation (HSCT), AdV infections can present as disseminated disease and can be life-threatening. Here, we present a review of AdV infection in the stem cell transplant setting, including AdV clinical presentation, epidemiology, and treatment, with a particular focus on novel virus-specific T cell (VST) therapy. Safe and effective treatments of AdV infection and disease are lacking; current therapies such as cidofovir are often accompanied by significant toxicity. Most recent advances in the treatment of AdV infection and disease have occurred in the realm of cytotoxic T cell therapy in which AdV is one of many viral targets. Notably, third-party VSTs have been observed to improve AdV viral load and improve disease symptoms without clear evidence for increased graft-versus-host disease risk. While donor-derived and third-party AdV-targeted VSTs offer promise in the treatment of severe and disseminated AdV infection and disease, randomized-controlled trials are needed to demonstrate VST safety and efficacy in the stem cell transplant population. Despite encouraging findings, questions remain about ideal therapy candidates, donor sources, and combinations of viral targets for effective VST therapy.
