Therapeutic Advances in Infectious Disease最新文献

Peptide-based vaccines, utilizing defined B- and T-cell epitopes, have emerged over the past two decades as promising alternatives to conventional vaccine platforms. Their key advantages, including excellent safety profiles, precise immunological targeting, and ease of manufacture, position them as a versatile tool in modern immunology. However, the widespread clinical application of these vaccines is significantly challenged by inherent limitations, most notably their low inherent immunogenicity and susceptibility to enzymatic degradation in vivo, leading to structural instability and short half-lives. This review systematically examines the innovative strategies being developed to overcome these critical obstacles. It delves into advances in rational vaccine design, highlighting the pivotal role of bioinformatics and computational tools for precise epitope selection and the engineering of sophisticated multi-epitope constructs that elicit broader immune responses. Furthermore, we provide a comprehensive analysis of novel drug delivery systems, such as a diverse range of nanoparticle carriers (e.g., liposomes, polymer-based), and review the mechanism of action of next-generation adjuvants. These technologies are crucial for enhancing antigen presentation, protecting the peptide payload, and promoting robust, durable cellular and humoral immunity. By synthesizing current literature from databases like PubMed and Google Scholar, this review offers a detailed overview of recent progress in peptide vaccine development against viral pathogens, drawing on key findings from both preclinical and clinical studies. It highlights key findings from preclinical and clinical studies and provides insights into the mechanistic actions and future potential of these precision vaccines in combating evolving viral threats.

Babesiosis and Lyme disease are tick-borne infections endemic to the northeastern and upper Midwestern United States. Although both diseases can involve multiple organ systems, acute liver failure (ALF) is exceedingly uncommon. Co-infection with Babesia microti and Borrelia burgdorferi may exacerbate disease severity, create diagnostic uncertainty, and delay appropriate therapy. We describe a 77-year-old man with type II diabetes mellitus, stage IV chronic kidney disease, and heart failure with preserved ejection fraction who presented with dyspnea, cough, and peripheral edema. Initial evaluation suggested decompensated heart failure and acute kidney injury consistent with cardiorenal syndrome. Within 24 h, however, he developed ALF (total bilirubin 6.8 mg/dL; aspartate aminotransferase 2656 U/L; alanine aminotransferase 1421 U/L; INR 3.5), thrombocytopenia (95 × 10⁹/L), acute anemia (hemoglobin 7.7 g/dL), and encephalopathy. Initial infectious, autoimmune, and ischemic evaluations were unrevealing. Despite empiric antimicrobial therapy with intravenous ceftriaxone, vancomycin, and doxycycline, his condition rapidly deteriorated, and he died. Postmortem testing identified B. microti parasitemia of 2.4% and B. burgdorferi co-infection. This case highlights the importance of considering tick-borne coinfections in patients presenting with ALF and shock, even in the absence of classic features such as fever, rash, or overt hemolysis. Increased clinician awareness of atypical presentations of endemic tick-borne diseases may help reduce diagnostic delays and improve outcomes in severe or unusual clinical scenarios.

Trichoderma is a genus of rare filamentous fungi that can cause invasive fungal infections in immunocompromised patients. We report a case of necrotizing gingival and sinus infection due to T. longibrachiatum in an allogeneic stem cell transplant recipient. The patient received a combination of antifungal and aggressive surgical debridement, achieving clinical cure. The treatment included amphotericin B, voriconazole and caspofungin with the latter switch to rezafungin to consolidate therapy. Rezafungin might represent a useful alternative for fungal infections with limited therapeutic options, but further studies are needed to confirm its role in Trichoderma spp. infections.

Background: Empirical antibiotic therapy (EAT) in febrile neutropenia (FN) remains challenging due to multidrug-resistant (MDR) Gram-negative bacteria, often leading to inappropriate empirical antibiotic therapy (IEAT).

Objective: To demonstrate that risk stratification based on machine learning (ML) and prior colonisation with MDR bacteria may support the tailoring of EAT in patients with haematological malignancies.

Design: Retrospective proof-of-concept cohort study.

Methods: All consecutive FN episodes in patients with haematological malignancies were retrospectively included from January 2020 to March 2023 at a tertiary-level university hospital. We compared real-world, clinician-driven empirical antibiotic use with a simulated approach guided by an ML-based risk stratification model combined with prior colonisation data. The main outcomes were antibiotic selection and rates of IEAT.

Results: A total of 553 FN episodes in 398 haematological patients were analysed. Bloodstream infection (BSI) occurred in 141/553 episodes (25.5%). Anti-pseudomonal (PsA) beta-lactams were prescribed in 515/553 episodes (93.1%), with carbapenems in 406/553 (73.4%). The clinician-driven approach resulted in 16/70 (22.9%) GNB-BSI episodes receiving IEAT. The ML plus colonisation-guided approach would have reduced the use of meropenem by 29.7% (-2.08 days; 95% CI, -2.42 to -1.73; p < 0.001) and anti-PsA beta-lactams by 6.7% (-0.47 days; 95% CI, -0.76 to -0.19; p = 0.001), and would also have led to a reduction in the rate of IEAT from 16/70 (22.9%) to 6/70 (8.6%) (p = 0.035).

Conclusion: ML-based risk stratification combined with colonisation status would allow for personalised antibiotic therapy in FN, potentially reducing IEAT and improving antimicrobial use. These results support integrating these tools into clinical practice.

Background: Complicated urinary tract infections (cUTIs) cause significant morbidity and mortality. Multidrug-resistant (MDR) organisms complicate cUTI management, highlighting the need for effective antimicrobials.

Objective: This scoping review was conducted to assess the role of plazomicin in managing cUTIs.

Eligibility criteria: This review included observational studies, clinical trials, qualitative studies, and in vitro studies published between 01 January 2018 and 15 July 2025.

Source of evidence: Searches were conducted on PubMed, MEDLINE, EMBASE, and Google Scholar.

Method: The screening process involved reviewing titles and abstracts, followed by full-text evaluation.

Results: Thirty studies were included in this review. Compared with meropenem, plazomicin demonstrated superior microbiological eradication at the test of cure (TOC; 89.5%), composite cure rate at the TOC (81.7%), and comparable clinical cure rates both at the TOC (89%) and end of intravenous therapy (96.3%). Adverse events, observed in 19.5% of patients, primarily included diarrhea, nausea, and renal dysfunction, indicating a favorable safety profile. In vitro data showed susceptibility rates for plazomicin ranging from 87% to 99.8% against Enterobacteriaceae, with superior activity over gentamicin, amikacin, and tobramycin. Plazomicin demonstrated synergistic effects with colistin, meropenem, and fosfomycin against extensively drug-resistant isolates and carbapenem-resistant Enterobacteriaceae.

Conclusion: This review underscores plazomicin as a promising treatment for MDR cUTIs. However, limited data from low- and middle-income countries like India highlight the need for real-world studies on its efficacy, safety, and cost-effectiveness in such countries.

Background: The emergence and spread of antimalarial drug resistance have created an urgent need for novel therapeutic agents. Imidazolopiperazines (IZPs) represent a promising new class of compounds with broad activity against multiple stages of the malaria parasite life cycle.

Objective: This scoping review aimed to map current evidence on the efficacy, mechanisms of action, resistance determinants, and clinical development of IZPs, particularly KAF156 (Ganaplacide) and its analog GNF179, to assess their potential as next-generation antimalarial agents.

Eligibility criteria: Peer-reviewed studies of clinical, in vivo, or in vitro were included if they investigated IZPs for antimalarial efficacy, mechanisms of action or resistance, safety, or comparison with other drugs. Only English-language publications were considered.

Sources of evidence: Searches were performed in PubMed, Google Scholar, ClinicalTrials.gov, and organizational databases (MMV and Novartis). Citation mapping using Litmaps identified additional related studies. The final search was completed on December 20, 2024.

Charting methods: Two reviewers independently screened, selected, and extracted data using a form capturing study characteristics, compounds, parasite stages, efficacy, mechanisms of action or resistance, and safety. Discrepancies were resolved by consensus. Data were synthesized descriptively and summarized by study type, parasite stage, compound, and outcome.

Results: IZPs demonstrate potent activity against asexual blood stages, liver stages, and gametocytes. Proposed mechanisms of action include mitochondrial disruption, sodium pump inhibition, and interference with protein trafficking. Resistance-associated mutations have been identified in genes such as Pfugt, Pfact, and Pfcarl. Clinical trials of KAF156, including combination therapy with lumefantrine, report favorable efficacy, safety, and tolerability, with side effects that are generally mild and manageable.

Conclusion: IZPs hold strong potential as next-generation antimalarial agents, particularly for combination therapies. Future research should prioritize clarifying mechanisms of action, monitoring resistance pathways, and optimizing clinical deployment strategies to address the ongoing challenges of antimalarial drug resistance and support malaria elimination goals.

Background: Uganda is among the 30 high tuberculosis (TB) burden countries, and still grapples with a suboptimal treatment success rate (the sum of cured and treatment completion), which stands at 89.1% for people living with HIV and 91.2% for those without HIV. The Teso region, one of the high TB burden regions in the country, has consistently had a lower treatment success rate (TSR).

Objectives: To determine the treatment success and associated factors among drug-susceptible TB individuals in the Teso region, Uganda.

Design: This retrospective study was conducted in the five (5) largest TB diagnostic units in the Teso region of Northeastern Uganda from 1st March 2025 to 28th March 2025.

Methods: Data were collected from the health facility's TB treatment register. The primary outcome was treatment success. Data were analyzed using Stata statistical software, version 15.0, and summarized into proportions and frequencies. Modified Poisson regression analysis was conducted to determine factors associated with treatment success and reported as adjusted prevalence ratios (aPR). A p < 0.05 was considered statistically significant.

Results: Data from 1009 individuals were included in the analysis; the median age was 45 years, with an interquartile range of (28-60). The majority of the individuals, 48.1% (n = 485), were aged 15-49 years. Just over half, 52.9% (n = 534), were male, and 54.5% (n = 550) had bacteriologically confirmed TB. The overall TSR was 91.9%. Factors associated with a higher treatment success were being female (aPR = 1.04; 95% CI: 1.002-1.07, p = 0.041). In contrast, being aged > 49 (Elderly) (aPR = 0.95; 95% CI: 0.89-0.99, p = 0.042) and living with HIV (aPR = 0.93; 95% CI: 0.88-0.98, p = 0.008) were associated with a lower likelihood of treatment success.

Conclusion: In this study, being female was associated with higher treatment success, while being older than 49 years and having HIV were associated with lower treatment success. This calls for early screening and strengthening TB preventive therapy among the people living with HIV, peer-to-peer support among the elderly for treatment adherence to improve TSR, and to achieve the goal of eradicating TB by 2030.

Micrococcus luteus (M. luteus) is a Gram-positive microorganism that typically dwells in environments such as soil, water, and human skin, hence, entitling it as a contaminant organism. However, there are instances where M. luteus affects immunocompromised patients, such as in infective endocarditis and septic arthritis, but typically among immunocompromised patients. However, an evolutionary change has been observed in the infectious capability of this organism especially with reports emerging on its instance among immunocompetent population. A 68-year-old female presented to the emergency medicine department with complaints of persistent fever and neck soreness. Patient's blood culture reports were positive for M. luteus and owing to her history of undergoing prosthetic valve replacement. A preliminary diagnosis of prosthetic valve infective endocarditis was made. However, since M. luteus was a typical skin contaminant, and its infective etiology was limited toward immunocompromised patients, blood cultures were repeated for confirmation. Repeat blood cultures ascertained the suspicion of M. luteus; hence, treatment with intravenous vancomycin was initiated. Patient was discharged after 8 week of treatment following complete eradication of infective markers and symptomatic improvement. Here, we report the novel occurrence of prosthetic valve infective endocarditis, by a typically contaminant organism, in an immunocompetent individual, hence, raising concerns on the evolutionary changes in the organism, M. luteus.

Background: Treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia with antipseudomonal beta-lactams (APBLs) is a common clinical practice in confirmed or suspected polymicrobial infections. Limited data exist to evaluate the impact of APBL treatment on outcomes in MSSA bacteremia.

Objectives: To determine whether differences in outcomes exist between patients with MSSA bacteremia treated with cefazolin/oxacillin (standard of care; SOC) versus APBLs.

Design: Retrospective cohort study.

Methods: Adult and pediatric patients hospitalized between June 2016 and June 2023 with at least one positive blood culture for MSSA who received at least 14 consecutive days of inpatient therapy with cefazolin, oxacillin, cefepime, piperacillin-tazobactam, or meropenem were included. Patients who received APBLs were compared to those who received SOC. The primary outcome was composite clinical failure (i.e., 30-day all-cause mortality and/or bacteremia recurrence within 30 days). Secondary outcomes included 60-day all-cause mortality, intensive care unit and hospital length of stay, 30-day readmission, time to bacteremia clearance, time to mortality, and adverse events (i.e., Clostridioides difficile infection, hepatotoxicity, and acute kidney injury).

Results: One hundred patients were included, with 50 patients in each group. The most common source of bacteremia was catheter-related (28% total), and twice as many patients met criteria for complicated MSSA bacteremia in the SOC versus APBL group (80% vs 40%, p < 0.0001). Three patients (6%) in the APBL group met the composite primary outcome compared to 1 (2%) in the SOC group (p = 0.62). There were no significant differences in secondary outcomes.

Conclusion: No differences in mortality or bacteremia recurrence were identified among patients with MSSA bacteremia treated with APBLs compared to SOC. Larger studies should be performed to confirm these findings.