Therapeutic Advances in Infectious Disease最新文献

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.

Human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection in Nigeria are medical conditions of public health importance because they double the country's and its citizens' burden. Several management measures, including artificial intelligence (AI), are crucial for properly diagnosing and preventing these diseases. This study explores the role of AI in managing HIV and TB co-infection in Nigeria. A comprehensive literature search strategy was developed using the keywords "HIV," "TB," "co-infection," "artificial intelligence," and "Nigeria" across six electronic databases: PubMed, Google Scholar, Cochrane Library, Web of Science, ResearchGate, and African Journals Online. The review focused on articles published between January 2014 and December 2022 to capture recent advancements and trends in AI applications in managing HIV and TB co-infection. Approximately 23%-26% of people with HIV in Nigeria are infected with both TB and HIV. People living with HIV in Nigeria are 26 times more likely to develop TB due to their weakened immune systems. The Early Warning Outbreak Recognition Systems is an AI system used for TB detection that is in practice in Nigeria. However, findings showed that AI models, including deep learning, machine learning, Computer-aided detection, Fuzzy cognitive maps, and Logistic regressions, the Twin model could be helpful in the accurate management of HIV/TB co-infection in Nigeria compared to traditional models, for example, inaccurate classification of radiographs and detection of HIV drug resistance. Despite the importance of AI toward managing these diseases, Nigeria faces challenges, including the unavailability of skilled personnel and AI experts, and the poor quality of the IT infrastructure, which are barriers to integrating AI into healthcare in the country. Strategic collaboration between the Nigerian government, digital health agencies, and healthcare organizations is crucial to implementing AI effectively for the treatment of HIV and TB co-infection in Nigeria. By embracing AI, Nigeria can revolutionize its healthcare system, improve patient outcomes, and address public health challenges such as HIV and TB co-infection.

Background: The use of fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the assessment of infectious diseases has been increasing, yet research on its impact during follow-up remains scarce.

Objectives: To evaluate the impact of follow-up FDG-PET/CT on managing focal infectious diseases.

Design: An observational, retrospective, single-center study.

Methods: Patients who underwent FDG-PET/CT for the diagnosis of focal infection and had a follow-up FDG-PET/CT between January 1, 2012 and October 31, 2023 were included. The impact of follow-up FDG-PET/CT on management was defined as findings leading to any change in antibiotic treatment or any source control interventions (impact group), which was compared to follow-up FDG-PET/CT that did not lead to any change in management (no-impact group).

Results: Eighty-nine patients were included, with a mean age of 62 ± 14.6 years. The most common infections were of skeletal (n = 34, 38.2%) and cardiovascular origin (n = 16, 17.9%). Overall, the follow-up FDG-PET/CT findings resulted in changing the management in 57 (64%) patients. It led to antibiotic change in 54 (60.7%) patients, and to source control intervention in 29 (32.6%) patients. Demographic and clinical characteristics of the impact group and the no-impact group were similar, except for a significantly higher rate of gram-positive bacteremia, which was detected in 26 (93%) patients with bacteremia in the impact group (mostly Staphylococcus aureus) compared to 8 (57%) of patients in the no-impact group, p = 0.01. Impact of FDG-PET/CT was associated with worsening clinical status, observed in 33 patients (57.9%) in the impact group compared to 6 (18.8%) in the no-impact group, p = 0.002.

Conclusion: Follow-up FDG-PET/CT appears to have a significant impact on managing selected patients with focal infections, particularly those caused by gram-positive bacteremia or with an unfavorable clinical course.

Background: Antibiotic exposure disrupts microbial communities in the gut and respiratory tract, causing functional changes that may have lasting health impacts and contribute to the spread of antibiotic resistance genes (ARGs) throughout life. However, age-stratified evidence of these effects, particularly in low- and middle-income countries (LMICs), remains limited.

Objective: This systematic review assessed the impact of antibiotics on gut and respiratory microbiomes and resistomes in LMICs, with separate analyses for adults and children.

Data sources: PubMed, Scopus, Web of Science, & ScienceDirect.

Methods: A comprehensive literature search was conducted using a predefined search strategy and eligibility criteria to identify relevant studies from LMICs. Twenty-five studies met the inclusion criteria: 23 examined the gut microbiome, and 2 focused on the respiratory microbiome. Key outcomes included microbial diversity (alpha/beta/gamma), taxonomic shifts, resistome profiles, functional changes, and recovery potentials, stratified by age group and body site.

Results: Antibiotic exposure was generally associated with reductions in microbial diversity and altered taxonomic composition, with children showing more pronounced and prolonged disruptions than adults. Analysis of resistome changes revealed a critical finding: while antibiotics consistently selected for ARGs matching the drug class administered, a substantial reservoir of non-matching, background ARGs, conferring resistance to beta-lactams, aminoglycosides, vancomycin, tetracyclines, was also highly prevalent across studies. This indicates a silent pre-existing resistome that is enriched by antibiotic pressure. ARGs were more abundant in adult resistomes, though functional changes occurred across age groups. Microbiome recovery was observed over time, but resistome recovery was limited.

Conclusion: Antibiotic use significantly disturbs the gut and respiratory microbiomes and promotes ARG enrichment, especially in children, who demonstrate greater susceptibility and lower recovery potential. These findings emphasise the need for targeted antibiotic stewardship, improved microbiome recovery research, and enhanced resistome monitoring in LMICs.

Trail registration: International Prospective Register of Systematic Reviews (PROSPERO), ID: CRD420250641394.

Background: Asymptomatic bacteriuria (ASB) is often overtreated, risking patient harm through unnecessary antimicrobial use and fostering antimicrobial resistance. Despite this, patients continue to be treated for ASB requiring targeted intervention for antimicrobial stewardship teams across health systems.

Objectives: This study assessed the impact of a multistep urinary tract infection (UTI)-focused stewardship initiative by comparing the incidence of asymptomatic urinary presentation (AUP) treatment before and after implementation.

Design: Retrospective cohort study.

Methods: Patients ⩾18 years at University of Kentucky HealthCare who received antimicrobial therapy with a urinalysis (UA) and/or urine culture (UCx) collected for a presumed UTI between January 2023 and March 2023 (pre-implementation) and January 2024 and March 2024 (post-implementation) were included in the study. Our primary outcome was to compare the frequency of AUP treatment between groups.

Results: Overall, 288 patients were included in the study, with 144 patients in both the pre- and post-implementation groups. Treatment of AUPs significantly decreased by 12% after initiative implementation (47% pre-implementation vs 35% post-implementation, p = 0.042). Additionally, we observed a significant difference in guideline-adherent management between the two groups (29% pre-implementation vs 44% post-implementation, p = 0.007). Patients were more likely to receive guideline-adherent UTI treatment durations (38% vs 53%, p = 0.009) and guideline-adherent definitive antibiotics (18% vs 35%, p < 0.001) post-implementation compared to pre-implementation.

Conclusion: Our stewardship initiative resulted in reduced treatment of AUPs and improved adherence to UTI management guidelines. Overall, a multifaceted stewardship initiative is a successful intervention to decrease the treatment of AUPs and unnecessary antibiotic utilization. However, additional frontline stewardship initiatives are likely warranted to decrease the unnecessary ordering of UAs.