Therapeutic Advances in Infectious Disease最新文献

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.

Arthropod-borne viruses (arboviruses) represent a major public health burden for people living or visiting tropical and subtropical countries, where an endemic/epidemic cycle has been successfully established for Orthoflavivirus denguei, Alphavirus chikungunya, and O. zikaense. The risk for the reemergence of other viruses in the urban cycle in the Americas, such as A. mayaro and O. flavi is also of major concern, which justifies the intensification of active surveillance in urban, rural, and sylvatic areas to determine the virus activity in different settings. Entomological surveillance consists mainly of collecting, identifying, and estimating the relative densities of the main disease-transmitting vector species, and more recently, estimating infection rates for the more relevant pathogens. The new approaches for monitoring arthropod vectors of medical importance pose new challenges, including maintaining the cold chain to preserve the pathogen infectivity or nucleic acid stability, especially for RNA genomes, such as those of the main arboviruses. Hence, alternatives such as mosquito traps equipped with solid-phase materials impregnated with honey baits for mosquito feeding, saliva expectoration, and nucleic acid stabilization have been gaining popularity as they can be used as an early warning system to provide arbovirus genetic information useful in molecular epidemiology studies. Here, we present the state of the art in the use of this approach and highlight the need for exploration of the potential of different available solid-phase materials for nucleic acid immobilization and stabilization during mosquito feeding on honey-baited traps. The current challenges for the successful implementation of feasible entomo-virological surveillance as a routine arbovirus surveillance tool in mosquitoes in urban and rural settings of endemic areas are also discussed.

Pseudomonas aeruginosa is one of the most clinically important Gram-negative bacteria and is related to many severe and life-threatening infections worldwide. It presents intrinsic resistance against many antibiotics and has the ability to acquire or develop additional mechanisms to overcome the action of all anti-pseudomonal drugs. Formerly abandoned antibiotics and new compounds such as cefiderocol and combinations of β-lactams with new β-lactamase inhibitors are considered for the treatment of infections due to multi- or extensively-drug-resistant strains. In the present review, the antimicrobial resistance mechanisms of P. aeruginosa and the potential treatment options for the difficult to treat P. aeruginosa infections are discussed in an attempt to correlate microbiological and laboratory data to the choice of optimal treatment in everyday clinical practice.

Background: Salmonella species are major pathogens responsible for gastroenteritis and typhoid fever. In 2017, Salmonella enterocolitis caused over 95 million cases of diarrhoea and 50,000 deaths globally, with India bearing more than 50% of the typhoid burden.

Objectives: To test the association of monthly mean and maximum temperature, precipitation and absolute humidity with the incidence of Salmonella bacteraemia in a metropolitan city in South India.

Design: A retrospective time-series analysis.

Methods: This study employed a retrospective time-series analysis to evaluate the influence of meteorological variables, including temperature, absolute humidity and precipitation, on Salmonella bacteraemia in a metropolitan city in South India.

Results: Between 2014 and 2019, a total of 492 blood culture-confirmed cases of Salmonella bacteraemia were identified in Mysuru, India. S. typhi was predominantly among younger patients, while non-typhoidal Salmonella was more frequent in older age groups. Resistance was highest to nalidixic acid (84%), with a rising trend in ciprofloxacin resistance. Increased mean temperature (lags 1-3 months) and absolute humidity were positively associated with Salmonella bacteraemia, while temperature variability was protective, and monsoon rainfall significantly increased the risk. Cumulative exposure-response analyses further showed elevated risks at higher humidity (>26 g/m³), temperatures (>34°C) and extreme precipitation (>250 mm), although confidence intervals were wide and most associations did not reach statistical significance.

Conclusion: This single-centre retrospective time-series analysis has demonstrated that meteorological variables impact the incidence of Salmonella bacteraemia, which could lead to increased antibiotic use and contribute to the development of resistance.

Background: Methicillin-susceptible Staphylococcus aureus (MSSA) is a leading cause of infective endocarditis (IE), associated with high morbidity and mortality. While antistaphylococcal penicillins (ASPs) are considered the standard treatment, cefazolin has emerged as a potential alternative due to its pharmacokinetic advantages and lower toxicity profile.

Objectives: To assess the efficacy and safety of cefazolin compared with ASPs in adult patients with MSSA infective endocarditis.

Design: Systematic review and meta-analysis.

Data sources and methods: We systematically searched MEDLINE, Embase, CENTRAL, Scopus, and Web of Science up to 2024. We included cohort studies and non-randomized trials comparing cefazolin and ASPs in adult patients with MSSA IE. Risk of bias was evaluated using the ROBINS-I tool. Meta-analyses were performed using random-effects models to estimate pooled odds ratios (ORs) and standardized mean differences (SMDs).

Results: Seven cohort studies involving 1685 patients (305 cefazolin; 1380 ASPs) were included. Thirty-day mortality, reported in two studies (n = 1083), was lower with cefazolin (OR 0.49; 95% CI 0.29-0.83; I² = 0%). Ninety-day mortality (three studies, n = 475) showed no significant difference (OR 1.00; 95% CI 0.63-1.57; I² = 0%). No significant differences were observed in relapse rates (OR 1.01; 95% CI 0.34-3.02; I² = 12.5%), hospital stay duration (SMD -0.06; 95% CI -0.27 to 0.14), or bacteremia duration (SMD -0.96; 95% CI -1.93 to 0.01). Safety data suggested a lower incidence of adverse events with cefazolin, although definitions varied across studies. Risk of bias was moderate in most studies.

Conclusion: Cefazolin demonstrated comparable efficacy to ASPs for the treatment of MSSA IE, with a potential reduction in short-term mortality and a favorable safety profile. These findings support cefazolin as a viable therapeutic alternative, but randomized controlled trials are needed to confirm its effectiveness and safety.

Trial registration: PROSPERO registration number: CRD42024593515.

Background: Tuberculosis (TB) remains a global public health priority, with 10.5 million new cases and 1.5 million deaths reported in 2023. Current diagnostic methods face limitations in sensitivity, biosafety, and accessibility, particularly in low-resource settings.

Objective: This study evaluates the diagnostic accuracy of a novel, Polymerase Chain Reaction (PCR) platform (Orange G3 TBC), comparing it with the WHO-endorsed GeneXpert Ultra system in Oruro, Bolivia.

Design: We conducted a randomized, double-blind study.

Methods: The study included 71 clinical samples (67 sputum samples and 4 cerebrospinal fluid samples) from patients with presumptive TB. All samples were tested with GeneXpert Ultra and the Orange G3 TBC platform, which incorporates a unique biosafe processing system. Statistical analysis included sensitivity, specificity, predictive values (positive predictive value (PPV) and negative predictive value (NPV)), likelihood ratios (LR+ and LR-), and correlation measures.

Results: Orange G3 TBC demonstrated strong performance metrics compared to GeneXpert Ultra: sensitivity = 90%, specificity = 97%, diagnostic efficiency = 96%, PPV = 82%, and NPV = 98%. Statistical analysis showed a high correlation between the two methods (Pearson's correlation = 0.834, Kappa = 0.832, LR+ = 27.3, LR- = 0.103).

Conclusion: The Orange G3 TBC platform offers comparable diagnostic accuracy to GeneXpert Ultra. The system is adaptable to resource-limited settings, making it a viable alternative for TB diagnosis in endemic regions.