Therapeutic Advances in Infectious Disease最新文献

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.

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.