Expert Review of Anti-infective Therapy最新文献

Introduction: SARS-CoV-2 infection and COVID-19 vaccination can both lead to serious cardiac conditions such as myocarditis, arrhythmia, acute myocardial infarction, and coagulopathy. Further studies are needed to better understand the risks and benefits of COVID-19 vaccination, and to determine the best course of action for individuals with preexisting heart conditions.

Areas covered: The current knowledge and challenges in understanding vaccine-associated heart issues concerning the COVID-19 pandemic are briefly summarized, highlighting similar cardiac conditions caused by either SARS-CoV-2 infection or COVID-19 vaccination and the potential clinical impacts.

Expert opinion: The short-term risks of severe cardiovascular side effects following COVID-19 vaccination are relatively low. However, further studies are needed to determine whether adverse vaccination events outweigh the long-term benefits in specific groups of individuals. Since cardiac inflammation, blood pressure dysregulation, coagulopathy, acute myocardial infarction, or arrhythmia could be the consequences of either SARS-CoV-2 infection or COVID-19 vaccination, clinical questions should be asked whether the COVID-19 vaccine worsens the condition in persons with preexisting heart diseases. It is important to carefully assess the potential risks and benefits of COVID-19 vaccination, especially for individuals with preexisting heart conditions, and to continue monitoring and studying the long-term effects of vaccination on cardiovascular health.

Background: Studies assessing the benefits of outpatient parenteral antimicrobial therapy (OPAT) have paid less attention to patient-centered factors such as patients' experiences and their health-related quality of life (HRQoL).

Research design and methods: Prospective before-and-after quasi-experimental study enrolled adult patients receiving OPAT at a tertiary hospital in Derbyshire, UK, between October 2022 and October 2023. Consenting patients completed paired EQ-5D-3 L questionnaires before OPAT initiation and upon completion of therapy or 30 days after its commencement (whichever occurred first). Changes and predictors of change in HRQoL indicators and associations with clinical outcomes (treatment failure, adverse events, and 30-day unplanned readmission) were examined.

Results: Health state index and visual analogue scale (EQ VAS) scores of 162 enrolled patients at baseline were significantly lower than the UK population averages, but the patients experienced significant improvements in both scores and in four EQ-5D dimensions (mobility, self-care, usual activities, and pain/discomfort). Baseline health index and EQ VAS scores were significant independent predictors of positive changes in HRQoL scores.

Conclusions: OPAT is associated with improved patient-reported quality of life and facilitates early return to work or school. Nevertheless, it is crucial to closely monitor patients with a lower baseline quality of life to optimize their overall OPAT experience.

Background: This study aimed to investigate the efficacy of bismuth added to a 2-week triple therapy consisting of tegoprazan (TPZ), amoxicillin, and clarithromycin for first-line Helicobacter pylori eradication.

Research design and methods: We reviewed the retrospective data of patients who received a 2-week TPZ-based triple therapy with or without 300 mg bismuth twice daily. The primary endpoint was the H. pylori eradication rate of adding bismuth to the TPZ-based triple regimen (TAC-B group), compared to no bismuth added (TAC group).

Results: In total, 306 and 256 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. The eradication success rates were significantly higher in the TAC-B group than in the TAC group (ITT, 82.9% vs. 71.8%, p = 0.029; PP, 95.8% vs. 87.5%, p = 0.027, respectively). The adherence rate to the eradication regimen was 100% in the TAC-B group and 97.0% in the TAC group. The adverse drug event rate in the TAC-B group was comparable to that in the TAC group (29.2% vs. 27.3%, p = 0.742). No use of bismuth was significantly associated with eradication failure (p = 0.038).

Conclusions: The bismuth add-on increased the first-line H. pylori eradication rate of 2-week TPZ-based triple therapy.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT05453994.

Introduction: Klebsiella pneumoniae is a major agent of healthcare-associated infections and a cause of some community-acquired infections, including severe bacteremic infections associated with metastatic abscesses in liver and other organs. Clinical relevance is compounded by its outstanding propensity to evolve antibiotic resistance. In particular, the emergence and dissemination of carbapenem resistance in K. pneumoniae has posed a major challenge due to the few residual treatment options, which have only recently been expanded by some new agents. The epidemiological success of carbapenem-resistant K. pneumoniae (CR-Kp) is mainly linked with clonal lineages that produce carbapenem-hydrolyzing enzymes (carbapenemases) encoded by plasmids.

Areas covered: Here, we provide an updated overview on the mechanisms underlying the emergence and dissemination of CR-Kp, focusing on the role that plasmids have played in this phenomenon and in the co-evolution of resistance and virulence in K. pneumoniae.

Expert opinion: CR-Kp have disseminated on a global scale, representing one of the most important contemporary public health issues. These strains are almost invariably associated with complex multi-drug resistance (MDR) phenotypes, which can also include recently approved antibiotics. The heterogeneity of the molecular bases responsible for these phenotypes poses significant hurdles for therapeutic and diagnostic purposes.

Background: This study assessed the clinical efficacy of nirmatrelvir plus ritonavir (NMV-r) in treating patients with COVID-19 who have preexisting cardiovascular diseases (CVDs).

Methods: Patients with underlying CVDs and COVID-19 were included from the TriNetX network. We employed a 1:1 propensity score matching to create two comparable cohorts: patients receiving NMV-r and those not receiving NMV-r. The primary outcome was the composite outcome of all-cause hospitalization or death within 30 days.

Results: Propensity score matching yielded two matched cohorts of 10,847 patients each. The composite outcomes of all-cause hospitalization or death within 30 days were 2.2% (239 patients) in the NMV-r cohort and 4.7% (512 patients) in the control cohort, indicating reduced risk in the NMV-r cohort (hazard ratio [HR], 0.475; 95% confidence interval [CI], 0407-0.533). The NMV-r cohort exhibited lower risks of all-cause hospitalization (HR, 0.525; 95% CI, 0.449-0.615) and mortality (HR, 0.113; 95% CI, 0.052-0.246) compared with the control group. A similar trend was observed across most of the subgroups.

Conclusions: Our findings indicate that NMV-r to treat COVID-19 could reduce all-cause hospitalization and death in patients with CVDs.

Introduction: Antimicrobial resistance in Latin America is a growing concern in both human and non-human animal populations. The economic burden that is likely to be imposed through increased resistance will cause further strains on public health systems and the population at large.

Areas covered: We propose the rapid adoption and implementation of phage therapy as a necessary addition to the medical arsenal to help mitigate antimicrobial resistance, with an emphasis on considering the potential benefits that highly biodiverse countries such as Ecuador may have on phage discovery. However, programs may count on limited government support and/or facilitation, which could slow progress.

Expert opinion: We highlight the need for educational campaigns to be implemented in parallel with the development of phage therapy programs, particularly to implement these novel treatments in rural and indigenous communities.

Introduction: Carbapenem resistant Enterobacterales (CRE) are a major threat to global health and hospital-onset CRE infections have risen during the COVID-19 pandemic. Novel antimicrobials are now available for the treatment of CRE infections. There remains an urgent need for new antimicrobials for CRE, especially for those producing metallo-β-lactamases.

Areas covered: This article discusses previously published research supporting currently available novel antimicrobials for the treatment of CRE infections. Newer compounds currently being evaluated in clinical trials are covered. A literature search was conducted in PubMed over all available dates for relevant published papers and conference abstracts with the search terms, 'CRE,' 'carbapenem-resistant Enterobacterales,' 'β-lactam-β-lactamase inhibitor,' 'KPC,' 'NDM,' 'metallo-β-lactamase,' 'ceftazidime-avibactam,' 'meropenem-vaborbactam,' 'imipenem-cilastatin-relebactam,' 'cefiderocol,' 'eravacycline,' 'plazomicin,' 'taniborbactam,' 'zidebactam,' and 'nacubactam.'

Expert opinion: Novel antimicrobials for CRE infections have been developed, most notably the β-lactam-β-lactamase inhibitor combinations, though treatment options for infections with metallo-β-lactamase producing Enterobacterales remain few and have limitations. Development of antibiotics with activity against metallo-β-lactamase producing Enterobacterales is eagerly awaited, and there are promising new compounds in clinical trials. Finally, more clinical research is needed to optimize and individualize treatment approaches, which will help guide antimicrobial stewardship initiatives aimed at reducing the spread of CRE and development of further resistance.

Introduction: Severe acute hepatitis (SAH) is defined by a severe inflammation of hepatocytes in the liver parenchyma which can lead to an acute liver failure, a clinical condition with high mortality rate that can be triggered by several factors but is usually associated to hepatotropic viruses' infection. In 2022, cases of children with severe acute hepatitis of unknown origin hospitalized in Glasgow, Scotland, were reported. Possible causes of this condition include, but are not limited to, undiagnosed viral (and non-viral) infections, autoimmune hepatitis, drug and/or chemical toxicity, mitochondrial chain respiratory and metabolic disorders.

Areas covered: Herpesviruses can cause severe acute hepatitis, but little is known about the role and the mechanisms of herpesviruses as a causative agent of this type of hepatitis. We review the role of herpesviruses as causative agent of SAH in children and other possible mechanisms involved in this disease.

Expert opinion: Differential diagnosis for herpesvirus in SAH should be implemented in all settings. Alternative fluids, such as saliva and dried blood, could be used in the diagnosis to overwhelm the availability of biological specimens at sufficient volume. In the future, genetic studies could also be added to increase the knowledge about severe acute hepatitis in children.

Background: The study aimed to evaluate health literacy, knowledge, household disposal, and misuse practices of antibiotics among the United Arab Emirates (UAE) residents.

Research design and methods: An observational cross-sectional study was conducted between May 1^st and August 31^st, 2022. The study encompassed a sample of 1074 participants.

Results: Participants involved in a medical field (OR: 1.98, 95% CI: 1.45-2.69, p < 0.001) were more likely to have adequate health literacy. Most participants rarely (n = 315; 29.33%) or sometimes (n = 292; 27.19%) sought help from a doctor or pharmacist with reading the instructions and leaflets of antibiotics. A bachelor`s degree was associated with a reduced odds ratio of self-medication with antibiotics (OR: 0.46, 95% CI: 0.29-0.75, p = 0.002). Only 10.61% of unneeded antibiotics were returned to the pharmacy, 79.42% were disposed of at home and 10% were disposed of using other disposal practices.

Conclusions: Higher levels of adequate health literacy were observed in those involved in the medical field and those with higher educational levels. The prevalence of self-medication with antibiotics among the UAE population was low. These findings highlight the importance of improving health literacy, promoting responsible antibiotic use, and encouraging proper disposal practices among the population.

Introduction: Staphylococcus aureus, a human commensal, is also one of the most common and serious pathogens for humans. In recent years, its capacity to survive and replicate in phagocytic and non-phagocytic cells has been largely demonstrated. In these intracellular niches, bacteria are shielded from the immune response and antibiotics, turning host cells into long-term infectious reservoirs. Moreover, neutrophils carry intracellular bacteria in the bloodstream, leading to systemic spreading of the disease. Despite the serious threat posed by intracellular S. aureus to human health, the molecular mechanisms behind its intracellular survival and subsequent antibiotic treatment failure remain elusive.

Area covered: We give an overview of the killing mechanisms of phagocytes and of the impressive arsenal of virulence factors, toxins and stress responses deployed by S. aureus as a response. We then discuss the different barriers to antibiotic activity in this intracellular niche and finally describe innovative strategies to target intracellular persisting reservoirs.

Expert opinion: Intracellular niches represent a challenge in terms of diagnostic and treatment. Further research using ad-hoc in-vivo models and single cell approaches are needed to better understand the molecular mechanisms underlying intracellular survival and tolerance to antibiotics in order to identify strategies to eliminate these persistent bacteria.