Expert Review of Anti-infective Therapy最新文献

Objectives: Evaluation of the antifungal properties of Tamarix nilotica fractions against Candida albicans clinical isolates.

Methods: The in vitro antifungal potential was evaluated by agar well diffusion and broth microdilution methods. The antibiofilm potential was assessed by crystal violet, scanning electron microscopy (SEM), and qRT-PCR. The in vivo antifungal activity was evaluated by determining the burden in the lung tissues of infected mice, histopathological, immunohistochemical studies, and ELISA.

Results: Both the dichloromethane (DCM) and ethyl acetate (EtOAc) fractions had minimum inhibitory concentration (MIC) values of 64-256 and 128-1024 μg/mL, respectively. SEM examination showed that the DCM fraction decreased the biofilm formation capacity of the treated isolates. A significant decline in biofilm gene expression was observed in 33.33% of the DCM-treated isolates. A considerable decline in the CFU/g lung count in infected mice was observed, and histopathological examinations revealed that the DCM fraction maintained the lung tissue architecture. Immunohistochemical investigations indicated that the DCM fraction significantly (p < 0.05) decreased the expression of pro-inflammatory and inflammatory cytokines (TNF-α, NF-kB, COX-2, IL-6, and IL-1β) in the immunostained lung sections. The phytochemical profiling of DCM and EtOAc fractions was performed using Liquid chromatography-mass spectrometry (LC-ESI-MS/MS).

Conclusion: T. nilotica DCM fraction could be a significant source of natural products with antifungal activity against C. albicans infections.

Introduction: Artificial intelligence (AI) and machine learning (ML) have the potential to revolutionize the management of febrile neutropenia (FN) and drive progress toward personalized medicine.

Areas covered: In this review, we detail how the collection of a large number of high-quality data can be used to conduct precise mathematical studies with ML and AI. We explain the foundations of these techniques, covering the fundamentals of supervised and unsupervised learning, as well as the most important challenges, e.g. data quality, 'black box' model interpretation and overfitting. To conclude, we provide detailed examples of how AI and ML have been used to enhance predictions of chemotherapy-induced FN, detection of bloodstream infections (BSIs) and multidrug-resistant (MDR) bacteria, and anticipation of severe complications and mortality.

Expert opinion: There is promising potential of implementing accurate AI and ML models whilst managing FN. However, their integration as viable clinical tools poses challenges, including technical and implementation barriers. Improving global accessibility, fostering interdisciplinary collaboration, and addressing ethical and security considerations are essential. By overcoming these challenges, we could transform personalized care for patients with FN.

Background: Based on gas chromatography - mass spectrometry (GC-MS) results of a previous study, six metabolites including alpha-terpineol, geranyl acetate, linalool, myrcenol, terpinolene, and thymol showed significantly higher amounts relative to other metabolites.

Methods: A continuation of the previous study, the interaction of these metabolites with the main virulence factors of P. aeruginosa (pseudomonas elastase and exotoxin A), Staphylococcus aureus (alpha-hemolysin and protein 2a), Mycobacterium tuberculosis (ESX-secreted protein B and the serine/threonine protein kinase), and Escherichia coli (heat-labile enterotoxin and Shiga toxin) were evaluated by molecular docking study and molecular simulation.

Results: In the case of Shiga toxin, higher and lower binding affinities were related to alpha-terpinolene and zincite with values of -5.8 and -2.6 kcal/mol, respectively. For alpha-hemolysin, terpinolene and alpha-terpinolene demonstrated higher binding affinities with similar energies of -5.9 kcal/mol. Thymol and geranyl acetate showed lower binding energy of -5.7 kcal/mol toward protein 2a. Furthermore, thymol had a higher binding affinity toward heat-labile enterotoxin and ESX-secreted protein B with values of -5.9 and -6.1 kcal/mol, respectively.

Conclusions: It is concluded that the availability of secondary metabolites of A. haussknechtii surrounding zinc oxide (ZnO) NPs can hinder P. aeruginosa by inactivating Pseudomonas elastase and exotoxin.

Objective: The study aimed to observe the efficacy and safety of an all-oral bedaquiline (BDQ)-containing regimen for pediatric multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) through a multicenter, retrospective study in China.

Methods: In the study, pediatric patients receiving all-oral BDQ-containing regimen (BDQ group) with clinical matched control group were included, the control group received an injection-containing regimen. The treatment outcomes and the incidence of adverse events (AEs) were compared and analyzed.

Results: 79 pediatric patients were enrolled, including 37 cases in BDQ group and 42 cases in the control group, the median age was 12 {8-16} and 11 {9-15} in both groups respectively. Favorable treatment outcome and cure rate in BDQ group were significantly higher than those in control group (100%vs 83.3%, p 0.03; 94.6%vs 63.3%, p 0.00). Median time of sputum culture conversion in BDQ group was significantly shorter than that in the control group (4 weeks vs 8 weeks, p 0.00). The incidence of AEs in the BDQ group was significantly less than that in the control group (48.6% vs 71.4%, p 0.03). No AEs leading to treatment discontinuation of BDQ occurred.

Conclusions: The all-oral BDQ-containing regimens may be effective and safe in the Chinese pediatric population.

Introduction: Previous studies in Pakistan have shown considerable over prescribing of antibiotics in patients hospitalized with COVID-19 despite very low prevalence of bacterial infections. Irrational use of antibiotics will worsen antimicrobial resistance (AMR).

Methods: Retrospective analysis of medical records of patients in the COVID-19 wards of three tertiary care hospitals to assess antibiotic use during the sixth COVID-19 wave.

Results: A total of 284 patients were included, most were male (66.9%), aged 30-50 years (50.7%) with diabetes mellitus the most common comorbidity. The most common symptoms at presentation were cough (47.9%) and arthralgia-myalgia (41.5%). Around 3% were asymptomatic, 34.9% had mild, 30.3% moderate, and 23.6% had severe disease, with 8.1% critical. Chest X-ray abnormalities were seen in 43.3% of patients and 37% had elevated white cell counts, with 35.2% having elevated C-reactive protein levels. Around 91% COVID-19 patients were prescribed antibiotics during their hospital stay, with only a few with proven bacterial co-infections or secondary bacterial infections. Most antibiotics were from the 'Watch' category (90.8%) followed by the 'Reserve' category (4.8%), similar to previous COVID-19 waves.

Conclusion: There continued to be excessive antibiotics use among hospitalized COVID-19 patients in Pakistan. Urgent measures are needed to address inappropriate prescribing including greater prescribing of Access antibiotics where pertinent.

Introduction: The introduction of direct-acting antivirals (DAAs) has significantly transformed the therapeutic landscape for chronic C hepatitis virus (HCV) infection. However, there is still room for further improvement in optimizing therapy efficacy and minimizing adverse effects.

Areas covered: This review is devoted to the rationale for adopting a personalized approach to HCV therapy. Specifically, we explore the role of host-related factors, such as sex or the presence of comorbidities. We thoroughly examine the implications of commonly encountered comorbidities, including HIV infection, chronic renal disease, liver cirrhosis, and other chronic viral hepatitis infections. Additionally, we discuss the prevalent drug-to-drug interactions between DAAs and other medications, while providing guidance on their management. Finally, we investigate viral-related issues that can influence treatment outcomes, such as viral genotype, quasi-species, and the presence of resistance-associated mutations.

Expert opinion: Despite pivotal trials demonstrating efficacy rates exceeding 90% for currently available DAA regimens, there are still opportunities to optimize therapy outcomes and tailor treatment to each patient. This can be achieved through a meticulous evaluation of the patient's specific clinical conditions and comorbidities, a vigilant approach to manage potential drug interactions, and diligent patient follow-up.

Introduction: The HIV/AIDS epidemic has been one of the greatest challenges in global health, significantly affecting women of reproductive potential. Considerable advances in antiretroviral therapy for women living with HIV have contributed to improvements in quality of life, better reproductive and birth outcomes, and a reduced risk of perinatal transmission.

Areas covered: Despite the progress made, persistent challenges in access and adherence to antiretroviral drugs may limit their benefits for some women. More pharmacokinetic and safety studies in pregnant and lactating women are urgently needed, as are prospective surveillance systems to evaluate associations between fetal and infant antiretroviral exposures, drug-drug interactions, and pregnancy outcomes.

Expert opinion: Multipurpose technologies, such as combined HIV and other STI or unintended pregnancy prevention, and innovative delivery methods, such as the development of long-acting antiretrovirals, have the potential to reduce adherence challenges and enhance quality of life for women with HIV. Parallel advances in drug safety testing and surveillance are needed to ensure the health and safety of women with or at risk for HIV and children at risk for perinatal transmission.

Introduction: Carbapenem-resistant Enterobacterales (CRE) due to Metallo-β-lactamase (MBL) production are treated with either polymyxins or the novel combination of ceftazidime-avibactam and aztreonam (AA). This study aims to evaluate the 30-day mortality of AA in patients with BSI caused by MBL-CRE infections.

Methodology: In this systematic review and meta-analysis, all articles up to June 2023 were screened using search terms like 'CRE', 'MBL', 'AA' and 'polymyxins'. The risk ratio for AA vs polymyxins was pooled using a random-effect model, and the results were represented by a point estimate with a 95% confidence interval.

Results: After removing the duplicates, the titles and abstracts of 455 articles were screened, followed by a full-text screening of 50 articles. A total of 24 articles were included for systematic review, and four comparative studies were included in the meta-analysis. All four studies had a moderate or serious risk of bias. The pooled risk ratio for 30-day mortality for AA vs. polymyxins was 0.51 (95%CI: 0.34-0.76), p < 0.001. There was no significant heterogeneity.

Conclusion: The meta-analysis from studies with a high risk of bias shows that AA is associated with lesser 30-day mortality when compared to polymyxins in patients with MBL-producing CRE BSI. Registration with PROSPERO- CRD42023433608.

Introduction: Cytomegalovirus (CMV) infection remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). While conventional antiviral agents such as ganciclovir can be used for CMV prophylaxis, toxicities such as myelosuppression are a major concern.

Area covered: This work aimed to summarize the latest information and practical issues regarding a new anti-CMV agent, letermovir (LET).

Expert opinion: LET inhibits CMV replication by binding to components of the DNA terminase complex. A phase 3 trial in allo-HSCT recipients showed a reduced incidence of clinically significant CMV infection in the LET group. In 2017, this agent was first approved for CMV prophylaxis in adult CMV-seropositive allo-HSCT recipients in the United States, and is now used worldwide. While LET has an excellent toxicity profile, there are issues to be aware of, such as interactions with other drug classes (e.g. immunosuppressants and antifungals) and reactivation of CMV infection following LET cessation. While LET is the current standard of care for CMV prophylaxis, there are no established protocols for preemptive treatment of asymptomatic CMV viremia or for treatment of developed CMV disease. Further research is needed to maximize the benefits of LET, including the discovery of biomarkers.