Expert Review of Anti-infective Therapy最新文献

Background: : This study aimed to check the effect of supplementation with low-dose group B vitamins on clinical and biochemical parameters on patients with coronavirus disease 2019 (COVID-19).

Research design and method: : This double-blind, randomized clinical trial was carried out on 85 critically ill patients with COVID-19. All patients received high protein prescriptions of 30 kcal/kg/d by enteral nutrition. The intervention group (n = 40) received vitamin B complex, including thiamine (10 mg), riboflavin (4 mg), nicotinamide (40 mg), and dexpanthenol (6 mg). The control group received similar nutritional supports, except for group B vitamins. Assessments were carried out at baseline and after 2 weeks of intervention.

Results: : Vitamin B supplementation had no effects on the biochemical and pathological parameters including kidney function, arterial blood gas parameters, Glasgow coma scale, cell blood count, and serum electrolytes of the intervention group compared with the control group. The 30-day mortality was insignificantly lower in the intervention group than in the control group (83.3% against 96.1%, P = 0.07).

Conclusions: The mortality rate of patients with COVID-19 might be improved by low-dose vitamin B supplementation.

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.

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.

Introduction: Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) continue to be common infections causing significant morbidity and mortality worldwide. The timely initiation of empiric antimicrobial therapy is essential. In this paper, we provide a focused expert opinion on the current and potential empiric antimicrobial treatment options in HABP and VABP in Canada influenced by antimicrobial resistance impacting the use of older agents as well as available new intravenous (IV) antimicrobials.

Areas covered: The authors discuss treatment options for HABP and VABP in Canada. In addition, we focus on the potential role of new IV antimicrobials recently introduced to Canada. A literature search of HABP and VABP treatments was performed via PubMed (up to March 2023), using the following key words: monotherapy, combination therapy, aminoglycosides, carbapenems, cephalosporins, fluoroquinolones, penicillins as well as amoxicillin/clavulanate, ceftobiprole, ceftolozane/tazobactam, dalbavancin, and fosfomycin.

Expert opinion: Empiric antimicrobial treatment for HABP and VABP in Canada continues to focus on both the severity of illness and the presence/absence of patient risk factors for antimicrobial resistance. The role of new IV antimicrobials in the empiric treatment for HABP and VABP depends on their antimicrobial activity and published data on efficacy and safety and influenced by Health Canada-approved indications.

Background: Irrational use of antibiotics intensifies resistance and jeopardizes advances made in modern medicine. We aimed to conduct a baseline gap analysis survey on antibiotic prescription practices across Pakistan.

Research design and methods: This multi-centered cross-sectional survey was conducted at six public sector tertiary care hospitals from February 2021 to March 2021. Data related to various variables including hospital infrastructure, policies and practices, monitoring and feedback, and epidemiological, clinical, and antibiotic prescription for surveyed patients was collected using World Health Organization (WHO) Point Prevalence Survey (PPS) methodology.

Results: In a survey of 837 inpatients, 78.5% were prescribed antibiotics. Most commonly prescribed antimicrobial was ceftriaxone (21.7%), followed by metronidazole (17.3%), cefoperazone-sulbactam (8.4%), amoxicillin-clavulanate (6.3%), and piperacillin/tazobactam (5.9%). Surgical prophylaxis (36.7%) and community-acquired infections (24.7%) were the main reasons for antibiotic prescriptions. Single antibiotics were given to 46.7% of patients, 39.9% received a combination of two antibiotics, and 12.5% were prescribed three or more antibiotics. Among six hospitals surveyed, two had drug and therapeutic committees, three had infection prevention and control committees, and one had an antibiotic formulary.

Conclusion: Findings demonstrate high consumption of broad-spectrum antimicrobials and emphasize the importance of expanding antimicrobial stewardship programs among hospitals. Mentoring clinical teams could help rationalize antimicrobial use.

Background: We aimed to assess the impact of antiviral drugs (fluvoxamine,remdesivir, lopinavir/ritonavir (LPV/r), molnupiravir, andnirmatrelvir/ritonavir (NRV/r)) on health care utilization (HCU) inCOVID-19 patients. We summarized findings from randomized controlledtrials (RCTs) and observational studies.

Methods: We systematically searched four medical databases (PubMed, Web of Science, Embase, Cochrane Library) for COVID-19 studies up to February 15, 2023. A comprehensive review, meta-analysis, sensitivity analysis, and subgroup analysis were conducted. Pooled effects with 95% confidence intervals (CIs) were calculated for antiviral drugs' impact on hospitalization, mechanical ventilation (MV), and intensive care unit (ICU) outcomes.

Results: Our analysis included 34 studies (584,978 patients). Meta-analysisindicated potential benefits: remdesivir and molnupiravir potentiallyreduced MV risk, and NRV/r correlated with lower hospitalizationrates. However, LPV/r did not notably curb HCU. Remdesivir waspreferable for high-risk COVID-19 patients, while molnupiravir andNRV/r were recommended for those aged 60 and above.

Conclusion: Remdesivir, molnupiravir, and NRV/r may reduce HCU during the COVID-19 pandemic. However, due to limited study details and significant heterogeneity in effect estimates, further precise evidence is crucial, especially concerning emerging variants.

Introduction: The emergence of the Omicron SARS-CoV-2 variant of concern in late November 2021 presaged yet another stage of the COVID-19 pandemic. Paxlovid, a co-packaged dosage form of two antiviral drugs (nirmatrelvir and ritonavir) developed by Pfizer, received its first FDA Emergency Use Authorization (EUA) and conditional marketing by European Medical Agency in patients at high risk of developing severe COVID-19.

Areas covered: We reviewed the timeline of the drug nirmatrelvir from its discovery to authorization by FDA. After 1 year of its authorization, numerous studies and reports on paxlovid's use and post-use consequences are available. This review summarizes the complete journey of paxlovid from its development, preclinical studies, clinical trials, regulatory approvals, ongoing clinical trials, and safety measures, followed by discussions on recent updates on drug-drug interactions, adverse effects, and relapse of COVID-19.

Expert opinion: Paxlovid, a new oral antiviral therapy for COVID-19, has shown promising results in clinical trials and has the potential to be effective against the pandemic, particularly for individuals at high risk of severe illness. Comorbidity usage and pharmacovigilance will play a significant stake in the future of paxlovid development. Second-generation M^pro inhibitors play an important role in the upcoming problems associated with COVID-19.

Introduction: The management of invasive fungal infections (IFIs) in low- and middle-income countries (LMIC) is a serious challenge due to limited epidemiology studies, sub-optimal laboratory facilities, gap in antifungal management training and resources. Limited studies highlighted distinctive epidemiology of IFIs in those countries, and difficulty in distinguishing from closely related infections. To overcome the gaps for appropriate management of IFIs, innovative approaches are required.

Areas covered: Extensive literature search and discussion with experts have helped us to summarize the epidemiology, diagnostic and management difficulties in managing IFIs in LMIC, and recommend certain solutions to overcome the challenges.

Expert opinion: The strategies to overcome the challenges in diagnosis may include local epidemiology study, training of healthcare workers, association of fungal infections with already existing budgeted national programs, development and incorporation of point-of-care test (POCT) for prompt diagnosis, simplifying clinical diagnostic criteria suitable for LMIC, judicious use of available expertise, and diagnostic stewardship. For management strategies judicious use of antifungal, partnering with industry for inexpensive antifungal agents, development of LMIC specific guidelines for cost-effective management of IFIs and fungal outbreaks, improvement of infection control practices, advocacy for implementation of WHO recommended antifungal use, and integration of IFIs with public health.