Therapeutic Advances in Infectious Disease最新文献

Background: Outpatient Parenteral Antimicrobial Therapy (OPAT) is considered a patient-friendly and cost-effective practice. Patients in the OPAT service can be at risk for developing adverse events. Due to extensive variations in practice, guidelines have been developed to minimize the risks.

Objectives: In this first worldwide survey on OPAT, we explored the current OPAT services around the world, adherence to recommendations and identified best practices and challenges from different perspectives.

Methods: An e-survey was conducted and consisted of questions about demographics, characteristics of the OPAT service, role of pharmacy, future developments, and respondents' views on improvements as well as best practices.

Results: A total of 126 responses from 28 countries were included. Seventy-eight percent (78%) of the respondents stated that their facility provides antimicrobial therapy in the outpatient setting, whereas 22% did not. Forty-two percent (42%) of the hospitals with OPAT services had a specialized OPAT service, while 14% lacked specialized services and 22% had a partially specialized team in place. In facilities with a specialized OPAT service, the number of mandatory infectious disease (ID) consultations before discharge and clinical monitoring by an ID specialist or OPAT team member, the frequency of monitoring, and the availability of an OPAT registry were higher. A multidisciplinary team's presence was commonly noted as best practices. On the other hand, respondents experienced difficulties with reimbursement and lack of standardization in the screening, follow-up and monitoring of patients.

Conclusion: This survey provides a better understanding of the implementation and practices of OPAT services globally and describes best practices and the challenges from different professionals.

Background: Ceftolozane/Tazobactam is a β-lactam/β-lactamase inhibitor combination with a high range of efficacy and broad-spectrum action against multidrug-resistant bacterial strains.

Objectives: The present study aimed to analyze the in vitro activity of Ceftolozane/Tazobactam against extended-spectrum β-lactamases (ESBLs)-producing Escherichia coli (ESBLs-EC) and Klebsiella pneumonia (ESBLs-KP) in the published literature to provide international data on the antimicrobial stewardship programs.

Design: Systematic review and meta-analysis.

Methods: A systematic literature search was conducted on the Web of Science, Embase, PubMed, Scopus, and Google Scholar electronic databases from the beginning of databases to December 2022 to cover all published articles relevant to our scope.

Results: At last, 31 publications that met our inclusion criteria were selected for data extraction and analysis by Comprehensive Meta-Analysis Software. The pooled prevalence of Ceftolozane/Tazobactam susceptibility for ESBLs-EC and ESBLs-KP was estimated at 91.3% [95% confidence interval (CI): 90.1-92.5%] and 65.6% (95% CI: 60.8-70.2%), respectively. There was significant heterogeneity among the 31 studies for ESBLs-EC (χ² = 91.621; p < 0.001; I² = 67.256%) and ESBLs-KP (χ² = 348.72; p < 0.001; I² = 91.4%). Most clinical isolates of ESBLs-EC had MIC₅₀ and MIC₉₀ at a concentration of 0.5 and 2 µg/mL [minimum inhibitory concentration (MIC) at which 50% and 90% of isolates were inhibited], respectively. In contrast, most clinical isolates of ESBLs-KP had MIC₅₀ and MIC₉₀ at a concentration of 1 and 32 µg/mL, respectively.

Conclusion: Based on the meta-analysis results, Ceftolozane/Tazobactam has a more promising in vitro antibacterial activity against ESBLs-EC isolates from different clinical sources than ESBLs-KP isolates. Therefore, Ceftolozane/Tazobactam can be a useful therapeutic drug as an alternative to carbapenems. Randomized clinical trials are needed to provide clinical evidence to support these observations.

Background: Healthcare workers were at the forefront of the COVID-19 pandemic. The acceptability and uptake of COVID-19 vaccines among healthcare workers was an important strategy in halting the spread of the virus as well as the antecedent implications on global health and the world economy.

Objectives: This study aims to determine the acceptability rate and barriers to COVID-19 vaccination of frontline healthcare workers in Awka, Nigeria.

Design: This is an analytical cross-sectional study.

Methods: An online cross-sectional survey was conducted from February 2022 to April 2022 to obtain the data for this study. One hundred healthcare workers were studied. Acceptability rate and barriers to uptake of COVID-19 vaccination were outcome measures.

Results: The COVID-19 vaccination rate was 45.0% among healthcare workers in study area of Awka metropolis. Ages 30-39 years had the highest acceptance rate of COVID-19 vaccination, 19 (47.5%; p = 0.262) with a more female preponderance of COVID-19 vaccine acceptance compared to males [26 (41.3%) vs 16 (42.2%), p = 0.721]. The place of residence of respondents (urban vs rural) and their marital status (married vs single) appeared not to influence the acceptance of COVID-19 vaccination [(38 (42.2%) vs 3 (33.3%); p = 0.667; 25 (36.8% vs 17 (54.8%); p = 0.433)]. Years of work experience (<10 years vs >10 years) significantly affected COVID-19 vaccine acceptance [27 (45.8%) vs 12 (52.2%); p = 0.029]. Educational status and monthly income appeared not to influence vaccine uptake (p > 0.05, for both). A significant number of respondents were not sure why they should or should not take the COVID-19 vaccine [49 (92.5%) vs 35 (83.3%); p = 0.001].

Conclusion: The COVID-19 vaccination rate is still poor among healthcare workers in Awka metropolis. The majority of respondents do not know why they should or should not take COVID-19 vaccine. We therefore recommend robust awareness campaigns that will explain in clear terms the essence and efficacy of COVID-19 vaccination in order to improve vaccine acceptance.

A sizable portion of the United States' population lives in a rural setting. Coupled with a limited number of infectious diseases providers, this has created a need for innovative practice models to deliver outpatient antimicrobial therapy and clinical monitoring in rural settings. This article reviews existing literature regarding outpatient parenteral antimicrobial therapy in rural settings and explores existing barriers and potential solutions that may be of assistance to providers looking to provide these services.

Background and aim: With conflicting data from previous observational studies on the relationship between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and pancreatic cancer (PC), we decided to conduct a systematic review and meta-analysis in order to evaluate any potential association.

Design: This is a systematic review and meta-analysis.

Methods: We conducted a search of three databases (PubMed, Embase, and Web of Science) from the time of their creation up to June 2023. The summary results, including hazard ratio (HR) with 95% confidence interval (CI), were pooled using a generic inverse variance method and a random-effects model. Furthermore, subgroup and sensitivity analyses were conducted.

Results: In this meta-analysis, 22 cohort studies with a total of 10,572,865 participants were analyzed. Meta-analysis from 15 cohort studies revealed that HBV infection was correlated with an increased risk of PC (HR = 1.53, 95% CI: 1.40-1.68, p < 0.00001) with no heterogeneity (I² = 0%, p = 0.49). Meta-analysis from 14 cohort studies showed that HCV infection was associated with an increased risk of PC (HR = 1.82, 95% CI: 1.51-2.21, p < 0.00001). Most of our subgroup analyses yielded similar results. Meta-analysis from four cohort studies indicated that co-infection with HBV and HCV was linked to an increased risk of PC (HR = 2.32, 95% CI: 1.40-3.85, p = 0.001) with no heterogeneity observed (I² = 0%, p = 0.60). The results of sensitivity analyses were robust.

Conclusion: Our meta-analysis showed that HBV/HCV infection or co-infection with HBV and HCV was associated with an increased risk of PC. Future prospective cohort studies need to take into account various ethnicities and any confounding factors, as well as investigate the potential mechanisms of PC development in those with HBV/HCV.

Trial registration: Open Science Framework registries (No: osf.io/n64ua).

Introduction: Millions of snake bites occur worldwide each year. Clinical practice guidelines generally do not recommend the use of prophylactic antibiotics.

Objective: To determine the sociodemographic, clinical, and pharmacological variables and the use of antibiotics in a group of patients with snake bites in Colombia.

Methods: A retrospective cross-sectional study was carried out. Patients affiliated with a Colombian health insurer who presented with snake bites between 2015 and 2022 were included. The cases were identified from the National Public Health Surveillance System. Sociodemographic, clinical and pharmacological variables were identified. Descriptive and bivariate analyses were performed.

Results: A total of 643 patients were analyzed, with a median age of 30.8 years, and 74.7% were men. The most frequently identified genus of snake was Bothrops (88.8%), and most incidents were classified as mild ophidian accidents (61.6%). A total of 59.7% of patients received snake antivenom. A total of 13.8% and 2.2% of the patients had cellulitis or abscesses, respectively. A total of 63.5% received antibiotics (50.6% for prophylaxis and 12.9% for treatment), especially cephalexin (25.9%), and most of the antibiotic management was considered inappropriate (91.7%).

Conclusion: Most patients with snake bites received antibiotics, especially for prophylactic purposes, a clinical behavior that goes against current evidence. The use of antibiotics with an unsuitable spectrum for the microorganisms that are usually found in the wounds of these patients is frequent. The development of local clinical practice guidelines is required to help reduce the overprescription of antibiotics, as the excessive use of antimicrobials is the main determinant of antimicrobial resistance.

Background: Currently, there is no safe and effective vaccine against leishmaniasis and existing therapies are inadequate due to high toxicity, cost and decreased efficacy caused by the emergence of resistant parasite strains. Some indazole derivatives have shown in vitro and in vivo activity against Trichomonas vaginalis and Trypanosoma cruzi. On that basis, 20 indazole derivatives were tested in vitro against Leishmania amazonensis.

Objective: To evaluate the in vitro activity of twenty 2-benzyl-5-nitroindazolin-3-one derivatives against L. amazonensis.

Design: For the selection of promising compounds, it is necessary to evaluate the indicators for in vitro activity. For this aim, a battery of studies for antileishmanial activity and cytotoxicity were implemented. These results enabled the determination of the substituents in the indazole derivatives responsible for activity and selectivity, through the analysis of the structure-activity relationship (SAR).

Methods: In vitro cytotoxicity against mouse peritoneal macrophages and growth inhibitory activity in promastigotes were evaluated for 20 compounds. Compounds that showed adequate selectivity were tested against intracellular amastigotes. The SAR from the results in promastigotes was represented using the SARANEA software.

Results: Eight compounds showed selectivity index >10% and 50% inhibitory concentration <1 µM against the promastigote stage. Against intracellular amastigotes, four were as active as Amphotericin B. The best results were obtained for 2-(benzyl-2,3-dihydro-5-nitro-3-oxoindazol-1-yl) ethyl acetate, with 50% inhibitory concentration of 0.46 ± 0.01 µM against amastigotes and a selectivity index of 875. The SAR study showed the positive effect on the selectivity of the hydrophilic fragments substituted in position 1 of 2-benzyl-5- nitroindazolin-3-one, which played a key role in improving the selectivity profile of this series of compounds.

Conclusion: 2-bencyl-5-nitroindazolin-3-one derivatives showed selective and potent in vitro activity, supporting further investigations on this family of compounds as potential antileishmanial hits.

Background: Pre-exposure prophylaxis (PrEP) is a valuable tool in the response to the HIV epidemic, recommended for groups with a higher risk of HIV infection, such as men who have sex with men (MSM), particularly in the context of high-risk sexual behavior such as chemsex.

Purpose: This study aimed to analyze the prevalence and factors associated with the intention to use PrEP among MSM who engage in chemsex in Brazil and Portugal.

Methods: This was a cross-sectional study of a secondary dataset from a larger study conducted between January 2020 and May 2021 throughout Brazil and Portugal involving 1852 MSM who engage in chemsex. An initial descriptive analysis was performed to calculate the absolute and relative frequencies of independent variables related to the intention to use PrEP among MSM. A multivariate regression model was developed to identify factors independently associated with the intention to use PrEP.

Results: Although a high level of PrEP knowledge (85.75%) was observed among MSM who engage in chemsex, the prevalence of intention to use PrEP was only 59.07%. Five variables were associated with a higher prevalence of intention to use PrEP [engaging in double penetration - adjusted prevalence ratio (aPR): 1.56, 95% CI: 1.44-1.69; being assigned female sex at birth - aPR: 1.34, 95% CI: 1.12-1.61; cruising - aPR: 1.21, 95% CI: 1.06-1.38; not using condoms - aPR: 1.20, 95% CI: 1.05-1.36; and being an immigrant - aPR: 1.16; 95% CI: 1.07-1.25], while having knowledge of postexposure prophylaxis (aPR: 0.91; 95% CI: 0.84-0.98), having a casual sexual partner (aPR: 0.86 and 0.85; 95% CI: 0.74-0.99 and 0.74-0.98), and engaging in group sex (aPR: 0.81; 95% CI: 0.73-0.90) were associated with a lower intention to use PrEP.

Conclusion: The intention to use PrEP among MSM who engage in chemsex was high, and several factors were associated with this intention. Understanding the factors associated with the intention to use PrEP among MSM practicing chemsex is crucial for developing targeted interventions to increase PrEP uptake in this population. The results of this study suggest that tailored approaches are necessary to promote PrEP use in this population.