Expert Review of Anti-infective Therapy最新文献

Introduction: Terbinafine is considered the gold standard for treating skin fungal infections and onychomycosis. However, recent reports suggest that dermatophytes are developing resistance to terbinafine and the other traditional antifungal agents, itraconazole and fluconazole. When there is resistance to terbinafine, itraconazole or fluconazole, or when these agents cannot used, for example, due to potential drug interactions with the patient's current medications, clinicians may need to consider off-label use of new generation azoles, such as voriconazole, posaconazole, fosravuconazole, or oteseconazole. It is essential to emphasize that we do not advocate the use of newer generation azoles unless traditional agents such as terbinafine, itraconazole, or fluconazole have been thoroughly evaluated as first-line therapies.

Areas covered: This article reviews the clinical evidence, safety, dosage regimens, pharmacokinetics, and management algorithm of new-generation azole antifungals.

Expert opinion: Antifungal stewardship should be the top priority when prescribing new-generation azoles. First-line antifungal therapy is terbinafine and itraconazole. Fluconazole is a consideration but is generally less effective and its use may be off-label in many countries. For difficult-to-treat skin fungal infections and onychomycosis, that have failed terbinafine, itraconazole and fluconazole, we propose consideration of off-label voriconazole or posaconazole.

Introduction: Hospital-acquired pneumonia (HAP) represents a significant cause of mortality among critically ill patients admitted to Intensive Care Units (ICUs). Timely and precise diagnosis is imperative to enhance therapeutic efficacy and patient outcomes. However, the diagnostic process is challenged by test limitations and a wide-ranging list of differential diagnoses, particularly in patients exhibiting escalating oxygen requirements, leukocytosis, and increased secretions.

Areas covered: This narrative review aims to update diagnostic modalities, facilitating the prompt identification of nosocomial pneumonia while guiding, developing, and assessing therapeutic interventions. A comprehensive literature review was conducted utilizing the MEDLINE/PubMed database from 2013 to April 2024.

Expert opinion: An integrated approach that integrates clinical, microbiological, and imaging tools is paramount. Progress in diagnostic techniques, including novel molecular methods, the expanding utilization and accuracy of bedside ultrasound, and the emergence of Artificial Intelligence, coupled with an improved comprehension of lung microbiota and host-pathogen interactions, continues to enhance our capability to accurately and swiftly identify HAP and its causative agents. This advancement enables the refinement of treatment strategies and facilitates the implementation of precision medicine approaches.

Introduction: The rising challenge of carbapenem-resistant Enterobacterales (CRE) infections in Indian healthcare settings calls for clear clinical guidance on the management of these infections. The Indian consensus on the management of CRE infection in critically ill patients (ICONIC-II) is a follow-up of the ICONIC-I study, which was undertaken in 2019.

Areas covered: A modified Delphi method was used to build expert consensus on CRE management in India, involving online surveys, face-to - face expert meetings, and a literature review. A panel of 12 experts was formed to develop potential clinical consensus statements (CCSs), which were rated through two survey rounds. The CCSs were finalized in a final face-to - face discussion. The finalized CCSs were categorized as consensus, near consensus, and no consensus.

Expert opinion: The outcomes included 46 CCSs (consensus: 40; near consensus: 3; and no consensus: 3). The expert panel discussed and achieved consensus on various strategies for managing CRE infections, emphasizing the significance of existing and emerging resistance mechanisms, prompt and tailored empiric therapy, and use of combination therapies. The consensus statements based on the collective expertise of the panel can potentially assist clinicians in the management of CRE infections that lack high-level evidence.

Introduction: The escalating threat of multidrug-resistant organisms necessitates constant exploration for novel antimicrobial agents. Eravacycline has emerged as a promising solution due to its unique chemical structure, which enhances potency and expands its spectrum of activity.

Area covered: This review provides a thorough examination of eravacycline, encompassing its in vitro activity against Gram-positive and Gram-negative aerobes, carbapenem-non-susceptible organisms, anaerobes, and other bacterial strains. Additionally, it evaluates evidence from clinical studies to establish its clinical effect and safety.

Expert opinion: Eravacycline, a synthetic fluorocycline, belongs to the tetracyclines class. Similar to other tetracycline, eravacycline exerts its antibacterial action by reversibly binding to the bacterial ribosomal 30S subunit. Eravacycline demonstrates potent in vitro activity against many Gram-positive and Gram-negative aerobes, anaerobes, and multidrug-resistant organisms. Randomized controlled trials and its associated meta-analysis affirm eravacycline's efficacy in treating complicated intra-abdominal infections. Moreover, real-world studies showcase eravacycline's adaptability and effectiveness in diverse clinical conditions, emphasizing its utility beyond labeled indications. Despite common gastrointestinal adverse events, eravacycline maintains an overall favorable safety profile, reinforcing its status as a tolerable antibiotic. However, ongoing research is essential for refining eravacycline's role, exploring combination therapy, and assessing its performance against biofilms, in combating challenging bacterial infections.

Introduction: Infectious diseases still cause a significant burden of morbidity and mortality among children in low- and middle-income countries (LMICs). There are ample opportunities for innovation in surveillance, prevention, and management, with the ultimate goal of improving survival.

Areas covered: This review discusses the current status in the use and development of innovative strategies for pediatric infectious diseases in LMICs by focusing on surveillance, diagnosis, prevention, and management. Topics covered are: Minimally Invasive Tissue Sampling as a technique to accurately ascertain the cause of death; Genetic Surveillance to trace the pathogen genomic diversity and emergence of resistance; Artificial Intelligence as a multidisciplinary tool; Portable noninvasive imaging methods; and Prognostic Biomarkers to triage and risk stratify pediatric patients.

Expert opinion: To overcome the specific hurdles in child health for LMICs, some innovative strategies appear at the forefront of research. If the development of these next-generation tools remains focused on accessibility, sustainability and capacity building, reshaping epidemiological surveillance, diagnosis, and treatment in LMICs, can become a reality and result in a significant public health impact. Their integration with existing healthcare infrastructures may revolutionize disease detection and surveillance, and improve child health and survival.

Background: This study evaluated drug use pattern among hospitalized children with severe acute respiratory infection (SARI) in Nigeria.

Research design and methods: A retrospective assessment of prescribed medicines for children aged 13 years and below who were admitted and treated for SARI from 1 January 2016 to 31 December 2018 was conducted. The WHO prescribing indicators and the Index of Rational Drug Prescribing were used to evaluate prescriptions.

Results: A total of 259 patients were included, mostly diagnosed with bronchopneumonia (56%). A summary of WHO-core prescribing indicators showed the average number of drugs per encounter was 3.9, medicines prescribed by generic name was 82.1%, and an encounter with at least an antibiotic was 99.7%. The percentage of drugs prescribed from the Essential Medicine List for children was 79%. The most frequently prescribed pharmacological class of medicines was antibiotics (41.4%). Cephalosporins (40.0%), aminoglycosides (34.1%), and penicillins (21.5%) were the most commonly prescribed antibiotic classes. Gentamicin (34.1%) and cefuroxime (21.5%) were the most commonly prescribed antibiotics.

Conclusions: Drug prescribing for hospitalized children with SARI was suboptimal, especially with regard to polypharmacy, antibiotics, and injection use. Interventions to promote rational use of medicines including antimicrobial stewardship interventions are recommended.

Background: The aim of this study was to evaluate the real-life efficacy of pangenotypic antivirals in HIV-HCV-positive patients.

Research design and methods: The analysis included 5650 subjects who were treated with pangenotypic anti-HCV drugs: 5142 were HCV-positive and 508 were HIV-HCV-positive.

Results: Patients with HCV-monoinfection were older (p < 0.0001), however patients with HCV-monoinfection had a higher proportion of advanced fibrosis F4 (p < 0.0001). There were no differences between the study groups in the rate of SVR12 in ITT-analysis (87,6% versus 93,9% in coinfection and monoinfection group, respectively; p > 0.05). However, there was a difference between study groups in PP-analysis, HIV/HCV and HCV, respectively 95.9% vs 97.9%, p = 0.0323. Additionally, there were a higher rate of patients who did not apply for follow-up (SVR12) in coinfected patients (7,9% vs 3,6% respectively p = 0.0001). In multivariante analysis, factors associated with worse response to the pangenotypic anti-HCV therapy included male sex, HCV genotype 3, stage of fibrosis and decompensation of liver function and HIV coinfection.

Conclusions: The real-life results of pangenotypic anti-HCV treatment are veryeffective in the group of HIV-HCV-coinfected patients. However, the finaleffectiveness is slightly lower than that obtained in HCV monoinfectedpatients.

Background: The aim of this study was to compare the safety and effectiveness of monotherapy versus combination therapy for the treatment of infections caused by S. maltophilia.

Methods: This retrospective, multicenter, cohort study included patients treated with either monotherapy or combination therapy for infections caused by S. maltophilia. Primary outcomes included overall in-hospital mortality, 30-day mortality, and clinical cure. Safety outcomes were also evaluated. Multivariable logistic regression was used as a control for confounding variables.

Results: A total of 407 patients were included, 330 patients received monotherapy and 77 patients received combination therapy. A total of 21% presented with concomitant bacteremia. After adjusting the differences between the two groups, there were no statistically significant differences between patients who received monotherapy versus combination therapy in clinical cure (55% vs 65%; OR, 0.72; 95% CI, 0.40-1.31) and overall in-hospital mortality (52% vs 49%; OR, 0.84; 95% CI, 0.45-1.57). However, patients who received monotherapy had a lower rate of 30-day mortality (28% vs 32%; OR, 0.45; 95% CI, 0.22-0.90) and acute kidney injury (9% vs 18%; OR, 0.35; 95% CI, 0.16-0.78).

Conclusion: Clinical outcomes did not significantly differ in patients who received combination therapy versus monotherapy. More data are needed to validate these findings.

Objectives: This study assessed the clinical effectiveness of the combination of nirmatrelvir and ritonavir (NMV-r) in treating nonhospitalized patients with COVID-19 who have preexisting psychiatric disorders.

Methods: Patients diagnosed with COVID-19 and psychiatric disorders between 1 March 2020, and 1 December 2022, were included using the TriNetX network. The primary outcome was the composite outcome of all-cause emergency department (ED) visits, hospitalization, or death within 30 days.

Results: Propensity score matching yielded two cohorts of 20,633 patients each. The composite outcome of all-cause ED visits, hospitalization, or death within 30 days was 3.57% (737 patients) in the NMV-r cohort and 5.69% (1176) in the control cohort, resulting in a reduced risk in the NMV-r cohort (HR: 0.657; 95% confidence interval (CI): 0.599-0.720). The NMV-r cohort exhibited a lower risk of all-cause hospitalization (HR: 0.385; 95% CI: 0.328-0.451) and all-cause death (HR: 0.110; 95% CI: 0.053-0.228) compared with the control group.

Conclusion: NMV-r could mitigate the risk of adverse outcomes in nonhospitalized patients with COVID-19 and preexisting psychiatric disorders. However, only a limited number of patients in this population received adequate treatment, thus emphasizing the importance of promoting its appropriate use.