CCPG1 involved in corneal Aspergillus fumigatus infection

AIM: To investigate whether non-canonical autophagy transport receptor cell cycle progression 1 (CCPG1) is involved in the corneal antifungal immune response. METHODS: Human corneal epithelial cells (HCECs) and human myeloid leukemia mononuclear cells (THP-1) macrophages stimulated by Aspergillus fumigatus (A. fumigatus) were used as cell models. The expression of CCPG1 mRNA was detected by qRT-PCR. Western blot was used to determine the protein expression of CCPG1 and interleukin-1β (IL-1β). The dectin-1 neutralizing antibody was used to detect the association between dectin-1 and CCPG1. Immunofluorescence was used to observe the colocalization of CCPG1 and C-type lectin-like receptor-1 (CLEC-1) in THP-1 macrophages. RESULTS: The expression of CCPG1 started to increase at 4h after infection and increased in a time-dependent manner in HCECs and THP-1 macrophages. With dectin-1 neutralizing antibody pretreatment, the expression of IL-1β was down-regulated. CCPG1 up-regulation in response to A. fumigatus infection was independent of dectin-1. Immunofluorescence showed the colocalization of CCPG1 and CLEC-1 in THP-1 macrophages. CONCLUSION: As a specific autophagy protein of non-canonical autophagy pathway, CCPG1 is involved in corneal infection with A. fumigatus.     

Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis

Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the “anti-biotic era”. Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins.In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.     

Systematic review of drug–drug interactions between rifamycins and anticoagulant and antiplatelet agents and considerations for management

Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%–74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3–5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%–67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.     

SAA、hs-CRP、IL-6联合检测在儿童感染性疾病中的诊断价值

目的:分析SAA、hs-CRP、IL-6联合检测在儿童感染性疾病中的诊断价值。方法:选择2019年1月~2020年10月某院收治的72例感染性疾病患儿开展研究,根据患儿的病原体检测结果划分为病毒感染组和细菌感染组各36例,另选择同期体检的36名健康儿童作为研究的参照组,分别比较3组的SAA、hs-CRP、IL-6等指标水平的差异。结果:细菌感染组的SAA、hs-CRP、IL-6等指标水平及阳性率均高于病毒感染组、参照组,同时病毒感染组的SAA、hs-CRP、IL-6等指标水平及阳性率高于参照组(P<0.05);SAA、hs-CRP、IL-6联合诊断的敏感度、准确度、阳性预测值、阴性预测值均高于SAA、hs-CRP、IL-6三个指标单独检测的敏感度、准确度、阳性预测值、阴性预测值,差异有统计学意义(P<0.05);联合检测的特异度与单独检测特异度对比无统计学意义(P>0.05)。结论:SAA、hs-CRP、IL-6联合诊断在儿童感染性疾病中具备较高的诊断价值,临床可将SAA、hs-CRP、IL-6作为该病的诊断辅助指标,有效提高疾病的诊断准确性。     

Surgical site infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of post‐operative surgical site infections (SSIs) in solid organ transplantation. SSIs are a significant cause of morbidity and mortality in SOT recipients. Depending on the organ transplanted, SSIs occur in 3%‐53% of patients, with the highest rates observed in small bowel/multivisceral, liver, and pancreas transplant recipients. These infections are classified by increasing invasiveness as superficial incisional, deep incisional, or organ/space SSIs. The spectrum of organisms implicated in SSIs in SOT recipients is more diverse than the general population due to other important factors such as the underlying end‐stage organ failure, immunosuppression, prolonged hospitalizations, organ transportation/preservation, and previous exposures to antibiotics in donors and recipients that could predispose to infections with multidrug‐resistant organisms. In this guideline, we describe the epidemiology, clinical presentation, differential diagnosis, potential pathogens, and management. We also provide recommendations for the selection, dosing, and duration of peri‐operative antibiotic prophylaxis to minimize post‐operative SSIs.     

Current status of countermeasures for infectious diseases and resistant microbes in the field of urology

A worldwide increase in antimicrobial‐resistant microbes due to the improper use of antimicrobial agents, along with a lack of progress in developing new antimicrobials, is becoming a societal problem. Although carbapenem‐resistant Enterobacteriaceae, which are resistant to carbapenem antimicrobials, first appeared in 1993, treatment options remain limited. Mechanisms behind antimicrobial resistance involve changes to microbial outer membranes, drug efflux pump abnormalities, β‐lactamase production and the creation of biofilms around cell bodies. Genetic information related to these forms of antimicrobial resistance exists on chromosomes and plasmids, and when located on the latter can easily be transmitted to other strains, no matter the species, which creates a risk of antimicrobial resistance spreading exceptionally rapidly. To prevent the spread of antimicrobial resistance, the World Health Organization in 2015 published an action plan on antimicrobial resistance, based on which World Health Organization member countries have laid out specific policies and targets. Urinary tract infections are a type of healthcare‐associated infection, and the sexually transmitted disease pathogen, Neisseria gonorrhoeae, has been included in a list of microbes that pose a risk to human health published by the US Centers for Disease Control and Prevention. Urologists face numerous problems when attempting to use antimicrobials properly, which is one method of dealing with antimicrobial resistance. Therefore, this article describes the current state of resistant microbes associated with urinary tract infections and countermeasures for antimicrobial resistance, including new antimicrobials.     

Socioeconomic deprivation is inversely associated with measles incidence: a longitudinal small-area analysis,Germany, 2001 to 2017

BackgroundAlthough measles is endemic throughout the World Health Organization European Region, few studies have analysed socioeconomic inequalities and spatiotemporal variations in the disease’s incidence.AimTo study the association between socioeconomic deprivation and measles incidence in Germany, while considering relevant demographic, spatial and temporal factors.MethodsWe conducted a longitudinal small-area analysis using nationally representative linked data in 401 districts (2001–2017). We used spatiotemporal Bayesian regression models to assess the potential effect of area deprivation on measles incidence, adjusted for demographic and geographical factors, as well as spatial and temporal effects. We estimated risk ratios (RR) for deprivation quintiles (Q1–Q5), and district-specific adjusted relative risks (ARR) to assess the area-level risk profile of measles in Germany.ResultsThe risk of measles incidence in areas with lowest deprivation quintile (Q1) was 1.58 times higher (95% credible interval (CrI): 1.32–2.00) than in those with highest deprivation (Q5). Areas with medium-low (Q2), medium (Q3) and medium-high deprivation (Q4) had higher adjusted risks of measles relative to areas with highest deprivation (Q5) (RR: 1.23, 95%CrI: 0.99–1.51; 1.05, 95%CrI: 0.87–1.26 and 1.23, 95%CrI: 1.05–1.43, respectively). We identified 54 districts at medium-high risk for measles (ARR > 2) in Germany, of which 22 were at high risk (ARR > 3).ConclusionSocioeconomic deprivation in Germany, one of Europe’s most populated countries, is inversely associated with measles incidence. This association persists after demographic and spatiotemporal factors are considered. The social, spatial and temporal patterns of elevated risk require targeted public health action and policy to address the complexity underlying measles epidemiology.     

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