Inpatient Proton Pump Inhibitor Administration and Hospital-Acquired Clostridium difficile Infection: Evidence and Possible Mechanism

The incidence of Clostridium difficile infection continues to increase globally. Particularly concerning are hospital-acquired cases that attribute significant morbidity, mortality, and expenditures to the health care system. Proton pump inhibitors, which are widely prescribed and generally considered to have minimal adverse effects, have recently come under scrutiny for positive associations with C. difficile infection development. This article will specifically review the current state of evidence demonstrating a positive association between nosocomial proton pump inhibitor administration and the incidence of hospital-acquired C. difficile infection. In addition, the article delivers state-of-the-art knowledge relative to mechanisms by which proton pump inhibitor exposure may propagate the manifestation of C. difficile infection.     

Microbiologic factors affecting Clostridium difficile recurrence

BackgroundRecurrent Clostridium difficile infection (rCDI) places a huge economic and practical burden on healthcare facilities. Furthermore, rCDI may affect quality of life, leaving patients in an rCDI cycle and dependant on antibiotic therapy.AimsTo discuss the importance of microbiologic factors in the development of rCDI.SourcesLiterature was drawn from a search of PubMed from 2000 onwards with the search term ‘recurrent Clostridium difficile infection’ and further references cited within these articles.ContentMeta-analyses and systematic reviews have shown that CDI and rCDI risk factors are similar. Development of rCDI is attendant on many factors, including immune status or function, comorbidities and concomitant treatments. Studies suggest that poor bacterial diversity is correlated with clinical rCDI. Narrow-spectrum gut microflora-sparing antimicrobials (e.g. surotomycin, cadazolid, ridinilazole) are in development for CDI treatment, while microbiota therapeutics (faecal microbiota transplantation, nontoxigenic C. difficile, stool substitutes) are increasingly being explored. rCDI can only occur when viable C. difficile spores are present, either within the gut lumen after infection or when reacquired from the environment. C. difficile spore germination can be influenced by gut environmental factors resulting from dysbiosis, and spore outgrowth may be affected stage by some antimicrobials (e.g. fidaxomicin, ramoplanin, oritavancin).ImplicationsrCDI is a significant challenge for healthcare professionals, requiring a multifaceted approach; optimized infection control to minimize reinfection; C. difficile–targeted antibiotics to minimize dysbiosis; and gut microflora restoration to promote colonization resistance. These elements should be informed by our understanding of the microbiologic factors involved in both C. difficile itself and the gut microbiome.     

Measuring the severity of Clostridium difficile infection: implications for management and drug development

The appropriate management of Clostridum difficile infection (CDI) has become a growing clinical and economic issue, as a new epidemic strain with enhanced virulence is causing increased morbidity and mortality. Presently, only two antibiotics (metronidazole and vancomycin) are routinely used to treat CDI. Both increasing disease severity and recurrent infections have been an impetus not only to develop new agents, but also to better recognize which patients are at highest risk for treatment failure and/or recurrence so that treatments can be optimized from the outset. The availability of a standardized and validated system for stratifying CDI severity could improve patient management and potentially accelerate the development of new treatment agents.     

四种重要生物恐怖毒素液相芯片多重检测方法的建立

目的建立包括蓖麻毒素B(Ricin toxion B,RTB)、肉毒梭菌毒素A(Clostri botulinum toxin A,CBTA)、金黄色葡萄球菌肠毒素B(Staphylococcal enterotoxin B,SEB)及产气荚膜毒素ε(Clostridium perfringens toxinε,CPTε)在内的4种重要生物恐怖因子的多重液相芯片检测方法。方法采用双抗夹心法原理和液相芯片技术平台,通过优化偶联抗体浓度和检测抗体浓度以及抗原抗体最佳孵育时间,建立4种生物恐怖因子液相芯片多重检测方法。结果反应条件优化实验结果表明,RTB、CBTA、SEA和CPTε偶联抗体的最佳用量分别为20μg、40μg、80μg、80μg;RTB、CBTA、SEA和CPTε检测抗体的最佳稀释比分别为1∶5000、1∶1000、1∶2000、1∶4000;4种毒素抗原抗体最佳孵育时间为60min。多重检测结果表明,本研究建立的毒素液相芯片多重检测方法可有效检测上述任意1种毒素、任意2种毒素组合、任意3种毒素组合并能同时检测4种毒素。灵敏度检测结果表明,RTB、CBTA、SEA、CPTε检测灵敏度分别为1 ng/ml、10 ng/ml、5 ng/ml、10 ng/ml。结论本研究建立的4种常见生物恐怖毒素液相芯片多重检测方法通过1次检测能同时检测RTB、CBTA、SEA、CPTε,是一种准确、灵敏、快速和高通量的检测方法。