Interaction of Clostridioides difficile infection with frailty and cognition in the elderly: a narrative review.

PURPOSE: Clostridioides difficile infection (CDI) is the leading cause of antibiotic-related diarrhea and healthcare-associated infections, affecting in particular elderly patients and their global health. This review updates the understanding of this infection, with focus on cognitive impairment and frailty as both risk factors and consequence of CDI, summarizing recent knowledge and potential mechanisms to this interplay. METHODS: A literature search was conducted including terms that would incorporate cognitive and functional impairment, aging, quality of life, morbidity and mortality with CDI, microbiome and the gut-brain axis. RESULTS: Advanced age remains a critical risk for severe disease, recurrence, and mortality in CDI. Observational and quality of life studies show evidence of functional loss in older people after acute CDI. In turn, frailty and cognitive impairment are independent predictors of death following CDI. CDI has long-term impact in the elderly, leading to increased risk of readmissions and mortality even months after the acute event. Immune senescence and the aging microbiota are key in susceptibility to CDI, with factors including inflammation and exposure to luminal microbial products playing a role in the gut-brain axis. CONCLUSIONS: Frailty and poor health status are risk factors for CDI in the elderly. CDI affects quality of life, cognition and functionality, contributing to a decline in patient health over time and leading to early and late mortality. Narrative synthesis of the evidence suggests a framework for viewing the cycle of functional and cognitive decline in the elderly with CDI, impacting the gut-brain and gut-muscle axes.

Discriminating Bacterial Infection from Other Causes of Fever Using Body Temperature Entropy Analysis.

Body temperature is usually employed in clinical practice by strict binary thresholding, aiming to classify patients as having fever or not. In the last years, other approaches based on the continuous analysis of body temperature time series have emerged. These are not only based on absolute thresholds but also on patterns and temporal dynamics of these time series, thus providing promising tools for early diagnosis. The present study applies three time series entropy calculation methods (Slope Entropy, Approximate Entropy, and Sample Entropy) to body temperature records of patients with bacterial infections and other causes of fever in search of possible differences that could be exploited for automatic classification. In the comparative analysis, Slope Entropy proved to be a stable and robust method that could bring higher sensitivity to the realm of entropy tools applied in this context of clinical thermometry. This method was able to find statistically significant differences between the two classes analyzed in all experiments, with sensitivity and specificity above 70% in most cases.

Tn2008-driven carbapenem resistance in Acinetobacter baumannii isolates from a period of increased incidence of infections in a Southwest Virginia hospital (USA).

OBJECTIVES: The objectives of this study were (i) to determine the genetic basis for carbapenem resistance in multidrug-resistant (MDR) Acinetobacter baumannii strains isolated from patients affected by a sudden increase in the incidence of infections by such organisms in a tertiary care hospital in Virginia, USA, in 2009-2010 and (ii) to examine whether such strains are commonly encountered in the hospital setting. METHODS: The whole genomes of one outbreak strain as well as one carbapenem-resistant and one carbapenem-sensitive strain from sporadic infections in 2010-2012 were sequenced and analysed. Then, 5 outbreak isolates and 57 sporadic isolates (of which 39 were carbapenem-resistant) were screened by PCR for relevant DNA elements identified in the genomics investigation. RESULTS: All three strains for which whole-genome sequences were obtained carried resistance genes linked to MDR phenotypes and a ca. 111-kbp plasmid (pCMCVTAb1) without drug resistance genes. Of these, the two carbapenem-resistant strains possessed a ca. 74-kbp plasmid (pCMCVTAb2) carrying a Tn2008 transposon that provides high-level carbapenem resistance. PCR analysis showed that all of the outbreak isolates carried both plasmids and Tn2008, and of the sporadic isolates 88% carried pCMCVTAb1, 25% contained pCMCVTAb2 and 50% of the latter group carried Tn2008. CONCLUSIONS: Carbapenem resistance in outbreak strains and 12% of sporadic isolates was due to the pCMCVTAb2-borne Tn2008. This is the first report of a Tn2008-driven outbreak of carbapenem-resistant A. baumannii infections in the Commonwealth of Virginia, which followed similar cases in Pennsylvania and Ohio.

Prognostic factors in cancer of unknown primary site.

AIMS AND BACKGROUND: Patients with cancer of an unknown primary site (CUP) usually have a poor outcome. The identification of prognostic factors that affect survival can help clinicians find a better approach to such cases in terms of diagnostic and therapeutic management. METHODS: We conducted a retrospective study including the cases of CUP recorded at the University Hospital 12 de Octubre Tumor Registry between 1999 and 2003. RESULTS: CUP was diagnosed in 265 patients during the analyzed period. One hundred and seventy-one were men (64.5%) and the mean age of the patients was 66.9 years (range 32-98 years). The median survival was 2.5 months, and the survival rate was 35.1% 6 months from diagnosis (95% CI: 28.9-41.3) and 24.5% 1 year from diagnosis (95% CI: 18.7-30.3). Univariate analysis revealed as significant predictive variables of a better outcome age under 70 years; involvement of a single organ; normal serum levels of alkaline phosphatase and albumin; normal erythrocyte sedimentation rate; normal levels of the serum tumor markers CEA, CA 19.9 and CA 15.3; squamous carcinoma histology; clinical presentation as lymph node enlargement; and the administration of treatment. Multivariate analysis showed that albumin and alkaline phosphatase levels, squamous carcinoma histology, age and treatment were the most important prognostic factors. Other variables analyzed (liver, bone or lung involvement, lactate dehydrogenase levels, gender) did not affect survival. CONCLUSIONS: CUP has a poor prognosis. Some prognostic factors that affect survival in these patients, however, may be identified.

Evolution of the incidence and aetiology of fever of unknown origin (FUO), and survival in HIV-infected patients after HAART (Highly Active Antiretroviral Therapy).

BACKGROUND: Fever of unknown origin (FUO) is common among HIV-infected patients with a CD4+ T-lymphocyte cell count below 200 cells/ml. The use of HAART has transformed the evolution of AIDS and related diseases. DESIGN AND METHOD: Case-control study, nested on a historical cohort of 3777 HIV-infected patients who were attended at "12 de Octubre" University Hospital in Madrid, Spain, between 1994 and 2000. RESULTS: 276 FUO episodes were recorded, 58 of which occurred in patients receiving HAART. The significant decrease on the accumulated FUO incidence along the study period of 7.3 episodes per 100 HIV-infected patients after 1997 corresponded with the introduction of HAART. FUO was more frequent in patients who did not receive HAART. The aetiological spectrum of FUO was transformed by the introduction of HAART: the incidence of tuberculosis decreased while that of leishmaniasis increased. The four year survival in the non-FUO group increased when compared to that of patients who had had FUO. Similarly, this four year survival increased in patients who received HAART at the time of FUO versus those not receiving it. CONCLUSIONS: Our results confirm that the incidence of FUO has significantly decreased with the introduction of HAART. HAART has also transformed the aetiological spectrum related to FUO considerably. The most frequent cause of FUO in non-HAART patients on this study was the disseminated infection by Mycobacterium avium intracellulare (MAI), followed by tuberculosis, while leishmaniasis was its most common cause in patients receiving HAART. Survival decreased in patients who developed FUO; however, patients who received HAART at the time of FUO had longer survival than patients who did not.

Protean manifestations of pleural empyema caused by Streptococcus pneumoniae in adults.

BACKGROUND: The aim of this study was to describe the clinical characteristics of pleural empyema caused by Streptococcus pneumoniae. METHODS: A retrospective cohort analysis was conducted at the University Hospital 12 de Octubre, Madrid (Spain). We included all adult patients with pleural empyema caused by S. pneumoniae diagnosed from 1998 to 2004. RESULTS: Eighteen cases of pleural empyema due to S. pneumoniae were analyzed. Fourteen patients had symptoms of respiratory infection, three had other symptoms, and one patient was asymptomatic. One-third of the patients did not have a pneumonia infiltrate visible on chest radiogram. In 46%, bacteremia was detected. All pleural fluids had a high white blood cell count, either with polymorphonuclear or lymphocytic predominance. Drainage with a chest tube was used in 94.4% of cases. Nine patients had a favorable outcome, five had to be admitted to the intensive care unit, and two died within the first week (mortality rate of 11.1%). CONCLUSIONS: Pleural empyema caused by S. pneumoniae has to be considered an aggressive disease that, occasionally, affects young and previously healthy individuals. Clinical manifestations are variable and pleural fluid can be a lymphocytic exudate. It has a noticeable associated morbidity and mortality, which must be kept in mind by clinicians when approaching a patient with a pleural effusion.