Hospital-acquired Clostridium difficile-associated disease in the intensive care unit setting: epidemiology, clinical course and outcome

<p>Abstract</p> <p>Background</p> <p><it>Clostridium difficile</it>-associated disease (CDAD) is a serious nosocomial infection, however few studies have assessed CDAD outcome in the intensive care unit (ICU). We evaluated the epidemiology, clinical course and outcome of hospital-acquired CDAD in the critical care setting.</p> <p>Methods</p> <p>We performed a historical cohort study on 58 adults with a positive <it>C. difficile </it>cytotoxin assay result occurring in intensive care units.</p> <p>Results</p> <p>Sixty-two percent of patients had concurrent infections, 50% of which were bloodstream infections. The most frequently prescribed antimicrobials prior to CDAD were anti-anaerobic agents (60.3%). Septic shock occurred in 32.8% of CDAD patients. The in-hospital mortality was 27.6%. Univariate analysis revealed that SOFA score, at least one organ failure and age were predictors of mortality. Charlson score ≥3, gender, concurrent infection, and number of days with diarrhea before a positive <it>C. difficile </it>toxin assay were not significant predictors of mortality on univariate analysis. Independent predictors for death were SOFA score at infection onset (per 1-point increment, OR 1.40; CI95 1.13–1.75) and age (per 1-year increment, OR 1.10; CI95 1.02–1.19).</p> <p>Conclusion</p> <p>In ICU patients with CDAD, advanced age and increased severity of illness at the onset of infection, as measured by the SOFA score, are independent predictors of death.</p

Development and optimization of quantitative PCR for the diagnosis of invasive aspergillosis with bronchoalveolar lavage fluid

Background: The diagnosis of invasive pulmonary aspergillosis (IPA) remains challenging. Culture and histopathological examination of bronchoalveolar lavage (BAL) fluid are useful but have suboptimal sensitivity and in the case of culture may require several days for fungal growth to be evident. Detection of Aspergillus DNA in BAL fluid by quantitative PCR (qPCR) offers the potential for earlier diagnosis and higher sensitivity. It is important to adopt quality control measures in PCR assays to address false positives and negatives which can hinder accurate evaluation of diagnostic performance. Methods: BAL fluid from 94 episodes of pneumonia in 81 patients was analyzed. Thirteen episodes were categorized as proven or probable IPA using Mycoses Study Group criteria. The pellet and the supernatant fractions of the BAL were separately assayed. A successful extraction was confirmed with a human 18S rRNA gene qPCR. Inhibition in each qPCR was measured using an exogenous DNA based internal amplification control (IAC). The presence of DNA from pathogens in the Aspergillus genus was detected using qPCR targeting fungal 18S rRNA gene. Results: Human 18S rRNA gene qPCR confirmed successful DNA extraction of all samples. IAC detected some degree of initial inhibition in 11 samples. When culture was used to diagnose IPA, the sensitivity and specificity were 84.5% and 100% respectively. Receiver-operating characteristic analysis of qPCR showed that a cutoff of 13 fg of Aspergillus genomic DNA generated a sensitivity, specificity, positive and negative predictive value of 77%, 88%, 50%, 96% respectively. BAL pellet and supernatant analyzed together resulted in sensitivity and specificity similar to BAL pellet alone. Some patients did not meet standard criteria for IPA, but had consistently high levels of Aspergillus DNA in BAL fluid by qPCR. Conclusion: The Aspergillus qPCR assay detected Aspergillus DNA in 76.9% of subjects with proven or probable IPA when the concentrated BAL fluid pellet fraction was used for diagnosis. There was no benefit from analyzing the BAL supernatant fraction. Use of both extraction and amplification controls provided optimal quality control for interpreting qPCR results and therefore may increase our understanding of the true potential of qPCR for the diagnosis of IPA.Supported by NIH grant R01 AI054703 from the National Institute of Allergy and Infectious Diseases

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe