Clostridioides difficile infection (CDI) epidemiology and patient characteristics in Switzerland.

OBJECTIVES: Clostridioides difficile infection (CDI) is a disease with high morbidity and mortality rates. The objective of this study was to describe CDI epidemiology and patient characteristics over a 5-year period in Switzerland and assess risk factors for mortality, recurrence and severe CDI. PATIENTS AND METHODS: We retrospectively included all consecutive CDI cases having occurred in adult patients hospitalized in two tertiary centers: the Lausanne University Hospital (1000 beds) and the University Hospital of Zurich (900 beds), between 2014 and 2018. Suspected cases of CDI were identified from the microbiology laboratory database on the basis of a positive test and confirmed by records review. RESULTS: During first CDI episodes, the median age was 67 years and the median Charlson comorbidity index (CCI) score was 5. All in all, 299 out of 826 patients (36.2%) had severe infection based on the Infectious Diseases Society of America criteria. In the multivariable analysis, CCI was associated with increased risk of mortality. None of the factors recorded on admission were significantly associated with increased risk of recurrence. In the multivariable analysis, male sex and CCI were associated with severity, while immunosuppression was associated with less severe presentation. CONCLUSIONS: If we did not identify any criteria on admission that could be predictive of recurrences, this could be explained the retrospective nature of the study. A higher comorbidity index is a key driver for severe CDI and mortality. Reporting of CDI is not mandatory in Switzerland; structuration of CDI reporting should be a short-term priority.

Exploring ways to improve CDI outcomes.

Clostridium difficile is an anaerobic spore-forming Gram-positive bacillus recognized as an evolving international health problem. Metronidazole and vancomycin were - until recently - the only drugs available to treat C. difficile infection (CDI). Better knowledge of the pathophysiology and the development of new drugs completely modified the management of initial episodes and recurrences of CDI. Fidaxomicin significantly reduced recurrences compared with vancomycin. New drugs are also currently evaluated (cadazolid, surotomycin, ridinilazole, rifaximin). Gut microbiota homeostasis was clearly shown to be a key determinant in recurrences as demonstrated by the development of gut microbiota transplantation and alternative microbiota substitution. Passive immunotherapy and vaccinal approaches are also currently being evaluated. In conclusion, CDI treatment has evolved with the development of new therapeutic pathways which now need to be implemented in international guidelines.

Biphasic lung injury during Streptococcus pneumoniae infection in a murine model.

OBJECTIVES: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. We aimed to analyze the epithelial response to S. pneumoniae-induced lung injury. METHODS: Using an in vitro model with 16HBE cells and experimental in vivo murine model of acute lung injury, we analyzed the epithelial response to S. pneumoniae. Lung epithelial cell monolayers were exposed to S. pneumoniae and permeability was assessed by transepithelial resistance (TER) measurement and organization and expression of junction proteins. Functional consequences were studied with an in vivo murine model measuring alveolar permeability, distal alveolar fluid clearance (DAFC), and the alveolar inflammatory response. RESULTS: In vitro, S. pneumoniae induced a dose-dependent decrease in transepithelial resistance, which was associated with significant modifications in the organization of junction proteins assessed by immunofluorescence staining and expression after 6hours of exposure. In vivo, S. pneumoniae induced a transient increase in alveolar permeability with an adequate increase in DAFC 6hours post infection. In a second phase, a permanent increased permeability was associated with a major decrease in DAFC. CONCLUSION: Overall, the epithelial response to S. pneumoniae followed a biphasic pattern with an initial reversible increase in permeability related to the alteration of tight and adherens junctions and a second phase associated with an epithelial injury with a major increase in permeability with a decreased DAFC reflecting an injured alveolar capillary barrier.

Treating Clostridium difficile infection in patients presenting with hematological malignancies: Are current guidelines applicable?

OBJECTIVES: Adults with hematological malignancies are at high-risk of Clostridium difficile infection (CDI), but no guidelines for CDI treatment are available in this population. Our primary objective was to evaluate the clinical outcomes in CDI patients with hematological malignancies. Our secondary objectives were to describe CDI severity using the main clinical guidelines and to evaluate the compliance of treatment choice with published guidelines. PATIENTS AND METHODS: Single-center, retrospective, observational case series including every consecutive adult patient with a confirmed diagnosis of CDI admitted in the hematology unit of our teaching hospital. Each CDI episode was classified as moderate, severe, or complicated according to the main clinical guidelines (IDSA 2010, AJG 2013, ESCMID 2014). RESULTS: Twenty-three episodes of CDI in 19 patients admitted to the hematology unit occurred between June 2012 and October 2013. Clinical cure was achieved for 20 episodes (87%). Ten weeks after diagnosis, global cure was reached for 14 episodes (61%) whereas recurrence occurred in two episodes (10%). The mortality rate reached 37% (7/19) but the attributable mortality rate was 5% (1/19). ESCMID criteria more frequently classified patients in the severe category compared with the two other classifications. Prescription compliance with clinical guidelines was observed in 61% of episodes with IDSA criteria, 43% with AJG, and 9% with ESCMID. CONCLUSIONS: IDSA and AJG assessment may underestimate the potential risk of unfavorable clinical outcome. Further prospective studies on a larger cohort are needed to develop adequate treatment guidelines for CDI in hematology settings.

Proposal for shorter antibiotic therapies.

OBJECTIVES: Reducing antibiotic consumption has now become a major public health priority. Reducing treatment duration is one of the means to achieve this objective. Guidelines on the therapeutic management of the most frequent infections recommend ranges of treatment duration in the ratio of one to two. The Recommendation Group of the French Infectious Diseases Society (SPILF) was asked to collect literature data to then recommend the shortest treatment durations possible for various infections. METHODS: Analysis of the literature focused on guidelines published in French and English, supported by a systematic search on PubMed. Articles dating from one year before the guidelines publication to August 31, 2015 were searched on the website. RESULTS: The shortest treatment durations based on the relevant clinical data were suggested for upper and lower respiratory tract infections, central venous catheter-related and uncomplicated primary bacteremia, infective endocarditis, bacterial meningitis, intra-abdominal, urinary tract, upper reproductive tract, bone and joint, skin and soft tissue infections, and febrile neutropenia. Details of analyzed articles were shown in tables. CONCLUSION: This work stresses the need for new well-conducted studies evaluating treatment durations for some common infections. Following the above-mentioned work focusing on existing literature data, the Recommendation Group of the SPILF suggests specific study proposals.

Cefoxitin: An alternative to carbapenems in urinary tract infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae.

BACKGROUND AND OBJECTIVES: Infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) have become a major public health issue worldwide. Cefoxitin is a second-generation cephalosporin and is associated with a strong in vitro activity against ESBL. PATIENTS AND METHODS: We conducted a prospective monocentric cohort study from 2012 to 2015 to evaluate the clinical efficacy and safety of cefoxitin in 15 patients treated for urinary tract infection (UTI) caused by ESBL-E, without any severity criteria. RESULTS: We included 15 patients; 11 were male patients with defined risk factors for ESBL-E. Ten patients presented with male UTI, three with pyelonephritis, and two with cystitis. Escherichia coli was the predominant pathogen. All patients had a positive outcome with a good tolerance (a skin rash without any sign of severity was observed in one patient). Microbiological cure was obtained in 9 patients out of 10 at the end of treatment. CONCLUSION: Cefoxitin is an alternative treatment to carbapenems for urinary tract infections caused by ESBL-producing Enterobacteriaceae.

Antiviral therapy of primary cytomegalovirus infection with vascular thrombosis in immunocompetent adults.

BACKGROUND: Vascular thromboembolism (VTE) complicating cytomegalovirus (CMV) primary infection is increasingly reported in immunocompetent adults. No guideline is, however, currently available for the management of these infections and particularly for the antiviral therapy indication. METHODS: We performed a literature review of VTE complicating CMV primary infection in immunocompetent adults using PubMed. RESULTS: Sixty-nine case patients of VTE complicating CMV primary infection were reported. The main sites of venous thrombosis were the splanchnic veins (30 patients) or those of the lower limbs (18 patients). One-third of patients presented with pulmonary embolism (25 patients). Forty-nine patients (76%) had at least one VTE risk factor, inherited or acquired thrombophilia for 37 patients (58%), and another risk factor for 27 patients (42%). Only 11 patients received an antiviral therapy. A positive outcome was observed in all patients. CONCLUSION: We suggest that antiviral therapy should be considered for patients presenting with severe VTE, VTE with a negative outcome despite anticoagulation, severe organ involvement, or for patients managed in the intensive care unit.

Strategies to reduce curative antibiotic therapy in intensive care units (adult and paediatric)

Emerging resistance to antibiotics shows no signs of decline. At the same time, few new antibacterials are being discovered. There is a worldwide recognition regarding the danger of this situation. The urgency of the situation and the conviction that practices should change led the Société de Réanimation de Langue Française (SRLF) and the Société Française d'Anesthésie et de Réanimation (SFAR) to set up a panel of experts from various disciplines. These experts met for the first time at the end of 2012 and have since met regularly to issue the following 67 recommendations, according to the rigorous GRADE methodology. Five fields were explored: i) the link between the resistance of bacteria and the use of antibiotics in intensive care; ii) which microbiological data and how to use them to reduce antibiotic consumption; iii) how should antibiotic therapy be chosen to limit consumption of antibiotics; iv) how can antibiotic administration be optimized; v) review and duration of antibiotic treatments. In each institution, the appropriation of these recommendations should arouse multidisciplinary discussions resulting in better knowledge of local epidemiology, rate of antibiotic use, and finally protocols for improving the stewardship of antibiotics. These efforts should contribute to limit the emergence of resistant bacteria.(AU)

Specific detection of type II human chorionic gonadotropin beta subunit produced by trophoblastic and neoplastic cells.

BACKGROUND: The sequence of the beta-subunit of human chorionic gonadotropin (hCGß) varies depending on whether hCGß is encoded by type I or type II genes. Type II genes are upregulated in trophoblast and cancer but hCGß can be detected in the serum of nonpregnant women and healthy individuals. We aimed to determine whether monoclonal antibody (mAb) FBT11-II specifically detects hCGß encoded by type II genes (type II hCGß). METHODS: Competitive inhibition assays with synthetic peptides, immunocytochemical and immunohistochemical studies, type II hCGß dosing immunoassays and sequencing of CGB genes were performed. RESULTS: Competitive inhibition assays determined that mAb FBT11-II recognizes the type II hCGß derived peptide. CGB mRNA sequencing of JEG-3 (trophoblastic) and T24 (bladder) cell lines confirmed that JEG-3 expresses type II genes while T24 expresses exclusively type I. FBT11-II only recognizes JEG-expressed hCGß. Placenta immunohistochemical studies confirmed that type II hCGß expression is restricted to the syncytiotrophoblast. Immunoassays detected type II hCGß in serum of patients with either nontrophoblastic cancers or fetal Down syndrome. CONCLUSION: Type II gene expression can be detected using FBT11-II. This specific recognition could improve the clinical usefulness of assays aimed at either managing aggressive tumors or screening for Down syndrome.

[Ebola and others, those viruses coming from far away]. / Ebola et autres, ces virus venus d'ailleurs.

In the last decade, we faced a large number of emerging pathogens. As a consequence we had to adapt our medical practice as well as our health system. This review summarizes the main features of the recent emerging pathogens with a particular focus on the recent and ongoing Ebola outbreak, we tried to evaluate the consequences on our national health management.

Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV cases.

BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus involved in severe acute respiratory distress syndrome (ARDS) and rapid renal failure. Hospital outbreak and nosocomial transmission were reported, however, several issues remain on the viral excretion course. OBJECTIVES: Describe the kinetics and pattern of viral excretion in two infected patients. STUDY DESIGN: After the initial diagnosis, blood, urine, rectal and respiratory samples were collected regularly, aliquoted and stored at -80°C. Real-time reverse transcriptase polymerase chain reaction assay targeted the UpE and Orf1a regions of the MERS-CoV genome. RESULTS: In patient 1, who died of refractory ARDS and renal failure, MERS-CoV RNA was detected in pharyngeal and tracheal swabs, as well blood samples and urine samples until the 30th day. Rectal swabs were negative. Patient 2 also developed multiple-organ failure, but survived, with persisting renal insufficiency (creatinine clearance at 30 mL/min) and persistent interstitial syndrome albeit weaned off mechanical ventilation and no longer requiring oxygen. Tracheal aspirations were positive until the 33rd day, while nasopharyngeal swabs were negative. All other biological samples were negative. DISCUSSION: Lower respiratory tract excretion of MERS-CoV could be observed for more than one month. The most severely ill patient presented an expression of the virus in blood and urine, consistent with a type-1 interferon mediated immunological response impaired in patient 1, but developed by patient 2. These results suggest that infection control precautions must be adequately evaluated in clinical wards and laboratories exposed to MERS-CoV.

First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission, France, May 2013.

In May 2013, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection was diagnosed in an adult male in France with severe respiratory illness, who had travelled to the United Arab Emirates before symptom onset. Contact tracing identified a secondary case in a patient hospitalised in the same hospital room. No other cases of MERS-CoV infection were identified among the index case's 123 contacts, nor among 39 contacts of the secondary case, during the 10-day follow-up period.

Candida albicans and Pseudomonas aeruginosa interactions: more than an opportunistic criminal association?

Pseudomonas aeruginosa and Candida albicans are frequently coexisting opportunistic pathogens, responsible for colonization and infection in predisposed patients. They share a virulence specificity relying on auto-inducing, cell density-dependent molecules named quorum-sensing (QS). C. albicans virulence depends on its QS that influences morphological switch from yeast to filamentous form. Similarly, the production of P. aeruginosa virulence factors depends partly on QS molecules. Interactions have been investigated and demonstrated in vitro. P. aeruginosa may kill C. albicans either by producing toxins, such as pyocyanin, or by direct contact on its biofilm-dependent filamentous form. Cross-kingdom communication is a more subtle interaction: C. albicans can adapt its morphology in the presence of P. aeruginosa QS molecules, and inhibit P. aeruginosa QS-dependent virulence factor secretion, through farnesol, one of its QS molecule. But the in vivo relevance of these interactions is still controversial, as models of airway colonization/infection by C. albicans followed by subsequent P. aeruginosa pneumonia give contradictory results, suggesting the probable involvement of the immune system as a third party player. Finally, the authors of clinical studies performed in ventilated patients, indicate that C. albicans colonization could be a risk factor for P. aeruginosa pneumonia. The clinical outcome of C. albicans and P. aeruginosa interaction is uncertain, the virulence modulation demonstrated in these interactions opens new possibilities for future anti-infectious therapeutics.