A Iten

A placebo-controlled trial of didanosine plus stavudine, with and without hydroxyurea, for Hiv infection

Objective:To explore the short-term effects on surrogate markers for HIV progression of didanosine (ddI) plus stavudine (d4T), with or without hydroxyurea. Design:Randomized, double-blinded, prospective study. Setting:Swiss HIV Cohort Study. Patients:A total of 144 patients (75% antiretroviral-naive) were studied (mean baseline HIV-1 RNA, 4.53 log10 copies/ml; mean CD4 cell count, 370 × 106/l). Intervention:Patients received ddI (200 mg twice daily) plus d4T (40 mg twice daily), with additional hydroxyurea (500 mg twice daily) or placebo. Main outcome measures:The primary endpoint was a reduction of viraemia below 200 copies/ml after 12 weeks. At that time, patients who did not reach the primary endpoint were withdrawn in the hydroxyurea arm, whereas patients in the placebo group had the option of adding hydroxyurea to ddI and d4T. All patients were followed until week 24. Results:After 12 weeks, 54% of the patients randomized to hydroxyurea had viraemia below 200 copies/ml, compared with 28% on placebo (P < 0.001). Using an ultrasensitive assay with a limit of detection of 20 copies/ml, 19% of patients receiving hydroxyurea had viraemia levels below 20 copies/ml, compared with 8% on placebo (P = 0.05). Mean decrease in HIV-1 RNA was 2.3 and 1.7 log10 copies/ml for hydroxyurea and placebo groups, respectively (P = 0.001). Hydroxyurea was found to induce lymphopenia (−124 × 106/l). Increase in CD4 cell counts was +28 × 106/l during hydroxyurea treatment compared with +107 × 106/l on placebo (P = 0.001). Conclusions:Hydroxyurea improved the antiviral activity of d4T and ddI over a 12-week period, but was associated with a smaller increase in CD4 cell counts due to hydroxyurea-induced lymphopenia.

Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report

BACKGROUND A detailed description of viral kinetics, duration of virus shedding, and intraviral evolution in different body sites is warranted to understand Ebola virus pathogenesis. Patients with Ebola virus infections admitted to university hospitals provide a unique opportunity to do such in-depth virological investigations. We describe the clinical, biological, and virological follow-up of a case of Ebola virus disease. METHODS A 43-year-old medical doctor who contracted an Ebola virus infection in Sierra Leone on Nov 16, 2014 (day 1), was airlifted to Geneva University Hospitals, Geneva, Switzerland, on day 5 after disease onset. The patient received an experimental antiviral treatment of monoclonal antibodies (ZMAb) and favipiravir. We monitored daily viral load kinetics, estimated viral clearance, calculated the half-life of the virus in plasma, and analysed the viral genome via high-throughput sequencing, in addition to clinical and biological signs. FINDINGS The patient recovered rapidly, despite an initial high viral load (about 1 × 10(7) RNA copies per mL 24 h after onset of fever). We noted a two-phase viral decay. The virus half-life decreased from about 26 h to 9·5 h after the experimental antiviral treatment. Compared with a consensus sequence of June 18, 2014, the isolate that infected this patient displayed only five synonymous nucleotide substitutions on the full genome (4901A→C, 7837C→T, 8712A→G, 9947T→C, 16201T→C) despite 5 months of human-to-human transmission. INTERPRETATION This study emphasises the importance of virological investigations to fully understand the course of Ebola virus disease and adaptation of the virus. Whether the viral decay was caused by the effects of the immune response alone, an additional benefit from the antiviral treatment, or a combination of both is unclear. In-depth virological analysis and randomised controlled trials are needed before any conclusion on the potential effect of antiviral treatment can be drawn. FUNDING Geneva University Hospitals, Swiss Office of Public Health, Swiss Agency for Development and Cooperation, and Swiss National Science Foundation.

Effect of screening for methicillin-resistant Staphylococcus aureus carriage by polymerase chain reaction on the duration of unnecessary preemptive contact isolation.

A high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage at hospital readmission among previous MRSA carriers warrants screening and preemptive isolation precautions. The replacement of culture on chromogenic agar with rapid quantitative polymerase chain reaction for readmission screening reduces the number of unnecessary preemptive isolation-days by 54% (from 6.88 to 3.14 isolation-days) and related costs by 45% (from US dollars 113.2 to US dollars 62.1) for patients who test negative for MRSA.

Single tube competitive PCR for quantitation of CMV DNA in the blood of HIV + and solid organ transplant patients

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in transplant and HIV-infected patients. However, CMV can also cause asymptomatic infection. An elevated blood viral load as assessed by various methods appears to be a predictor for symptomatic infections, and can be used to identify patients at the highest risk of developing CMV disease. We developed a single tube competitive quantitative PCR assay for CMV DNA, using as a competitor a plasmid carrying the target sequence for amplification with an internal deletion. The analysis of data from repeated extractions and amplifications of samples showed that the coefficient of variation of the assay was typically less than 20%. Clinical samples from 14 HIV-infected and 13 solid organ transplant patients were analyzed. Widely varying CMV DNA levels were found in leukocytes, with a positive correlation with the measure of infectivity in the leukocytes by quantitative culture on fibroblasts. The highest CMV DNA content in leukocytes was found in two patients with presumptive CMV disease. In HIV patients, the amount of DNA in leukocytes was much larger than in solid organ transplant recipients, when standardized for infectivity. Although based on a very limited number of patients, this observation probably points to a difference in the biology of CMV infection in these two categories of susceptible individuals. CMV DNA was also found in the plasma of some of the patients with a high CMV DNA leukocyte load. The present test should be useful for identifying patients at high risk of developing CMV disease, for monitoring therapeutic efficacy of antiviral regimens and to improve the understanding the pathogenesis of CMV infection.

Efficacy of a new educational tool to improve Handrubbing technique amongst healthcare workers: a controlled, before-after study

Introduction Hand hygiene is a key component of infection control in healthcare. WHO recommends that healthcare workers perform six specific poses during each hand hygiene action. SureWash (Glanta Ltd, Dublin, Ireland) is a novel device that uses video-measurement technology and immediate feedback to teach this technique. We assessed the impact of self-directed SureWash use on healthcare worker hand hygiene technique and evaluated the devices diagnostic capacity. Methods A controlled before-after study: subjects in Group A were exposed to the SureWash for four weeks followed by Group B for 12 weeks. Each subjects hand hygiene technique was assessed by blinded observers at baseline (T0) and following intervention periods (T1 and T2). Primary outcome was performance of a complete hand hygiene action, requiring all six poses during an action lasting ≥20 seconds. The number of poses per hand hygiene action (maximum 6) was assessed in a post-hoc analysis. SureWashs diagnostic capacity compared to human observers was assessed using ROC curve analysis. Results Thirty-four and 29 healthcare workers were recruited to groups A and B, respectively. No participants performed a complete action at baseline. At T1, one Group A participant and no Group B participants performed a complete action. At baseline, the median number of poses performed per action was 2.0 and 1.0 in Groups A and B, respectively (p = 0.12). At T1, the number of poses per action was greater in Group A (post-intervention) than Group B (control): median 3.8 and 2.0, respectively (p<0.001). In Group A, the number of poses performed twelve weeks post-intervention (median 3.0) remained higher than baseline (p<0.001). The area under the ROC curves for the 6 poses ranged from 0.59 to 0.88. Discussion While no impact on complete actions was demonstrated, SureWash significantly increased the number of poses per hand hygiene action and demonstrated good diagnostic capacity.

Transmission and effect of multiple clusters of seasonal influenza in a Swiss geriatric hospital.

To investigate a nosocomial outbreak of influenza.

Prevalence and acquisition rate of methicillin resistant Staphylococcus aureus (MRSA) in internal medicine wards at the University Hospital of Geneva (HUG)

We aimed to determine the prevalence and acquisition rate of MRSA among patients admitted to internal medicine ward at HUG.

The 2014–2015 Ebola outbreak in West Africa: Hands On

The International Consortium for Prevention and Infection Control (ICPIC) organises a biannual conference (ICPIC) on various subjects related to infection prevention, treatment and control. During ICPIC 2015, held in Geneva in June 2015, a full one-day session focused on the 2014–2015 Ebola virus disease (EVD) outbreak in West Africa. This article is a non-exhaustive compilation of these discussions. It concentrates on lessons learned and imagining a way forward for the communities most affected by the epidemic. The reader can access video recordings of all lectures delivered during this one-day session, as referenced. Topics include the timeline of the international response, linkages between the dynamics of the epidemic and infection prevention and control, the importance of community engagement, and updates on virology, diagnosis, treatment and vaccination issues. The paper also includes discussions from public health, infectious diseases, critical care and infection control experts who cared for patients with EVD in Africa, in Europe, and in the United Sates and were involved in Ebola preparedness in both high- and low-resource settings and countries. This review concludes that too little is known about the pathogenesis and treatment of EVD, therefore basic and applied research in this area are urgently required. Furthermore, it is clear that epidemic preparedness needs to improve globally, in particular through the strengthening of health systems at local and national levels. There is a strong need for culturally sensitive approaches to public health which could be designed and delivered by social scientists and medical professionals working together. As of December 2015, this epidemic killed more than 11,000 people and infected more than 28,000; it has also generated more than 17,000 survivors and orphans, many of whom face somatic and psychological complications. The continued treatment and rehabilitation of these people is a public health priority, which also requires an integration of specific medical and social science approaches, not always available in West Africa.

Does colonization with methicillin-susceptible Staphylococcus aureus protect against nosocomial acquisition of methicillin-resistant S. aureus?

OBJECTIVE To test the hypothesis that methicillin-susceptible Staphylococcus aureus (MSSA) carriage may protect against nosocomial methicillin-resistant S. aureus (MRSA) acquisition by competing for colonization of the anterior nares. DESIGN Prospective cohort and nested case-control study. SETTING Swiss university hospital. PATIENTS All adult patients admitted to 14 wards of the general medicine division between April 1 and October 31, 2007. METHODS Patients were screened for MRSA and MSSA carriage at admission to and discharge from the division. Associations between nosocomial MRSA acquisition and MSSA colonization at admission and other confounders were analyzed by univariable and multivariable analysis. RESULTS Of 898 patients included, 183 (20%) were treated with antibiotics. Nosocomial MRSA acquisition occurred in 70 (8%) of the patients (case patients); 828 (92%) of the patients (control subjects) were free of MRSA colonization at discharge. MSSA carriage at admission was 20% and 21% for case patients and control subjects, respectively. After adjustment by multivariate logistic regression, no association was observed between MSSA colonization at admission and nosocomial MRSA acquisition (adjusted odds ratio [aOR], 1.2 [95% confidence interval (CI), 0.6-2.3]). By contrast, 4 independent predictors of nosocomial MRSA acquisition were identified: older age (aOR per 1-year increment, 1.05 [95% CI, 1.02-1.08]); increased length of stay (aOR per 1-day increment, 1.05 [95% CI, 1.02-1.09]); increased nursing workload index (aOR per 1-point increment, 1.02 [95% CI, 1.01-1.04]); and previous treatment with macrolides (aOR, 5.6 [95% CI, 1.8-17.7]). CONCLUSIONS Endogenous MSSA colonization does not appear to protect against nosocomial MRSA acquisition in a population of medical patients without frequent antibiotic exposure.

Methicillin-resistant Staphylococcus aureus risk profiling: who are we missing?

BackgroundTargeted screening of patients at high risk for methicillin-resistant Staphylococcus aureus (MRSA) carriage is an important component of MRSA control programs, which rely on prediction tools to identify those high-risk patients. Most previous risk studies reported a substantial rate of patients who are eligible for screening, but failed to be enrolled. The characteristics of these missed patients are seldom described. We aimed to determine the rate and characteristics of patients who were missed by a MRSA screening programme at our institution to see how the failure to include these patients might impact the accuracy of clinical prediction tools.FindingsFrom March-June 2010 all patients admitted to 13 internal medicine wards at the University of Geneva Hospital (HUG) were prospectively screened for MRSA carriage. Of 1968 patients admitted to the ward, 267 patients (13.6%) failed to undergo appropriate MRSA screening. Forty-one (2.4%) screened patients were MRSA carriers at admission. On multivariate regression, patients who were missed by screening were more likely to be aged < 50 years (OR 2.4 [1.4-3.9]), transferred to internal medicine from another ward in the hospital (OR 2.8 [1.1-7.1]), and have a history of malignancy (OR 3.2[2.1-5.1]). There was no significant difference in the rate of previous MRSA carriage between screened and unscreened patients.ConclusionsOur findings highlight the potential bias that “missed” patients may introduce into MRSA risk scores. Reporting on the proportions and characteristics of missed patients is essential for accurate interpretation of MRSA prediction tools.