Author Interviews, Flu - Influenza, Pharmacology, Pulmonary Disease / 09.12.2015 Interview with: Dr. Irene Braithwaite Deputy Director Medical Research Institute of New Zealand Wellington NZ Medical Research: What is the background for this study? What are the main findings? Dr. Braithwaite: We know from animal models that the reduction of fever is associated with an increased risk of dying from influenza. We also know that some influenza viruses cannot replicate well in the human febrile range (38 to 40 Celsius). Yet, guidelines on the management of community acquired influenza infection in humans is to rest, maintain hydration and to take antipyretics such as paracetamol on the basis that this may help and is unlikely to cause harm. We undertook this study to see whether using regular paracetamol during influenza infection might be harmful, as it may allow the influenza virus to replicate more readily, and increase and/or prolong symptoms. To the best of our knowledge, this is the first randomised controlled trial comparing the effects of regular paracetamol (1gram four times daily for five days) versus placebo in human adults infected with influenza. We found that there was no difference in influenza viral loads, temperature or influenza symptoms between the regular paracetamol group and placebo group. (more…)
Author Interviews, HIV, Immunotherapy, PLoS / 04.12.2015 Interview with: Andreas Meyerhans, PhD ICREA Research Professor at the University Pompeu Fabra Infection Biology Group Department of Experimental and Health Sciences Universitat Pompeu Fabra Barcelona Spain Medical Research: What is the background for this study? What are the main findings? Dr. Meyerhans: In brief, chronic HIV infections lead to a dampening of HIV-specific killer cells. This phenomenon is named exhaustion and is mediated by inhibitory proteins, such as PD-1, on the cell surface. A consequence of exhaustion is a reduction of the immune control over virus expansion. We have studied the effect of blocking the negative signaling from the inhibitory proteins by means of PD-1/PD-L1 pathway inhibition on effector and regulatory T cells (Treg). We found that one can augment antiviral immune control only when the virus load was well controlled in the HIV-infected individuals i.e. by antiviral drugs. In that case, PD-1/PD-L1 pathway blockage led to an expansion of anti-HIV killer cells over Treg cells. This latter are suppressive white blood cells also subject to the same inhibitory pathway regulation. In contrast, when blood cells from viremic HIV-infected individuals were analyzed, Treg cells expanded efficiently and thus reduced the effector to regulatory T cell ratio that controls HIV. Taken together, our data point to Treg cells as an important component in the outcome of PD-1/PD-L1 pathway inhibitor therapies and suggest a net gain in anti-HIV immune responses only when the HIV loads are well controlled during the administration of these novel compounds. (more…)
Author Interviews, CDC, Gender Differences, HIV / 03.12.2015 Interview with: Dr. Andrew Auld MD, MSc Medical Epidemiologist Division of Global HIV & TB CDC MedicalResearch: What is the background for this study? Dr. Auld: Equitable access to antiretroviral therapy for men and women living with HIV is a principle endorsed by most countries and funding bodies, including the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). This analysis, including more than 765,000 adult patients starting antiretroviral therapy in 12 countries (10 African countries, Haiti, and Vietnam), is the most up-to-date and comprehensive assessment of differences in HIV treatment access among men and women with HIV in developing countries. MedicalResearch: What are the main findings? Dr. Auld: Investigators showed that in all 10 African countries and Haiti, women with HIV were far more likely to be on treatment than men. In these 11 countries, women were 23%–83% more likely to access antiretroviral therapy than men with HIV. In addition, in six African countries and Haiti, gender imbalance in HIV treatment access appears to be getting worse over time. (more…)
Author Interviews, Infections, Nature / 02.12.2015 Interview with: Professor Søren Riis Paludan DMSc, PhD Department of Biomedicine Aarhus University Denmark Medical Research: What is the background for this study? What are the main findings? Prof. Paluden: We were interested in understanding the first immune reactions that occur when an organism meets an infectious agent (virus or bacteria). The main finding is that we have identified an immune reaction that is activated as the microbe disturbed the mucus layer at mucosal surfaces. This is an immune reaction occuring earlier than what has been thought previously, and may represent a mechanism that enables the organism to fight most microbes that we meet without mounting strong immune responses. This is important, since strong immune reactions - in addition to contributing to elimination of microbes - also have negative effects such as fever, etc. (more…)
Author Interviews, HIV, NEJM, Sexual Health / 02.12.2015 Interview with: Dr Jean-Michel Molina Department of Infectious Diseases Saint-Louis Hospital and University of Paris Diderot Paris France MedicalResearch: What is the background for this study? What are the main findings? Dr. Molina: Men who have sex with men (MSM) are disproportionately affected by HIV worldwide and represent the today in Europe the largest group in which new HIV infections are diagnosed with no decrease over the last 8 years. The first study assessing preexposure prophylaxis (PrEP) efficacy among MSM was published in 2010 (the Iprex study) which reported for the first time a 44% reduced incidence of HIV in those randomized to receive daily tenofovir/emtricitabine  TDF/FTC (one pill per day) as compared to placebo. Adherence to a daily pill regimen was found to be challenging however since only half of the participants (according to drug detection in blood) were taking their daily regimen. Post-hoc analyses suggested that among those with drugs detectable in plasma, PrEP efficacy could be as high as 92%. However, long term adherence to a daily regimen represents the Achille’s heel of daily PrEP, as shown later in other large PrEP trials among women in Africa (VOICE and Fem-PrEP). Based on data from animal models we wished to assess whether PrEP with TDF/FTC taken on demand, at the time of sexual activity, could improve adherence, thereby efficacy and also improve safety and cost. In this randomized double blind placebo controlled trial, on demand PrEP with TDF/FTC reduced the incidence of HIV by 86% in the intent to treat analysis as compared to placebo, and the only 2 participants who became infected in the TDF/FTC arm after more than a year of follow-up, had discontinued the use of PrEP months before infection. The ANRS Ipergay study reports therefore a very high efficacy of PrEP, similar to that also reported in another PrEP study carried out in the UK among MSM with daily TDF/FTC (PROUD), which results were disclosed at the same time. Both studies have increased awareness about the real potential of PrEP and have had a strong impact on WHO and European guidelines. (more…)
Author Interviews, Hospital Acquired, Infections / 27.11.2015 Interview with: Prof. Jean-Yves Maillard Professor of Pharmaceutical Microbiology College of Biomedical and Life Sciences Cardiff School of Pharmacy and Pharmaceutical Sciences Cardiff University Cardiff United Kingdom Medical Research: What is the background for this study? What are the main findings? Prof. Maillard: Environmental surfaces in healthcare and other settings become contaminated with a variety of infectious agents which may survive long enough to infect susceptible hosts, either directly or through secondary vehicles such as hands. Therefore, routine decontamination of environmental surfaces, in particular those that are frequently touched, is crucial to reduce the risk of infections. Such decontamination is often performed by wiping the target surface with disinfectant-soaked or pre-wetted wipes. However, the label claims of wipes marketed for this purpose are often based upon testing that does not reflect their field use, where contact times are frequently no more than a few seconds with wide variations in the pressure applied during wiping. In addition, wipes impregnated with a disinfectant or detergent can potentially transfer microbial contaminants to a wider area, when the same wipe is used on multiple surfaces. A device called the ‘Wiperator’ was invented to address these issues. It can be used to test wipes with predetermined pressures, wiping times and number of wiping strokes, using a standardized rotary action. It can not only assess the decontaminating efficiency of the test wipe, but also its ability to transfer the acquired contamination to clean surfaces. The test procedure developed using the device is now a standard (E2967) of ASTM International, a highly-respected standards-setting organization. The Wiperator was used in a multi-laboratory collaborative to test commercially-available wipes for their ability to decontaminate metal disks that had been experimentally-contaminated with vegetative bacteria representing healthcare-associated pathogens. The used wipes were subsequently tested for their potential to transfer viable bacteria to clean surfaces. The contact time for wiping and transfer was 10 seconds. Only one of the wipes tested reduced the contamination to an undetectable level while not transferring any viable bacteria to a clean surface. All others left behind detectable levels of contamination on the wiped disks and transferred the contamination to clean surfaces. (more…)
Author Interviews, Clots - Coagulation, Infections / 19.11.2015 Interview with: Professor Adam Cunningham PhD Institute of Immunology and Immunotherapy MRC Centre for Immune Regulation University of Birmingham Medical Research: What is the background for this study? Dr. Cunningham: Our original question was “Why do people die from Salmonella infections that spread beyond the gut”. Some reasons are known but these do not account for all. In particular infants in sub-Saharan Africa seem particularly prone to Salmonella infections that in the West do no more than cause a self-limiting gastroenteritis. A puzzling feature of many of infections in such infants is that they do not have many bacteria in the blood, probably <10 / ml of blood, yet this low density is a strong predictor of death. Therefore, we thought that it may be the host response to the infection that complicates its control and contributes. (more…)
Author Interviews, JAMA, Outcomes & Safety, Urinary Tract Infections, Urology / 19.11.2015 Interview with: Jerome A. Leis, MD MSc FRCPC Staff physician, General Internal Medicine and Infectious Diseases Physician Lead, Antimicrobial Stewardship Team Staff member, Centre for Quality Improvement and Patient Safety Sunnybrook Health Sciences Centre Assistant Professor, Department of Medicine, University of Toronto Medical Research: What is the background for this study? What are the main findings? Dr. Leis: Overuse of urinary catheters leads to significant morbidity among hospitalized patients.  In most hospitals, discontinuation of urinary catheters relies on individual providers remembering to re-assess whether patients have an ongoing reason for a urinary catheter.  We engaged all of the attending physicians to agree on the appropriate reasons for leaving a urinary catheter in place and developed a medical directive for nurses to remove all urinary catheters lacking these indications.  This nurse-led intervention resulted in a significant reduction in urinary catheter use and catheter-associated urinary tract infections, compared with wards that continued to rely on usual practice. (more…)
Author Interviews, STD / 18.11.2015 Interview with: Dr Pam Sonnenberg  Reader in Infectious Disease Epidemiology Research Department of Infection & Population Health University College London London MedicalResearch: What is the background for this study? What are the main findings? Dr. Sonnenberg:  This study strengthens growing evidence that Mycoplasma genitalium (MG) is a sexually transmitted infection (STI). Analyses of over 4500 of urine samples from Britain’s third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) showed that MG was prevalent in up to 1% of the general population aged 16-44, who had reported at least one sexual partner. Prevalence was much higher in those who had reported more than four sexual partners in the past year – 5.2% in men and 3.1% in women. Absence of the infection in over 200 16-17 year olds who had not had vaginal, anal, or oral sex provided further evidence that MG is transmitted sexually. The study also analysed risk factors for  Mycoplasma genitalium, such as ethnicity, number of partners, and areas of deprivation. There were strong associations with risky sexual behaviours, with similar behavioural risk factors to other known STIs. The authors found that men of Black ethnicity and those living in the most deprived areas were more likely to test positive for MG. Over 90% of Mycoplasma genitalium in men and over two-thirds of MG cases in women were in those aged 25–44 years; an age group who would not be included in STI prevention measures currently aimed at young people in Britain. Interestingly, the majority of participants who tested positive for MG did not report any STI symptoms in the last month. Over half of women did not report any symptoms, but among those who did, bleeding after sex was most common. Over 90% of MG positive men did not report any symptoms. (more…)
Author Interviews, JAMA, Pediatrics, Respiratory / 17.11.2015 Interview with: Leonard B. Bacharier, MD Professor of pediatrics Clinical Director, Division of Allergy, Immunology and Pulmonary Medicine St Louis School of Medicine Washington University St Louis, Missouri  Medical Research: What is the background for this study? What are the main findings? Dr. Bacharier: Oral corticosteroids such as prednisone have become the standard of care for children whose colds tend to progress and lead to severe wheezing and difficulty breathing. “But there are some studies that suggest these treatments don’t consistently work for young children. That’s why we want to find ways to prevent upper respiratory infections from progressing to lower respiratory tract illnesses. Once the episode gets going, standard interventions are less effective than would be desired”​​​​​​​​​​​​​​​​, reported Dr. Bacharier. (more…)
Author Interviews, CDC, Infections, OBGYNE, STD / 13.11.2015 Interview with: Dr. Virginia Bowen PhD Epidemic Intelligence Service Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention,CDC  Medical Research: What is the background for this study? What are the main findings? Dr. Bowen: Congenital syphilis (CS) occurs when a mother infected with syphilis transmits the infection to her child during the course of pregnancy. Our study looked at recent trends in CS between 2008 and 2014. After four years of decline, Congenital syphilis rates increased by 38% from 2012 to 2014. The findings from this report show we are missing opportunities to screen and treat pregnant women for STDs. Syphilis in pregnant women can cause miscarriages, premature births, stillbirths, or death of newborn babies. We have effective tests and treatment for syphilis – there’s no excuse for allowing it to resurge. Every case of CS is one too many. (more…)
Author Interviews, Biomarkers, Lyme, Rheumatology / 10.11.2015 Interview with: Robert B. Lochhead PhD Clinical Fellow in Medicine  Division of Rheumatology, Allergy & Immunology Massachusetts General Hospital Harvard Medical School, Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Lochhead: Lyme arthritis (LA), caused by the tick-borne spirochete Borrelia burgdorferi, usually resolves appropriately with antibiotic treatment, called antibiotic-responsive Lyme arthritis. However, in some patients, arthritis persists for months or years after spirochetal killing with oral and IV antibiotic therapy, called antibiotic-refractory Lyme arthritis. Synovial lesions in these patients show marked synovial proliferation, inflammation, and vascularization, accompanied by autoimmune T and B cell responses. MicroRNAs (miRNAs) regulate many biological processes including inflammation, immune responses, and cell proliferation, and are effective biomarkers that may reveal molecular mechanisms of disease. Our objective here was to identify extracellular miRNAs (ex-miRNAs) in synovial fluid (SF) that distinguish regulated (responsive) from dysregulated (refractory) immune responses in Lyme arthritis, thereby providing insights into underlying biological processes and potential diagnostic biomarkers to distinguish between  these disease courses. (more…)
Author Interviews, Infections, Pediatrics, Respiratory / 06.11.2015 Interview with: Dominik Mertz, MD, MSc, FMH (CH) Assistant Professor, McMaster University Department of Medicine, Division of Infectious Diseases Associate Membership Department of Clinical Epidemiology and Biostatistics / Pathology and Molecular Medicine Medical Director Infection Prevention & Control, Hamilton Health Sciences Juravinski Hospital and Cancer Center Hamilton, ON, Canada  Medical Research: What is the background for this study? What are the main findings? Dr. Mertz: There was a perception that there was an increase in ICU admissions and deaths, initially in Kansas City and Chicago, which was found to be related to the enterovirus strain EV-D68, which had previously not resulted in any major outbreaks in North America. We have one of the first laboratories that was able to provide a specific EV-D68 PCR routine testing allowing us identify EV-D68 cases and to compare the outcomes in patients infected with this strain to children infected by other rhino/enteroviruses. We found a substantial overlap in how the patients presented between patients with EV-D68 and non-EV-D68 infection. It seems that children infected with EV-D68 were in deed at higher risk for having respiratory distress and needing hospital admission, with children with allergies being at a higher risk. We did not find an increase in more severe outcomes, though, i.e. no higher risk for ICU admission (23 vs 15%) and 0 deaths in the EV-D68 group. We also did not find any evidence of in-hospital transmission of EV-D68. (more…)
Author Interviews, CDC, Infections / 05.11.2015 Interview with: Sam Crowe, PhD, MPH Epidemic Intelligence Service Officer Enteric Diseases Epidemiology Branch Division of Foodborne, Waterborne, and Environmental Diseases Centers for Disease Control and Prevention Medical Research: What were the leading causes of multistate foodborne outbreaks and the most common contaminated foods during the study period? Dr. Crowe: Salmonella, Shiga toxin-producing Escherichia coli, and Listeria monocytogenes were the leading pathogens causing multistate foodborne outbreaks. In order of frequency, fruits, vegetable row crops, beef, sprouts, and seeded vegetables were the leading contaminated foods. Medical Research: How severe are multistate foodborne outbreaks? Dr. Crowe: From 2010 through 2014, multistate foodborne outbreaks accounted for only 3% of all U.S. foodborne outbreaks detected, but caused over one third of the hospitalizations and more than half of the deaths. Medical Research: Are these outbreaks occurring more frequently? Dr. Crowe: Multistate foodborne outbreaks are being identified more often in the United States because of better surveillance. Greater centralization of food processing and distribution practices also could be increasing the frequency and size of multistate foodborne outbreaks. This is why your business should Look for Ruggedised Industrial Pointing Devices Today, to ensure your business is staying up with the industry standards. (more…)
Author Interviews, Columbia, Compliance, HIV, JAMA, Pediatrics / 04.11.2015 Interview with: Dr. Louise Kuhn PhD Professor, Epidemiology Sergievsky Center Columbia University  Medical Research: What is the background for this study? What are the main findings? Dr. Kuhn: Ritonavir-boosted lopinavir-based antiretroviral therapy is recommended as first-line treatment for HIV-infected infants and young children while efavirenz is recommended for adults and older children. There are several advantages of transitioning HIV-infected children to efavirenz-based treatment as they get older.  These advantages include the possibility of once-daily dosing, simplification of co-treatment for tuberculosis, avoidance of some metabolic toxicities, preservation of ritonavir-boosted lopinavir for second-line treatment, and alignment of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz-based treatment in children exposed to nevirapine for prevention of mother-to-child transmission.  This is because efavirenz and nevirapine are in the same drug class and the majority of children who become infected despite exposure to nevirapine used for prevention have mutations in their virus that usually predict resistance to this drug class. In this study, we randomized HIV-infected children to two different treatment strategies: In the control strategy they remained on their initial ritonavir-boosted lopinavir regimen; in the alternative strategy they transitioned to an efavirenz-based regimen.  All children had been exposed to nevirapine used (unsuccessfully) to prevent mother to child HIV transmission and were virologically-suppressed (HIV in blood < 50 copies/ml) at the time of enrollment into the study.  We observed excellent virological control in both groups with fewer than 3% of children having levels of HIV in their blood greater than 1000 copies/ml.  Sustained suppression of virus in blood below 50 copies/ml throughout follow-up was achieved in 82% of the children transitioned to efavirenz-based treatment compared to 72% of children remaining on the control treatment. (more…)
Antibiotic Resistance, Author Interviews, CDC, Infections / 04.11.2015

Dr. Bob Kirkcaldy MD, MPH Epidemiologist, Division of STD Prevention Interview with: Dr. Bob Kirkcaldy MD, MPH Epidemiologist, Division of STD Prevention CDC Medical Research: What is the background for this study? What are the main findings? Dr. Kirkcaldy: Gonorrhea is a common sexually transmitted disease that, if untreated, can cause severe reproductive health complications. While gonorrhea is very common, it is often symptomless and many may not realize they have it. 333,004 cases were diagnosed in 2013, but more than 820,000 are estimated to occur annually. Because antibiotic resistance has jeopardized treatment for gonorrhea, CDC’s Gonoccocal Isolate Surveillance Project (GISP) monitors antimicrobial susceptibility and tracks patterns of resistance among antibiotics currently used to treat gonorrhea. From 2006-2009, susceptibility to the oral cephalosporin antibiotic cefixime declined in GISP, threatening the effectiveness of this drug. Continued use of cefixime in the face of declining susceptibility could theoretically foster broad resistance to the cephalosporin class (including ceftriaxone, the last treatment option). So in 2012,  CDC changed its treatment recommendations to recommend only dual gonorrhea treatment with injectable ceftriaxone plus oral azithromycin. The most recent data from GISP analyzed urethral gonorrhea samples of men from STD clinics in 34 cities from 2006-2014 and found resistance to cefixime increased in 2014 after two years of dramatic decreases. While CDC’s STD Treatment Guidelines suggest cefixime should only be considered as an alternative treatment for gonorrhea when ceftriaxone is not available, trends of cefixime susceptibility have historically been a precursor to trends in ceftriaxone so it’s important to continue monitoring cefixime to be able to anticipate what might happen with other drugs in the future. GISP data also found that resistance remained stable for ceftriaxone and resistance levels remain highest among men who have sex with men (MSM). We’re concerned about the increase in resistance for cefixime; however, more years of data are needed to know if the 2014 increase is the beginning of a new trend. (more…)
Author Interviews, Emory, Flu - Influenza, Vaccine Studies / 02.11.2015 Interview with: Saad Omer MBBS MPH PhD Associate Professor Emory Vaccine Center Associate Professor Global Health and Epidemiology Rollins School of Public Health Emory University MedicalResearch: Can you give us a little background on this study? Dr. Omer: My background is in global health, epidemiology and pediatrics and I have been fortunate to conduct field and clinical vaccine trials in a number of countries and with multiple infectious diseases including influenza, polio, measles and pneumococcal vaccines. We were familiar with the data on investigating the potential effects of statins on other infections i.e. sepsis and community acquire pneumonia including Dr. Vandermeer’s study in 2012 suggesting that “statin use may be associated with reduced mortality in patients hospitalized with influenza”. Statins have lipid-lowering effects but they also exhibit anti-inflammatory and immunomodulatory properties. For lack of a better image, I think of statins as acting like a ‘big hammer made of Jell-O’: they have a broad, small dampening effect on immune response (as opposed to a narrow or deep effect). (more…)
Author Interviews, CDC, Cost of Health Care, HPV, Vaccine Studies / 30.10.2015 Interview with: Shannon Stokley, MPH Epidemiologist in the CDC Immunization Services Division Medical Research: What is the background for this study? What are the main findings? Response: To determine whether the recommended HPV vaccination series is currently being administered to adolescents with health insurance, CDC and the National Committee for Quality Assurance (NCQA) assessed 2013 data from the Healthcare Effectiveness Data and Information Set (HEDIS). The HEDIS HPV Vaccine for Female Adolescents performance measure evaluates the proportion of female adolescent members in commercial and Medicaid health plans who complete the recommended HPV vaccination series by age 13 years. In 2013, in the United States, the median HPV vaccination coverage level for female adolescents among commercial and Medicaid plans was 12% and 19%, respectively (ranges = 0%–34% for commercial plans, 5%–52% for Medicaid plans). The results of this study indicate that there are significant opportunities for improvement as HPV vaccination coverage among female adolescents was low for both commercial and Medicaid plans. (more…)
Author Interviews, Diabetes, Infections, Surgical Research / 29.10.2015

Emily Toth Martin, Ph.D. MPH Assistant Professor, Epidemiology University of Michigan School of Public Interview with: Emily Toth Martin, Ph.D. MPH Assistant Professor, Epidemiology University of Michigan School of Public Health  Medical Research: What is the background for this study? What are the main findings? Response: Surgical site infections are responsible for billions in health care costs in the U.S. We are working to identify groups of people who are particularly impacted by surgical site infections. By looking at the results of 94 studies, we were able to take a 60,000 foot view of the connection between diabetes and surgical site infection. We found that diabetes raises the risk of infection across many types of surgeries. (more…)
Author Interviews, Geriatrics, Infections / 28.10.2015 Interview with: Christian Hammer, PhD École Polytechnique Fédérale de Lausanne Swiss Institute of Bioinformatics Lausanne, Switzerland Clinical Neuroscience Max Planck Institute of Experimental Medicine Göttingen, Germany Medical Research: What is the background for this study? What are the main findings? Dr. Hammer: The immune response after viral infection or vaccination varies considerably from person to person, which is important because these differences can account for clinical outcome or vaccine effectiveness. It has been shown before that part of this variability is heritable, indicating the possibility that differences in our genes might be involved. To test this, we performed a genome-wide association study in more than 2,300 individuals, using high-performance computing to analyze whether differences in the abundance of antibodies against 14 common viruses are caused by variable sites in our genome. We looked at about 6 million of these variants and found that a region on chromosome 6 that harbors many genes involved in immune regulation showed highly significant associations with immune response to influenza A virus, Epstein-Barr virus (EBV), JC polyomavirus, and Merkel Cell polyomavirus. The genetic variants result in structural differences in proteins whose job it is to present fragments of pathogens that have been taken up by cells to the immune system. Interestingly, a given variant can lead to an increased immune response to one virus, e.g. influenza A, and at the same time to a decreased immune response to another, e.g. EBV, which is likely due to an altered ability of the protein to bind and present specific viruses, depending on the genetic background. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Electronic Records, Infections, Mayo Clinic / 26.10.2015 Interview with: DrPablo Moreno Franco MD Assistant Professor of Medicine MAYO Clinic Medical Research: What is the background for this study? What are the main findings? Dr. Pablo Franco: Early alerts and prompt management of patient with severe sepsis and septic shock (SS/S) starting in the emergency department (ED) have been shown to improve mortality and other pertinent outcomes. With this in mind, we formed a multidisciplinary sepsis and shock response team (SSRT) in September 2013. Automated electronic sniffer alerted ED providers for possible sepsis and when S/SS was identified, they were encouraged to activate SSRT. SSRT-Compliance-Study-Cohort Two blinded reviewers retrospectively abstracted data on clinical trajectory and outcomes of all patients with sepsis and SS/S admitted at a single academic medical center between September 2013 and September 2014. Given importance of timely recognition and interventions in S/SS, we specifically focused on 2 periods: 0-4 hours and 4-12 hours after hospital admission. Additionally, we compared the compliance to “standard of care” between the SSRT pre-implementation period and the study period. There were 167 patients admitted with sepsis, among which there were 3 SSRT activations and sepsis mortality was 3.6%. There were 176 patients with SS, SSRT was called in 42 (23%) and SS mortality was 8.5%. CCS was involved in 66 patients and mortality was 6.9% if SSRT was activated, versus 21.6% if SSRT was not activated. There were 76 patients with septic shock, SSRT was called in 44 (57%) and septic shock mortality was 25%. Critical Care Service (CCS) was involved in 68 patients and mortality rates with and without SSRT were 30.9% and 15.4%, respectively. The all-or-none compliance with applicable goals of resuscitation improved from the baseline 0% to over 50% at the study period end. Overall observed/expected sepsis mortality index improved from 1.38 pre-SSRT to 0.68 post-SSRT implementation. (more…)
Author Interviews, Biomarkers, Infections / 24.10.2015 Interview with: Dr. Johannes Kettunen Computational Medicine, Institute of Health Sciences, University of Oulu National Institute for Health and Welfare, Helsinki NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio Finland   Medical Research: What is the background for this study? What are the main findings? Dr. Kettunen: The initial discovery of the mortality biomarkers was made 1.5 years ago when we published the first paper describing four biomarkers indicative of 5-year mortality in two cohorts totaling over 17 000 population based samples ( We wanted to understand the molecular background of the strongest mortality predictor and this is how the current study was started. Here,  The network was enriched with defense response genes and we had an idea to test if the biomarker was predictive of future severe infections. We were able to show that chronic inflammation creates extra stress to immune system and predisposes to future infections. (more…)
Author Interviews, Infections, NEJM, OBGYNE / 24.10.2015

Alfredo Mayor Aparicio PhD Associate Research Professor Barcelona Institute for Global Interview with: Alfredo Mayor Aparicio PhD Associate Research Professor Barcelona Institute for Global Health Medical Research: What is the background for this study? What are the main findings? Dr. Mayor: The malaria parasite is a well-adapted pathogen which can persist and reappear in areas where infection is no longer circulating or at very low levels. Prevention of such reinfections and resurgences is critical for the current goal of malaria eradication. However, little is known about the determinants and consequences of malaria declines and resurgences. For this reason, understanding the relationship between malaria transmission, immunity and disease burdens is essential to rationalise malaria interventions aimed at reducing host-parasite encounters. We have described changes in prevalence among pregnant women delivering between 2003 and 2012 at antenatal clinics in Southern Mozambique, and showed that a reduction of malaria-specific immunity associated with drops in transmission is accompanied with an increase the severity of malaria infection among those women becoming infected. These results suggest that success of control and elimination activities may lead through a transitional period where infrequent infections will likely slowdown the rate of acquisition of host defenses and will be thus associated with more deleterious effects during pregnancy, thus requiring more precise diagnosis and surveillance methods, as well as improved prevention. (more…)
Author Interviews, C. difficile, Gastrointestinal Disease, Transplantation / 22.10.2015 Interview with: Monika Fischer, MD, MSCR Assistant Professor of Clinical Medicine Division of Gastroenterology and Hepatology Indiana University Indianapolis, IN 46202  Medical Research: What is the background for this study? What are the main findings? Dr. Fischer: Cumulative evidence based upon case series and randomized trials suggest high success rate with 10-20 % failing a single FMT (fecal microbiota transplant). Predictors of failures are not known. In a collaborative study between Indiana and Brown Universities we aimed to identify clinical predictors of FMT failure. Results were the following:
  • N= 345 patients
    • Brown: N=166
    • IU: N=179
  • Average age: 62 years
  • Females: 72%
  • IBD: 18%
  • Immunosuppression: 24%
  • Indication for FMT
    • Recurrent CDI: 74%
    • Refractory CDI: 26%
    • Severe/complicated CDI: 13%
  • Inpatient FMT: 17%
  • Patient directed donor: 40%
Overall failure rate was 23.7%. Broken down by fecal microbiota transplant indication, while only 18% of patients failed and  needed further therapy in the non-severe category, 1 in 2 (50%) severe C. difficile infection (CDI) patients failed a single fecal microbiota transplant and needed further therapy for cure. (more…)
Author Interviews, Infections, Lancet, Outcomes & Safety, Respiratory / 22.10.2015 Interview with: Yuichiro Shindo, M.D., Ph.D. Assistant Professor Institute for Advanced Research, Nagoya University, Department of Respiratory Medicine, Nagoya University Graduate School of Medicine Showa-ku, Nagoya Japan Medical Research: What is the background for this study? What are the main findings? Dr. Shindo: Appropriate initial antibiotic treatment is essential for the treatment of pneumonia.  However, many patients may develop adverse outcomes, even if they receive appropriate initial antibiotics.  To our knowledge, there have been no studies that clearly demonstrated the risk factors in patients who receive appropriate antibiotic treatment.  If these factors are clarified, we can identify those patients with pneumonia for whom adjunctive therapy other than antibiotic treatment can prove beneficial in terms of improved outcomes.  This study aimed to clarify the risk factors for 30-day mortality in patients who received appropriate initial antibiotic treatment and elucidate potential candidates for adjunctive therapy. In this study, the 30-day mortality in 579 pneumonia patients who received appropriate initial antibiotics was 10.5%.  The independent risk factors included albumin < 3.0 mg/dL, nonambulatory status, pH < 7.35, respiration rate ≥ 30/min, and blood urea nitrogen ≥ 20 mg/dL.  The 30-day mortality for the number of risk factors was 0.8% (0), 1.2% (1), 16.8% (2), 22.5% (3), and 43.8% (4–5). (more…)
Author Interviews, C. difficile, Gastrointestinal Disease, Mayo Clinic, Microbiome, Transplantation / 22.10.2015 Interview with: Dr. Sahil Khanna MBBS Assistant Professor of Medicine Mayo Clinic Medical Research: What is the background for this study? What are the main findings? Response: C. difficile infection patients are at a high risk of complications such as treatment failure. Gut microbiota signatures associated with CDI have been described but it is unclear if differences in gut microbiota play a role in response to therapy. No studies have identified predictors of treatment failure and we aimed to identified gut microbiota signatures to predict response to treatment for primary C. difficile . While there were no clinical predictors of treatment response, there were increases in certain genera in patients with successful treatment response in the fecal samples at initial diagnosis compared to non-responders. A risk index built from this panel of microbes highly differentiated between patients based on response and ROC curve analysis showed that this risk index was a strong predictor of treatment response, with a high area under the curve of 0.83.. (more…)
Anemia, Author Interviews, Infections, Kidney Disease, UCSF / 21.10.2015

Dr. Julie H. Ishida MD San Francisco Veterans Affairs Medical Center Nephrology Section San Francisco, Interview with: Dr. Julie H. Ishida MD San Francisco Veterans Affairs Medical Center Nephrology Section San Francisco, CA Medical Research: What is the background for this study? What are the main findings? Dr. Ishida: Intravenous iron is important in the treatment of anemia of end-stage renal disease, but it is biologically plausible that iron may increase infection risk. While results from epidemiologic studies evaluating the association between intravenous iron and infection in hemodialysis patients have been conflicting, guidelines for the treatment of anemia of chronic kidney disease have recommended caution in prescribing, avoidance and withholding of intravenous iron in the setting of active infection. However, no data specifically support the recommendation to withhold intravenous iron during active infection. Our study observed that among hemodialysis patients hospitalized for bacterial infection who had been receiving intravenous iron as an outpatient, continued receipt of intravenous iron was not associated with higher all-cause mortality, readmission for infection, or longer hospital stay. (more…)
Author Interviews, Case Western, Hand Washing, Infections / 17.10.2015 Interview with: Curtis J. Donskey, MD Professor of Medicine Case Western Reserve University Staff Physician, Infectious Diseases Section, Louis Stokes Cleveland VA Medical Center Medical Research: What is the background for this study? Dr. Donskey: Personal protective equipment (PPE) is intended to protect healthcare personnel by preventing them from acquiring an infection and to protect patients by preventing pathogen transmission. This study focused on gloves and gowns which are designed to reduce contamination of the skin and clothing of personnel. There are several concerns about the effectiveness of gloves and gowns.
  • First, several studies have demonstrated that personnel may acquire pathogens such as Clostridium difficile and methicillin-resistant Staphylococcus aureus (MRSA) on their hands and clothing during patient care activities despite wearing gloves and gowns.
  • Second, some studies involving simulations have suggested that contamination of the skin and clothing occurs frequently during removal of gloves and gowns.
  • Finally, lapses in technique for PPE removal may contribute to acquisition of potentially fatal pathogens such as Ebola virus. These concerns highlight the urgent need for improved strategies to prevent contamination of personnel during PPE removal.
We had 3 goals in the study.
  • First, we wanted to determine if contamination with a fluorescent lotion during glove and gown removal would correlate well with contamination with a benign virus. We did this because the fluorescent lotion method could potentially be very useful for training personnel because you can easily visualize contamination with a black light and provide immediate feedback.
  • Second, we used the fluorescent lotion method to evaluate contamination of the skin and clothing of personnel from 4 hospitals during removal of contaminated gloves or gowns.
  • Finally, we tested whether an intervention would reduce contamination in one of the 4 hospitals. The intervention included practice in removal of contaminated gloves and gowns with immediate visual feedback based on fluorescent lotion contamination of skin and clothing.
Medical Research: What are the main findings? Dr. Donskey: Our first key finding was that contamination with the fluorescent lotion correlated well with contamination with the benign virus. This was an important finding because it suggests that the fluorescent lotion method is a useful surrogate method to assess pathogen contamination during Personal protective equipment removal. Our second key finding was that contamination of the skin and clothing of personnel occurred frequently during removal of contaminated gloves or gowns. For 435 total simulations, contamination occurred 46% of the time, with similar results for each the 4 study hospitals (43%-50%). Incorrect donning or doffing technique was common and was associated with an increase in contamination (70% of the time with incorrect technique versus 30% with correct technique). Our final key finding was that the intervention was very effective in reducing contamination during PPE removal. Immediately after the training session, the frequency of contamination decreased from 60% to 20% and then was 12% at 1 and 3 months after the intervention. (more…)
Author Interviews, Infections, Lymphoma / 16.10.2015 Interview with: Matthieu Million, MD, PhD Assistant of Professor RAOULT French National referral center for Q fever Service de Maladies Infectieuses du Professeur BROUQUI Chemin des Bourrely Marseille Medical Research: What is the background for this study? What are the main findings? Dr. Million: Human lymphomas have been associated with many infectious agents including viruses (HCV, HIV) but also bacteria (Helicobacter pylori). Q fever, the infection by Coxiella burnetii, mainly acquired from domestic (cattle, sheep, goats but also dog and cats) or wild animals (deer), has been associated with many lymphoproliferative disorders (hyperlymphocytosis, mononucleosic syndrome). We observed a lymphoma developing in a patient followed up for Q fever that prompted us to investigate the association between the two diseases. In this study, we reported 11 cases of B-cell lymphoma developing after Coxiella burnetii primary-infection, we found an increased incidence of lymphoma in Q fever patients, particularly those with persistent focalized infection, and we detected the viable bacterium within lymphoma tissues. More specifically, we found that this bacterium infect the plasmacytoid dendritic cells (pDCs) in patients with C. burnetii-related lymphoma. This is particularly important since these cells are critical modulating their immune microenvironment including the natural antitumoral activity. Moreover, we found that peripheral blood mononuclear cells of these patients overproduce interleukin-10 even in the absence of the bacterium. This suggests that a persistent reprogramming of their immune cells have been triggered by the infection. Finally, we showed that these patients have very high levels of the anti-inflammatory Interleukin-10 in their serum, suggesting a systemic immune escape favoring the development of cancer. Coxiella burnetii is associated with an increased risk of lymphoma, its presence in the tumor microenvironment may favor lymphomagenesis. C. burnetii should be added to the list of bacteria that promote human B-cell non-Hodgkin lymphoma. (more…)
Author Interviews, Brigham & Women's - Harvard, Frailty, Geriatrics, Infections / 12.10.2015

Farrin A. Manian, MD, MPH, FACP, FIDSA, FSHEA Inpatient Clinician Educator, Department of Medicine, Massachusetts General Hospital Visiting Associate Professor, Harvard Medical School, Boston, MA Interview with: Farrin A. Manian, MD, MPH, FACP, FIDSA, FSHEA Inpatient Clinician Educator, Department of Medicine, Massachusetts General Hospital Visiting Associate Professor, Harvard Medical School Boston, MA 02114 Medical Research: What is the background for this study? What are the main findings? Dr. Manian:  Falls are a leading cause of injury and death, afflicting about one-third of adults over 65 years of age annually.  Although there are many potential causes for falls, infections have received very little attention, with previous published reports primarily revolving around institutionalized elderly with dementia and urinary tract infection. We found that the spectrum of patients at risk for falls precipitated by infections goes far beyond the institutionalized elderly with dementia and urinary tract infection.  In fact, the majority of our patients fell at home and did not have a diagnosis of dementia.  In addition, besides urinary tract infections which accounted for 44.1% of cases, bloodstream (40.0%) and lower respiratory tract infections (23.0%) were also frequently represented.  Although the mean age of our patients was 76 years, 18% were younger than 65 years.  We also found that the signs and symptoms of these infections at the time of the presentation for the fall were often non-specific (e.g. weakness or mental status changes) or absent, with only 44% of patients meeting the criteria for systemic inflammatory response syndrome and only 20% having fever or abnormal temperature possibly related in part to advanced age.  These factors may make it difficult for the patient, family members and healthcare providers to readily consider infections contributing to the fall.  In fact a coexisting systemic infection was not initially suspected by providing clinicians in 40% of our patients and 31% of those who were later diagnosed with a bloodstream infection. (more…)