New evidence supports high-dose influenza vaccines

People older than 65 years are at particularly high risk for influenza-related medical complications including hospitalizations and death. In 2009, the FDA approved a trivalent inactivated vaccine with four-times the hemagglutinin antigen per strain, which was thought to improve immune response in seniors.

Background data has largely supported high-dose vaccination among seniors. In a multicenter, randomized controlled trial of high vs standard dose vaccine that included almost 32,000 patients during 2011/12 and 2012/13, 1.4% of high-dose and 1.9% standard-dose patients had an influenza-confirmed influenza-like illness, resulting in a relative efficacy of 24%. Adverse events were slightly, but significantly lower in the high-dose group but 3 high-dose recipients had serious vaccine-related events (which all resolved) vs none in the standard-dose group. A very large Medicare study during 2012/13 and 2013/14 reported similar benefits but only during 2012/13 when H3N2 was more common. Perhaps it is difficult to measure a benefit during more mild, H1N1 seasons? There have been other studies supporting the effectiveness and cost-effectiveness (at least during the 2011/12 and 2012/13 H3N2 seasons) of high-dose vaccine.

One of the larger groups of seniors in the US are patients in the Veterans Health Administration (VHA) system, so it makes sense to measure the benefits of high-dose vaccine using the VHA integrated EMR. In the June 1st JID, authors reported results of a large (industry-funded) retrospective cohort study completed using data from the 2015/16 influenza season (an H1N1 year) that included seniors with at least one inpatient or outpatient visit during the prior year (2014/15). The primary outcome was any hospitalization for pneumonia or influenza. The study used a number of nice methods to adjust for confounding including matching on baseline characteristics and the Care Assessment Need (CAN) score, that is a proxy for frailty. They also adjusted for residual confounding using the prior event rate ratio (PERR) method, which you can read more about here. Basically, PERR adjusts for outcome rates in the baseline period (before vaccination) by dividing the relative rate post-vaccination by the relative rate pre-vaccination (in the baseline period).

The final cohort (before matching) included 104,965 standard-dose and 125,776 high-dose recipients during the 2015/16  influenza season. The matched cohort had 49,091 standard-dose and 24,682  high-dose patients. Using the unmatched and matched cohorts, and using the PERR method with each, the relative vaccine effectiveness of high-dose influenza vaccine was 23% and 25%, respectively. This suggests that high-dose vaccine was effective in preventing influenza or pneumonia-associated hospitalizations among VHA patients.

These results are encouraging since they were from a more mild H1N1 season. Even more encouraging, the authors plan to automate the data extraction process and report vaccine effectiveness within 3 months of the end of each influenza season. But one note of caution, having a high-dose vaccine that is 25% more effective isn't a huge improvement, since influenza vaccines in general aren't very effective. So high-dose influenza vaccine is a small step in the right direction - but more research and new influenza vaccines are needed.

A Research Agenda for MDRO Prevention

Of course, I don't need to explain the clinical importance of multi-drug resistant bacterial pathogens to readers of this blog. I probably don't need to remind you that "more research is needed" either - that's why we have controversies! But, I should probably point you to five papers recently published in ICHE that outline the future research agenda for MDRO prevention in the US Veterans Health Administration (the VA).

For our non-US readers, the VHA is the largest integrated healthcare system in the United States with over 130 acute care facilities, 1000 outpatient clinics, numerous long-term care facilities and 9 million enrolled patients. The VA has been a leader in medical and health services research for decades and has been well-ahead of the curve in application of interventions to prevent MDRO including its MRSA prevention bundle and antibiotic stewardship initiative.

To continue the VA's success in MDRO prevention and link future research questions to the greatest clinical need, we invited a multidisciplinary group with 37 participants to Iowa City in September 2016. The aim of the panel was to outline the VHA's research agenda for MDRO prevention. Dan Livorsi describes the process we used to identify the domains and research questions in an introductory editorial. The outlined research agenda was broad in scope and included efficacy, effectiveness and implementation questions. In addition, many of these questions are broadly applicable to study in non-VA and non-US hospitals. We are all more alike than different.

Research questions fell into four domains:

1. Transmission dynamics: Resistant pathogens are spread via human hands and environmental surfaces. Disrupting this transmission is essential to controlling MDROs.

2. Antimicrobial stewardship: Strategies to reduce and improve the use of antimicrobials will slow the emergence of resistant pathogens.

3. Microbiome: There may be ways to manipulate or augment the human microbiome to eradicate or prevent colonization with resistant pathogens.

4. Special populations: Strategies need to be tailored to patient populations with distinct underlying conditions and in nontraditional care settings.

All 5 papers are open access. Thanks ICHE!  And thank you to the brilliant group of VA investigators, clinicians and operational partners who traveled to Iowa City and contributed to this effort. We all hope it's helpful.

VA Funds Two New Antimicrobial Resistance and HAI Prevention Programs

Dr. Nasia Safdar

It wasn't long ago, that many of us were concerned about the lack of attention that antimicrobial resistance was receiving, particularly in regard to funding for research and also infection prevention programs. Yet over the last few years, there has been increased attention throughout the US including the release of the National Action Plan to Combat Antibiotic-Resistant Bacteria and increased funding for CDC, NIH and AHRQ. Besides the lack of novel interventions that extra research funding will help tackle, another huge barrier to preventing MDRO and HAI is lack of information on how to successfully implement the few interventions we have within hospitals and healthcare systems.

It is this gap between efficacy and effectiveness that VA's Quality Enhancement Research Initiative (QUERI) seeks to fill. QUERI's mission is to "improve the health of Veterans by supporting the more rapid implementation of effective clinical practices into routine care." And it is the goal of QUERI investigators to "ask crucial questions regarding the intended and unintended impacts of implementing new treatments or programs – and the best strategies for speeding their adoption into practice."

Dr. Charlesnika Evans

With that background it is incredibly exciting to announce that VA has funded two new QUERI programs that target MDRO and HAI.

The first program titled "Building Implementation Science for VA Healthcare-Associated Infection Prevention" is led by Dr. Nasia Safdar in Madison. Dr. Safdar and her team partnered with VA's National Center for Patient Safety to achieve two broad aims. First, they will implement and evaluate an evidence-based intervention - daily chlorhexidine bathing of hospitalized Veterans for prevention of HAI. Second, they will establish a VHIN (VA Healthcare-Associated Infection Prevention Network) and assess current practices and needs related to HAI prevention. The long-term goal is to utilize the VHIN as a platform for VA facilities seeking to undertake pragmatic implementation science initiatives related to HAI prevention. You can read much more about her program that began in October 2015, here.

Dr. Michael Rubin

The second program titled "Combating Antimicrobial Resistance through Rapid Implementation of Available Guidelines and Evidence" or CARRIAGE is set to begin in October 2016 and aims to address the growing concern of antimicrobial resistance through strategies implemented across VA patient care settings. The three projects will evaluate hand hygiene surveillance methods, enhance the implementation of new CRE prevention guidelines and promote judicious use of antibiotics through a multi-hospital antibiotic timeout program. The program directors are Michael Rubin, MD PhD (Salt Lake City) Charlesnika Evans, PhD, MPH (Hines, IL); and Eli Perencevich, MD MS (COI alert)

The next few years promise to be an exciting time for MDRO and HAI prevention in VA and throughout the US as we develop, test and implement new methods to enhance patient safety.

More good news about MRSA. This time from VA.

It's not often that good news about hospital-acquired infections (HAI) is reported in the media. When was the last time you read an article congratulating a hospital for having lower CLABSI rates or good hand hygiene compliance? It's even rarer to hear good news about VA Medical Centers. While the quality of care in VA often meets or exceeds that in the private sector, it's rarely reported, since high quality runs contrary to established memes.

That's what's unique about today's 'Opinionator' article in the NYTimes. It reports greater improvement in MRSA infections in VA vs non-VA hospitals. To those of us that study HAI and resistant bacteria, this isn't that surprising. Integrated, public (national) health care systems, like VA, have built in incentives to prevent infections since they see the direct benefits of reduced costs and better outcomes - incentives that aren't well-aligned in other hospitals. However, to most folks it is probably surprising that VA was an early adopter of a bundled approach to MRSA prevention and has set the bar for the rest of the country.

Dan and I are both quoted in the article, so I encourage you to read it. However, I'd also like to highlight one section:

"The V.A.’s achievement is even more remarkable because its patients are older and sicker than patients in other hospitals. (Most patients are Vietnam-era vets. None are healthy young women giving birth, a large patient group in most hospitals.) They are twice as likely to come to the hospital already testing positive for MRSA. The greater the percentage of people who have the bacteria, the harder it is to control its spread. Because their immune systems are weaker, V.A. patients are also more likely to go from testing positive to full infection."

The fact that VA patients are older, sicker and often poorer than other hospitalized patients is frequently missed in the wider discussion about quality measures. When you have all the cards stacked against you and you still deliver high-quality and safe care, it should be recognized. Nice when it is.