The relationship between burden of disease and research funding is an important metric to consider when determining funding priorities that impact public health. Hospital-acquired infections (HAIs) are associated with a considerable burden of disease. The Centers for Disease Control and Prevention (CDC) estimates that each year in the United States there are about 1.7 million HAIs and 99,000 associated deaths.[6] The mean direct costs of HAIs (in 2005 dollars) range from $1,257 per case for catheter-associated urinary tract infections to $22,875 per case for ventilator-associated pneumonia.[7]

The pathogens that cause the majority of serious HAIs are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species- commonly referred to as ESKAPE bacteria.[8] Recently though, Clostridium difficile has emerged as an important nosocomial pathogen. In 2007, C. difficile was ranked as one of the 20 leading causes of death for people aged 65 and older.[9] Thus, this study has included C. difficile in the ESKAPE bacteria definition, henceforth known as ESCKAPE bacteria.

As mentioned, the funding trend for antimicrobial resistance studies during FY2007 through FY2009 shows a large increase during the first year and then a smaller increase in the subsequent year. This trend is also observed when the grants are stratified by pathogen of interest; non-bacterial (> 90% being viruses) and bacterial (combination of ESCKAPE, Mycobacterium, and other bacterial pathogens) (Figure ​(Figure1).1). Both groups show similar overall trend, consistent with the total funds trend, however the funding for bacterial pathogens has seen a smaller increase than non-bacterial pathogens during FY2008 to FY2009.

The total funding for all ESKCAPE pathogens was $ 22,005,943 in FY2007, $ 30,810,153 in FY2008 and $ 49,801,227 in FY2009. Staphylococcus aureus grants received $ 29,193,264 in FY2009, the highest funding amount of all the ESCKAPE pathogens. Enterobacter species received $ 378,005 in FY2009, the lowest amount of all the ESCKAPE pathogens. In FY2009, Enterococcus faecium, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Clostridium difficile grants received $602,635, $1,412,872, $2,329,872, $11,708,364, and $4,778,850 respectively. The funding trend for all ESCKAPE pathogens increased during the three year study period, except Enterobacter species due to lack of data for years prior to 2009 (Figure ​(Figure2).2). Total grant funding increased by 40% for the first year and increased by 61% the following year. The majority of the grant funding was related to Staphylococcus aureus, which increased approximately 2.5 times from FY2007 to FY2009.

In 2005, there were an estimated 18,650 deaths among people infected with MRSA.[10] Based on FY2009 funding data for Staphylococcus aureus, approximately $1,565 of research funding was spent per death. In 2007, 6,372 people infected with Clostridium difficile died.[9] Based on FY2009 funding data, approximately $750 of research funding was spent per C. difficile death. According to the NIH RePORT database, NIAID funding for HIV/AIDS was estimated to be $1.302 billion. This is similar to previous reports of $1.244 billion of NIAID funds allocated to HIV/AIDS in 2009.[11] Roughly 17,000 - 18,000 HIV deaths occur annually in the U.S.[12] Based on these rough numbers approximately $72,000 - $76,000 per HIV/AIDS death was spent for research.

Our search results were compared to the grants listed in the "Antimicrobial Resistance" category of the NIH RePORT Research, Condition, and Disease Categories (RCDC) (http://report.nih.gov/rcdc/categories/) (Figure ​(Figure3).3). Unlike our search, the NIH grants listed in the RCDC Antimicrobial Resistance category only covered the search term "Antimicrobial resistance" for FY2008 and FY2009. However, the overall results are similar; from FY2008 to FY2009 general funding in the RCDC Antimicrobial Resistance category increased by 25%, ESCKAPE pathogen funding increased by 24%, and about half of the funding is devoted to bacterial pathogens. The results that we reported are slightly different from the RCDC results because we included the "Hospital-associated infection" search term, which would have added more non-resistant bacterial grants to our search results.

The response to the public-health crisis of antibacterial resistance could be similar to the strategies used to counter HIV. For the past 30 years, NIH-funded research has made great progress in implementing various prevention measures, including reducing the transmission rate of perinatal HIV, HIV drug development and treatment, and a potential vaccine.[16,17] In 2009, the NIH awarded $1.302 billion in research funding for HIV/AIDS.[NIH Research Portfolio Online Reporting Tools (RePORT) http://projectreporter.nih.gov]. As a marker of NIH's HIV research success, in the U.S. in 2005, there were more deaths attributed to MRSA infections than attributable to HIV/AIDS.[18]

The NIH is not blind to the emerging problem of antibiotic resistance, and in response created the 'antimicrobial resistance' funding category. However, the title 'antimicrobial' includes viruses and parasites as well as antibiotic-resistant bacteria. Even though funding continues to increase in the antibiotic-resistance category, we found that only half of the funding is going to antibacterial research and the large increases in funding have targeted non-bacterial pathogens. The ESCKAPE pathogens are inherently different compared to viruses such as HIV and other pathogens such as Mycobacterium tuberculosis, thus they require specific attention.[8] From a mortality stand point, even though in the United States MRSA and HIV may be on par with each other, the research dollars invested shows a stark difference ($1,565 vs. $72,000 per death) when only considering NIAID research dollars. Considering other agency dollars, not to mention funding from pharmaceutical companies, will only widen this gap further. In order to have the hope in making the tremendous advances seen in HIV research, antibacterial research would need increased backing. Separate RCDC funding categories in "Antibacterial Resistance" and "Hospital-acquired infections" might be needed in order to highlight the need for more research dollars and attention to this ongoing crisis.

Our estimates may be limited since we only assessed NIAID funding, and not other institutes in the NIH or other agencies such as the CDC, the Agency for Healthcare Research and Quality (AHRQ), or Veteran's Health Administration. However, NIAID is the major agency within NIH that focuses on antimicrobial research. NIAID currently spends $800 million per year in antimicrobial research, which includes $200 million annually in research to better understand the causes, consequences, and treatments of drug resistance.[19] CDC has allocated approximately $17 million for antimicrobial resistance, which is mainly for preparedness, detection, and control purposes not for research.[20] Congress appropriated $5 million for MRSA and related hospital-associated infections in 2007-2008, then in 2009 $17 million ($8 million for MRSA and the remaining for other HAI) to AHRQ.[21] The VHA receives approximately $500 million in medical research but most of the funding is divided among other projects such as Gulf War illnesses, genomics, prosthetics, diabetes, and heart disease.[22] Very little is given to antimicrobial research. The combined total from these various agencies is a fraction of what the NIAID funds, thus our research is representative of the funding situation of antimicrobial research. Our data may be limited by missing information in the NIH RePORT website. However, this is the best public access source of NIAID research funding and should be up to date for FY2007-2009. Finally, our estimates of the amount of research funding spent per S. aureus or C. difficile death may be an overestimate or underestimate since we do not have mortality data from FY2009. However, the number of deaths associated with MRSA or C. difficile should not have significantly declined because no new antibiotics have become available since 2005.