A recent article by National Institute of Allergy and Infectious Diseases (NIAID) staff emphasized that NIAID funds over $800 million annually to study antimicrobial resistance. I’ve heard this same argument many times, and, every time, people always grumble about how that money includes all microorganisms, as opposed to bacterial antibiotic resistance (NIAID never breaks the money down by organism). In particular, the ESKAPE organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanni, Pseudomonas aeruginosa, and Enterobacter species), most of which are ‘boring’ commensals, are not emphasized even though they represent a tremendous health burden in developed and developing countries.
Last month, Louis Rice, in The Journal of Infectious Diseases, criticized NIAID for not emphasizing resistance in opportunistic commensals:
NIAID funding of antimicrobial research has grown considerably over the past decade, now totaling more than $800 million annually. In considering this very large number, it is important to realize that it represents NIAID’s total commitment to all areas defined as being related to antimicrobial therapy. This category includes research on antibacterial, antifungal, antiparasitic, and antiviral therapies, whether related to the treatment of diseases or to their prevention through the use of vaccines. It is therefore difficult to get a firm grip on what level of support is devoted to antibacterial therapy and resistance, particularly in reference to the ESKAPE bugs.
Regarding research specific to issues involving antimicrobial resistance, Peters et al. indicate that NIAID is currently spending more than $200 million. In considering this amount, it is important to recognize that it also includes support for research on resistance to antiviral (including HIV), antifungal, and antiparasitic (including antimalarial) agents. Within the bacterial category, research on resistance to drugs targeting Mycobacterium tuberculosis is included. It is not possible to tease from this analysis the level of commitment NIAID has made to the study of resistance in the ESKAPE bugs.
The problem is that ESKAPE organisms are boring, unlike the Big Three–HIV, malaria, and TB (italics mine):
The enormous importance of HIV, malarial parasites, and M. tuberculosis to public health around the world should never be doubted. However, antimicrobial resistance in these microorganisms is fundamentally different from that observed in the ESKAPE bugs. Resistance in the ESKAPE bugs is primarily (although no longer exclusively) associated with the nosocomial environment. Nosocomial transmission of HIV through transfusion or contaminated needles, of malaria through transfusion, or of tuberculosis through contaminated aerosols constitute only a very small minority of transmission events. It is also fair to say, given what we know about the mechanisms of antimicrobial resistance in HIV, Plasmodium species, and M. tuberculosis, that the lessons learned from their study are unlikely to have a major impact on our understanding of resistance in the ESKAPE bacteria, because of the abundance of plasmids, transposons, and frequent genetic exchanges that characterize the latter microorganisms. Moreover, the enormous importance of HIV, malaria, and tuberculosis worldwide has attracted the sustained interest and philanthropy of many other organizations…. In an era of limited resources, it is critical that we assess the incremental value of NIAID dollars invested in these well-funded areas compared with other areas that are not the beneficiaries of commitments from foundations.
As I’ve noted repeatedly on the blog, there’s so much we don’t know about antibiotic resistance in boring, relatively well-understood bacteria (italics mine):
One need only survey our knowledge of some very basic questions regarding antibacterial therapy compared with to our knowledge of the use of anti-HIV drugs to realize that whatever quantity of NIAID dollars has been devoted to antibacterial research is not enough. For most bacterial infections, minimal lengths of treatment have never been defined. The benefit of antimicrobial therapy over placebo for many common infections (such as otitis media or sinusitis) remains murky. The use of combinations of antibiotics is widespread, without conclusive evidence of benefit in most circumstances. There are far more questions than answers about the utility of basic infection-control measures. Even if we had that information, there has been very little research into the best mechanisms for disseminating the knowledge in a way that will change physicians’ practices. In each of these areas (optimal antimicrobial therapy, infection control, physician and patient behavior), our evidence-based knowledge in the area of HIV (accumulated for <3 decades) far outstrips our knowledge in the area of antibacterial therapy (around for nearly 8 decades).
The roots of this disappointing progress in our knowledge are not surprising. For decades many people believed that resistance was a problem for the pharmaceutical industry to solve. The fact that the pharmaceutical industry would not favor research on ways of minimizing antimicrobial use somehow escaped us. The regrettable recent departure of most big pharmaceutical companies from the area of antibacterial development has made it clear that a pharmaceutically sponsored solution was always a myth. It is also a fact that many different federal agencies (the NIH, the Centers for Disease Control and Prevention [CDC], the Department of Agriculture, the Food and Drug Administration, and the Department of Veterans Affairs) focused on the narrow strips of the issue perceived as being relevant to their missions. The result was that the big picture did not receive the attention it deserved.
Rice correctly identifies the problem. However, I think he proposes the wrong solution: the Strategies to Address Antimicrobial Resistance (STAAR) Act. I’ll talk about that tomorrow.