A call to arms for docs: super bugs, no drugs

October 2004

---Richard F. Jacobs, MD

The vulnerability of the Iraqi pipeline and its impact on world oil supplies leading to record prices for crude oil makes the headlines every day and impacts the daily lives of U.S. consumers. The supply of oil with uncertainties in Yukos Inc., the Russian legislature and the court system frustrate commodities traders and weigh heavy on the minds of the U.S. government administration.

What seems to not be garnering as much attention is another pipeline. The research, investment, development and availability of new antibiotics in the war on super bugs have stagnated, and there is a public health crisis brewing in the world.

The Infectious Diseases Society of America (IDSA) and its Task Force on Antimicrobial Availability have published a report, “Bad Bugs, No Drugs,” which is available on the IDSA Web site (www.idsociety.org/badbugsnodrugs). This document focuses on the current situation related to antibiotic resistance and the lack of development of new antibiotics as a looming public health crisis in the near future. The IDSA leadership has taken this message to Capitol Hill and has begun educating legislators about the lack of new antibiotic development by pharmaceutical companies.

They have made recommendations for action by physicians, the pharmaceutical industry, the FDA, the NIH and the U.S. government. It is a time for a “call to arms” among physicians to advocate for these recommendations, to give thoughtful consideration to other strategies and to act now before we re-enter the pre-antibiotic era due to evolving antibiotic resistance and a dry pipeline.

More common

How many of you have had to deal with community-acquired methicillin-resistant Staphylococcus aureus, penicillin- or cephalosporin-resistant Streptococcus pneumoniae, vancomycin-resistant enterococcus or multidrug-resistant gram-negative infections in the past year? In the past 20 years, we have become much more accustomed to dealing with hospital-acquired infections due to antibiotic-resistant pathogens.

A listing of estimated causes of hospital-acquired infections by selected resistant bacteria in the United States in 2002 is provided by this IDSA publication in Table 1. The percentage of drug resistance in hospital-acquired infections in 2002 is provided in Table 2. In our experience at Arkansas Children’s Hospital, these community- and hospital-acquired resistant bacteria have become daily occurrences. The rapidity with which these pathogens have spread is alarming and is highlighted in Chart 1 for three of the more worrisome of these developments. Although we have had to alter our presumptive antibiotic therapy for most infectious diseases (meningitis, pneumonia, empyema, sepsis and osteomyelitis) due to these developments, we have not found ourselves without effective therapy — yet! It only takes a relatively short run through history to see what we could be facing in the near future without antibiotic discovery, research and development.

In 2002, out of 89 new drugs brought to U.S. physicians for use, no new antibiotics were approved. Until recently, research and development efforts have provided us with new antibiotics in time to treat these infections that had become resistant to older antibiotics. This is no longer the case. The history of antibiotic discovery and approval is a story worthy of a novel with many exciting and victorious interludes of “good vs. evil.” Table 3 provides you with a chronology of antibiotic discovery and approval in the United States.

The approval of only two new antibiotics with novel activity in this war against drug-resistant pathogens since 1998 is highlighted in Table 4. Just as Theoden made his battle cry during the ride of the Rohirrim to war in the battle of Minas Tirith “Death! And the sun rises,” in “The Return of the King,” our war against evil (drug-resistant bacteria) appears bleak (Chart 2).

As the past-president of the Pediatric Infectious Diseases Society and the liaison to the IDSA Board of Directors, I have witnessed the cultivation of this strategy and plan to arm physicians with the antibiotics needed to carry on our war on bacterial infections.

The call to arms

What is this “call to arms”? First, it is the recognition and education of all stakeholders that this is a looming public health crisis, no less potentially catastrophic than the concerns of Bioshield and the defense of our citizens against a biological attack. This is more important and more likely to impact the lives of our citizens.

It is also not mutually exclusive of the potential impact on biological warfare. Biological weaponry using antibiotic-resistant pathogens should be on the minds of our government.

IDSA recommendations

The IDSA is recommending a multipronged approach to limit the impact of antibiotic resistance on patients and the public.

Its efforts include educating physicians, patients and parents about the appropriate use of antibiotics (sound familiar?); developing and applying infection control and immunization policies and practices to prevent transmission (sound familiar?); surveying clinical and prescription data (sound familiar?); and developing safer alternatives to antibiotic use in agriculture (sound familiar?). These important messages must continue to be a part of this program.

The primary purpose of this new document and initiative, however, is “to call attention to a frightening twist in the antibiotic resistance problem that has not received adequate attention from federal policymakers: The pharmaceutical pipeline for new antibiotics is drying up.” The IDSA’s “call to arms” is based on its challenge: “Both the public and private sectors appear to have been lulled into a false sense of security based on past successes.”

To conclude this urgent need for attention to the antibiotic pipeline, the IDSA offers a strategy and recommendations.

“The potential crisis at hand is the result of a marked decrease in industry R&D, government inaction and the increasing prevalence of resistant bacteria. Infectious diseases physicians are alarmed by the prospect that effective antibiotics may not be available to treat seriously ill patients in the near future.” I encourage all physicians to go to the IDSA Web site or obtain a copy of this publication and begin working within your professional societies, medical organizations and local hospitals to educate your officials, patients and parents and let this campaign be a visible point of importance to your elected officials (or those trying to get elected!).

Less research funding

The current administration’s projected reductions in research funding and investment in medical research and narrow view of this and other important medical issues should alarm us all. To reduce the national deficit by reducing the investment in medical research, discovery and development of new antibiotics and programs that have advanced our lives and economy will be a mistake of unforgettable proportions in history. So, this is a “call to arms” for the readership of Infectious Diseases in Children. To ignore it is to ignore your patients.

	In the past 20 years, pediatricians have become much more accustomed to dealing with hospital-acquired infectious due to antibiotic resistant pathogens, like methicillin-resistant Staphylococcus aureus, vancomycin- resistant enterococcus or fluoroquinolone-resistant Pseudomonas.
INFECTIOUS DISEASES IN CHILDREN
Source: Reprinted with permission from IDSA

Value adjustment

My last point is to recommend an editorial published by Richard P. Wenzel, MD, entitled “The Antibiotic Pipeline — Challenges, Costs and Values” in The New England Journal of Medicine, Aug. 5, 2004. In this thoughtful editorial, Dr. Wenzel highlights the impact of mortality due to bacterial infections in the pre-antibiotic era. He identifies three adverse circumstances that threaten the antibiotic era: high levels of antibiotic resistance among important pathogens, an uneven supply of novel classes of antibiotics and a dramatic reduction in the number of pharmaceutical companies engaged in the discovery and development of anti-infective agents. He notes that the key metric used by pharmaceutical companies to prioritize investments in industry is the risk-adjusted net present value. This is the return in future dollars after adjustment for the investment and any lost income, usually expressed in millions of dollars.

So, here is our second challenge: changing the “values” of our patients, parents and government. We have become an instant gratification, zero-tolerance society that always reacts to crisis instead of identifying a problem and working just as hard to prevent it. Until it affects our lives, we ignore it. We have some converts, those patients and families with antibiotic-resistant bacterial infections whom we have been treating, but most of America and our news media–driven government have not acted.

It is time for all of us to use this IDSA document and similar supporting evidence to change the values of our patients away from performance-enhancing drugs (not just body-sculpture or weight loss — you know what I really mean!) and focus on more important priorities.

The primary resources for this historical and public health–based editorial acknowledge the generous availability of the IDSA publication with tables and charts.

We all owe a debt of gratitude to the IDSA, the members of the Task Force and the Public Policy office of the association for their diligence in this important arena.

INFECTIOUS DISEASES IN CHILDREN

Source: Reprinted with permission from IDSA

For more information:

• Wenzel RP. The antibiotic pipeline — challenges, costs and values. N Engl J Med. 2004;351(6):523-526.
• “Bad Bugs, No Drugs: As Antibiotic Discovery Stagnates ... A Public Health Crisis Brews,” copyright 2004, Infectious Diseases Society of America, www.idsociety.org/badbugsnodrugs.