Antimicrobial Resistance

Emerging Infectious Threats
Present and Future Considerations for Emerging Infectious Diseases and Drug-Resistant Pathogens

By Kris Ellis

Over the past few years, public health officials and healthcare workers (HCWs) have been confronted with a number of distinctive new infectious diseases. With the possibility of global transmission in a relatively short amount of time, these emerging infectious diseases (EIDs) have provided significant challenges to the scientific and medical communities. Nowhere is this challenge greater than in hospitals and other healthcare facilities. In addition to EIDs, the threat of antibacterial-antimicrobial-resistant organisms continues to grow. In order to protect their patients, communities and themselves, infection control practitioners (ICPs) and HCWs must be prepared to deal with any and all infectious agents that cross their paths. As fl u season approaches, facilities across the country have many bugs on their radars.

Severe Acute Respiratory Syndrome (SARS) burst onto the scene in 2003 and gave everyone a taste of just how quickly a dangerous new pathogen could become widespread. There has been a recent lull in SARS activity, but vigilance remains important. Although we havent seen a new case in the last few months, it is a disease that we always need to be aware of, says Denise Cardo, MD, director of the Centers for Disease Control and Prevention (CDC)s Division of Healthcare Quality Promotion Program. We are alert at the CDC, and I think ICPs should continue to be alert because early detection and following the guidelines for preventing transmission are the main ways of containing SARS. Another seasonal outbreak is always within the realm of possibility. SARS is caused by a coronavirus, and we know that those are seasonal, notes Cardo.

Another virus that has seen recent seasonal prominence is West Nile virus (WNV). Originally detected in the United States in the summer of 1999, WNV has continued to infect humans in subsequent summers via mosquito bites. As of Sept. 14, 2004, 1,386 cases of human infection had been reported for the year.1 WNV risk seems to have a geographic correlation, tending to be more pervasive in the western United States.

West Nile, from the infection control perspective, is a little bit easier in terms of preventing transmission in hospitals than SARS because its not easy to transmit from person to person, says Cardo. Transmission  is possible, however, through blood transfusion and organ donation. It does highlight the importance of following all the basic precautions that we recommend, especially when you have the potential of contact with blood, Cardo continues.

While flu season is always formidable for many areas of the country, the possibility of pandemic influenza is a particularly serious concern. New strains of the fl u virus can arise quite rapidly and set off this global epidemic, in which a large percentage of the worlds population could be extremely susceptible. In 1918, pandemic influenza was responsible for more than 20 million deaths worldwide. It is widely acknowledged that pandemics of influenza are likely to occur in the future, although it is impossible to predict or guarantee.

Establishing preparedness and planning for this kind of large-scale scenario can be daunting. It really brings us back to the lessons we learned with SARS the importance of identifying patients with the disease or at risk for the disease, and knowing how to manage those patients when they are hospitalized, says Cardo. Also, doing everything that has been recommended to prevent transmission; we dont have new recommendations its just the recommendations that have been established for infection control precautions that should be followed. Cardo also points out that facilities must do all they can to ensure adequate amounts of supplies such as personal protective equipment (PPE) are on hand. Its also very important to make sure you have a plan as a healthcare facility for how to communicate with other facilities and health departments, because they may need help or they may need to provide help to other facilities that have large numbers of patients, she continues.

A final and vital component of readiness for influenza season, whether a pandemic strain is present or not, is vaccination. Cardo stresses this fact and laments the low percentages of HCW vaccination. Despite all the efforts to increase vaccination, even with a huge number of cases, weve seen that vaccination for HCWs is not achieved more than 50 percent, she says. This is something we really need to make sure we get better adherence to. If we have a pandemic or even a huge number of cases without a pandemic, we may have transmission from HCWs to patients, but also if HCWs get sick, they will be unable to work, so it really poses a major problem and thats something that can be prevented.

Experts are also watching avian influenza A (H5N1) very closely. A natural pathogen in birds, avian influenza has recently shown the capacity to infect humans as well. I think one concern, in addition to seeing human cases in Asia, is that they have also seen potential transmission to pigs, says Cardo. This mutagenic capability is distressing in that it may signal easier transmission to humans in the future. Cardo underscores the same kinds of preparations as are applicable with any type of influenza in dealing with this virus. With influenza, I think either the fl u that were expecting to have or the bird fl u should highlight the same concerns, she says. It is recommended that state and local health departments, hospitals and clinicians maintain heightened surveillance efforts as outlined by CDC guidelines released in February 2004. As with SARS, this includes paying close attention to travel history and exposure risk in patients displaying symptoms of respiratory infection.

Because infectious agents are so unpredictable, it is important that HCWs remain alert and active in identifying potentially new bugs and manifestations of disease. Monkeypox is a good example of how you always need to pay attention to unusual diseases, says Cardo. She explains that identification of a disease such as monkeypox requires careful attention to any deviation from normal disease and infection patterns. We always need to be alert for unusual presentations, either skin lesions or other symptoms that are not commonly seen; this should be a trigger for people to think about a new infection, Cardo continues. Its very difficult to predict if were going to see monkeypox again. The CDC suggests that patients with fever and vesiculopustular rash be evaluated for possible exposure to wild or exotic mammalian pets, such as prairie dogs or African rodents, or persons with monkeypox. There has been no evidence of direct person-to-person transmission of monkeypox in the United States as of yet, but it is thought to be possible.

At the other end of the spectrum are existing infectious diseases that have become somewhat resurgent. Tuberculosis (TB) continues to be a worldwide health threat and has actually become more prevalent over the last 10 years. Some feel that the current World Health Organization (WHO) treatment policy has proven inadequate and that more extensive prevention and treatment strategies are necessary.2 I always feel that we need to be concerned about TB, says Cardo. Some of the principles we use for TB detection and prevention are exactly the same as we use for SARS; that is, early detection, administrative measures, isolation and personal protective equipment. Cardo also stresses the importance of evaluating risk factors as part of diagnosing respiratory infection. The thing some people forget is to look at risk factors and not just symptoms, she says. We should be thinking about this all of the time with TB.

Although specific knowledge of each and every emerging and existing infectious disease is a necessity for ICPs and HCWs, the big picture remains an essential focus in terms of infection control. I think if people follow the basic established infection control recommendations such as hand hygiene and personal protective equipment, we may be able to prevent most infections, instead of just thinking in terms of specific pathogens, says Cardo. In this sense, ICPs are a vital source of education and knowledge for HCWs in their facilities, according to Cardo. They (ICPs) need to train and re-train people on how to think about new infections and on the basics of infection control. Cardo points out that this lesson was brought home by last years SARS outbreak. I think using SARS is a good example to show people how to be prepared and alert and how to communicate with public health organizations and other healthcare facilities, she says. SARS was a very good lesson in terms of showing that infection control should be everybodys business.

Antimicrobial Resistance

While emerging infectious diseases raise concern over their potential to wreak havoc on public health, multi-drug-resistant pathogens are creating problems of their own. The Infectious Disease Society of America (IDSA) has recently published a white paper titled, Bad Bugs, No Drugs: As Antibiotic R&D Stagnates a Public Health Crisis Brews, that addresses the dangers of these pathogens and the drastic decrease in antibiotic research and development over the past few years.

History since 1940 dictates that the bacteria become resistant and as there are fewer and fewer drugs, then we have to use the existing drugs with greater frequency, which further increases the likelihood that resistance is going to occur sooner rather than later, says David N. Gilbert, MD, past-president of IDSA, and director of medical education for Providence Portland Medical Center. ICPs are very aware of the increasing resistance of common bacterial pathogens, Gilbert continues. Were currently having the epidemic of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) on top of our chronic problem of hospital-acquired MRSA. The pneumoccoci are increasingly resistant to penicillin, macrolides and tetracyclines. The gram-negative rods are becoming resistant, even E. coli is becoming resistant to the flouro-quinonones. Then, we have ICU organisms like pseudomonas and acinetobacter that are becoming resistant to everything.

Compounding the problem of increasing pathogenic resistance is the fact that most large pharmaceutical companies are no longer aggressively pursuing antibiotic R&D. The pipeline is pretty dry, and thats the issue, says Gilbert. There have been very few new drugs introduced and those that have been recently introduced are mainly variations on the old themes rather than brand new entities. According to Bad Bugs, No Drugs, only 10 new antibiotics have been approved since 1998, and most of these belong to existing classes.

The absence of sufficient incentives for the development of novel antibiotic compounds is at the root of this problem, according to the IDSAs report. The great investment in terms of time and money that must be made to discover new treatment options is oftentimes not able to produce a comparable return. As businesses that answer to their shareholders, pharmaceutical companies have recently been more apt to focus on classes of drugs that make more business sense. If the big companies that have the wherewithal to do significant discovery work disappear, then were left with depending on the small companies, and it takes them a long time to go through the process, says Gilbert. It takes hundreds of millions of dollars, and its a throw of the dice.

The IDSA concludes that policymakers must step in to address the situation without delay. Ive been using the 9/11 analogy that the airplanes are approaching the twin towers, only this time we know its going to happen, says Gilbert. Many of the potential solutions require political action, so the Society is politically active in trying to get new legislation that will incentivize the pharmaceutical companies.

Bad Bugs, No Drugs provides several specific recommendations for legislators in this respect. Among these is the establishment of an independent Commission to Prioritize Antimicrobial Discovery (CPAD) by Congress. The Food and Drug Administration (FDA) and the National Institute of Allergy and Infectious Diseases (NIAID) are also urged to work together to create joint programs to help streamline antibiotic drug development. A number of other methods designed to stimulate renewed antibiotic R&D in the pharmaceutical industry are also suggested, including tax incentives and patent extensions for pharmaceutical companies, and the creation of a government-sponsored guaranteed market for antibiotics.

Although federal aid for established, profitable corporations like large pharmaceutical companies may not seem like the most judicious political philosophy to some, Gilbert points out that inaction may prove to be much more costly in the long run. We, the rest of the citizens, will end up paying a pretty penny because our ICUs are going to be full of people with very resistant organisms for which we have few or no drugs, he says. Its short-term vs. long-term.

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