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 healthofficials and healthcare workers (HCWs) have been confronted with a number ofdistinctive new infectious diseases. With the possibility of global transmissionin a relatively short amount of time, these emerging infectious diseases (EIDs)have provided significant challenges to the scientific and medicalcommunities. Nowhere is this challenge greater than in hospitals and otherhealthcare facilities. In addition to EIDs, the threat ofantibacterial-antimicrobial-resistant organisms continues to grow. In order toprotect their patients, communities and themselves, infection controlpractitioners (ICPs) and HCWs must be prepared to deal with any and allinfectious agents that cross their paths. As fl u season approaches, facilitiesacross the country have many bugs on their radars.

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

Another virus that has seen recent seasonal prominence is WestNile virus (WNV). Originally detected in the United States in the summer of1999, WNV has continued to infect humans in subsequent summers via mosquitobites. As of Sept. 14, 2004, 1,386 cases of human infection had been reportedfor the year.1 WNV risk seems to have a geographic correlation, tending to bemore pervasive in the western United States.

West Nile, from the infection control perspective, is alittle bit easier in terms of preventing transmission in hospitals than SARSbecause its not easy to transmit from person to person, says Cardo.Transmission  is possible, however, through blood transfusionand organ donation. It does highlight the importance of following all thebasic precautions that we recommend, especially when you have the potential ofcontact with blood, Cardo continues.

While flu season is always formidable for many areas of thecountry, the possibility of pandemic influenza is a particularly seriousconcern. New strains of the fl u virus can arise quite rapidly and setoff this global epidemic, in which a large percentage of the worldspopulation could be extremely susceptible. In 1918, pandemic influenza wasresponsible for more than 20 million deaths worldwide. It is widely acknowledgedthat pandemics of influenza are likely to occur in the future, although it isimpossible to predict or guarantee.

Establishing preparedness and planning for this kind oflarge-scale scenario can be daunting. It really brings us back to the lessonswe learned with SARS the importance of identifying patients with the diseaseor at risk for the disease, and knowing how to manage those patients when theyare hospitalized, says Cardo. Also, doing everything that has beenrecommended to prevent transmission; we dont have new recommendations itsjust the recommendations that have been established for infection controlprecautions that should be followed. Cardo also points out that facilitiesmust do all they can to ensure adequate amounts of supplies such as personalprotective equipment (PPE) are on hand. Its also very important to makesure you have a plan as a healthcare facility for how to communicate with otherfacilities and health departments, because they may need help or they may needto provide help to other facilities that have large numbers of patients, shecontinues.

A final and vital component of readiness for influenzaseason, whether a pandemic strain is present or not, is vaccination. Cardostresses this fact and laments the low percentages of HCW vaccination. Despiteall the efforts to increase vaccination, even with a huge number of cases, weveseen that vaccination for HCWs is not achieved more than 50 percent, she says. This is something we really need to make sure weget better adherence to. If we have a pandemic or even a huge number of caseswithout a pandemic, we may have transmission from HCWs to patients, but also ifHCWs get sick, they will be unable to work, so it really poses a major problemand thats something that can be prevented.

Experts are also watching avian influenza A (H5N1) veryclosely. A natural pathogen in birds, avian influenza has recently shown thecapacity to infect humans as well. I think one concern, in addition to seeinghuman cases in Asia, is that they have also seen potential transmission to pigs,says Cardo. This mutagenic capability is distressing in that it may signaleasier transmission to humans in the future. Cardo underscores the same kinds ofpreparations as are applicable with any type of influenza in dealing with thisvirus. With influenza, I think either the fl u that were expecting tohave or the bird fl u should highlight the same concerns, she says. It isrecommended that state and local health departments, hospitals and cliniciansmaintain heightened surveillance efforts as outlined by CDC guidelines releasedin February 2004. As with SARS, this includes paying close attention to travelhistory and exposure risk in patients displaying symptoms of respiratoryinfection.

Because infectious agents are so unpredictable, it isimportant that HCWs remain alert and active in identifying potentially new bugsand manifestations of disease. Monkeypox is a good example of how you alwaysneed to pay attention to unusual diseases, says Cardo. She explains thatidentification of a disease such as monkeypox requires careful attention to anydeviation from normal disease and infection patterns. We always need to bealert for unusual presentations, either skin lesions or other symptoms that arenot commonly seen; this should be a trigger for people to think about a newinfection, Cardo continues. Its very difficult to predict if were going to seemonkeypox again. The CDC suggests that patients with fever and vesiculopustularrash be evaluated for possible exposure to wild or exotic mammalian pets, suchas prairie dogs or African rodents, or persons with monkeypox. There has been noevidence of direct person-to-person transmission of monkeypox in the UnitedStates as of yet, but it is thought to be possible.

At the other end of the spectrum are existing infectiousdiseases that have become somewhat resurgent. Tuberculosis (TB) continues to bea worldwide health threat and has actually become more prevalent over the last10 years. Some feel that the current World Health Organization (WHO) treatmentpolicy has proven inadequate and that more extensive prevention and treatmentstrategies are necessary.2 I always feel that we need to be concerned aboutTB, says Cardo. Some of the principles we use for TB detection andprevention are exactly the same as we use for SARS; that is, early detection,administrative measures, isolation and personal protective equipment. Cardoalso stresses the importance of evaluating risk factors as part of diagnosingrespiratory infection. The thing some people forget is to look at riskfactors and not just symptoms, she says. We should be thinking about thisall of the time with TB.

Although specific knowledge of each and every emerging andexisting infectious disease is a necessity for ICPs and HCWs, the big pictureremains an essential focus in terms of infection control. I think if peoplefollow the basic established infection control recommendations such as handhygiene and personal protective equipment, we may be able to prevent mostinfections, instead of just thinking in terms of specific pathogens, says Cardo. In this sense, ICPs are a vital source of education and knowledge forHCWs in their facilities, according to Cardo. They (ICPs) need to train andre-train people on how to think about new infections and on the basics ofinfection control. Cardo points out that this lesson was brought home by lastyears SARS outbreak. I think using SARS is a good example to show peoplehow to be prepared and alert and how to communicate with public healthorganizations and other healthcare facilities, she says. SARS was a verygood lesson in terms of showing that infection control should be everybodysbusiness.

Antimicrobial Resistance

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

History since 1940 dictates that the bacteria becomeresistant and as there are fewer and fewer drugs, then we have to use theexisting drugs with greater frequency, which further increases the likelihoodthat resistance is going to occur sooner rather than later, says David N. Gilbert, MD, past-president of IDSA, anddirector of medical education for Providence Portland Medical Center. ICPsare very aware of the increasing resistance of common bacterial pathogens,Gilbert continues. Were currently having the epidemic ofcommunity-acquired methicillin-resistant Staphylococcus aureus (MRSA) ontop 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 ICUorganisms like pseudomonas and acinetobacter that are becoming resistant toeverything.

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

The absence of sufficient incentives for the development ofnovel antibiotic compounds is at the root of this problem, according to the IDSAsreport. The great investment in terms of time and money that must be made todiscover new treatment options is oftentimes not able to produce a comparablereturn. As businesses that answer to their shareholders, pharmaceuticalcompanies have recently been more apt to focus on classes of drugs that makemore business sense. If the big companies that have the wherewithal to dosignificant discovery work disappear, then were left with depending on thesmall 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 ofthe dice.

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

Bad Bugs, No Drugs provides several specificrecommendations for legislators in this respect. Among these is theestablishment of an independent Commission to Prioritize Antimicrobial Discovery(CPAD) by Congress. The Food and Drug Administration (FDA) and the NationalInstitute of Allergy and Infectious Diseases (NIAID) are also urged to worktogether to create joint programs to help streamline antibiotic drugdevelopment. A number of other methods designed to stimulate renewed antibioticR&D in the pharmaceutical industry are also suggested, including taxincentives and patent extensions for pharmaceutical companies, and the creationof a government-sponsored guaranteed market for antibiotics.

Although federal aid for established, profitable corporationslike large pharmaceutical companies may not seem like the most judiciouspolitical philosophy to some, Gilbert points out that inaction may prove to bemuch more costly in the long run. We, the rest of the citizens, will end uppaying a pretty penny because our ICUs are going to be full of people with veryresistant organisms for which we have few or no drugs, he says. Itsshort-term vs. long-term.