on another old problem: war-related infections. Accounts of the antibiotic revolution often point out how a combination of antibiotics and improved surgical interventions enable the treatment of wound infections that once killed soldiers more frequently than the trauma of the wounds themselves. World War I was the last war in which infectious diseases—not just wound infections but also diarrhea and pneumonia—were the main cause of soldiers’ deaths.
An ominous development in the past decade or so has been the appearance of a soil bacterium, Acinetobacter baumannii, first as a wound infection problem in soldiers and now as a dangerous hospital-acquired infection. A. baumannii was not a stranger to microbiologists, as there had been a few outbreaks in intensive care wards, but A. baumannii began to attract real attention around 2003 when it started showing up in military hospitals during the Iraq War. Its claim to fame is that it was one of the first bacteria to be called “panresistant” because it is resistant to almost all antibiotics. Before the emergence of panresistant A. baumannii, the worst threat in terms of antibiotic resistance was another soil bacterium, Pseudomonas aeruginosa, which has long been known as an infectious disease problem in burn victims and cystic fibrosis patients. A number of other soil bacteria and bacteria normally found in or on the human body (such as MRSA, mentioned previously) also seem to be resistant to multiple antibiotics. Unfortunately, these ubiquitous bacteria have emerged as common causes of hospital-acquired infections.
A new understanding of antibiotic resistance is that the physiological state of a bacterium can be as important as its complement of resistance genes. Many bacteria can form biofilms, multilayer groupings of bacteria that are held together by a sticky polysaccharide matrix secreted by the bacteria. Biofilms are found in many places in nature, most notably in areas such as streams, where the fast flow of water makes it necessary for bacteria to resort to biofilm formation to stay in a particular site. In hospital patients, biofilms seem to form very readily on plastic or metal implants. Although we do not yet fully understand the reason, bacteria in these biofilms are significantly less susceptible to antibiotics and are therefore quite difficult to eliminate. All too frequently, patients with a biofilm-contaminated implant have to undergo additional surgery to remove the implant so that antibiotics can be used to eliminate any remaining bacteria. After the infection is cleared, a second implantation can be attempted.
Bioterrorism
No discussion of current infectious disease issues would be complete without mention of bioterrorism. Germ warfare—the use of infectious microorganisms as weapons—is an old idea that has, fortunately, never worked very well. The nature of germ warfare has changed in recent years. In the past, the purpose of germ warfare was to kill or incapacitate large numbers of soldiers. Recently, the aim of terrorists’ actions has changed. Now, the goal is to frighten the general population (hence the name “bioterrorism”). A small number of deaths are sufficient to achieve this goal.
Among bacteria, Bacillus anthracis, the causative agent of anthrax disease, has been identified as a particularly useful weapon by bioterrorists. B. anthracis, as a spore-forming Gram-positive bacterium, is easier to store and “weaponize” than a more fragile organism, such as the Gram-negative Yersinia pestis, the causative agent of bubonic plague. In spore form, B. anthracis is also easier to handle than the highly contagious smallpox virus. The U.S. Army was worried enough about possible anthrax attacks to administer the anthrax vaccine to soldiers going to Iraq and Afghanistan. This sparked controversy because the efficacy and safety of the available anthrax vaccines were contentious issues at the time. Unfortunately, the anthrax attacks through the U.S. postal system in late 2001 only served to exacerbate the fear and solidify the realization that bioterrorism is a reality that we must now address.
An alternative bacterial choice of bioterrorists is Clostridium botulinum, another spore-forming bacterium that produces botulinum neurotoxin. Producing botulinum neurotoxin in your garage is inadvisable and can be extremely hazardous to your health, but this toxin is produced commercially (as Botox) for use in a variety of medical and cosmetic applications, ranging from correcting facial tics and strabismus (cross eyed) to eliminating wrinkles and preventing scarring from reconstructive surgery. Thus, it is conceivable that terrorists might hijack commercially produced Botox from factories that produce it. Whether emptying vials of toxin into a city’s water supply would actually result in any deaths is not clear, as dilution and breakdown of the purified toxin protein in the environment will occur. It is, however, better to err on the side of caution. The most recent concern, though so far only theoretical, is that botulinum toxin might be deliberately introduced into milk, juice, or soft drinks during processing.
A New Respect for Prevention
Major changes that hold great promise for the future have been occurring in the approach to controlling infectious diseases. Traditionally, medical establishments in developed countries have opted for a treatment-based approach. Although vaccinations were given to prevent some diseases and doctors used antibiotics prophylactically to prevent others, such as postsurgical infections or infections in cancer chemotherapy patients, the most common approach to treating infectious diseases was to wait for an infected person to seek medical help before intervening in the disease process. This approach has been criticized for being expensive and for allowing diseases to gain a foothold in the body before action is taken—a delay that in some cases results in long-term damage to the patient, even if the treatment successfully eliminates the infecting bacterium from the body.
Treatment-based approaches have also become much less effective as increasingly resistant bacteria make it more difficult to choose the appropriate antibiotic treatment. To better combat this escalating problem, it is important to understand the reasons for the rise in antibiotic resistance, particularly in hospital settings. If a bacterial infection is not cleared immediately, sepsis can kill a patient in just a few hours. Thus, since waiting for proper diagnostics can be fatal to the patient, the physicians’ responses have generally been to use more advanced, broad-spectrum antibiotics to treat all bacterial infections, regardless of whether they might be treatable with less expensive, narrow-spectrum antibiotics. Adding the diagnostic testing to the decision process also raises the overall cost of the clinical visit, something that not only delays treatment, but also is actively discouraged by health insurance companies. Physicians have been advised to use the frontline antibiotics first, but also to send samples to the microbiological laboratory for antibiotic resistance evaluation and then adjust the therapy if laboratory results indicate another, more appropriate treatment regimen. Nevertheless, the overall result is increased selective pressure on the bacteria to develop resistance against the frontline antibiotics.
A far preferable approach to controlling a disease is preventing it in the first place. This approach has been successful in ensuring the safety of food and water. Now, more and more public health officials, hospital managers, and executives of health management organizations (HMOs) are rediscovering that prevention is also far more effective—and far less expensive—than treatment after infection has occurred. Prevention is suddenly center stage again. But, for a preventive approach to work, it is first necessary to have extensive information about the epidemiology of disease (i.e., information about disease patterns, their geographic distribution, and determinants of health-related states). It is also necessary to have a large-scale networking infrastructure in place that can serve as an early warning system to detect signals indicating new disease trends. Led by the CDC and the WHO, a variety of such epidemiological surveillance programs have been implemented to monitor the appearance of new diseases, the increased incidence of existing diseases, and the occurrence of antibiotic-resistant bacteria. Indeed, the CDC website (http://www.cdc.gov/) is now an extensive portal for the latest information about various infectious diseases, including scientific and medical information about a disease and its causative agent, up-to-date disease trends, precautionary measures, and travel alerts.
The CDC has been monitoring a subset of particularly problematic infectious diseases for years, but the list of diseases covered had been far from exhaustive. Now, many more infectious diseases, such as infections with pathogenic E. coli and Chlamydia, have been placed on the list of reportable
