Airborne Superbugs: Can Hospital-Acquired Infections Cause Community Epidemics?

Much attention has been focused recently on pathogenic microorganisms and the threat these microorganisms are to communities. Especially problematic are microorganisms that have developed resistance to antibiotic treatment and that have begun to spread beyond the bounds of hospital walls. The most dangerous are those that may spread by the airborne route, which include methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant tuberculosis (XTB). Pathogens that develop pan-drug resistance (PDR) might be considered “superbugs” because they are virtually invulnerable to standard drug treatments. Once these microbes develop immunity to antibiotic treatment and cause outbreaks in hospital environments they may, and have on occasion, spread into local communities. How great an epidemic threat these microorganisms are to communities is a question worth examining in more detail.

Nosocomial, or hospital-acquired, infections have been around as long as hospitals have been operating. But it is only in the last few decades that antibiotic and other treatments for these diseases have begun failing (ASM, 1994). The failure of any treatment leads to further spread if the infection cannot be contained by other means, such as quarantine. Airborne epidemics can spread rapidly and pervasively through a non-immune population (Weinstein, 2004). Thanks to favorable indoor environments airborne epidemics tend to be self-perpetuating, as opposed to foodborne and waterborne epidemics, which tend to be local and short-lived. Most of the drug-resistant pathogens circulating today are capable of airborne transmission (Kowalski, 2006).

Table 1 identifies all of the nosocomial agents that may transmit at least partly by the airborne route, and these include bacteria, viruses, and fungi (Kowalski 2006). These microbes are ranked by estimated order of occurrence and are classified as contagious, noncontagious and endogenous (present as part of normal human flora). The primary infections caused are identified, including surgical site infections (SSI).

Because the types of drug treatment differ between these three groups, the nature of the drug resistance also varies. But one factor is common to all these microbes—increasing drug resistance tends to facilitate their multiplication and spread, sometimes beyond the bounds of hospital walls.

The reasons for the resurgence of infectious diseases are complex and include factors such as increased urbanization and crowding, environmental changes, and worldwide commerce and travel (Pimentel et al, 1998, Platt, 1996) contribute to the resurgence. Some specific causes are population growth and an enormous number of susceptible people living in poor and crowded urban areas, inadequate and deteriorating public health infrastructures worldwide and misuse of antibiotics or other drugs, which can hasten the evolution of resistant microbes (Ewald, 1994). Misusing drug includes prescribing them without proper indications, prescribing the wrong drugs or the wrong doses and having poor patient compliance with treatment regimens (WHO “World Heath Organization Fact Sheet No. 194”).

Bacteria that cause respiratory infections have been developing increased drug resistance over the past few decades (WHO “World Heath Organization Fact Sheet No. 194”). Other non-respiratory bacteria have experienced the same drug-resistance and increasing incidence. Viral respiratory pathogens represent a significant fraction of nosocomial infections and are subject to rapid evolutionary change (Ewald, 1994). Fungal pathogens also have been on the rise recently, in part due to the prevalence of immunodeficiency diseases that facilitate their spread (Ampel, 1996).

The public often imagines that doctors have unlimited arsenals of weapons to fight microbial infections, but in fact, there are a mere seven classes of antibiotics, a similarly small number of fungicidal agents, and there are less vaccines than there are viruses (Ryan, 1994). The result is that as each new treatment becomes ineffective, the arsenal of treatments begins shrinking to dangerously low levels. Some predict that one day new medicines will become obsolete faster than new ones are developed.

Some microbes possess the abilities to resist one or more types of treatments, while others may be multi-drug resistant (MDR). Still, others are subject to the phenomenon of pan-drug resistance, which is defined as those microbes that resist all seven major classes of antimicrobial agents: penicillins, cephalosporins, carbapenems, monobactams, quinolones, aminoglycosides and polymyxins (Falagas and Kasiakou, 2005). Drug resistance is defined in terms of an IC50 value, or the concentration that causes 50% growth inhibition, and resistance is defined as a 10-fold increase in IC50 values (Andre et al 2004, Andersson et al 2003).

A wide body of evidence is available regarding the drug resistance of individual species of nosocomial pathogens. A selection of data and representative sources are provided here as examples of the scope of the problem.

At least 11 major microbes, including species of Streptococcus and Staphylococcus, already are highly resistant to standard antibiotic treatment (Pimentel et al 1998). Rapid increase in drug resistance by disease organisms is caused by the widespread use and overuse of more than 300 antibiotics by the medical profession (ASM “Report of the ASM task force on antibiotic resistance”). In addition, one-half of the antibiotics used in the United States to treat humans also are used to treat disease-infected domestic animals. The concurrent use of antibiotics for both humans and livestock enhances selection for drug-resistant microbes, further exacerbating the problem of antibiotic resistance (Pimentel et al, 1998).

Although drug resistance often has been associated with nosocomial infections, innate resistance of bacteria is increasingly being reported. MDR Haemophilus influenzae are being increasingly reported from all over the world (Jain, 1997). Alcaligenes and Acinetobacter species have acquired a wide range of drug resistance. Multidrug resistant strains of Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, have been recognized among casualties returning from battlefields (Davis et al, 2005). Clinically isolated Pseudomonas aeruginosa have acquired resistance to fluoroquinolones and amikacin, approximately 20% and 5%, respectively.

Dr. William Jarvis of the Centers for Disease Control & Prevention warns that, “In at least 70% of the hospital-acquired infections that occur, the organism is resistant to at least one antibiotic.” Bacteria acquire up to 90% of their genetic material from distantly related bacteria species, according to new research from the University of Arizona in Tucson. It is even possible for unrelated species to exchange bits of genetic information that allow them to develop drug resistance.

The drug resistance of streptococcal infections, which can cause Scarlet Fever, has increased from 0.8% to 28% in the past decade, according to figures from the Institute of Environmental Science and Research in New Zealand. MRSA has shown up outside hospital settings and has even become a problem in athletics, where it may contaminate sports equipment and facilities (”Benching Bacteria from Athletics: New Sporting Goods Line Answers Call for Protection Against Antibiotic-Resistant Staph Infections”). Multidrug-resistant tuberculosis has caused a resurgence in this disease worldwide, and close to one million people die each year from this disease, once thought to be under control in the West (WHO Europe “World Health Organization Europe Fact Sheet 07/02”). Burkholderia pseudomallei, the causative agent of melioidosis, has shown increasing resistance to antibiotics and has resulted in severe problems with treatment regimes, leading to intensification of the search for new drugs (Perumal et al, 2006).

The evolution of drug resistance in microbes can be surprisingly rapid. In 1979, only 6% of European pneumococcus strains were resistant to penicillin, but one decade later that percentage had grown to 44% (Platt, 1996).

Viruses are treated with vaccines and antiviral agents, not with antibiotics, and these have generally remained effective over the years. The trouble is that each new variant of a virus generally requires a specific antiviral agent and a specific vaccine (Ryan, 1994). Viruses can mutate rapidly, more rapidly than any bacteria, and a vaccine must be quickly developed at the first appearance of any new variant or virus (ASM “Report of the ASM task force on antibiotic resistance”). The greatest concern with viruses is not their abilities to resist treatment, but their propensity to cause explosive epidemics before a vaccine or effective treatment can be developed. Influenza and SARS virus are two examples of viruses that can cause high fatality rates without treatment.

A major problem with antiviral drugs is the high frequencies of drug-resistant mutants. There are experimental and clinically approved drugs that are effective, dramatically reducing virus yields or providing good relief of symptoms in patients, but the drugs ultimately have limited usefulness, because viruses that escape the initial inhibition are frequently drug-resistant (Huang, 2005). The rapid development of drug resistance by retroviruses and RNA viruses is due to their high mutation rates. That is, viruses can mutate into viruses faster than new vaccines can be developed. Indeed, it is not unreasonable to propose that the large diversity of RNA viruses is in large part due to their high mutation rates, which allow them to mutate and adapt to new niches very rapidly.

A recent report on the global prevalence of adamantane-resistant influenza A viruses indicated a significant increase of drug resistance, from 1.8% during the 2001-02 influenza season to 12.3% during the 2003-04 season (Bright et al, 2005). Vaccines can become ineffective due to slight changes in the viruses.

Over the past decade, the increasing incidence of serious fungal infections, along with increased antifungal drug use, has led to the emergence of drug-resistant fungal pathogens. Antifungal drug resistance has been reported by a number of researchers in pathogenic fungi including Histoplasma capsulatum, Cryptococcus neoformans, and other fungal species (VandenBossche et al, 1998). Although such fungal infections are not normally nosocomial, they are associated with human immunodeficiency virus (HIV) and, also illustrate how hospital treatment may enhance some community-acquired infections.

Antifungal drug resistance has become an increasing problem with the development of a larger compendium of antifungal agents. Fungal diseases are increasing among patients infected with (HIV) type 1. Increasing evidence suggests that prolonged use of these antifungal drug treatments results in both clinical and microbiologic resistance (Ampel et al, 1996).

Microbes that exist environmentally or as endogenous microflora in humans may develop drug resistance and when such infections hail from the community rather than from hospitals, they are referred to as community-acquired infections. Increasing drug resistance has occurred among such community-acquired microbes such as Haemophilus, Cardiobacterium, members of the Enterobacteriaceae, Pseudomonas species and others (Baddour et al, 2005).

MRSA has been reported in prisons, sports facilities and residential homes.

The MRSA superbug is no longer confined to hospitals and new strains are killing young, healthy people (Moellering, 2006). Necrotising fasciitis, better known as a flesh-eating disease, will kill one in five patients even with treatment. The CDC has warned that outbreaks from small pets like hamsters, mice and rats have sickened many people in various states with dangerous multidrug-resistant bacteria. Farm animals also have been found to be infected and these carriers provide yet another reservoir, outside of communities and hospital environments, in which superbugs may develop drug resistance and mutate or evolve into new variants (Pimentel et al, 1998).

The multifaceted problem of drug resistance in nosocomial pathogens threatens to extend explosively beyond the boundaries of health care settings and we are witnessing their occurrences in communities, prisons, athletic facilities, agricultural environments and even battlefields. It may be time to consider more drastic solutions than drug treatment alone, and options may include disease management methods such as quarantine and health education, and engineering methods such as air treatment. The latter approach has great unexplored potential. Although it may not be a complete solution, it may, if implemented on a wide enough basis, be capable of limiting epidemics and providing healthy, safe environments in which to live and work.