Multi-resistant bugs require a multi-pronged approach

Bacterial infections can either be acquired in the community or the hospital, with the latter traditionally home to the majority of multi-resistant pathogens. Antibiotics are the mainstay in the treatment of these infections and are among the most commonly prescribed drugs in hospitals. However, although some are effective, they do not always succeed in eradicating micro-organisms.

Antibiotic-resistant organisms have caused clinical problems since anti-infectives were introduced into medical practice and, during the past few decades, the incidence of these micro-organisms has reached worrying levels and is still accelerating globally.

Increasing resistance

Furthermore, antimicrobial resistance in common pathogens in the community has increased, demonstrating that healthcare facilities are not the only place for the emergence and transmission of resistant strains. To make matters worse, multi-resistant organisms arising in the community can also enter and spread within healthcare facilities, increasing the existing problems in these institutions.

One of the main reasons for the rise of multi-resistance is the fact that evidence of the beneficial effects of higher doses of antibiotics has resulted in increased antibiotic use for acute exacerbations and maintenance care. In addition, antibiotic use is often prescribed inappropriately because of a lack of knowledge about infectious diseases and antimicrobial therapy.

The microbiology organisms have also changed during the past two decades, with new multi-resistant bacterial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) emerging.

The consequences of these difficult-to-treat pathogens are two-fold. Infection with a multi-resistant pathogen is associated with higher morbidity and mortality and of the approximately two million Americans yearly infected by bacteria during hospital stays, some 90,000 die. Furthermore, resistant pathogens lead to higher healthcare costs because they often require more expensive drugs and longer hospital stays. The Infectious Diseases Society of America (IDSA) estimates the total cost to society to be nearly $5 billion each year.

New development needed

In 2003, the IDSA appointed a special committee charged with evaluating current trends related to the research, development, and manufacture of antibiotics and making recommendations to promote the value of these products and ensure their future availability. This antimicrobial availability task force (AATF) released a new hit list of dangerous bugs on March 1, 2006 and renewed its call for attention to be given to the difficulties surrounding multi-resistant bacterial pathogens.

The group promotes a multi-pronged approach to limit the impact of resistant organisms on patients and the public. The most important of these efforts is the development of new antibiotics, and stimulating comprehensive legislation that promotes these developments.

Many major pharmaceutical firms have refocused their interests upon drugs that are more profitable, such as anti-cholesterol drugs, which need to be taken throughout a patient's life. Smaller companies are trying to attend to the medical need, but it is not clear if they will have the financial capacities, clinical development infrastructure, or partnering opportunities that would allow their products to reach the market.

Drug companies are starting to become interested in antibiotics again, as Pfizer's Zeven and Johnson & Johnson's doripenem and ceftobiprole demonstrate. But the IDSA authors state that, while MRSA receives substantial R&D attention, the other five of the six dangerous bugs from their hit list are left behind. Many of the problem pathogens are characterized by small and unpredictable markets, and the costs of late-stage clinical development are high.

Encouraging commercial efforts

With this in mind, the IDSA proposes that legislation be passed to encourage the pharmaceutical industry to re-enter the field of antibiotics. The organization says US Congress should establish a commission to set antimicrobial discovery priorities, companies that develop novel antibiotics should be rewarded with market exclusivity rights, and research, development and manufacturing should be encouraged through tax credits. In its 2004 report "Bad bugs no drugs," the IDSA stipulates a list of specific potential legislative solutions, administrative recommendations, and funding requests that should support this objective.

Nevertheless, there are other solutions that can contribute to this problem, such as educating physicians, patients, and parents about the appropriate use of antibiotics. Additionally, it is important to develop and apply infection control and immunization policies and practices to prevent transmission. Numerous agency-based and governmental reports have been generated, but these programs often solely observe, and fail to act.

The lack of consistency in practice delays local and national efforts to control multi-resistant bacterial pathogens. Pessimistic attitudes and perceptions about control efforts, especially the negative view that problems with these micro organisms will remain no matter what is done, must be attended to. Finally, disruption of the cycle of person-to-person transmission must be recognized and dealt with appropriately.

When the difficulties surrounding the treatment of patients infected with one of the multi-resistant organisms are approached from multiple directions, there might be room for future cures.

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