Antibiotics may rightly be called wonder drugs, but their use over the last 80 years has come at a price. Through evolutionary mechanisms assisted by overuse and misuse, bacteria develop resistance to new antibiotic compounds soon after their introduction. Today, some of the most virulent bacterial pathogens are resistant to all but one or two agents.
Our experience with one topical antibiotic, mupirocin, demonstrates that resistance can emerge even against agents that are not administered systemically.
GlaxoSmithKline’s Bactroban (mupirocin ointment) anti-infective was introduced in 1985 and rapidly adopted into clinical practice for treating topical Staphylococcus infections and colonizations. Numerous studies demonstrated mupirocin’s effectiveness in treating primary skin infections, surgical incisions, and accidental wounds. Bactroban soon became the agent of choice for these indications; within 15 years the drug was registered in 90 countries for eradication of Staphylococcus, including such virulent strains as methicillin-resistant S. aureus (MRSA).
Resistance to mupirocin began to emerge shortly after the drug’s introduction. By 2007 Simor et al. reported that the incidence of mupirocin-resistant Staphylococcus aureus increased from 1.6% during the period 1995–1999, to 7% between 2000 and 2004. Resistance was related to a mutation on a gene coding for the enzyme isoleucyl-tRNA synthetase. Moreover, it became apparent that MRSA could confer resistance to mupirocin through gene transfer to other bacteria treatment.
A more recent study, by Fawley et al, on perioperative patients, confirmed that 7% of Staphylococcus isolates from nasal passages of orthopedic/vascular patients were mupirocin-resistant, a figure that rises to 9% among elderly patients. In 2007, David Warren and coworkers reported that 13.2% of MRSA isolates from patients at Washington University hospital were mupirocin-resistant. These figures have immediate consequences, as Graber et al. noted failures in decolonization in patients infected with mupirocin-resistant MRSA.
Bacterial resistance to antibiotics generally rose throughout the 1990s and 2000s, and will continue to increase despite efforts to introduce “clean” treatment practices in hospitals. The availability of over-the-counter antimicrobial agents, particularly those that were once sold only by prescription, can potentially reverse the positive impact of best hospital practices, and lead to pockets of high bacterial resistance that will be difficult to eradicate.
For example, a study by Upton and coworkers reported that mupirocin resistance in New Zealand hospitals had reached 28% by 1999, due in part to sales of mupirocin over the counter. Upton urged that “current patterns of mupirocin consumption be reviewed and its use rationalized to maximize the chances of this antibiotic retaining beneficial antistaphylococcal activity.”
Mupirocin is a good antibiotic, but therein lies the problem. Bacteria have evolved over hundreds of millions of years to evade and adapt to antibiotic mechanisms, particularly when these agents are administered systemically. It, therefore, makes no sense to expose every organ and system to antibiotic treatment when an infection is localized to one area that is easily accessible to topical agents. An unintended consequence of the overuse of systemic antibiotics has been the rise of resistant strains on the skin, which complicates treatment even in accessible areas of the body.