The Pharmacist’s Role in Preventing Antibiotic Resistance

Medscape | Antibiotics and vaccines are undoubtedly among the most significant discoveries in human history. Their use has saved countless lives from once-lethal infections. Unfortunately, antibiotics are also the only drugs in which widespread use decreases their utility. In contrast to medications that alter human biochemical processes, such as the clotting cascade and heart rate, antibiotics are engaged in a war with an enemy that is fighting back. Bacteria alter themselves to resist the effects of antibiotics, allowing them to multiply and continue spreading disease. This issue has become one of the nation’s most pressing health problems, and its magnitude is accelerating. In order to combat antibiotic resistance and preserve our miracle drugs, pharmacists must be knowledgeable about the issue and actively involved in the solution.

Increasing Antibiotic Resistance

According to the Centers for Disease Control & Prevention (CDC), nearly 2 million people in the United States acquire bacterial infections during their hospital stay annually, and over 70% of the bacteria that cause these infections are resistant to at least one of the drugs normally used to treat them.^[1] These drug-resistant bacteria include not only well-known offenders such as methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, but also strains of Klebsiella pneumoniae that have developed resistance to all available beta-lactams.^[2] For some organisms, clinicians have been forced to turn to polymyxins, an older class of antibiotics that was previously abandoned, in lieu of the “safer” aminoglycosides.^[3]

Resistance in the community setting is just as concerning. In one national cohort, community-associated MRSA was the most common identified cause of skin infections among patients who visited emergency rooms.^[4] Common pathogens seen in the community setting such as Escherichia coli and Neisseria gonorrhoeae have become resistant to fluoroquinolones, agents that were considered first-line therapies for infections caused by these pathogens in the past.^[5,6]

Decreased Development

Possibly more unsettling than the increase in antibiotic resistance is the decrease in antibiotic research and development. As of 2009, no new classes of antibiotics were in late-stage development, and only 16 antibiotics are in late-stage development at all.^[2] Not all of these 16 agents will be approved, as evidenced by the fact that of the six that have undergone FDA review, only two were approved (telavancin and ceftaroline). The oxazolidinones (linezolid) in 2000 and the lipopeptides (daptomycin) in 2003 were the only novel systemic antibiotic classes developed since 1968.^[7]

There are many reasons for the lack of antibiotic development. Antibiotics are typically only taken for days at a time, which does not guarantee substantial profit for drug companies. When antibiotics are approved, the natural inclination of many practitioners is to reserve them for more resistant or serious infections, which ironically compounds the economic disincentive for further antibiotic development. Additionally, clinical trials for antibiotics are not easily conducted. As antibiotics must be given acutely for most infections, prior antimicrobial use significantly confounds any measurable benefit. Also, since multiple organisms can cause most infections, companies seeking approval for candidate antibiotics often must include other antibiotics in combination with the candidate drug in clinical trials, which may contribute to the therapeutic effect and make the effect of the candidate antibiotic difficult to measure. The difficulty in finding patients with infections caused by microorganisms of interest is another concern. This issue was recently demonstrated by a trial of linezolid (Zyvox-Pfizer, Inc.) in MRSA pneumonia, where ~1,200 patients were enrolled and treated to find ~400 that were eligible, and the number of patients screened was likely even higher.^[8] Antibiotics must be studied for each infection in which they are indicated, which presents the issue of small sample sizes since infections are not typically chronic or nearly as widespread as diseases such as hypertension.

Investigating clinical utility in the treatment of resistant bacteria is even more difficult to study. Enrolling patients in studies of new antibiotics who have organisms that are resistant to active controls is not ethical. This presents a true concern, since it is these resistant strains that require new options. New types of studies for alternative drug approval may be needed to increase the availability of antibiotics for these infections.

Society Undervalues Antibiotics

In the 21st century, most people lack the historic perspective of what society was like before antibiotics became widely available. Antibiotics transformed medicine, yet in an era where the majority of bacterial infections are routinely treatable this is easily forgotten. Infections that are easily treated today were frequently lethal in the pre-antibiotic era. A review of historically controlled studies of early antibiotics showed a decline in mortality from community-associated pneumonia (CAP) from 38% to 12% due to antibiotic use, corresponding to a number needed to treat to save one life of four.^[9] Even young, otherwise healthy patients had mortality rates from CAP of 10% in the pre-antibiotic era, much higher than the <1% with antibiotics.^[9] Penicillin reduced the mortality rate from cellulitis from 11% to <1%.^[10] These common infections were feared in the pre-antibiotic era but are now routinely treated.

Free Antibiotics

“You didn’t pay for the germs. Why pay for the antibiotics?” This is one of the tag lines used to promote free antibiotic programs found at various pharmacies that allow patients to receive generic antibiotics for free. In a time of economic instability, the notion of pharmacies extending generosity towards customers by giving away medicine seems refreshing. However, it may contribute to the undervaluing of antibiotics by society. By making antibiotics available to patients for free, their perceived value may be lessened.

Economic Value

Since antibiotics are highly effective at curing many once-lethal diseases, the economic value of antibiotics is difficult to measure. In oncology, a drug that prolongs life by several months is considered a success and is likely to become a standard of care, probably at a substantial cost. A successful antibiotic cures infection and prolongs life indefinitely, but the price that payers are willing to pay is substantially lower. Per-unit costs with newly approved antibiotics may be higher than in other disease states but may be justified by the short courses of therapy that most infections require. For example, a patient with sinusitis may take an antibiotic for 5 to 10 days, but the same patient may take a cholesterol-lowering agent or antihypertensive drug for the rest of his or her life. These economic disincentives prevent further antibiotic development.