Old Drugs to the Rescue

With options dwindling in the fight against drug-resistant bacteria, old standbys take center stage.

Antimicrobial resistance isn’t just old news, it’s a continuing threat to our existence globally. Consider this: a single organism, methicillin-resistant Staphylococcus aureus (MRSA), kills more Americans annually—approximately 19,000—than emphysema, HIV/AIDS, Parkinson’s disease, and homicide combined.

Compounding the problem is the dearth of new antimicrobials in the drug development pipeline, especially for antibiotic-resistant Gram-negative bacteria. The selection of antimicrobial drugs available to clinicians is shrinking, too, as manufacturers withdraw unprofitable drugs, regulatory requirements create flaming hoops manufacturers are unwilling to jump through, or various other issues cause temporary shortages.

French researchers, appreciating that older and sometime forgotten antibiotics may have some potential utility in the fight against resistant organisms, have collected information concerning availability of these agents in Europe, the United States, Canada, and Australia. An expert clinical microbiology panel identified 33 systemic antibacterial drugs for use in treating infections caused by resistant bacteria, with 14 having potential activity against resistant strains. Surveying hospital pharmacists, microbiologists, and infectious disease specialists in 38 countries, they found that 22 of the 33 drugs were unavailable in fewer than 20 of 38 countries. Manufacturers did not market most of the antibiotics for economic reasons.

The authors indicate that 4 agents are the most promising: temocillin and mecillinam for extended-spectrum beta-lactamase—producing organisms and fosfomycin and colistin to treat infections caused by carbapenem-resistant Gram-negative bacilli. These agents were unavailable in most countries surveyed, and were often only available in developing nations. They are attractive options, however because they are usually marketed as generics, are low in cost, and are generally considered safe and tolerable.

The researchers, whose study appears in Clinical Infectious Diseases, consider the lack of availability of these antibiotics a global crisis. They urge the global health community to work towards better availability of these antibiotics on a global scale. The authors also noted troublesome discrepancies between the data sent by the national contacts, and the data available on national authorities’ Web sites and/or in standard drug references.

Looking to the future, international microbiologists and drug manufacturers should consider the importance and potential utility of these agents. Treating clinicians can also consider “forgotten” antibiotics when faced with resistant pathogens if susceptibility testing and interpretive criteria are available. The authors also note that improvements in marketing, distribution, dispensing, and data availability are needed. When manufacturers withdraw antimicrobials in individual countries because it is economically unfeasible to continue marketing them, regulatory agencies should have backup plans for cases of urgent medical need.

It can be difficult to convince patients that antibiotics are not appropriate for many common conditions, but the rise of drug-resistant bacteria—and the lack of treatment options—demonstrates how important that conversation can be at the counter. As the most accessible health care provider, pharmacists can counsel patients about the appropriate use of antibiotics to help ensure that more widely available antibiotics and antimicrobials continue to remain effective.