In the Journals

Access to old antibiotics may be key to alleviating antimicrobial shortages

While developing strategies to promote sustainable antimicrobial production, WHO and the European Commission should consider fostering the registration of and universal access to old antibiotics that could assist in addressing current antimicrobial shortages, according to a commentary published in Clinical Microbiology and Infection.

“Despite most guidelines recommending old antibiotics that are still effective, mostly available as generics, these antibiotics are not universally marketed or available,” Céline Pulcini, MD, DESC, PhD, of Nancy University Hospital and University of Lorraine, France, and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and colleagues wrote. “Physicians may be forced to use less optimal, often broad-spectrum antibiotics instead [which may be] less effective, may have more adverse effects and may drive the selection of resistance.”

Céline Pulcini

The researchers note that a 2011 survey by the ESCMID Study Group for Antimicrobial stewardship (ESGAP) revealed that only 20 of 38 countries — including countries in Europe, the U.S., Canada and Australia — had received marketing for a selection of old but potentially beneficial antibiotics, with only 22 of the 33 antibiotics taken into consideration. By 2015, fewer antibiotics were available in these countries.

According to Pulcini and colleagues, the limited or lacking supply observed in 2011 was influenced by economic motives. This held true in 2015, with high registration costs and small market sizes that would result in limited volume sales and low prices. The researchers speculate that this created “a perceived lack of return on investment for pharmaceutical companies.”

The shortage of antibiotics, including IV flucloxacillin, IV fosfomycin and ticarcillin–clavulanic acid, create issues beyond marketing concerns. Between 2001 and 2013, the U.S. experienced shortages of 148 antibiotics. Of these, 22% had multiple shortage periods. Additionally, 0.35 other antibiotics shortages have been observed every month since 2007.

Although the widespread shortage of antimicrobials is of major worldwide concern, the researchers write that no coordinated response to this issue has been created. They suggest a variety of steps that could assist in preventing antimicrobial resistance and global shortages:

  • Define (through the WHO Essential Medicines List and/or an ad hoc WHO working group) the set of “key access” antibiotics for which there should be universal access.
  • Access could be defined as: “An adult or child are able to receive when clinically required the appropriate antibiotic for their clinical infection syndrome at an appropriate dose, duration, formulation, quality and price.”
  • Monitor the current global availability of these key access antibiotics. This includes both use — through the WHO Surveillance on Antimicrobial Use program — and supply through a survey of global generic antibiotic producers of these key access antibiotics, including the formulations and costs. Monitor shortages through a centralized mechanism.
  • Conduct an antibiotic access gap analysis between clinical need and appropriate medicine availability. This needs to include an assessment of this variation by region and age.
  • Re-evaluate the pharmacokinetic/pharmacodynamic targets for these out-of-patent antibiotics in the context of the global variation in rates of resistance.
  • Consider the potential roles and feasibility of a Global Antibiotic Access and Conservation Fund, initially with the objective of implementing the five actions mentioned above.

“Significantly improved global access to key older antibiotics in their optimal formulation, quality and cost could result from a coordinated set of actions that several countries and WHO might be willing to support or engage in,” Pulcini and colleagues wrote. – by Katherine Bortz

Disclosure: The researchers report no relevant financial disclosures.

While developing strategies to promote sustainable antimicrobial production, WHO and the European Commission should consider fostering the registration of and universal access to old antibiotics that could assist in addressing current antimicrobial shortages, according to a commentary published in Clinical Microbiology and Infection.

“Despite most guidelines recommending old antibiotics that are still effective, mostly available as generics, these antibiotics are not universally marketed or available,” Céline Pulcini, MD, DESC, PhD, of Nancy University Hospital and University of Lorraine, France, and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and colleagues wrote. “Physicians may be forced to use less optimal, often broad-spectrum antibiotics instead [which may be] less effective, may have more adverse effects and may drive the selection of resistance.”

Céline Pulcini

The researchers note that a 2011 survey by the ESCMID Study Group for Antimicrobial stewardship (ESGAP) revealed that only 20 of 38 countries — including countries in Europe, the U.S., Canada and Australia — had received marketing for a selection of old but potentially beneficial antibiotics, with only 22 of the 33 antibiotics taken into consideration. By 2015, fewer antibiotics were available in these countries.

According to Pulcini and colleagues, the limited or lacking supply observed in 2011 was influenced by economic motives. This held true in 2015, with high registration costs and small market sizes that would result in limited volume sales and low prices. The researchers speculate that this created “a perceived lack of return on investment for pharmaceutical companies.”

The shortage of antibiotics, including IV flucloxacillin, IV fosfomycin and ticarcillin–clavulanic acid, create issues beyond marketing concerns. Between 2001 and 2013, the U.S. experienced shortages of 148 antibiotics. Of these, 22% had multiple shortage periods. Additionally, 0.35 other antibiotics shortages have been observed every month since 2007.

Although the widespread shortage of antimicrobials is of major worldwide concern, the researchers write that no coordinated response to this issue has been created. They suggest a variety of steps that could assist in preventing antimicrobial resistance and global shortages:

  • Define (through the WHO Essential Medicines List and/or an ad hoc WHO working group) the set of “key access” antibiotics for which there should be universal access.
  • Access could be defined as: “An adult or child are able to receive when clinically required the appropriate antibiotic for their clinical infection syndrome at an appropriate dose, duration, formulation, quality and price.”
  • Monitor the current global availability of these key access antibiotics. This includes both use — through the WHO Surveillance on Antimicrobial Use program — and supply through a survey of global generic antibiotic producers of these key access antibiotics, including the formulations and costs. Monitor shortages through a centralized mechanism.
  • Conduct an antibiotic access gap analysis between clinical need and appropriate medicine availability. This needs to include an assessment of this variation by region and age.
  • Re-evaluate the pharmacokinetic/pharmacodynamic targets for these out-of-patent antibiotics in the context of the global variation in rates of resistance.
  • Consider the potential roles and feasibility of a Global Antibiotic Access and Conservation Fund, initially with the objective of implementing the five actions mentioned above.

“Significantly improved global access to key older antibiotics in their optimal formulation, quality and cost could result from a coordinated set of actions that several countries and WHO might be willing to support or engage in,” Pulcini and colleagues wrote. – by Katherine Bortz

Disclosure: The researchers report no relevant financial disclosures.