Slow Uptake Among Physicians of Effective Antibiotics to Treat Superbugs

As a growing number of infections become resistant to antibiotic medications, it is becoming crucially important that providers not only practice antibiotic stewardship but also use effective antibiotics when they are needed. However, a new study published in Open Forum Infectious Diseases¹ found that new and effective antibiotics are rarely prescribed in carbapenem-resistant Enterobacteriaceae (CRE) infections, which are a family of the most drug-resistant bacteria.

The World Health Organization recently ranked antibiotic resistance as one of the top 10 global health threats in 2019. CDC estimates that 2 million Americans are infected with antibiotic-resistant bacteria every year and at least 23,000 people die from the bacteria.

The new research showed that effective antibiotics are only being used in one-fourth of CRE infections, indicating a slow uptake of such high-priority antibiotics. The findings have led the authors to call for additional research into behavioral and economic factors impacting the use of these new antibiotics.

"The infectious diseases community spent the past decade saying, 'We need new antibiotics, this is a top priority,' and now we're at risk of sounding like the boy who cried wolf," lead author Cornelius J. Clancy, MD, associate professor of medicine and director of the mycology program and XDR Pathogen Laboratory in the University of Pittsburgh's Division of Infectious Diseases, said in a statement. "We have a responsibility to learn why it takes so long for antibiotics to be adopted into practice and figure out what we need to do to ensure the best antibiotics quickly reach the patients who desperately need them."

Clancy and his team surveyed hospital-based pharmacists in the US regarding their antibiotic positioning against CRE infections. They used IQVIA prescription data and Driving Re-investment in Research and Development and Responsible Antibiotic Use estimates to determine the number of all infections and CRE infections treated with different antibiotics in the United States.

They were looking to compare the intravenous use of polymyxins, the longstanding first-line antibiotics against CRE infections, with the newer agents of ceftazidime-avibactam, meropenem-vaborbactam, and plazomicin, which have been found to be more effective and less toxic.

The data showed that polymyxins remained widely used. In cases in which the newer agents should constitute first-line treatment, the 3 newer agents were only used in about 35% of CRE infections (ranging from 23% to 62%). These findings come 4 years after the FDA approved ceftazidime-avibactam, which was the first of the new agents.

The authors admitted that costs likely constrained some use since, in 75-kilogram adults, the wholesale acquisition costs for a 14-day course of the agents were $15,070 for ceftazidime-avibactam, $13,860 for meropenem-vaborbactam, and $13,320 for plazomicin.

"Cost is a limitation, but I'm not convinced it is the sole cause of our findings," said Clancy. "Clinicians may not be prescribing the new drugs due to concerns about accelerating antibiotic-resistance or because initial studies on their effectiveness were relatively small. We need to get at the root causes of the disconnect between what the doctors prescribe and what the pharmacists we surveyed believe they should be prescribing, and then find a solution."

The findings come just 2 months after research published in Nature Microbiology² that found penicillin in combination with clavulanic acid, which is widely available, could be used to treat Methicillin-resistant Staphylococcus aureus, known as MRSA, which has become a widespread problem in hospital- and community-acquired infections.

"MRSA and other antibiotic-resistant infections are a major threat to modern medicine and we urgently need to find new ways to tackle them,” senior author Mark Holmes, PhD, MA, VetMB, of the Department of Veterinary Medicine at the University of Cambridge, said in a statement. “Developing new medicines is extremely important, but can be a lengthy and expensive process. Our works suggests that already widely-available medicines could be used to treat one of the world's major strains of MRSA."

The challenge is that public awareness of antibiotic resistance and the trouble it causes has grown. A Kaiser Family Foundation poll from June 2019 found that not only have 71% of Americans heard of antibiotic resistance and know what it means, but also 53% said overuse of antibiotics is a major problem.

As a result, 45% of adults admitted they have not taken their antibiotics as prescribed by a doctor. This sort of behavior has actually led to antibiotic resistance.

Dennis Gingrich, MD, FAAFP, professor, Department of Family and Community Medicine, Department of Humanities, Pennsylvania State College of Medicine, previously told The American Journal of Managed Care® that not taking the full course of an antibiotic as directed or using other people’s leftover antibiotics actually contributes to the increase in antibiotic resistance.

“These practices will increase the risk of antibiotic resistance by allowing the bacteria to be exposed to short ineffective courses of antibiotics that really just generate antibiotic resistant bacteria,” Gingrich explained.

References

1. Clancy CJ, Potoski BA, Buehrle D, Nguyen MH. Estimating the treatment of carbapenem-resistant enterobacteriaceae infections in the United States using antibiotic prescription data [published online July 28, 2019]. Open Forum Infect Dis. doi: 10.1093/ofid/ofz344.

2. Harrison EM, Ba X, Coll F, et al. Genomic identification of cryptic susceptibility to penicillins and β-lactamase inhibitors in methicillin-resistant Staphylococcus aureus [published June 24, 2019]. Nat Microbiol. doi: 10.1038/s41564-019-0471-0.