A disaster of our own making with antimicrobial resistance

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Antimicrobial Resistance (AMR), the calamitous health crisis responsible for plaguing Americans at the rate of 2.8 million cases of infection annually, sparked bipartisan congressional discussion as lawmakers revisited the 2021 PASTEUR and DISARM Acts to confront the AMR crisis. This is not enough. No matter how many new drugs we introduce, AMR will remain a global health crisis given that antibiotics are administered inefficiently. While renewed investment in the development of antibiotics is critical, AMR rates will persist so long as systemic drug administration remains medicine’s preferred option.

Antibiotics are essential in preventing bacterial infection, but as antimicrobial resistance rises, we risk being left defenseless. Recent studies have found it is often not antibiotics themselves, but how they are administered that undermine their effectiveness and promote resistance. Focusing our attention solely on creating next-generation antimicrobials steals focus from the equally important task of addressing the antibiotic misuse that continues to plague the U.S. health care system.

Otherwise, we are headed toward a microbial apocalypse. The World Health Organization estimates see 10 million annual AMR-related deaths globally by 2050. In 2016, the Centers for Disease Control and Prevention (CDC) estimated that, despite antimicrobial stewardship (AMS) measures to reduce the impact of antibiotic misuse, an average of one-in-three antibiotic prescriptions were unnecessary, directly leading to increased risks of toxicity and AMR. COVID-19 undoubtedly made these numbers soar as clinicians were forced to skip AMS measures to keep patients out of hospitals.

On March 28, 2022, the Biden administration announced a historic investment in pandemic preparedness and biodefence with the FY23 President’s Budget proposal allocating $88.2 billion across Health and Human Services (HHS) departments. While bills such as PASTEUR and DISARM encourage the development of new antibiotics, it is incumbent upon policymakers to maximize the amount of these funds intended to advance drug administration technologies that use existing antibiotics more effectively via innovative methods. 

If It’s Broken…

AMR has been a problem for more than 80 years. Penicillin (PCN) resistance in E. coli was first reported in 1940 and led to the introduction of PCN-G; two short years later PCN-G resistant Staphylococcus aureus (S. aureus) emerged. This pattern became predictable. Methicillin, introduced in 1959, subsequently produced methicillin-resistant S. aureus (MRSA) in 1961. The introduction of carbenicillin in 1967 preceded carbenicillin-resistant Pseudomonas in 1969. This steady recurrence of new drug introduction followed by new resistant bacteria ultimately prompted the UN’s 2021 call to action referring to AMR as a “silent tsunami.”

A critical assessment of proposed measures to stop AMR show how we might turn the tables on drug resistance. Narrowing the scope of fighting AMR to focus on preventing surgical site infections (SSI) serves as a fundamental starting point to address the greater issue.

Current SSI prevention practices in operating rooms across the U.S. contribute to drug resistance. Prophylactic administration of intravenous antibiotics preoperatively delivers a high systemic dose to penetrate the affected area. But this approach has a reproducible failure rate and may pose an increased risk to the patient for toxicity, infection by resistant organisms, and alterations in the patient’s microbiome, often leading to hospital readmission. The failure of this approach is clear: SSIs make up 40 percent of hospital acquired infections.

… Fix it!

Alternative solutions — including bacteriophage therapy, predatory bacteria, and direct application approaches — are in development. These methods are poised to revolutionize recovery, allowing patients to spend less time in the hospital, decreasing risk for nosocomial infections, and optimizing clinical outcomes. However, each method requires further study due to existing high-risk profiles such as toxicity, autoimmune response, and potential for tissue damage. Local drug administration is clearly the future of infection prevention.

Delivering lower dose extended-release antibiotics, local drug administration enables direct antibiotic application to the surgical wound without exposing patients to unnecessary risks. However, these innovations are still in development and require further scientific validation and resources to bring them forward into practical use. Policymakers must meet the immediate emergency of AMR while setting the stage for the next generation of antibiotics to remain effective after they are introduced.

Clawing our way out of the pandemic starkly illustrated the need to focus funding where it will do the most good. Lawmakers who set policies and in the fight against AMR must remember that only by funding innovation can they turn the tables on AMR. Time is of the essence, and the solutions are within reach.

Ori Warshavsky is Chief Operating Officer of US, PolyPid, a bio-pharmaceutical company that seeks on develop, manufacture and commercialize novel therapies to improve surgical outcomes.

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