Although much of the COVID-19 crisis today results from the nature of the viral pathogen, multiple gaps in pandemic preparedness are also major contributing factors. Perhaps nowhere is this inadequacy more evident than in the dearth of safe, effective antibiotics that address today’s antimicrobial resistance (AMR) landscape.
Antibiotics are important components of an end-to-end response to any pandemic, including viral infections, such as COVID-19, which are commonly associated with secondary bacterial infections, including pneumonia. The need for new antibiotics investment is real and it is urgent, but we have fallen behind the innovation curve in our never-ending battle against bacteria.
Ninety-five percent of this biotech sector’s innovation occurs in small, single-product companies, most of whose products are still in clinical development. Unfortunately, almost all of these companies are either exiting the business, struggling on the brink of financial collapse or have already gone bankrupt; no doubt we’ll see more go under in the next six to 12 months. This ‘perfect storm’ in the antibiotics marketplace is driving us back to the pre-penicillin era, and the consequences will be devastating to all of humanity.
Antibiotics are essential elements of the treatment paradigm for COVID-19 and for protecting against future infectious disease pandemics. From our experience with other viral pandemics – MERS in 2012, H1N1 influenza in 2009 and pandemic flu in 1918/19 – we know that secondary bacterial infections, including those from methicillin-resistant Staphylococcus aureus (MRSA) and other drug-resistant bacteria, are major contributors to disease severity and mortality.
In the face of viral pandemics, antibiotics undoubtedly save lives. But AMR complicates the treatment of patients with viral infections and is associated with higher mortality rates. COVID-19 is no different in this respect: there is now clear and growing clinical evidence that secondary bacterial infections, including those caused by multidrug-resistant species, occur in about 15% of COVID-19 patients and are lethal in about 50% of patients who contract them.
However, when caring for patients presenting nearly en masse with severe viral respiratory infections, physicians don’t have the luxury of time to await culture results confirming secondary bacterial infections; they will take immediate steps to protect patients’ lives with upfront, broad-spectrum antibiotics with proven efficacy. And they must pick the right antibiotic the first time, one that is effective against a range of potential causal pathogens, with low likelihoods of AMR and serious safety issues. Today, there is no time for a ‘second bite at the apple’, because COVID-19 patients are dying so quickly.
The question is: Do we have access to the antibiotics we need? The short answer is: No.
It’s already clear older, generic antibiotics are failing and AMR is growing. For example, in the US, antibiotic failure occurs in about 22% of patients with community-acquired bacterial pneumonia (CABP) and when that occurs, it is associated with a four-fold higher mortality rate. In the EU, Italy has one of the highest levels of AMR among member states. Rates of non-prescription antibiotic use are high in several EU countries, including Italy and Spain, and a majority of pharmacists in both countries willingly sell antibiotics over the counter (OTC). Such indiscriminate use of antibiotics undoubtedly contributes to the prevalence of AMR and may account for the high COVID-19 death tolls in Italy and Spain.
But not only do we lack the right antibiotics, we don’t have enough of them. For example, doctors in France conducting a small study in COVID-19 patients were having trouble obtaining enough azithromycin to use in combination with chloroquine. This highlights the problem of maintaining adequate stocks of antibiotics under normal conditions; under the extraordinary conditions imposed by COVID-19, the stockpile of effective antibiotics is limited.
We needed the right antibiotics yesterday, but we don’t have them because of a combination of outdated clinical guidelines, and reimbursement policies that prioritise costs over saving lives and actively discourage appropriate use of newer antibiotics that address AMR.
In the US, the reimbursement system encourages use of the least expensive antibiotics, which results in patients today receiving antibiotics that are often less effective and less safe than newly approved antibiotics. The situation is similar in Europe, where substitution of prescribed drugs with generics is either allowed or obligatory. These practices lead to poorer outcomes and increased mortality, and they fail to reward antibiotics companies for their innovation. Consequently, the pipeline of promising new antibiotics is drying up.
The subscription model for antibiotics proposed by the UK is likewise unworkable. The model aims to spur investment in the antibiotics sector, but it is unclear whether payment would vary with each antibiotic or take a ‘one size fits all’ approach. Moreover, it would apply only to antibiotics the National Health Service (NHS) considers useful or worthwhile, based on undisclosed criteria, and instead of being used now, antibiotics purchased under this proposal could be held in reserve for a future AMR crisis.
None of these reimbursement models accelerates patients’ access to the newer antibiotics nor incentivises investors to support companies focused on the development and commercialisation of the next generation of antibiotics.
COVID-19 serves as a stark reminder that we do not have enough effective antibiotics – let alone enough new ones – to fight the potentially lethal secondary bacterial infections that often accompany a viral pandemic. We should already have the antibiotics we need, but we have failed to prepare.
Future pandemics are inevitable. To combat them, we will need antibiotics that are both safe and effective against the evolving AMR landscape. If we are to be prepared next time, it is vitally important to build a robust and secure foundation for the development and commercialisation of new antibiotics now.
Evan Loh is chief executive of Paratek Pharmaceuticals and chair of the Antimicrobials Working Group
