Shortages of first-line antibiotics, which are essential to treat a wide range of common infections, are a major public health threat
Fragile supply and shortages of first-line antibiotics — medicines used to prevent and treat a wide range of common bacterial infections — is a growing problem that is often neglected in deliberations on mitigation of antimicrobial resistance (AMR). Resistance to antibiotics has emerged as one of the biggest public health challenges of our times, threatening our ability to treat a number of infectious diseases and undoing much of the advances on healthcare made in the last few decades.
Increasingly, member states of the World Health Organization (WHO) and forums of governments such as the Group of 20 are focusing attention on policies that encourage individual ministries of health to regulate overuse and irrational use of existing antibiotics and globally at research and development (R&D) of new antibiotics to treat resistant infections. However, access to antibiotics is often addressed as an afterthought.
WHO categorises the first-line, narrow spectrum drugs as ‘Access’ group antibiotics, which should be widely available, affordable and quality-assured. It advocates that 60 per cent of the global consumption of all antibiotics should come from this category.
The other categories — Watch and Reserve Group — are recommended for specific, limited indications or for situations when all alternative antibiotics have failed. Any shortages or inconsistencies in the supply of first-line, narrow-spectrum ‘Access’ antibiotics can adversely affect people who otherwise go untreated or are forced to use second- or third-line ‘Watch and Reserve’ antibiotics.
This is further fuelling drug resistance against them. It is a major barrier for people in the short-term, an obstacle to rational use, and, as such, an overlooked driver of antibiotic resistance. Without resolving shortages and supply instability, we cannot address AMR successfully.
As a humanitarian medical organisation, Médecins Sans Frontières (MSF) has documented recurrent shortages, inconsistencies in the supply chain, lack of appropriate formulations and insufficient suppliers for some ‘Access’ group antibiotics — such as penicillins, gentamicin and co-trimoxazole — for its medical operations.
Our supply division faces a multitude of challenges, including a lack of quality-assured sources and manufacturers enforcing minimum purchase order quantities that are difficult to meet.
Treatment of a broad range of bacterial infections — from sepsis and meningitis, toxoplasmosis, typhoid fever, to diphtheria, syphilis, pneumonia and others — is thus impacted. MSF is not alone in its experience.
A lengthy and ongoing penicillin shortage is currently affecting several countries across the world, including India, where several of its health interventions including the programme to eliminate mother to child transmission of syphilis and to treat infants at risk of congenital syphilis is facing a challenge with the availability and supply of penicillin. Other public health interventions are facing similar shortages of penicillin.
Health systems also face supply challenges. In Australia, the paediatric suspension of co-trimoxazole syrup has been out of stock for months, which has affected the treatment of a large number of aboriginal children with school sores.
Similarly in India, the National AIDS Control Programme too has faced supply instability for co-trimoxazole syrup — an essential antibiotic — for opportunistic infections preventive therapy in infants and children with HIV. This is despite the fact that India is a major drug manufacturing country whose burden of infectious diseases is among the highest in the world.
A 2013 study from New Delhi exposed a sub-optimal availability of some ‘Access’ group antibiotics, such as benzathine penicillin and amoxicillin, while other ‘Watch’ and ‘Reserve’ group antibiotics, such as fluoroquinolones and carbapenems, were freely available.
A more recent PLoS study in India has documented the increasing consumption rates of last-resort antibiotics, such as carbapenems, lincosamides, glycopeptides, third-generation cephalosporins, linezolid and daptomycin, which belong to WHO’s ‘Watch and Reserve’ groups of antibiotics — thus, needlessly exposing patients and increasing the risk of drug-resistant bacteria to develop.
Such irrational use of antibiotics implies that ‘market failure’ has set in. The pharmaceutical industry does not see profit in producing relatively inexpensive ‘Access’ group antibiotics, while drugs that guarantee higher pay offs are ensured a reliable supply. Low margins — where sales are linked to the public sector and poor patients who have limited ability to pay — have prompted several producers in the domestic industry to discontinue manufacture and supply, rendering global access vulnerable.
This, in turn, has sparked the exit of active pharmaceutical ingredients (API) manufacturers for some ‘Access’ group antibiotics and the manufacturing of APIs for some antibiotics is thus, becoming increasingly fragile.
Furthermore, if ‘Watch’ and ‘Reserve’ group antibiotics are promoted, marketed and prescribed over first-line treatment in the unregulated private sector, then demand for ‘Access’ antibiotics will fall, further disrupting the market and increasing the likelihood of insufficient supply.
A Lancet study in 2017 confirmed that Indian domestic generic producers were predominantly selling irrational fixed dose combinations that contain ‘Watch’ and ‘Reserve’ group antibiotics, driving up sales of these categories rapidly by 73 per cent and 174 per cent respectively between 2007 and 2012.
India has a key role to play in not just improving the appropriate and ethical use of antibiotics, but also addressing the issues of shortages and supply instability of first-line ‘Access’ group antibiotics.
In this context, the recommendations of the United Nations Interagency Coordination Group (IACG) on Antimicrobial Resistance in a recent report that was submitted to the UN Secretary General are of particular importance for India. The IACG report advocates for improved forecasting, strengthening of procurement and supply chain management of antibiotics and the establishment of public or government-contracted production facilities to help mitigate shortages and ensure sustainable production and supply of antibiotics.
India has a long history of public sector manufacturing in pharmaceuticals although a number of facilities are facing a state of neglect, struggling financially and have lost their capacity to produce, while others have been sold. However, some capacity still continues to exist. Karnataka Antibiotics & Pharmaceuticals Ltd (KAPL) — a government enterprise — is a supplier of antibiotics such as penicillin to some health programmes.
The Kerala government’s recent efforts, for example, to revive the Kerala State Drugs & Pharmaceuticals Ltd could be crucial to secure supply of ‘Access’ group antibiotics for the domestic market and public sector procurement by state governments. Other models such as Low Cost Standard Therapeutics — a not-for-profit trust and manufacturer of essential medicines not linked to unethical promotion and extraction of vast profit margins — also exist, and could produce ‘Access’ group antibiotics.
Policies and mechanisms
Revival of public sector manufacturing alone will not address the crisis of instable supply and shortages of these essential antibiotics. It is unacceptable if an antibiotic needed to treat an infection is not available because we don’t have a national system for coordinating and maintaining antibiotic supply.
Mechanisms for collective data-sharing, improved forecasting and pooled procurement to meet the demand for ‘Access’ group antibiotics among hospitals, public health programmes, central and state procurement agencies across the country are also needed.
Multiple examples of such regional and global pooled procurement mechanisms currently exist around the world, including the Global Drug Facility for TB that was set up to address the problem of antibiotic shortages and absence of quality-assured sources in the area of drug-resistant TB.
Introducing a similar model in India for ‘access’ group antibiotics would not only reduce prices with manufacturers but also guarantee a more sustainable supply for treatment providers and access for patients. Policymakers need to secure a stable supply of all essential antibiotics and help save the lives of millions.
Dusan Jasovsky a pharmacist, Jyotsna Singh a health writer and Leena Menghaney a lawyer work with the Access Campaign at the international humanitarian medical organisation Médecins Sans Frontières/Doctors Without Borders.