New research suggests only a fraction of multidrug-resistant bacterial infections in low- and middle-income countries (LMICs) are being treated with the right antibiotics.
In a modeling study published this week in The Lancet Infectious Diseases, researchers estimated that of the nearly 1.5 million people in eight LMICs who had carbapenem-resistant gram-negative (CRGN) bacterial infections in 2019, fewer than 7% were treated appropriately. The authors of the study say the findings highlight an issue that's being increasingly raised by global health officials and antimicrobial resistance (AMR) experts.
"For years, the dominant narrative has been that antibiotics are being overused, but the stark reality is that many people with highly drug-resistant infections in low- and middle-income countries are not getting access to the antibiotics they need," senior study author Jennifer Cohn, MD, Global Access Director for the Global Antibiotic Research and Development Partnership (GARDP), said in a press release.
Substantial gaps in appropriate treatment
For the study, researchers with GARDP, the University of Pennsylvania Perelman School of Medicine, and the University of Maryland School of Medicine used 2019 data from the Global Research on Antimicrobial Resistance (GRAM) study to estimate the number of deaths associated with CRGN bacterial infections in eight LMICs (Bangladesh, Brazil, Egypt, India, Kenya, Mexico, Pakistan, and South Africa) known to have a high burden of CRGN infections. The specific pathogens analyzed were Acinetobacter baumannii, Citrobacter spp, Enterobacter spp, Escherichia coli, Klebsiella pneumoniae, Serratia spp, and Pseudomonas aeruginosa.
The researchers then divided the number of estimated deaths by the case-fatality rate to calculate the total number of CRGN bacterial infections in the eight countries. They used 2019 IQVIA sales data to estimate how many people in those countries received treatment with several antibiotics that are active against CRGN bacteria.
Across the eight selected countries, the researchers estimated 478,790 CRGN bacterial infection-related deaths and 1,496,219 CRGN bacterial infections that required one of the six antibiotics. Most of the infections occurred in South Asia, with 71% occurring in India alone.
But only 103,467 courses of antibiotics active against CRGN bacterial infections were procured in the study countries, for a treatment gap of 1,392,572 patients, or only 6.9% the patients who potentially could have received appropriate treatment. Procurement rates ranged from 14.9% in Egypt and Mexico to 0.2% in Kenya. India procured 80.5% of the treatment courses, but that only covered 7.8% of the country's total need.
For years, the dominant narrative has been that antibiotics are being overused, but the stark reality is that many people with highly drug-resistant infections in low- and middle-income countries are not getting access to the antibiotics they need.
Even with more restrictive assumptions, the analysis still showed a substantial treatment gap, with only 14.2% of patients receiving appropriate treatment. Tigecycline (45.3% of procured courses) and colistin (37%) were the two most procured antibiotics, and ceftazidime-avibactam (0.8%) was the least procured.
"Although our results are only indicative and have limitations, they show that there is almost certainly a substantial gap in the appropriate treatment of CRGN bacterial infections in LMIC," the study authors wrote. "Our results focus on the year 2019, but given the continued rise in CRGN bacterial infections, the effects of the COVID-19 pandemic, and dramatic reductions in global foreign aid, we believe that this gap might have increased."
The authors say lack of access to healthcare facilities in the eight countries and inadequate diagnostics to guide appropriate treatment are likely playing a role in these treatment gaps. But the findings also indicate that patients in these and other LMICs simply cannot get the antibiotics needed to properly treat multidrug-resistant bacteria.
New data on global antibiotic consumption released earlier this week by the World Health Organization (WHO) underscore the problem. The data show that eight countries in 2022—six LMICs and two low-income—reported no consumption of Reserve antibiotics, a category developed by the WHO to describe last-resort antibiotics for multidrug-resistant infections.
In a commentary that accompanies the study, AMR experts from the University of Oxford say the substantial mismatch between the number of multidrug-resistant infections and the number of appropriate treatments available in the eight LMICs is an issue that needs to be urgently addressed.
"Put simply, AMR is increasing, and most of the affected patients (who are concentrated in LMICs) have no access to the antimicrobials needed to treat drug-resistant infections," Elizabeth Ashley, PhD, and Vilada Chansamouth, PhD, MSc, wrote. "Without a mechanism to increase access to Reserve antibiotics in LMICs, mortality associated with AMR will increase."
'Radical shift' needed
While focusing on efforts to reduce the overuse of antibiotics, global health officials have acknowledged that limited access to appropriate antibiotics is also contributing to the spread of AMR. In the political declaration that emerged from the 2024 United Nations High-Level Meeting on AMR, member states were tasked with ensuring equitable and timely access to antibiotics.
"The irony of AMR is that it's fueled by overuse of antibiotics," WHO Director-General Tedros Adhanom Ghebreyesus, PhD, said at the meeting. "And yet more people die from lack of access to antibiotics."
GARDP is among the groups trying to address the problem. In 2022, the group signed an agreement with Japanese drugmaker Shionogi and the Clinton Health Access Initiative to manufacture and commercialize cefiderocol—approved in 2019 for treating multidrug-resistant bacterial infections—in up to 135 countries. GARDP is currently working with the WHO to identify countries where cefiderocol is most needed and where barriers to access exist.
GARDP Executive Director Manica Balasegaram, MRCP, MSc, said the findings of the study show that a "radical shift" toward improved access and research and development on new antibiotic treatments is needed to ensure that people in all countries get the antibiotics they need.
"Ultimately the priority should be saving people's lives," he said.
