The World Faces Hurdles in the Fight Against Antibiotic Resistance

Antibiotic resistance is a global problem. Efforts to address the problem are especially vexing in Africa, Asia, and Latin America, according to a trio of speakers at the annual conference of the Infectious Diseases Society of America (IDSA) in New Orleans, Louisiana on October 26.

“The first perspective I have on the issue of antimicrobial resistance, which may differ from the situation here in the United States, is the issue of access versus excess. In Africa, more children under 5 years die of lack of access to antimicrobials than from drug-resistance infections,” said Marc Mendelson, PhD, MBBS, FRCP (UK), DTM&H, professor of Infectious Diseases, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa, in his session.

“The hammer blow of death due to antimicrobial resistance will fall in Africa and Asia. It’s a developmental issue because we are going to have huge morbidity and a huge financial impact, with billions of dollars wiped off. It’s a developmental issue in the sense that you really need to make changes to how we deal with infection. What you take for granted in the United States in terms of having clean water and sanitation is not the case in Africa,” Dr. Mendelson explained. Limited access to immunization is another issue, even with the knowledge that immunization reduces the use of antibiotics.

Implementing a national antimicrobial resistance policy needs to be done with the understanding that there are multiple targets. No discussion in Africa can rightfully focus solely on anti-tuberculosis resistance at the expense of HIV, as was done in the past. “It’s really important when countries are faced with developing national action plans that they understand and take the time to address some of the issues before they go to antimicrobial resistance,” Dr. Mendelson added.

Models of antimicrobial stewardship developed in high-resource countries are unlikely to be relevant in more economically-challenged countries. Stewardship that hinges on the availability of doctors will not work in Africa, since doctors are relatively rare. Efforts that focus on local healthcare workers have a better chance of finding traction.

Other important aspects include the decades-old problem of curbing the use of antibiotics as growth aid in poultry and swine production, and in communicating antimicrobial resistance to the public in a way that is both meaningful and understandable.

Antimicrobial resistance in Asia is a challenge that reflects the economic diversity, ranging from the first-world level economies and social support systems in Japan and South Korea, to a raft of low/low-middle income countries that includes India, according to Sumanth Gandra, MD, Center for Disease Dynamics, Economics & Policy, Washington, DC.

Antibiotic resistance is related to national per-capita income, with richer countries having less of a problem than poorer countries where the level of antibiotic use is climbing and where infrastructure to address the spread of resistance is poor.

Extended-spectrum beta-lactamase (ESBL) producing Escherichia coli and carbapenem-resistant Klebsiella species are rampant in Asia, particularly in India and China. This prevalence has been driven in large part by the increased use of antibiotics, mainly cephalosporins, in Asia in general, and in India and China in particular, from 2000 to 2010. An important reason for the increases in India and China is antibiotic use in food production. “There has been an increasing demand for food. As the economic conditions have improved there has been increasing demand for meat,” explained Dr. Gandra.

India is a global center of antibiotic manufacture. 80% of the active pharmaceutical ingredients used by pharmaceutical companies worldwide, including the United States and Europe, are made in China. Following their manufacture, most of these ingredients are exported to India for processing and subsequent worldwide sale. The good manufacturing practices in China and India do not include environmental safeguards.

“Unfortunately, environmental regulations are currently left up national regulators, who are not inclined to do much. In India, the effluent discharge load of ciprofloxacin in 2007 was 45 kg per day — the amount consumed in Sweden, which has a population of 9 million, over 5 days,” said Dr. Gandra.

Fixed-dose combinations of antibiotics that have not been researched for their efficacy are commonly available in India. Furthermore, sanitation is abysmal in many regions in these countries, fueling the spread of antibiotic resistance.

Latin America also faces problems with antimicrobial resistance that can reflect its equatorial climate, which are ideal for the growth and dissemination of pathogenic bacteria. Addressing the microbial burden requires healthcare expenditures that are financially crushing for Latin America.

One consequence has been the spread of carbapenemase-producing Klebsiella pneumonia, ESBL-producing Escherichia coli, and carbapenem-resistant Acinetobacter species and Pseudomonas aeruginosa. As in Asia, the indiscriminate use of antibiotics in food production is a huge problem.

“Carbapenemase production is the main mechanism of resistance reported so far, especially KPC-2 and carbapenem-hydrolyzing class D beta-lactamase in K. pneumonia and Acinetobacter spp., respectively. Implementation of strict infection control measures is one of the most important measures to counteract antimicrobial resistance in the Latin American region,” said Anna Gales, MD, PhD, in her talk.

​ DISCLOSURES

Marc Mendelson: Non-product promotion lectures on stewardship from GSK, Aspen, MSD, Cipla, Galderma, Pfizer, and Pharma Dynamics; Non-product promotion lectures on influenza from Sanofi Pasteur; Travel grants from MSD to attend ECCMID 2013-2016; Advisory board: Pfizer for pneumococcal conjugate vaccine-13

Sumanth Gandra: none

Ana Gales: Consultant, Scientific advisor and Speaker’s bureau, Consulting fee and Speaker honorarium for MSD and AstraZeneca; Research funding from AstraZeneca

Ana Gales:

SOURCES

• Photos and tape of IDSA presentations
• Laxminarayan R et al. Lancet 2015 387:168-175
• Fairall L et al. Lancet 2012 380:889-898

PRESENTATIONS

Global Perspectives in Antimicrobial Resistance

• An African perspective on antimicrobial resistance; Marc Mendelson, MD, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
• Asian perspective; Sumanth Gandra, MD, MPH, Center for Disease Dynamics, Economics & Policy, Washington, DC
• Views from Latin America; Ana Gales, MD, PHD, Universidade Federal de Sao Paulo, Braganca Paulista, Brazil

​Brian Hoyle, PhD, is a medical and science writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager of a provincial government water testing lab. He can be reached at hoyle@square-rainbow.com.