“The thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with penicillin resistant organism. I hope this evil can be averted.“ by Sir Alexander Fleming.
(Noted in an interview, New York Times, 1945)
With the discovery of penicillin, Sir Alexander Fleming raised his concerns regarding the misuse of antibiotics almost immediately. Almost 70 years later, relatively easy availability and higher consumption have lead to higher incidence of inappropriate use of antibiotics and greater levels of antimicrobial resistance in many countries. Thus, the fears expressed at the time of discovery of the first antibiotic are now turning out to be true.
Some of the statistics in figure 1 show how the prevalence rate of AMR has been on the rise in recent years. Based on the report “The Review on Antimicrobial Resistance, Chaired by Jim O’Neill”; by 2050, 10 million people are expected to die every year and it would cost the world close to USD 100 trillion.(5)
Globally, AMR has increased with India having one of the highest average AMR prevalence rate of 55% infections being caused by antibiotic resistant bacteria every year. Even the developed countries such as Italy, USA and Greece have significant occurrence of AMR leading to increased healthcare costs and mortality.
Figure 1: Comparative analysis of AMR across countries(1)
AMR in the USA
In the USA, CDC estimates that over 2 million illnesses and 23,000 deaths per year are attributable to antibiotic resistance.(3)
Most alarming of all the diseases are the ones caused by multidrug-resistant microbes, which are virtually non-treatable and thereby contribute to higher threat of mortality and healthcare cost. The emergence and spread of multidrug-resistant organisms (MDROs) across global healthcare networks poses a serious threat to society at large.
CDC has classified MDROs into 3 categories as:
- Urgent: These antibiotic-resistant organisms have significant risks identified across several criteria. These threats may not be currently widespread but have the potential to become so and require urgent public health attention to identify infections and to limit transmission.
- Serious: They are not considered urgent, but these threats will worsen and may become urgent without ongoing public health monitoring and prevention activities.
- Concerning: These bacterial pathogens cause severe illness. Threats in this category require monitoring and in some cases rapid incident or outbreak response.
Table 1: CDC classification of top 17 antibiotic-resistant threats in the USA
|Urgent Threats||Clostridium difficile|
|Carbapenem-resistant Enterobacteriaceae (CRE)|
|Drug-resistant Neisseria gonorrhoeae|
|Serious Threats||Multidrug-resistant Acinetobacter|
|Extended spectrum β-lactamase producing Enterobacteriaceae (ESBLs)|
|Vancomycin resistant Enterococcus (VRE)|
|Multidrug-resistant Pseudomonas aeruginosa|
|Drug-resistant Non-typhoidal Salmonella|
|Drug-resistant Salmonella Typhi|
|Methicillin-resistant Staphylococcus aureus (MRSA)|
|Drug-resistant Streptococcus pneumoniae|
|Concerning Threats||Vancomycin-resistant Staphylococcus aureus (VRSA)|
|Erythromycin-resistant Group A Streptococcus|
|Clindamycin-resistant Group B Streptococcus|
Figure 2 : Share of MDROs in total AMR infections in the USA(2013 data)(2)
Facts and figures associated with MDROs in the USA (2)
- Pneumococcal pneumonia: Each year, ~160,000 children younger than 5 years old and over 600,000 adults are hospitalized with pneumococcal pneumonia. Out of the over 2 million illnesses, ~52% of infections are from Drug-resistant Streptococcus pneumoniae. The excess costs associated with this is approximately $96 million
- Campylobacter: It is estimated to cause ~3 million infections, 13,000 hospitalizations, and 120 deaths each year in the United States
- Clostridium difficile: almost 250,000 people each year require hospital care for C. difficile infections and cost at least $1 billion per year
- Neisseria Gonorrhoeae: CDC estimates that more than 800,000 cases occur annually in the United States, out of which 30% i.e 246,000 cases have been reported resistant to any antibiotic treating gonorrhea
- Non-typhoidal Salmonella: ~1.2 million illnesses, 23,000 hospitalizations, and 450 deaths each year in the United States due to its resistance
- Methicillin-resistant Staphylococcus aureus (MRSA): CDC estimates 80,461 invasive MRSA infections and 11,285 related deaths occurred in 2011
- Shigella: It causes ~500,000 diarrheal illnesses, 5,500 hospitalizations, and 40 deaths each year in the United States
- Extended-spectrum Beta-lactamase: An estimated 140,000 healthcare-associated Enterobacteriaceae infections occur in the United States each year. ~26,000 infections and 1,700 deaths are attributable to Extended-spectrum Beta-lactamase (ESBL) producing Enterobacteriaceae
- Vancomycin Resistant Enterococcus (VRE): An estimated 66,000 healthcare-associated Enterococcus infections occur in the United States each year. It accounts for 20,000 infections and 1,300 deaths among hospitalized patients each year
- Carbapenem-resistant Enterobacteriaceae (CRE): More than 9,000 infections occur each year, ~600 deaths are caused by carbapenem-resistant Klebsiella spp. and carbapenem-resistant E. coli.
- Acinetobacter : An estimated 12,000 infections occur in the United States each year. ~7,000 (or 63%) of these are multidrug resistant, and about 500 deaths are attributed to these infections
- Pseudomonas aeruginosa: 51,000 infections occur in the United States each year. More than 6,000 (or 13%) of these are multidrug-resistant, with ~400 deaths per year
- Salmonella Typhi causes ~7 million illnesses worldwide. In USA, ~5,700 illnesses and 620 hospitalizations occur each year
- Of all the cases of Tuberculosis in the United States, antibiotic resistance was identified in almost 10% of them
The above mentioned facts reminds me of a famous essay of 1968 by Garrett Hardin, where he wrote about the grass in shared pastures being eaten up because no one was watching over them. In this case it refers to the unregulated use of antibiotics in veterinary, agri-food and humans.
The misuse of antimicrobial drugs worldwide shows “tragedy of commons” 4. Unfortunately, We have reached an ecological tragedy akin to the “tragedy of the commons”!!