Colistin resistance and its implications in rare disease treatment

Colistin resistance and its implications in rare disease treatment

In 2015, alarms sounded in the global healthcare community as news of the first ever case of colistin-resistant bacteria were reported in China.1 It has now spread around the globe, with findings being reported all over Asia, Europe, and most recently, North America. Colistin is an extremely potent antibiotic that is utilized only as a last line of defense against multi-drug resistant superbugs.1 It was initially abandoned following its discovery in the 1960s due to its toxic effects on the brain and liver.2 However, with dramatically fewer discoveries of antibiotics in the 2000s, and drug-resistant bacteria on the rise, its use has been reluctantly reinstated.2 “We’ve run out of our good drugs. Out of desperation, we had to revive this old drug because it’s all we have left,” states Dr. Price, a professor of environmental health at George Washington University.3 For many years, scientists had the misunderstanding that colistin resistance was not possible.1 Its sudden emergence came as a shock and now threatens the very use of antibiotics in healthcare, with particularly dangerous ramifications concerning rare disease treatment.

Colistin resistance will have a detrimental effect on the lives of rare disease patients who require surgical interventions. Antibiotics not only control for infectious diseases but also enables many advanced clinical procedures such as surgery.4 The current model of treatment for rare disease patients recommends the prescription of antibiotics before the actual surgical procedure. This serves as a preventative measure against bacterial infection following the surgery and is known as antibiotic prophylaxis. Such precautionary actions are extremely paramount for the post-surgical survival rate of these patients since, the manifestation of rare diseases, in most instances, occurs during childhood.4 In fact, more than 50% of people affected by rare diseases are infants, with 30% of children not living past their 5th birthday.5 The early incidence of rare diseases, unfortunately, coincides with the developmental period of the immune system, which leads to these patients being particularly vulnerable to infections following open surgical procedures.6,7

The immune system is a functional unit of the body that is composed of a network of interdependent cells, substances, and organs that work together to protect the body from bacterial, parasitic, and viral infections.8 During the neonatal period and early childhood, the immune system is still maturing. This is the reason why children under the age of seven can have up to six times more instances of the common cold than healthy adults.9 Under normal circumstances, with each sickness (whether it be the cold or the chickenpox), the children's immune system is strengthened and learns to resist infections more effectively.6,8 However, in the case of rare disease patients, their bodies are dedicating a considerable amount of resources to recover from the invasive surgical procedure, resulting in a particularly weakened immune state. The prescription of antibiotics before and after surgery serve to mitigate the risk of infection during this delicate recovery period.

How did colistin resistance catch the scientific community so off guard? Due to the extreme caution surrounding its use in medicine, many experts lived under the misapprehension that you could never get colistin resistance.10 Such stringent regulation of antibiotic use, however, does not exist in the meat industry and reports revealed that colistin is included in the diet of cows, pigs, and chickens. In 2015, a report by the QYResearch Medical Research Center stated that 12,500 tons of colistin were used globally in the meat industry every year. This number is projected to increase to 16,000 tons by the year 2021. The industrial farming conditions are extremely unsanitary and become an optimal breeding ground for diseases.10 While colistin mitigated the risk of infection for the livestock, it was the ideal situation for bacterial resistance to develop.3,11 “Any antibiotic class used for humans should never be used for animals,” states Dr. Wright, a microbiologist at McMaster University specializing in antibiotic resistance. “I just find it absolutely mind-boggling that we’re going into 2016 and we’re still having this discussion.”3 The widespread use of colistin elicited a selective pressure on the bacteria, where conditions favored the survival and proliferation of drug-resistant bacterial strains. What is worse, the gene that elicits colistin resistance (MCR-1) is vector-mediated, meaning the genetic material can be transferred to other species of bacteria.12 This is known as horizontal gene transfer and enables the colistin resistance to disperse across a region quickly, through many different species of bacteria. The rampant spread of this gene to multiple bacterial species would drastically reduce the efficacy of colistin, and this would be the beginning of what researchers and doctors have been long afraid of, deadly incurable bacterial infections.3

The loss of colistin efficacy would compromise even the simplest surgical treatment options for rare diseases due to the dangerous ramifications infections can have on these young patients. Evidence suggests that colistin use in children poses a low risk of long-term damage and is safe to use under a controlled dosage.13 Additionally, colistin has been proven to be useful in helping children combat multi-drug resistant bacterial infections.13

The following case highlights the magnitude of consequences colistin resistance can have in regards to rare disease treatment.

Scenario: A child suffers from cherubism, a rare progressive pediatric disorder characterized by abnormal bone tissue in the posterior region of the face.14 He requires a simple reconstruction surgery to obtain a natural jaw shape.14

Even the above non-life threatening procedure would now place the patient at risk of incurable, life-threatening infections that even colistin would be unable to treat. One can only imagine the harsh reality for these children if they are forced to live with the painful physical manifestations of such rare diseases. Not only would the spread of colistin resistance pose an increased risk for fatal infections, but it would compromise the treatment procedures developed thanks to the collaborative efforts of advocacy groups, researchers and healthcare professionals over the last couple of decades.

The emergence of colistin resistance is a global red flag and a call to action in standardizing antibiotic use in the meat industry. Experts in the scientific community have been warning of the impact that multi-drug resistant bacteria can have on the healthcare system, and its effects are already being seen in the rising cases of post-surgical infectious complications. The use of antibiotics needs to be carefully moderated and controlled to give children suffering from rare diseases a fighting chance against infections after surgery.

Works Cited:

1. Liu Y-Y, Wang Y, Walsh TR, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016;16(2):161-168. doi:10.1016/S1473-3099(15)00424-7.

2. Aminov RI. A Brief History of the Antibiotic Era: Lessons Learned and Challenges for the Future. Front Microbiol. 2010;1:134. doi:10.3389/fmicb.2010.00134.

3. JENNIFER YANG. “Disturbing” drug-resistant superbug gene has been detected in Canada. The Star. 2016.

4. Keys to help rare disease patients insure a successful surgery. Glob Genes.

5. Rare diseases: Facts and Statistics. Global Genes.

6. Ygberg S, Nilsson A. The developing immune system - from foetus to toddler. Acta Paediatr. 2012;101(2):120-127. doi:10.1111/j.1651-2227.2011.02494.x.

7. Barker GM, O’Brien SM, Welke KF, et al. Major Infection After Pediatric Cardiac Surgery: A Risk Estimation Model. Ann Thorac Surg. 2010;89(3):843-850. doi:10.1016/j.athoracsur.2009.11.048.

8. Immune system development.

9. Team HE. Common Cold Risk Factors. Healthline. Published 2016.

10. Kelland K. Alarming new “superbug” gene found in animals and people in China. Reuters.

11. Syed-Abdul S, Jian W-S, Lee P, Li Y-C, Hsu M-H. Superbug demands organizational change of the healthcare system. J Pharmacol Pharmacother. 2011;2(2):132-133. doi:10.4103/0976-500X.81915.

12. McGann P, Snesrud E, Maybank R, et al. Escherichia coli Harboring mcr-1 and blaCTX-M on a Novel IncF Plasmid: First Report of mcr-1 in the United States. Antimicrob Agents Chemother. 2016;60(7):4420-4421. doi:10.1128/AAC.01103-16.

13. Tamma PD, Newland JG, Pannaraj PS, et al. The use of intravenous colistin among children in the United States: results from a multicenter, case series. Pediatr Infect Dis J. 2013;32(1):17-22. doi:10.1097/INF.0b013e3182703790.

14. Papadaki ME, Lietman SA, Levine MA, Olsen BR, Kaban LB, Reichenberger EJ. Cherubism: best clinical practice. Orphanet J Rare Dis. 2012;7(Suppl 1):S6-S6. doi:10.1186/1750-1172-7-S1-S6.

Cite This Article:

Chon J., Zheng K., Chan G., Ho J. Colistin resistance and its implications in rare disease treatment. Illustrated by W. Zhang. Rare Disease Review. January 2017. DOI:10.13140/RG.2.2.22051.66086.

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