Antibiotic Resistance

Written by: Dominick Cicala and Nicholas Stumme

Kenna had just turned 9 years old when she began to feel feverish. After a trip to the doctors, they thought it was a stomach bug and sent her home to rest. After not improving, a second look by doctors found a noxious bacterial infection that was collapsing her lungs, destroying her left femur, and was close to killing her. After three different, powerful antibiotics were used, her infection began to slowly subside. What Kenna had was known as methicillin-resistant Staphylococcus aureus, or MRSA.(1) This bacteria highlights an issue so potentially catastrophic that our medical system is in jeopardy of failing.(2)  Thousands of species of bacteria like MRSA have obtained what is known as “antibiotic resistance” or “multi-drug resistance” genes that make them practically invincible to our antibiotics. We do not have a plan to stop it.

Okay, are you sure you are not dramatizing the problem?

Well, let us think about what antibiotics do. They kill bacteria when they are given to someone. Hence, how can one conduct open heart surgery for heart disease, the leading cause of death in Americans, when doctors cannot control any massive infections that will inevitably result? How can a chemotherapy patient receive drugs that destroy their immune system when there are no antibiotics to protect them? How can a doctor save a badly burnt limb without antibiotics to kill bacteria that are taking over the tissue?  Clearly antibiotics are the backbone of almost all modern medicine.. Without them, it is estimated that 444 million people worldwide would die a year from bacterial infections!(3)

How long do we have until our antibiotics run out?

There is not a set date on when current antibiotics will be useless. Rather, as time goes on, more and more people will die per year as antibiotic resistance takes its toll. For example, the World Health Organization estimates by 2050, 10 million will die a year from antibiotic resistant bacteria alone. That’s billions in economic damage, just like the 2008-2009 financial crisis.(4) In fact, many researchers are completely giving up on advancing antibiotics and increasingly turning to using viruses.

Why can we not discover new antibiotics?

The short answer is that most of the low hanging fruit, such as penicillin, have already been picked. What is really needed is new classes of antibiotics (a class represents a specific way antibiotics attack bacteria), since different antibiotic classes can still damage antibiotic resistant bacteria. For example, penicillin is unusable today from bacterial mutations, but other antibiotics like cephalosporins, can still work.(5) The big issue is that bacteria have learned to protect themselves against multiple classes of antibiotics by pumping antibiotics out of them faster than they enter, which modifies the antibiotics so they cannot work and blocks their entry into the cell. That is why antibiotic resistance has only recently become a problem and was not something the older generations had to worry about. A new antibiotic class has not been discovered since the 1980’s.(6) Older generations had the benefit of new classes being discovered in rapid succession so that even if resistance developed to one class or specific antibiotic, they could switch easily to something new that the bacteria have no resistance for.

What hope do we have left?

 Luckily, there are promising leads. One way is by attacking bacteria systems designed to block antibiotics with a drug which will allow the original antibiotic to kill the bacteria as expected.(7) Another way is using viruses called bacteriophages that only target the antibiotic resistant bacteria causing the infection.(8) This means that the entire infection can be cleared with minimal collateral damage to good bacteria that is normally caught in the crossfire between the antibiotic and bad bacteria. Furthermore, another method is to alternate antibiotics for the same infection. When bacteria become resistant, they often only mutate to protect from the antibiotic at hand. By changing to another antibiotic of a different class, this can function as a surprise attack that the bacteria has no defenses prepared for. When they mutate to protect against that, the first antibiotic is reintroduced since the bacteria will lose their old protections since they are unhelpful! Ingenious!(9)

These are great strategies for scientists, but what can I do to turn the tide in humanity’s favor against antibiotic resistance?

We as a society need to be better with antibiotic consumption. Sometimes we are prescribed antibiotics when we have symptoms that may be caused by bacteria or may be caused by many other factors. When these are given when unneeded, then low levels of bacteria always circulating with antibiotic resistant genes will be the only survivors. Without any competition (since all their competitors died from the antibiotic), they can proliferate and expand exponentially in number that otherwise would have been blocked by the other non-resistant bacteria.(10)  Hence, take them when you have a known bacterial infection or need to prevent one! Another way we can help is by properly disposing of our old antibiotics. Throwing them in the trash or toilet can drive the same resistance seen prior and result in antibiotic-resistant bacteria existing throughout the environment.(11) Instead, use available disposal programs such as the upcoming National Drug Prescription Take Back Day on April 22, 2023 at official drop-off locations!(12) Lastly, the easiest way to stop the spread of antibiotic-resistant bacteria is to prevent infections in the first place. Cooking food thoroughly, washing hands, and staying away from others when sick are great strategies to control any antibiotic-resistant or non-resistant bacteria present without having to rely on antibiotics. We do not wish to have any more Kenna’s, so these tools we have are extremely important in not just preserving public health, but also ours’.

References

(1) Infectious Diseases Society of America. https://www.idsociety.org/public-health/patient-stories/kenna-van-kirk/ (accessed Feb 25, 2023)

(2) Zhou, N; Cheng, Z; Zhang, X; Lv, C; Guo, C; Liu, H; Dong, K; Zhang, Y; Liu, C; Chang, Y; Chen, S; Guo, X; Zhou, X; Li, M; Zhu, Y. Global antimicrobial resistance: a system-wide comprehensive investigation using the Global One Health Index. Infect. Dis. Poverty 2022, 11

(3) Aslam, B; Wang, W; Arshad, MI; Khurshid, M; Muzammil, S; Rasool, MH; Nisar, MA; Alvi, RF; Aslam, MA; Qamar, MU; Salamat, MKF; Baloch, Z. Antibiotic resistance: a rundown of a global crisis. Infect Drug Resist 2018, 11, 1645-1658

(4) O’Neil, J. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations; HM Government, Wellcome trust: December, 2014.

(5) Bui, T; Preuss, C. Cephalosporins, StatPearls Publishing, 2022.

(6) Silver, L. Challenges of Antibacterial Discovery, In Clinical Microbiology Reviews; 1; 24; American Society for Microbiology, 2011; 71-109. https://doi.org/10.1128/CMR.00030-10 

(7) Petchiappan, A; Chatterji, D. Antibiotic Resistance: Current Perspectives. ACS Omega 2017, 2, 7400-7409 

(8) Chan, B; Sistrom, M; Wertz, J; Kortright, K; Narayan, D; Turner, P. Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa. Sci Rep 2016, 6

(9) Richardson, L. Understanding and overcoming antibiotic resistance. PLoS Biol 2017, 15, 8

(10) World Health Organization. Antibiotic resistance. https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance (accessed March 2, 2023)

(11) Anwar, W; Iqbal, Q; Saleem, F. Improper disposal of unused antibiotics: an often overlooked driver of antimicrobial resistance. Expert Rev Anti Infect Ther 2020, 18, 8

(12) National Prescription Drug Take Back Day. https://www.deadiversion.usdoj.gov/drug_disposal/takeback/ (accessed March 2, 2023)

Photo provided by Chloe King of her doing a science experiment in one of her classes.