Reactions to Antibiotics: Genetic Susceptibility

Imagine being sick, feeling like a truck ran you over… You head to the doctor and receive a prescription for an antibiotic. After dragging yourself through the pharmacy drive-through, you go straight home and take your first dose, expecting relief to soon follow. But low and behold, a little while later you’re covered with an itchy rash and on the phone with your doctor about a possible antibiotic allergy.

Allergic reactions to antibiotics are fairly common, and many children are diagnosed each year with allergies to different antibiotics.

Genetics plays a role in who is more likely to have an allergic reaction to antibiotics, but genetics isn’t the only reason. This article digs into the research on antibiotic adverse reactions and the genetic variants that increase the risk.

This article is for general informational purposes. Talk to your doctor and pharmacist if you have questions about specific medications.

Antibiotic Reactions: from allergy to liver damage

Adverse drug reactions are more common than you would think. A recent study showed that adverse drug reactions kill more than 100,000 people a year in the US and almost 200,000/year in Europe.[ref]

One type of adverse drug reaction is an allergy or adverse reaction to antibiotics.

For many, antibiotic allergies cause a mild skin rash or hives, but for some, the reaction can be much more serious or even life-threatening.[ref]

The flip side is that antibiotic allergies are often over-diagnosed. It can happen when a rash occurs, and the cause isn’t totally clear. For example, if a child develops a rash or hives while on an antibiotic, it may be a reaction to the antibiotic or simply due to illness. A diagnosis of possible penicillin (or another antibiotic) allergy goes into the electronic health record.

The problem with overdiagnosis is that either broad-spectrum or inferior antibiotics are then prescribed for that person – often for years or decades. Overuse of broad-spectrum antibiotics can lead to antibiotic-resistant strains. Inferior antibiotics can lead to poor resolution of the illness.[ref]

Sulfa Drug Allergies:

While uncommon, antibiotics that contain sulfonamides may trigger a severe reaction in a few people. Two commonly prescribed antibiotics that contain sulfonamides include:

  • Sulfamethoxazole-trimethoprim (Bactrim or Septra)
  • Erythromycin-sulfisoxazole

Reactions to sulfa drugs can be severe. While called a ‘sulfa allergy’, it is technically an IgE reaction that isn’t an allergy, per se, but a potentially life-threatening delayed reaction, often occurring a week or two after starting the antibiotic.[ref]

Penicillin allergies:

Discovered by Alexander Fleming, penicillins have been widely used since the 1940s. Before discovering penicillins, there were no effective treatments for bacterial infections, such as pneumonia, gonorrhea, meningitis, sepsis, and more. While there are modern problems with overuse, antibiotics really are a miracle drug that has saved millions of lives.[ref]

About 10% of the US has a diagnosis of being allergic to penicillin or other β-Lactam antibiotics. β-Lactam antibiotics include penicillins, cephalosporins, carbapenems, and monobactams.[ref]

As I mentioned above, overdiagnosis of penicillin allergy is common.

A skin prick test can confirm the penicillin allergy. Studies show that around 4% of people with a penicillin allergy diagnosis are actually allergic to it.[ref]

One study states: “The overlabeling of pediatric antibiotic allergy represents a huge burden in society. Given that up to 10% of the US population is labeled as penicillin allergic, it can be estimated that at least 5 million children in this country are labeled with penicillin allergy. We now understand that most of the cutaneous symptoms that are interpreted as drug allergy are likely viral induced or due to a drug–virus interaction, and they usually do not represent a long-lasting, drug-specific, adaptive immune response to the antibiotic that a child received. “[ref]

Delayed reactions to antibiotics

Reactions to antibiotics don’t always happen immediately. Sometimes antibiotics can induce a later reaction or trigger longer-term issues.

For example, one study found that an IgE-related gene, MS4A2, was related to the risk of eczema. But that risk substantially increased when combined with antibiotic use in childhood. Eczema is an itchy, red skin rash that is often related to increased IgE antibodies.[ref]

Other adverse effects of antibiotics

Antibiotics may increase the risk of kidney stones for some people. Recent research points to the interaction between Oxalobacter formigenes, the bacteria that degrades oxalates, and kidney stone formation. People who take antibiotics, especially long-term or repeatedly, are more likely to kill off the oxalate degrading bacteria, thus increasing the risk of kidney stones.[ref]

Liver damage is another adverse effect of certain types of antibiotics. While the liver can usually heal from the damage, it can be life-threatening in some patients.[ref]


Antibiotic Reactions Genotype Report

Genetic variants combine with other factors in susceptibility to antibiotic reactions.

Please keep in mind that an increased genetic risk does NOT mean that you will automatically be allergic to a drug. Instead, this means that your relative risk of an adverse reaction is higher than if you didn’t carry the variant. Many people with the variants below will never have an adverse reaction to an antibiotic.

Take this information as a ‘heads up‘ to be aware of adverse reactions and seek medical treatment if needed.

The following genetic variants are linked to an increased relative risk of adverse reactions to antibiotics.

MS4A2 Gene:

Check your genetic data for rs569108 (23andMe v4,5; AncestryDNA):

  • A/A: typical
  • A/G: no increased risk
  • G/G: increased risk of eczema with childhood antibiotic use[ref]

Members: Your genotype for rs569108 is .

IL-13 gene:

Check your genetic data for rs20541 (23andMe v4, v5; AncestryDNA):

  • G/G: typical
  • A/G: increased risk of atopic dermatitis with childhood antibiotic use
  • A/A: increased risk of atopic dermatitis with childhood antibiotic use[ref]

Members: Your genotype for rs20541 is .

HLA-B*5501

Check your genetic data for rs114892859 (23andMe v5)

  • T/T – increased risk of penicillin allergy. (1% of pop) HLA-B∗55:01[ref], increased risk of adverse reaction with clindamycin[ref]
  • G/T: increased risk of penicillin allergy. (1% of pop) HLA-B∗55:01; increased risk of adverse reactions with clindamycin[ref]
  • G/G: typical

Members: Your genotype for rs114892859 is .

PTPN22 gene:

Check your genetic data for rs2476601 (23andMe v4; AncestryDNA):

  • G/G: typical
  • A/G: slightly increased relative risk of liver injury with augmentin[ref]
  • A/A: increased risk of penicillin allergy[ref], slightly increased relative risk of liver injury with augmentin[ref]

Members: Your genotype for rs2476601 is .

HLA-DR*5701

Check your genetic data for rs2395029 (23andMe v4, v5; AncestryDNA):

  • T/T: typical
  • G/T: 45 to 80-fold increased risk of drug-induced liver injury with flucloxacillin[ref][ref]
  • G/G: 80-fold increased risk of drug-induced liver injury with flucloxacillin[ref]

Members: Your genotype for rs2395029 is .

HLA-DRB1*1501-DQB1*0602

Check your genetic data for rs3135388 (23andMe v4, v5; AncestryDNA):

  • A/A: increased relative risk of liver injury with augmentin[ref]
  • A/G: increased relative risk of liver injury with augmentin
  • G/G: typical

Members: Your genotype for rs3135388 is .

HLA-B*5801

Check your genetic data for rs9263726 (23andMe v4, v5):

  • A/A: likely two copies of HLA-B*5801 (research done in Japanese ancestry)[ref]; increased relative risk of reaction to sulfamethoxazole (Bactrim)[ref]
  • A/G: likely one copy of HLA-B*5801; increased relative risk of reaction to sulfamethoxazole (Bactrim)
  • G/G: typical

Members: Your genotype for rs9263726 is .

HLA-A*0201

Check your genetic data for rs2523822 (23andMe v4, v5; AncestryDNA):

  • A/A: typical
  • A/G: increased relative risk of drug-induced liver disease with augmentin
  • G/G: increased relative risk of drug-induced liver disease with augmentin[ref]

Members: Your genotype for rs2523822 is .

LGALS3 gene:

Check your genetic data for rs11125 (23andMe v5)

  • A/A: typical
  • A/T: increased risk of beta-lactam antibiotic allergy
  • T/T: 4 to 5-fold increased risk of beta-lactam antibiotic allergy[ref]

Members: Your genotype for rs11125 is .

GSTM1 gene:

Check your genetic data for rs366631 (23andMe v4 only):

  • A/A: deletion (null) increased risk of adverse cutaneous reactions to sulphonamides in AIDS[ref]
  • A/G: GSTM1 present
  • G/G: GSTM1 present

Members: Your genotype for rs366631 is .

G6PD deficiency interaction with sulfamethoxazole and trimethoprim (Bactrim) causes reduced glutathione levels and increased risk of hemolytic anemia).[ref] Read more about G6PD deficiency and genetics.


Lifehacks:

Double check your antibiotic allergy diagnosis:

Misdiagnosis of penicillin and other antibiotic allergies is a real problem because it limits your options for the best type of antibiotic for certain bacterial infections. For example, using certain antibiotics to avoid penicillin-based drugs may increase your risk of C. difficile infection.[ref] If you were diagnosed with an antibiotic allergy (especially in childhood), you might want to talk with your doctor about getting an allergy test done to confirm it.

Alternatives to antibiotics:

There are many reasons to avoid overusing antibiotics. From a public health perspective, limiting antibiotic use means that we are likely to have fewer antibiotic-resistant bacterial strains emerge. However, it needs to be balanced on an individual basis as to what is best for you.

Before I explain the research on natural options for fighting bacterial infections, I want to be clear that antibiotics are sometimes completely necessary, literally lifesaving. If you are sick with a bacterial infection, talk with your doctor about whether a natural approach could work – and discuss at what point you may need to switch to a prescription antibiotic.

Spices have been used for centuries to flavor food and to prevent spoiling. Modern science shows that many of our traditionally used spices are potent natural antimicrobials.

Oregano oil has antimicrobial activity, inhibiting the reproduction of SaureusBacillus subtilis, and Ecoli. In fact, oregano essential oil is one of the most effective natural antibiotics for many different bacterial species.[ref]

Rosemary essential oil kills E. coli in a petri dish.[ref][ref] I didn’t find any clinical trials, though, that tested the use in people.

Garlic has been used for centuries as an antimicrobial. Research shows that garlic or garlic extract can inhibit Salmonella, E. coli, Staphylococcus aureus, and other bacteria.

Thyme, cinnamon, clove, ginger, and cumin – traditional spices from different cultures worldwide – all have antimicrobial properties.[ref]

Decreasing urinary tract infections (UTIs) without antibiotics:

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.