Antibiotic

Adverse reactions to antibiotics and Glucose-6-Phosphate Dehydrogenase deficiency

-Manoja Eswara, Ph.D.

People experiencing adverse reactions to antibiotics such as Ciprofloxacin, Sulfadiazine, or other sulfa-containing drugs should consider test for Glucose 6 Phosphate Dehydrogenase (G6PD) gene that encodes for an essential enzyme responsible for protecting cells from oxidative stress. G6PD deficiency is the lead cause of Acute Hemolytic Anemia (AHA), a condition that damages the Red Blood Cells (RBCs). While the G6PD enzyme is needed for every cell in the body, RBCs are most sensitive to its function. Because the G6PD gene is located on X chromosome it is affecting mostly males, but can also impact women. The gene encoding this enzyme is known to have a number of alterations/ mutations, some of which can impact enzyme’s function and lead to deficiency. Patients expressing these mutant enzymes do well under normal circumstances, but when exposed to medications, chemicals or even certain food that trigger to certain oxidative response, they develop Acute Hemolytic Anemia. AHA is characterized by fever, yellow coloring of the skin and mucous membrane (jaundice), fatigue, rapid pulse and fast breathing, which can be life threatening in case of children.

Gene-drug interaction:

G6PD-deficient individuals are very sensitive to various drugs that interact with Hemoglobin and Oxygen and cause oxidative damage to the body. These drugs include certain antimalarials (Chloroquine), analgesics (methadone), antibiotics (Ciprofloxacin, sulfa-containing drugs), and many more. G6PD-deficient individuals display variable sensitivity to the dosage and route of administration of these drugs. The list of drugs keeps getting updated (check out www.g6pd.org, www.g6pddeficiency.org) and it is important to avoid or alter the drug usage.

Gene-food interaction:

Another well-established trigger for G6PD-deficiency mediated hemolysis is Fava beans. Termed as Favism, some G6PD- deficient individuals develop a rapid adverse reaction after consuming fava beans or by inhaling the pollen. Favism mostly affects male children and is more prevalent in the Middle East and Europe. Research identified that chemicals vicine and convicine that are rich in fava beans, compared to other beans, are the cause for AHA. Other foods that are linked to Favism include bitter melon, blueberries and certain dietary supplements such as iron additives, ascorbic acid, food coloring etc. Therefore, it is very important to note reactions to these foods and avoid them.

Other triggers for developing G6PD-related AHA include medical illnesses caused by viral, bacterial or pathogen infections. Oxidative radicals generated by our body to fight these pathogens can stimulate AHA.

Inheritance of G6PD deficiency: The gene coding for the G6PD enzyme is present on the X-chromosome. G6PD-deficient mostly affects males because male off springs contain only one X-chromosome (from the mother), therefore a mutation in the gene results in a defective enzyme. However, females have two X-chromosomes, one each from father and mother; therefore females mostly contain at least one normal gene and are thus less affected by these mutations.

Around 400 genetic variants of the enzyme are known so far, with the exact mutation identified in 186 instances. The G6PD mutant enzymes have a broad range of efficiency, thereby rendering the patients to variable sensitivity to specific dugs. While G6PD mutations are present across all the ethnicities, certain variants seem to occur more frequently in certain populations, making them more susceptible to drug reactions.

Testing options for G6PD-deficiency include genetic and biochemical tests. Genetic analysis of mutations at the DNA level is a powerful, emerging way to identify predisposition to medical conditions and predict response to drugs, termed as Pharmacogenetics.

G6PD is the most mutated metabolic enzyme known, with almost 400 mutations causing G6PD-deficiency. These mutations are very closely spaced and it is not possible to accurately demarcate and identify them using the genotyping technology used in these Pharmacogenetic tests.  Therefore, Pillcheck does not include G6PD in its list of markers that are tested. There are certain Pharmacogenetic tests in the market that include G6PD in their list of markers tested, however, it is very important to realize that they test for only one or two common mutations and are thus not at all comprehensive to detect all G6PD mutations and may provide a false negative result.

The only definitive way to determine the mutations in G6PD is by DNA sequencing, however, the technology is very expensive and is available in only specialized settings. Therefore, biochemical testing for G6PD activity is more reliable in the case of G6PD-deficiency. G6PD screening tests are also recommended as a preventive measure before prescribing high oxidant drugs that pose the risk of AHA in G6PD-deficient individuals. Also, population screening is routinely performed in certain geographic areas that are known to be at high risk for G6PD-deficiency.

If you have suffered from an adverse reaction to Ciprofloxacin, Sulfadiazine, or other sulfa-containing drugs or foods please ask your physician to refer you for biochemical blood test for G6PD activity.


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