Antimicrobials

Side Effects of Antimicrobials

Antimicrobial drug toxicity can affect the liver, kidneys, GI tract, cardiovascular system, nervous system, respiratory system, skin, bones, teeth, and blood-forming tissue, and allergic reactions are not uncommon.

Antimicrobials are by design biologically active chemicals. There is an inherent risk of side effects when introducing biologically active chemicals to a patient, and there is a wide array of side effects associated with antimicrobials. Side effects of antimicrobials occur in most major organ systems. Even when antimicrobials are targeted to specific microbial components lacking in animals, there are often alternate targets in animals that are affected. There is also a risk of allergic reaction to drugs.

The kidneys and liver filter and purify the blood, leading to accumulation of many antimicrobials in these organs. Side effects of antimicrobials are common in these organs. Polymyxin and bacitracin antibiotics are both primarily used as topical ointments because they accumulate to toxic levels in the kidneys, causing damage when administered orally or intravenously. Liver toxicity resulting from antimicrobials is most common during treatment for tuberculosis, when patients are often administered several antibiotics simultaneously. Antimicrobials may not have direct toxicity, but can cause the production of other toxins. For example, there may be some inherent liver toxicity in rifamycin, but it also alters the activity of enzymes in the liver, causing them to metabolize other drugs into metabolites with more potent liver toxicity.

Tissues of the nervous system are targeted by nonselective membrane-disrupting antimicrobials, such as the polymyxins and some aminoglycoside protein synthesis inhibitors. Some quinolone antibiotics have neurotoxic and cardiovascular toxicity. Chloramphenicol inhibits bacterial protein synthesis but also reduces bone marrow and blood cell production, limiting its use to infections resistant to other treatments.

Even commonly used antibiotics, such as penicillin, have side effects. Patients on penicillin derivatives may experience diarrhea and skin rashes. A secondary infection, called a superinfection, can occur following antibiotic treatment when a second pathogen is resistant to the original antibiotics. Superinfections are common and include candidiasis fungal infection of the tongue and diarrhea caused by Clostridium difficile.

Allergic reactions to antibiotics are also reasonably common. Allergies are particularly common for penicillin and sulfonamide antibiotics. Allergic reactions to these are often mild, causing hives and rashes, though especially in reactions to sulfonamides the rashes may become quite severe. Though rare, in some cases penicillin can cause much more severe respiratory inflammation, anaphylaxis, and death.

Antibiotics have no specificity to individual infectious species. They also inhibit and kill nontarget species. The composition of an individual's resident bacterial microflora, and its function, is altered by antibiotics, leading to a range of indirect downstream effects. The diversity of patients' gut microbes declines during antibiotic treatment. Species composition recovers after the course of antibiotics is complete, but it does not return to the original composition and can be altered for years. Gene expression in gut microbes shifts rapidly after the onset of an antibiotic course and has effects nutrient processing. Antibiotic alterations to nontarget organisms are also problematic because they increase the proportion of gut microbes carrying antibiotic-resistance genes. Noninfectious organisms with antibiotic-resistance genes act as a reservoir for those genes and can horizontally transfer them to infectious microbes.