13.4D: Effects of Drug Combinations

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Antimicrobial drugs can interact with other drugs in deleterious ways or can be used in combination to combat microbial infections.

Learning Objectives

Give examples of interactions that can render an antimicrobial ineffective

Key Points

The interaction between one antimicrobial agent and another is very complex, along with the way they target microbes and the organism.
While it is not certain that a drug may interact with antibiotics, it is considered wise to err on the side that there are potentially unknown and harmful interactions from mixing drugs.
The use of more than one antimicrobial agent is an effective and widely used practice to reduce the chance that microbes will resist a treatment.

Key Terms

contraindication: In medicine, a contraindication is a condition or factor that serves as a reason to withhold a certain medical treatment.
tuberculosis: An infectious disease of humans and animals caused by a species of mycobacterium mainly infecting the lungs where it causes tubercles characterized by the expectoration of mucus and sputum, fever, weight loss, and chest pain, and transmitted through inhalation or ingestion of bacteria.
combination therapy: Combination therapy is the use of more than one medication or other therapy. Most often, these terms refer to the simultaneous administration of two or more medications to treat a single disease.

Pharmacodynamics is the field that attempts to understand the unintended effects of the use of two or more drugs. Pharmacodynamics is the study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body. It also looks at the mechanisms of drug action and the relationship between drug concentration and effect. These changes are extraordinarily difficult to classify given the wide variety of modes of action that exist and the fact that many drugs can cause their effect through a number of different mechanisms. This wide diversity also means that, in all but the most obvious cases, it is important to investigate and understand these mechanisms. The well-founded suspicion exists that there are more unknown interactions than known ones.

Two well described interactions between antimicrobial drugs and other drugs are between antibiotics and alcohol and antibiotics and the birth control pill. Interactions between alcohol and certain antibacterials may occur, cause side-effects, and decrease effectiveness of antibacterial therapy. Potential risks of side-effects and effectiveness depend on the type of antibacterial administered. Despite the lack of a categorical contraindication, the belief that alcohol and antibacterials should never be mixed is widespread. Some antibacterials may inhibit the breakdown of alcohol, which may result in alcohol-induced vomiting, nausea, and shortness of breath. Other effects of alcohol on antibacterial activity include altered activity of the liver enzymes that break down the antibacterial compound. In addition, serum levels bacteriostatic antibacterials may be reduced by alcohol consumption, resulting in reduced efficacy and diminished pharmacotherapeutic effect.

Another well studied interaction is between antibiotics and the contraceptive pill. The majority of studies indicate that antibiotics do not interfere with contraceptive pills. In cases where antibacterials have been suggested to affect the efficiency of birth control pills may be due to an increase in the activities of hepatic liver enzymes causing increased breakdown of the pill’s active ingredients. Effects on the intestinal flora, which might result in reduced absorption of estrogens in the colon, have also been suggested, but such suggestions have been inconclusive and controversial. Clinicians have recommended that extra contraceptive measures be applied during therapies using antibacterials that are suspected to interact with oral contraceptives.

Additionally, when dealing with a microbial infection, sometimes the use of two or more antibiotics can effectively combat the infection while each drug individually has little or no effect. This method is called combination therapy and is used when the nature of a microbial infection is unknown, as typified by the combination of the antibiotics ampicillin and sulbactam. The use of two antibiotics with different modes of microbial inhibition increases the chance that the treatment will combat the microbial infection. Further, tuberculosis has been treated with combination therapy for over fifty years. This is due to the phenomenon of resistance, whereby a micro-organism gains the ability to resist an antimicrobial drug, while initially the drug effectively slowed the growth of or even killed the target micro-organism. Treating tuberculosis, or other pathogenic microbes with more than one antibiotic reduces the chance that the microbe will adapt and survive the treatment, especially if the two drugs have different methods of reducing the microbe’s normal functions.

Figure: **Tuberculosis**: This x-ray of a tuberculosis patient shows the lung on the left side completely infected and the right lung partially infected (the dark areas), with tuberculosis.