Antibiotics are also given for prophylaxis. This is often the case when patients are scheduled to undergo a procedure (i.e., surgery) in which the likelihood of dangerous microbial contamination is high during or after the procedure. Prophylactic antibiotic therapy is used to prevent an infection. The risk of infection varies depending on the procedure being performed. For example, the risk of infection in a patient undergoing coronary artery bypass surgery (with standard preoperative cleansing of the body) is relatively low compared with that in a person undergoing intraabdominal surgery for the treatment of injuries sustained in a motor vehicle accident. In the latter case, contamination with bacteria from the gastrointestinal (GI) tract is more likely to be present in the abdominal cavity. This would constitute a contaminated or “dirty” surgical field, and therefore the likelihood of clinically serious infection would be much higher. Antibiotic therapy would likely be required for a longer period after the procedure. To be effective, prophylactic antibiotics need to be given before the procedure, generally 30 minutes before the incision to ensure adequate tissue penetration. The Surgical Care Improvement Project (SCIP) is a national performance improvement project that provides hospitals with evidence-based recommendations on the administration of prophylactic antibiotics. More information can be found at www.jointcommission.org/surgical_care_improvement_project/.

To optimize antibiotic therapy, the patient is continuously monitored for both therapeutic efficacy and adverse drug effects. A therapeutic response to antibiotics is one in which there is a decrease in the specific signs and symptoms of infection compared with the baseline findings (e.g., fever, elevated WBC count, redness, inflammation, drainage, pain). Antibiotic therapy is said to be subtherapeutic when these signs and symptoms do not improve. This can result from use of an incorrect route of drug administration, inadequate drainage of an abscess, poor drug penetration to the infected area, insufficient serum levels of the drug, or bacterial resistance to the drug. Antibiotic therapy is considered toxic when the serum levels of the antibiotic are too high or when the patient has an allergic or other major adverse reaction to the drug. These reactions include rash, itching, hives, fever, chills, joint pain, difficulty breathing, or wheezing. Relatively minor adverse drug reactions such as nausea, vomiting, and diarrhea are quite common with antibiotic therapy and are usually not severe enough to require drug discontinuation.

Superinfection can occur when antibiotics reduce or completely eliminate the normal bacterial flora, which consist of certain bacteria and fungi that are needed to maintain normal function in various organs. When these bacteria or fungi are killed by antibiotics, other bacteria or fungi are permitted to take over and cause infection. An example of a superinfection caused by antibiotics is the development of a vaginal yeast infection when the normal vaginal bacterial flora is reduced by antibiotic therapy and yeast growth is no longer kept in balance. Antibiotic use is strongly associated with the potential for the development of diarrhea. Antibiotic-associated diarrhea is a common adverse effect of antibiotics. However, it becomes a serious superinfection when it causes antibiotic-associated colitis, also known as pseudomembranous colitis or simply C. difficile infection. This happens because antibiotics disrupt the normal gut flora and can cause an overgrowth of Clostridium difficile. The most common symptoms of C. difficile colitis are watery diarrhea, abdominal pain, and fever. Whenever a patient who was previously treated with antibiotics develops watery diarrhea, the patient needs to be tested for C. difficile infection. If the results are positive, the patient will need to be treated for this serious superinfection. Infections with C. difficile are increasingly becoming resistant to standard therapy.

Another type of superinfection occurs when a second infection closely follows the initial infection and comes from an external source (as opposed to normal body flora). A common example is a case in which a patient who has a viral respiratory infection develops a secondary bacterial infection. This is likely due to weakening of the patient’s immune system function by the primary viral infection. Although the viral infection will not respond to antibiotic therapy, antibiotics may be needed to treat the secondary bacterial infection. This situation calls for some diagnostic finesse on the part of the prescriber, who needs to avoid prescribing unnecessary antibiotics for a viral infection. The presence of colored sputum (e.g., green or yellow) may or may not be a sign of a bacterial superinfection during a viral respiratory illness. Patients will often expect to receive an antibiotic prescription even when they show no signs of a bacterial superinfection. From their perspective, they know they are “sick” and want “some medicine” to expedite their recovery from illness. This can create both diagnostic confusion and an emotional dilemma for the prescriber.

Over the decades, many easily treatable bacterial infections have become resistant to antibiotic therapy. One major cause of this phenomenon is considered to be the overprescribing of antibiotics, often in the clinical situations described earlier. Antibiotic resistance is now considered one of the world’s most pressing public health problems. Another factor that contributes to this problem is the tendency of many patients not to complete their antibiotic regimen. Patients must be counseled to take the entire course of prescribed antibiotic drugs, even if they feel that they are no longer ill.

Food-drug and drug-drug interactions are common problems when antibiotics are taken. One of the more common food-drug interactions is that between milk or cheese and tetracycline, which results in decreased GI absorption of tetracycline. An example of a drug-drug interaction is that between quinolone antibiotics and antacids or multivitamins with iron, which leads to decreased absorption of quinolones. This is especially important, as will be discussed later, because quinolone antibiotics are used orally to treat serious infections. If they are not absorbed, treatment failure is likely to ensue.

Other important factors that must be understood to use antibiotics appropriately are host-specific factors, or host factors. These are factors that pertain specifically to a given patient, and they can have an important bearing on the success or failure of antibiotic therapy. Some of these host factors are age, allergy history, kidney and liver function, pregnancy status, genetic characteristics, site of infection, and host defenses.

Age-related host factors are those that apply to patients at either end of the age spectrum. For example, infants and children may not be able to take certain antibiotics such as tetracyclines, which affect developing teeth or bones; quinolones, which may affect bone or cartilage development in children; and sulfonamides, which may displace bilirubin from albumin and precipitate kernicterus (hyperbilirubinemia) in neonates. The aging process affects the function of various organ systems. As people age, there is a gradual decline in the function of the kidneys and liver, the organs primarily responsible for metabolizing and eliminating antibiotics. Therefore, depending on the level of kidney or liver function of a given older adult, dosage adjustments may be necessary. Pharmacists often play a role in evaluating the dosages of antibiotics and other medications to ensure optimal dosing for a given patient’s level of organ function.

A patient history of allergic reaction to an antibiotic is important in the selection of the most appropriate antibiotic. Penicillins and sulfonamides are two broad classes of antibiotic to which many people have allergic anaphylactic reactions. Symptoms of anaphylaxis include flushing, itching, hives, anxiety, fast irregular pulse, and throat and tongue swelling. The most dangerous such reaction is anaphylactic shock, in which a patient can suffocate from drug-induced respiratory arrest. Although this outcome is the most extreme, the potential for it does underscore the importance of consistently assessing patients for drug allergies and documenting any known allergies clearly in the medical record. All reported drug allergies are to be taken seriously and investigated further before a final decision is made about whether to administer a given drug. Many patients will say that they are “allergic” to a medication when in fact what they experienced was a common mild adverse effect such as stomach upset or nausea. Patients who report drug allergies need to be asked open-ended questions to elicit descriptions of prior allergic reactions so that the actual severity of the reaction can be assessed. The most common severe reactions to any medication that need to be noted in the patient’s chart are any difficulty breathing; significant rash, hives, or other skin reaction; and severe GI intolerance. Although some antibiotics are ideally taken on an empty stomach, eating a small amount of food with the medication may be sufficient to help the patient tolerate it and realize its therapeutic benefits.

Pregnancy-related host factors are also important to the selection of appropriate antibiotics, because several antibiotics can pass through the placenta and cause harm to the developing fetus. Drugs that cause development abnormalities in the fetus are called teratogens. Their use by pregnant women can result in birth defects.

Some patients also have certain genetic abnormalities that result in various enzyme deficiencies. These conditions can adversely affect drug actions in the body. Two of the most common examples of such genetic host factors are glucose-6-phosphate dehydrogenase (G6PD) deficiency and slow acetylation. The administration of antibiotics such as sulfonamides, nitrofurantoin, and dapsone to a person with G6PD deficiency may result in the hemolysis, or destruction, of red blood cells. Patients who are slow acetylators have a physiologic makeup that causes certain drugs to be metabolized more slowly than usual in a chemical step known as acetylation. This can lead to toxicity from drug accumulation (see Chapter 4).

The anatomic site of the infection is a very important host factor to consider when deciding not only which antibiotic to use but also the dosage, route of administration, and duration of therapy. Some antibiotics do not penetrate into the site of infection, such as the lung or bone or abscesses, which can lead to treatment failures.

Consideration of these host factors helps prescribers and pharmacists to ensure optimal drug selection for each individual patient. Continued patient assessment and proper monitoring of antibiotic therapy increase the likelihood that this therapy will be safe and effective.

Antibiotics

Antibiotics are classified into broad categories based on their chemical structure. The common categories include sulfonamides, penicillins, cephalosporins, macrolides, quinolones, aminoglycosides, and tetracyclines. In addition to chemical structure, other characteristics that distinguish classes of drugs include antibacterial spectrum, mechanism of action, potency, toxicity, and pharmacokinetic properties. The four most common mechanisms of antibiotic action are: (1) interference with bacterial cell wall synthesis, (2) interference with protein synthesis, (3) interference with replication of nucleic acids (deoxyribonucleic acid [DNA] and ribonucleic acid [RNA]), and (4) antimetabolite action that disrupts critical metabolic reactions inside the bacterial cell. Figure 38-3 portrays these mechanisms in combating bacterial infections and indicates which mechanism is used by several major antibiotic classes.

Perhaps the greatest challenge in understanding antimicrobial therapy is remembering the types and species of microorganisms against which a given drug can act. The list of microorganisms that a given drug has activity against can be quite extensive and can seem daunting to the inexperienced practitioner. Most antimicrobials have activity against only one type of microbe (e.g., bacteria, viruses, fungi, protozoans). However, a few drugs do have activity against more than one class of organisms.

The field of infectious disease treatment is continually evolving, largely because of the continual emergence of resistant bacterial strains. For this reason, drug indications change frequently, often from year to year, as various bacterial species become resistant to previously effective antiinfective therapy. It is always appropriate to check the most current reference materials or consult with colleagues (e.g., nurses, pharmacists, prescribers) when questions remain. Pharmacists are excellent resources regarding antibiotics. Many hospitals now have pharmacists who are specially trained in the treatment of infectious diseases.

The penicillins are a very large group of chemically related antibiotics that were first derived from a mold (fungus) often seen on bread or fruit. The penicillins can be divided into four subgroups based on their structure and the spectrum of bacteria they are active against: natural penicillins, penicillinase-resistant penicillins, aminopenicillins, and extended-spectrum penicillins. Examples of antibiotics in each subgroup and a brief description of their characteristics are given in Table 38-3.

Penicillins are bactericidal antibiotics, meaning they kill a wide variety of gram-positive and some gram-negative bacteria. However, some bacteria have acquired the capacity to produce enzymes capable of destroying penicillins. These enzymes are called beta-lactamases, and they can inactivate the penicillin molecules by opening the beta-lactam ring. The beta-lactamases that specifically inactivate penicillin molecules are called penicillinases. Bacterial strains that produce these drug-inactivating enzymes were a therapeutic obstacle until drugs were synthesized that inhibit these enzymes. Three of these beta-lactamase inhibitors are clavulanic acid (also called clavulanate), tazobactam, and sulbactam. These drugs bind with the beta-lactamase enzyme itself to prevent the enzyme from breaking down the penicillin molecule, although they are not always effective. The following are examples of currently available combinations of a penicillin and a beta-lactamase inhibitor:

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