Realize It Module 4 Standard Path: Foundational Pharmacology & Medication Administration

When treating meningitis, two approaches may be used

(1) We can select a drug that readily crosses the blood-brain barrier, and (2) we can inject an antibiotic directly into the subarachnoid space. When exudate and other fluids hinder drug access, surgical drainage is indicated.

There are two principal mechanisms by which one drug can alter the distribution of another

(1) competition for protein binding and (2) alteration of extracellular pH.

Drugs can interact through four basic mechanisms

(1) direct chemical or physical interaction, (2) pharmacokinetic interaction, (3) pharmacodynamic interaction, and (4) combined toxicity.

The principal adverse effects of sulfonamides are

(1) hypersensitivity reactions, ranging from photosensitivity to Stevens-Johnson syndrome; (2) hemolytic anemia; (3) kernicterus; and (4) renal damage.

Disadvantages of Antibiotic Combinations The use of multiple antibiotics has several drawbacks

(1) increased risk of toxic and allergic reactions, (2) possible antagonism of antimicrobial effects, (3) increased risk of superinfection, (4) selection of drug-resistant bacteria, and (5) increased cost. Accordingly, antimicrobial combinations should be employed only when clearly indicated.

Pharmacodynamic interactions are of two basic types

(1) interactions in which the interacting drugs act at the same site and (2) interactions in which the interacting drugs act at separate sites. Pharmacodynamic interactions may be potentiative or inhibitory, and can be of great clinical significance.

How Do Antibiotics Promote Resistance?

(1) microbes secrete compounds that are toxic to other microbes and (2) microbes within a given ecologic niche (e.g., large intestine, urogenital tract, skin) compete with each other for available nutrients. Under drug-free conditions, the various microbes in a given niche keep each other in check. Furthermore, if none of these organisms are drug resistant, introduction of antibiotics will be equally detrimental to all members of the population and therefore will not promote the growth of any individual microbe. However, if a drug-resistant organism is present, antibiotics will create selection pressure favoring its growth by killing off sensitive organisms. In doing so, the drug will eliminate the toxins they produce and facilitate survival of the microbe that is drug resistant. Also, elimination of sensitive organisms will remove competition for available nutrients, thereby making conditions even more favorable for the resistant microbe to flourish. Hence, although drug resistance is of no benefit to an organism when there are no antibiotics present when antibiotics are introduced, they create selection pressure favoring overgrowth of microbes that are resistant.

When two drugs interact, there are three possible outcomes

(1) one drug may intensify the effects of the other, (2) one drug may reduce the effects of the other, or (3) the combination may produce a new response not seen with either drug alone.

When choosing an antibiotic, three principal factors must be considered

(1) the identity of the infecting organism, (2) drug sensitivity of the infecting organism, and (3) host factors, such as the site of infection and the status of host defenses.

Cephalosporins- Evaluating Therapeutic Effects-Monitor for indications of antimicrobial effects

(e.g., reduction in fever, pain, or inflammation; improved appetite or sense of well-being).

Therapy With Antibiotic Combinations

,routine use of two or more antibiotics should be discouraged. When an infection is caused by a single identified microbe, treatment with just one drug is usually most appropriate.

Adverse Effect

-Fluoroquinolones can cause: tendinitis and tendon rupture, usually in the Achilles tendon. Use with caution in patients at elevated risk (i.e., patients age 60 and older, patients taking glucocorticoids, and patients who have undergone a heart, liver, or kidney transplantation). Inform patients about the risk of tendon damage, and instruct them to report early signs of tendon injury (pain, swelling, inflammation), and to refrain from exercise until tendinitis has been ruled out. If tendinitis is diagnosed, the fluoroquinolone should be discontinued.

There are several mechanisms by which one drug can alter the absorption of another

1. By elevating gastric pH, antacids can decrease the ionization of basic drugs in the stomach, increasing the ability of basic drugs to cross membranes and be absorbed. Antacids have the opposite effect on acidic drugs. 2. Laxatives can reduce absorption of other oral drugs by accelerating their passage through the intestine. 3. Drugs that depress peristalsis (e.g., morphine, atropine) prolong drug transit time in the intestine, thereby increasing the time for absorption.4.Drugs that induce vomiting can decrease absorption of oral drugs. 5.Drugs that are administered orally but do not undergo absorption (e.g., cholestyramine and certain other adsorbent drugs) can adsorb other drugs onto themselves, thereby preventing absorption of the other drugs into the blood. 6. Drugs that reduce regional blood flow can reduce absorption of other drugs from that region. For example, when epinephrine is injected together with a local anesthetic (as is often done), the epinephrine causes local vasoconstriction, thereby reducing regional blood flow and delaying absorption of the anesthetic.

Fluoroquinolones

1. Ciprofloxacin 2.Gemifloxacin 3.Levofloxacin 4.Moxifloxacin 5.Ofloxacin

Nursing measures for patients receiving medication are directed toward the patient's achievement of the following goals (4)

1. Expected therapeutic effects will be demonstrated within a specified time frame 2. Expected change in symptoms 3. Maintenance of therapeutic blood levels of medication 4. The patient will demonstrate knowledge regarding his or her medications

drug-food combinations that can increase toxicity include the following

1. Theophylline (an asthma medicine) plus caffeine, which can result in excessive CNS excitation 2. Potassium-sparing diuretics (e.g., spironolactone) plus salt substitutes, which can result in dangerously high potassium levels 3. Aluminum-containing antacids (e.g., Maalox) plus citrus beverages (e.g., orange juice), which can result in excessive absorption of aluminum

Adverse interactions can be minimized in several ways:

1. minimize the number of drugs a patient receives. 2. avoid detrimental interactions is to take a thorough drug 3. adjusting the dosage when an inducer of metabolism is added to or deleted from the regimen 4. adjusting the timing of administration to minimize interference with absorption 5. monitoring for early signs of toxicity when combinations of toxic agents cannot be avoided, 6. and being especially vigilant when the patient is taking a drug with a narrow therapeutic range.

Duration of antibiotic therapy depends on a number of variables

1. status of host defenses 2. the site of the infection 3.and the identity of the infecting organism.

Drugs that induce PGP can have the following impact on other drugs

1.Reduced absorption—by increasing drug export from cells of the intestinal epithelium into the intestinal lumen 2. Reduced fetal drug exposure—by increasing drug export from placental cells into the maternal blood 3. Reduced brain drug exposure—by increasing drug export from cells of brain capillaries into the blood 4. Increased drug elimination—by increasing drug export from liver into the bile and from renal tubular cells into the urine

As a rule, antibiotic resistance is associated with

1.extended hospitalization, 2.significant morbidity, 3. and excess mortality.

Additional information to be assessed includes (5)

1.the patient's health status, 2..current and past illnesses, 3.laboratory test results, 4.known drug allergies, 5. and religious beliefs and/or cultural practices.

Misuse of antibiotics is common. According to the CDC, about

50% of antibiotic prescriptions are either inappropriate or entirely unnecessary.

Advise patients to take their fluoroquinolone no sooner than

6 hours after ingesting cationic compounds, including iron salts, zinc salts, sucralfate, calcium supplements, dairy products, and aluminum- or magnesium-containing antacids.

Human Factor Medication error Computer error

: Incorrect programming into the database resulted in improper drug labeling that caused a medication error.

Vancomycin-Intravenous

:For systemic infections, and possibly for CDI.

Intravenous fluoroquinolones

Administer IV fluoroquinolones by slow infusion (over 60 minutes or longer).

Erythromycin administration Intravenous.

Administer by slow infusion and in dilute solution to minimize thrombophlebitis.

Implementation

Administration

Administration Tetracyclines- Oral.

Advise patients to take most oral tetracyclines on an empty stomach (1 hour before meals or 2 hours after) and with a full glass of water. Minocycline may be taken with food.Instruct patients to allow at least 2 hours between ingestion of tetracyclines and these chelators: milk products, calcium supplements, iron supplements, magnesium-containing laxatives, and most antacids.

Erythromycin administration -Oral.

Advise patients to take oral preparations on an empty stomach (1 hour before meals or 2 hours after) and with a full glass of water. However, if GI upset occurs, administration may be done with meals.

Sulfonamide Administration

Advise patients to take oral sulfonamides on an empty stomach and with a full glass of water.

Which Antibiotics Promote Resistance?

All antimicrobial drugs promote the emergence of drug-resistant organisms.

Sulfonamide Routes

All currently available systemic sulfonamides are administered orally. Topical formulations are available for dermatologic and ophthalmic use.

Erythromycin Identifying High-Risk Patients

All forms of erythromycin should be avoided by patients with QT prolongation and by those taking inhibitors of CYP3A4.

Route-Systemic.

All tetracyclines are used systemically. Specific routes for individual agents are shown in Table 86.2.

Minimizing Adverse Effects

Although serious adverse reactions are rare, TMP/SMZ can cause all the toxicities associated with sulfonamides and trimethoprim used alone. Thus, the nursing implications summarized previously regarding adverse effects of the sulfonamides alone and trimethoprim alone also apply to the combination of TMP/SMZ.

Preventing Resistance

Although the use of multiple antibiotics is usually associated with promoting drug resistance, there is one infectious disease—tuberculosis—in which drug combinations are employed for the specific purpose of suppressing the emergence of resistant bacteria.

Aminoglycosides

Amikacin, Gentamicin, Kanamycin, Neomycin, Paromomycin, Streptomycin, Tobramycin

Aminoglycosides -Minimizing Adverse Interactions Penicillins.

Aminoglycosides can be inactivated by high concentrations of penicillins. Never mix penicillins and aminoglycosides in the same IV solution.

Minimizing Adverse Effects- Aminoglycosides Nephrotoxicity.

Aminoglycosides can cause acute tubular necrosis, which is usually reversible. To evaluate renal injury, monitor serum creatinine and BUN. If oliguria or anuria develops, withhold the aminoglycoside and notify the prescriber.

Minimizing Adverse Effects- Aminoglycosides-Ototoxicity.

Aminoglycosides can damage the inner ears, causing irreversible impairment of hearing and balance. Monitor for ototoxicity, using audiometry in high-risk patients. Instruct patients to report symptoms of ototoxicity (tinnitus, high-frequency hearing loss, persistent headache, nausea, unsteadiness, dizziness, vertigo). If ototoxicity is detected, aminoglycosides should be withdrawn.

Minimizing Adverse Effects- Aminoglycosides Neuromuscular Blockade.

Aminoglycosides can inhibit neuromuscular transmission, causing potentially fatal respiratory depression. Carefully observe patients with myasthenia gravis and patients receiving skeletal muscle relaxants or general anesthetics. Aminoglycoside-induced neuromuscular blockade can be reversed with IV calcium gluconate.

Aminoglycosides -Minimizing Adverse InteractionsSkeletal Muscle Relaxants.

Aminoglycosides can intensify neuromuscular blockade induced by pancuronium and other skeletal muscle relaxants. When aminoglycosides are used concurrently with these agents, exercise caution to avoid respiratory arrest.

Aminoglycosides Identifying High-Risk Patients

Aminoglycosides must be used with caution in patients with renal impairment, pre-existing hearing impairment, and myasthenia gravis, and in patients receiving ototoxic drugs (especially ethacrynic acid), nephrotoxic drugs (e.g., amphotericin B, cephalosporins, vancomycin, cyclosporine, NSAIDs), and neuromuscular blocking agents.

Penicillin names

Amoxicillin, Amoxicillin/clavulanate, Ampicilli, Ampicillin/sulbactam, Dicloxacillin, Nafcillin, Oxacillin, Penicillin G, Penicillin V, Piperacillin,, Piperacillin/tazobactam

Mixed Infections

An infection may be caused by more than one microbe. Multiple infectious organisms are common in brain abscesses, pelvic infections, and infections resulting from perforation of abdominal organs. When the infectious microbes differ from one another in drug susceptibility, treatment with more than one antibiotic is required.

Life Stage- Breast-feeding women

Antibiotics can enter breast milk, possibly affecting the nursing infant. Sulfonamides, for example, can reach levels in milk that are sufficient to cause kernicterus in nursing newborns. As a general guideline, antibiotics and all other drugs should be avoided by women who are breast-feeding.

Life Stage- Pregnant Women

Antimicrobial drugs can cross the placenta, posing a risk to the developing fetus. For example, when gentamicin is used during pregnancy, irreversible hearing loss in the infant may result. Antibiotic use during pregnancy may also pose a risk to the expectant mother.

Clindamycin causes a high incidence of

CDAD.

Clostridium difficile Infection (CDI).-All cephalosporins, and especially the broad-spectrum agents, can promote

CDI, which can cause diarrhea and pseudomembranous colitis. Notify the prescriber if diarrhea occurs. If CDI is diagnosed, discontinue the cephalosporin. Treat with metronidazole or vancomycin, depending on the severity of the infection.

Cephalosporins medications

Cefaclor,Cefadroxil,Cefazolin,Cefdinir,Cefditoren,Cefepime,Cefixime,Cefotaxime,CefotetanCefoxitin,Cefpodoxime,Cefprozil,Ceftaroline,Ceftazidime,Ceftibuten,Ceftriaxone,CefuroximCephalexin

Oral fluoroquinolones

Ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, and ofloxacin.

Intravenous Fluoroquinolones

Ciprofloxacin, levofloxacin, and moxifloxacin.

Minimizing Adverse Effects Clindamycin -Clostridium difficile-Associated Diarrhea.

Clindamycin can promote CDAD, a potentially fatal superinfection. Prominent symptoms are profuse watery diarrhea, abdominal pain, fever, and leukocytosis. Stools often contain mucus and blood. Instruct patients to report significant diarrhea (more than five watery stools per day). If CDAD is diagnosed, discontinue clindamycin. Treat with oral vancomycin or metronidazole and vigorous replacement of fluids and electrolytes. Drugs that decrease bowel motility (e.g., opioids, anticholinergics) may worsen symptoms and should be avoided.

Tetracyclines

Demeclocycline, Doxycycline, Minocycline, Tetracycline

Sulfonamides Minimizing Adverse Effects-Renal Damage.

Deposition of sulfonamide crystals can injure the kidneys. To minimize crystalluria, it is important to maintain hydration sufficient to produce a daily urine flow of 1200 mL in adults. Alkalinization of urine (e.g., with sodium bicarbonate) can also help. Advise outpatients to consume 8 to 10 glasses of water per day.

Administration vancomycin Rectal.

Dissolve in 100 mL of normal saline, and administer as a retention enema.

Route-Topical.

Doxycycline and minocycline are used topically to treat periodontal disease.

inducing agents

Drugs that stimulate the synthesis of CYP isoenzymes. The classic example of an inducing agent is phenobarbital, a member of the barbiturate family. By increasing the synthesis of specific CYP isoenzymes, phenobarbital and other inducing agents can stimulate their own metabolism as well as that of other drugs.

Organisms for which drug resistance is now a serious problem include

Enterococcus faecium, Staphylococcus aureus, Enterobacter species, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella species, and Clostridium difficile.

Erythromycin route- Oral.

Erythromycin base, erythromycin ethylsuccinate, and erythromycin stearate.

Erythromycin Therapeutic Goal

Erythromycin is indicated for whooping cough, diphtheria, chancroid, chlamydial infections, and other infections caused by erythromycin-sensitive organisms. The drug is also used as a substitute for penicillin G in penicillin-allergic patients.

Erythromycin route- Intravenous.

Erythromycin lactobionate.

Aminoglycosides -Minimizing Adverse Interactions Ototoxic and Nephrotoxic Drugs.

Exercise caution when using aminoglycosides in combination with other nephrotoxic or ototoxic drugs. Increased nephrotoxicity may occur with amphotericin B, cephalosporins, polymyxins, vancomycin, cyclosporine, and NSAIDs. Increased ototoxicity may occur with ethacrynic acid.

Decreased Absorption

Food frequently decreases the rate of drug absorption and occasionally decreases the extent of absorption. Reducing the rate of absorption merely delays the onset of effects; peak effects are not lowered. In contrast, reducing the extent of absorption reduces the intensity of peak responses.

Vancomycin Oral.

For CDI and other intestinal infections.

Decreased Toxicity- In some situations, an antibiotic combination can reduce toxicity to the host ex

For example, by combining flucytosine with amphotericin B in the treatment of fungal meningitis, the dosage of amphotericin B can be reduced, thereby decreasing the risk of amphotericin-induced damage to the kidneys.

Because of the pH partitioning effect, a drug with the ability to change extracellular pH can alter the distribution of other drugs. Example

For example, if a drug were to increase extracellular pH, that drug would increase the ionization of acidic drugs in extracellular fluids (i.e., plasma and interstitial fluid). As a result, acidic drugs would be drawn from within cells (where the pH was below that of the extracellular fluid) into the extracellular space. Hence, the alteration in pH would change drug distribution.

The ability of drugs to alter pH and thereby alter the distribution of other drugs can be put to practical use in the management of poisoning

For example, symptoms of aspirin toxicity can be reduced with sodium bicarbonate, a drug that elevates extracellular pH. By increasing the pH outside cells, bicarbonate causes aspirin to move from intracellular sites into the interstitial fluid and plasma, thereby minimizing injury to cells.

Erythromycin Adverse effects- Gastrointestinal Effects.

Gastrointestinal disturbances (epigastric pain, nausea, vomiting, diarrhea) can be reduced by administering erythromycin with meals. Advise patients to notify the prescriber if GI reactions are severe or persistent.

Aminoglycosides Administration- Topical.

Gentamicin, neomycin, tobramycin.

Aminoglycosides Administration- Intramuscular and Intravenous.

Gentamicin, tobramycin, amikacin, kanamycin.

Erythromycin Adverse effects QT Prolongation and Sudden Cardiac Death.

High levels of erythromycin can prolong the QT interval, thereby posing a risk of a potentially fatal cardiac dysrhythmia. Avoid erythromycin in patients with pre-existing QT prolongation and in those taking drugs that can increase erythromycin levels.

Trimethoprim route Oral

IV (for severe infections).

Trimethoprim/sulfamethoxazole Dosage Adjustment

In patients with renal impairment (creatinine clearance of 15 to 30 mL/min), decrease dosage by 50%. If creatinine clearance falls below 15 mL/min, discontinue drug use.

Decreased Toxicity

In some situations, an antibiotic combination can reduce toxicity to the host. For example, by combining flucytosine with amphotericin B in the treatment of fungal meningitis, the dosage of amphotericin B can be reduced, thereby decreasing the risk of amphotericin-induced damage to the kidneys.

Enhanced Antibacterial Action

In specific infections, a combination of antibiotics can have greater antibacterial action than a single agent. This is true of the combined use of penicillin plus an aminoglycoside in the treatment of enterococcal endocarditis. Penicillin acts to weaken the bacterial cell wall; the aminoglycoside acts to suppress protein synthesis. The combination has enhanced antibacterial action because, by weakening the cell wall, penicillin facilitates penetration of the aminoglycoside to its intracellular site of action.

Life Stage- Older adults

In the older adult, heightened drug sensitivity is due in large part to reduced rates of drug metabolism and drug excretion, which can result in accumulation of antibiotics to toxic levels.

Trimethoprim/ Sulfamethoxazole Therapeutic Goal

Indications include UTIs caused by E. coli and other susceptible organisms, shigellosis, and PCP.

Life Stage- Infants

Infants are highly vulnerable to drug toxicity. Because of poorly developed kidney and liver function, neonates eliminate drugs slowly. Use of sulfonamides in newborns can produce kernicterus, a severe neurologic disorder caused by displacement of bilirubin from plasma proteins (see Chapter 88 ).

Administration Oral

Inform patients taking ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, and ofloxacin that dosing can be done with or without food.

Tetracyclines adverse effects- Gastrointestinal Irritation.

Inform patients that GI distress (epigastric burning, cramps, nausea, vomiting, diarrhea) can be reduced by taking tetracyclines with meals, although absorption may be reduced.

Administration vancomycin Intravenous.

Infuse slowly, over 60 minutes or longer. Use a dilute solution and rotate the infusion site.

Sulfonamide Therapeutic Goal

Initial treatment of uncomplicated UTIs caused by E. coli and other susceptible organisms.

Administration vancomycin Oral.

Instruct patients to complete the prescribed course of therapy even though symptoms may abate before the full course is over.

Trimethoprim/Sulfamethoxazole Administration

Instruct patients to complete the prescribed course of treatment, even though symptoms may abate before the full course is over.

inhibitory interactions

Interactions that result in reduced drug effects are often termed . Inhibitory interactions that reduce toxicity are beneficial. Conversely, inhibitory interactions that reduce therapeutic effects are detrimental.

Allergic Reactions-Penicillin allergy is common. Very rarely, life-threatening anaphylaxis occurs

Interview the patient for a history of penicillin allergy.

Administration tetracyclines- Parenteral.

Intravenous administration is performed only when oral administration is ineffective or cannot be tolerated.

Aminoglycosides Monitoring Summary

Monitor aminoglycoside levels (peaks and troughs), inner ear function (hearing and balance), and kidney function (creatinine clearance, BUN, and urine output).

Vancomycin- Evaluating Therapeutic Effects

Monitor for indications of antimicrobial effects (e.g., reduction in fever, pain, or inflammation; improved appetite or sense of well-being; decreased diarrhea in patients with CDI).

Aminoglycosides Administration- Oral.

Neomycin, paromomycin.

Vancomycin adverse effects Nephrotoxic Drugs.

Nephrotoxic drugs—including aminoglycosides, cyclosporine, and NSAIDs—can increase the risk of kidney damage. Concurrent use of these agents should be avoided, if possible.

Clindamycin Medication routes

Oral, IM, IV, intravaginal.

Aminoglycosides - Dosing Schedule

Parenteral aminoglycosides may be given as one large dose each day or in two or three divided doses administered at equally spaced intervals around-the-clock.

Sulfonamides Minimizing Adverse Effects-Cross-Hypersensitivity.

People who are hypersensitive to sulfonamide antibiotics may also be hypersensitive to chemically related drugs—thiazide diuretics, loop diuretics, and sulfonylurea-type oral hypoglycemics—as well as to penicillins and other drugs that induce allergic reactions.

Foreign materials (e.g., cardiac pacemakers, prosthetic joints and heart valves, synthetic vascular shunts) present a special local problem

Phagocytes react to these objects and attempt to destroy them. Because of this behavior, the phagocytes are less able to attack bacteria, thereby allowing microbes to flourish. Treatment of these infections often results in failure or relapse. In many cases, the infection can be eliminated only by removing the foreign material.

Sulfonamides Minimizing Adverse Effects- Photosensitivity.

Photosensitivity reactions may occur. Advise patients to avoid prolonged exposure to sunlight,: wear protective clothing, and apply sunscreen to exposed skin.

Adverse Effect- QT Prolongation. Moxifloxacin can prolong the

QT interval, thereby posing a risk of severe cardiac dysrhythmias. Generally, avoid this drug in patients with hypokalemia or pre-existing QT prolongation and in those taking prodysrhythmic drugs.

Vancomycin Adverse effectsRed Man Syndrome.

Rapid infusion can cause "red man syndrome," characterized by flushing, rash, pruritus, urticaria, tachycardia, and hypotension. To minimize risk, infuse vancomycin slowly, over 60 minutes or longer.

Creation of a Unique Response

Rarely, the combination of two drugs produces a new response not seen with either agent alone. To illustrate, consider the combination of alcohol with disulfiram [Antabuse], a drug used to treat alcoholism. When alcohol and disulfiram are combined, a host of unpleasant and dangerous responses can result. These effects do not occur when disulfiram or alcohol is used alone.

Penicillin- Monitoring Kidney Function

Renal impairment can cause penicillins to accumulate to toxic levels, and hence monitoring kidney function can help avoid injury. Measuring intake and output is especially helpful in patients with kidney disease, acutely ill patients, and the very old and very young. Notify the prescriber if a significant change in intake/output ratio develops.

Altered metabolism is one of the most important—and most complex—mechanisms by which drugs interact. What is it?

Some drugs increase the metabolism of other drugs, and some drugs decrease the metabolism of other drugs. Drugs that increase the metabolism of other drugs do so by inducing the synthesis of hepatic drug-metabolizing enzymes. Drugs that decrease the metabolism of other drugs do so by inhibiting those enzymes.

Dosage and Duration of Treatment

Success requires that the antibiotic be present at the site of infection in an effective concentration for a sufficient time. Dosages should be adjusted to produce drug concentrations that are equal to or greater than the MIC for the infection being treated. Drug levels 4 to 8 times the MIC are often desirable.

Sulfonamides (Systemic)

Sulfadiazine, Sulfamethoxazole (available only in combination with trimethoprim), Sulfisoxazole (available only in combination with erythromycin)

Sulfonamide- Identifying High-Risk Patients

Sulfonamides are contraindicated for nursing mothers, pregnant women in the first trimester and near term, and infants younger than 2 months. In addition, sulfonamides are contraindicated for patients with a history of severe hypersensitivity to sulfonamides and chemically related drugs, including thiazide diuretics, loop diuretics, and sulfonylurea-type oral hypoglycemics.

Sulfonamide therapeutic Goal

Sulfonamides are used primarily for UTIs caused by E. coli and other susceptible organisms. Additional indications for TMP/SMZ include shigellosis and PCP.

Sulfonamides Minimizing Adverse Effects-Hematologic Effects.

Sulfonamides can cause hemolytic anemia and other blood dyscrasias (agranulocytosis, leukopenia, thrombocytopenia, aplastic anemia). Observe patients for signs of hemolysis (fever, pallor, jaundice). When sulfonamide therapy is prolonged, periodic blood cell counts should be made.

Sulfonamides Minimizing Adverse Effects- Kernicterus.

Sulfonamides can cause kernicterus in newborns. Do not give these drugs to pregnant women near term, nursing mothers, or infants younger than 2 months.

Sulfonamides Minimizing Adverse Effects- Hypersensitivity Reactions.

Sulfonamides can induce severe hypersensitivity reactions (e.g., Stevens-Johnson syndrome). Do not give sulfonamides to patients with a history of severe hypersensitivity to sulfonamides or to chemically related drugs, including sulfonylureas, thiazide diuretics, and loop diuretics. Instruct patients to discontinue drug use and notify their provider at the first sign of hypersensitivity (e.g., rash).

Sulfonamides Metabolism-Related Interactions.

Sulfonamides can intensify the effects of warfarin, phenytoin, and sulfonylurea-type oral hypoglycemics (e.g., glipizide). When combined with sulfonamides, these drugs may require a reduction in dosage.

Aminoglycosides0 Oral Therapy.

Suppression of bowel flora before elective colorectal surgery.

Trimethoprim/ Sulfamethoxazole Minimizing Adverse Interactions

TMP/SMZ has the same drug interactions as sulfonamides and trimethoprim used alone. Therefore, the nursing implications summarized previously regarding drug interactions of the sulfonamides alone and trimethoprim alone also apply to the combination of TMP/SMZ.

Trimethoprim/Sulfamethoxazole-Identifying High-Risk Patients

TMP/SMZ is contraindicated for nursing mothers, pregnant patients in the first trimester or near term, infants younger than 2 months, patients with folate deficiency (manifested as megaloblastic anemia), and patients with a history of hypersensitivity to sulfonamides and chemically related drugs, including thiazide diuretics, loop diuretics, and sulfonylurea-type oral hypoglycemics.

Tetracyclines adverse effects- Hepatotoxicity.

Tetracyclines can cause fatty infiltration of the liver, resulting in jaundice and, rarely, massive liver failure. The risk of liver injury can be reduced by avoiding high-dose IV therapy and by withholding tetracyclines from pregnant and postpartum women who have kidney disease.

Tetracyclines adverse effects- Effects on Teeth.

Tetracyclines can discolor developing teeth. To prevent this, avoid tetracyclines in pregnant women and breast-feeding women and in children younger than 8 years.

Tetracyclines adverse effects- Renal Toxicity

Tetracyclines can exacerbate pre-existing renal impairment. Tetracycline and demeclocycline should not be used by patients with kidney disease.

Tetracyclines adverse effects- Photosensitivity.

Tetracyclines can increase the sensitivity of the skin to ultraviolet light, thereby increasing the risk of sunburn. Advise patients to avoid prolonged exposure to sunlight, wear protective clothing, and apply sunscreen to exposed skin.

Tetracyclines adverse effects- Superinfection.

Tetracyclines can promote bacterial superinfection of the bowel, resulting in severe diarrhea. Instruct patients to notify the prescriber if significant diarrhea develops. If superinfection is diagnosed, discontinue tetracyclines immediately. Treatment of C. difficile-associated diarrhea (CDAD) consists of oral vancomycin or metronidazole, plus fluid and electrolyte replacement.

Drug interactions can affect all four of the basic pharmacokinetic processes. How?

That is, when two drugs are taken together, one may alter the absorption, distribution, metabolism, or excretion of the other.

Increased Adverse Effects

The interaction between aspirin and warfarin represents a potentially detrimental potentiative interaction. Both aspirin and warfarin suppress formation of blood clots. Aspirin does this through antiplatelet activity and warfarin does this through anticoagulant activity. As a result, if aspirin and warfarin are taken concurrently, the risk of bleeding is significantly increased. Clearly, potentiative interactions such as this are undesirable.

Reduced Therapeutic Effects

The interaction between propranolol and albuterol represents a detrimental inhibitory interaction. Albuterol is taken by people with asthma to dilate the bronchi. Propranolol, a drug for cardiovascular disorders, can act in the lung to block the effects of albuterol. Hence, if propranolol and albuterol are taken together, propranolol can reduce albuterol's therapeutic effects. Inhibitory actions such as this, which can result in therapeutic failure, are clearly detrimental.

Increased Therapeutic Effects

The interaction between sulbactam and ampicillin represents a beneficial potentiative interaction. When administered alone, ampicillin undergoes rapid inactivation by bacterial enzymes. Sulbactam inhibits those enzymes and, thereby, prolongs and intensifies ampicillin's therapeutic effects.

Initial Therapy of Severe Infection

The most common indication for using multiple antibiotics is initial therapy of a severe infection of unknown etiology, especially in the neutropenic host.

Initial Therapy of Severe Infection

The most common indication for using multiple antibiotics is initial therapy of a severe infection of unknown etiology, especially in the neutropenic host. Until the infecting organism has been identified, wide antimicrobial coverage is appropriate. Just how broad the coverage should be depends on the clinician's skill in narrowing the field of potential pathogens. Once the identity of the infecting microbe is known, drug selection can be adjusted accordingly. As discussed earlier, samples for culture should be obtained before drug therapy starts.

Cephalosporins Baseline Data

The prescriber may order tests to determine the identity and drug sensitivity of the infecting organism. Take samples for culture before initiating treatment.

Penicillin- Baseline Data

The prescriber may order tests to identify the infecting organism and its drug sensitivity. Take samples for microbiologic culture before starting treatment.

Vancomycin dosing- Intravenous.

The recommended dosage is: 15 to 20 mg/kg every 8 to 12 hours, possibly preceded by a loading dose (25 to 30 mg/kg) in patients with severe infection. Dosage must be reduced in patients with renal impairment. Adjust the dosage to achieve an effective trough serum level: 15 to 20 mcg/mL for serious infections and 10 mcg/mL for less serious infections.

Life Stage- Children/adolescents

The tetracyclines provide another example of toxicity unique to the young: These antibiotics bind to developing teeth, causing discoloration.

Disadvantages of Antibiotic Combinations

The use of multiple antibiotics has several drawbacks, including (1) increased risk of toxic and allergic reactions, (2) possible antagonism of antimicrobial effects, (3) increased risk of superinfection, (4) selection of drug-resistant bacteria, and (5) increased cost. Accordingly, antimicrobial combinations should be employed only when clearly indicated.

Reduced Adverse Effects

The use of naloxone to treat morphine overdose is an excellent example of a beneficial inhibitory interaction. When administered in excessive dosage, morphine can produce coma and profound respiratory depression; death can result. Naloxone, a drug that blocks morphine's actions, can completely reverse all symptoms of toxicity. The benefits of such an inhibitory interaction are obvious.

Vancomycin adverse effects Thrombophlebitis

To help avoid this common reaction, use vancomycin in dilute solution and change the infusion site often.

Penicillin-Therapeutic Goal

Treatment of infections caused by sensitive bacteria.

Therapeutic Goal of cephalosporins

Treatment of infections caused by susceptible organisms.

Aminoglycosides Topical Therapy.

Treatment of local infections of the eyes, ears, and skin.

Tetracycline-Therapeutic Goal

Treatment of tetracycline-sensitive infections, acne, and periodontal disease.

Direct interactions occur most commonly when drugs are combined in IV solutions

True

Direct physical and chemical interactions usually render both drugs inactive

True

Never leave medications at the bedside for the patient to take later

True

Penicillin is bactericidal. T/F

True

TMP/SMZ is a preferred drug for

UTIs and is the drug of choice for PCP in patients with AIDS and other immunodeficiency states.

Trimethoprim is used primarily for

UTIs.

Adverse effects Vancomycin- Renal Failure.

Vancomycin can cause dose-related nephrotoxicity. To minimize risk, ensure that serum trough levels are no greater than required. If significant kidney damage develops, as indicated by a 50% increase in serum creatinine level, dosage should be reduced.

Intensification of Effects

When a patient is taking two medications, one drug may intensify, or potentiate, the effects of the other. This type of interaction is often termed a potentiative interaction. Potentiative interactions may be beneficial or detrimental. Examples of beneficial and detrimental potentiative interactions follow.

Antimicrobial Effects of Antibiotic Combinations

When two antibiotics are used together, the result may be additive, potentiative, or, in certain cases, antagonistic. An additive response is one in which the antimicrobial effect of the combination is equal to the sum of the effects of the two drugs alone. A potentiative interaction (also called a synergistic interaction) is one in which the effect of the combination is greater than the sum of the effects of the individual agents. A classic example of potentiation is produced by trimethoprim plus sulfamethoxazole, drugs that inhibit sequential steps in the synthesis of tetrahydrofolic acid.

Increased Absorption

With some drugs, food increases the extent of absorption. When this occurs, peak effects are heightened. For example, a high-calorie meal more than doubles the absorption of saquinavir [Invirase], a drug for HIV infection. If saquinavir is taken without food, absorption may be insufficient for antiviral activity.

Rarely, a patient with a history of anaphylaxis nonetheless requires penicillin. To minimize the risk of a severe reaction, administer penicillin according to

a desensitization schedule. Be aware, however, that the procedure does not guarantee that anaphylaxis will not occur. Accordingly, have epinephrine and facilities for respiratory support immediately available.

Clindamycin administration Instruct patients to take oral clindamycin with

a full glass of water.Instruct patients to complete the prescribed course of treatment, even though symptoms may abate before the full course is over.

Surgery- Prophylaxis is also beneficial for women undergoing

a hysterectomy or an emergency cesarean section.

Each nursing diagnosis statement identifies what

a patient problem and suggests expected patient outcomes.

Penicillin-For patients with prior allergic responses

a skin test may be ordered to assess current allergy status. Exercise caution: The skin test itself can cause a severe reaction. When skin tests are performed, epinephrine and facilities for respiratory support should be immediately available.

Penicillin- In patients with a history of penicillin allergy

a skin test may be performed to determine current allergic status.

Instruct patients to complete the prescribed course of therapy even though symptoms may

abate before the full course is over.

Instruct patients to complete the prescribed course of treatment, even though symptoms ma

abate before the full course is over.

if tetracyclines are administered with milk products or calcium supplements

absorption is reduced and antibacterial effects may be lost.

High-fiber foods can reduce

absorption of some drugs. For example, absorption of digoxin [Lanoxin], used for cardiac disorders, is reduced significantly by wheat bran, rolled oats, and sunflower seeds. Because digoxin has a narrow therapeutic range, reduced absorption can result in therapeutic failure.

broad-spectrum antibiotics are

active against a wide variety of microbes.

Drugs are also labeled as narrow-spectrum, meaning

active against on a few species of microorganisms, or broad-spectrum, which are active against a wide variety of microbes.

When two antibiotics are used together, the result may be

additive, potentiative, or, in certain cases, antagonistic.

Estimates indicate that between 30% and 50% of the antibiotics used in the United States are

administered for prophylaxis. That is, these agents are given to prevent an infection rather than to treat an established infection.

Alcohol. Cefazolin and cefotetan can cause

alcohol intolerance. A serious disulfiram-like reaction may occur if alcohol is consumed. Advise patients about alcohol intolerance, and warn them not to drink alcoholic beverages.

Identifying High-Risk Patients-Cephalosporins are contraindicated for patients with a history of

allergic reactions to cephalosporins or of severe allergic reactions to penicillins.

Even though two drugs have different mechanisms of action and act at separate sites, if both drugs influence the same physiologic process, then one drug can

alter responses produced by the other.

Clindamycin is used primarily as an

alternative to penicillin for serious gram-positive anaerobic infections.

Conjugation takes place primarily

among gram-negative bacteria. Genetic material may be transferred between members of the same species or between members of different species. Because the transfer of R factors is not species specific, it is possible for pathogenic bacteria to acquire R factors from the normal flora of the body. Because R factors are becoming common in normal flora, the possibility of transferring resistance from normal flora to pathogens is a significant clinical concern.

Penicillin-Instruct outpatients to report any signs of

an allergic response (e.g., skin rash, itching, hives).

Inhibition occurs when

an antagonist drug blocks access of an agonist drug to its receptor.

Metronidazole is used to treat

anaerobic bacteria and is important in the treatment of c. difficile.

The term ______ is often used interchangeably with antimicrobial

antibiotic

narrow-spectrum antibiotics

are active against only a few species of microorganisms.

healthcare-associated infections (HAIs)

are among the most difficult to treat. According to the Centers for Disease Control and Prevention (CDC), 1 of every 25 patients will fall victim to an HAI..

Bactericidal drugs

are directly lethal to bacteria at clinically achievable concentrations.

Penicillin- Administration- During IM injection, aspirate to avoid injection into an

artery. Take care to avoid injection into a nerve.

Inducing agents can increase the rate of drug metabolism by how much

as much as two- to threefold. This increase develops over 7 to 10 days. Rates of metabolism return to normal 7 to 10 days after the inducing agent has been withdrawn.

Bacterial Endocarditis- Individuals with congenital or valvular heart disease and those with prosthetic heart valves are unusually susceptible to

bacterial endocarditis. For these people, endocarditis can develop following certain dental and medical procedures that dislodge bacteria into the bloodstream. Thus, before undergoing such procedures, these patients may need prophylactic antimicrobial medication.

Antimicrobial agents treat

bacterial infections. .

Penicillin agents are

bactericidal and are beta-lactam antibiotics.

Antagonism is most likely when a

bacteriostatic agent (e.g., tetracycline) is combined with a bactericidal drug (e.g., penicillin). Antagonism occurs because bactericidal drugs are usually effective only against organisms that are actively growing. Hence, when bacterial growth has been suppressed by a bacteriostatic drug, the effects of a bactericidal agent can be reduced. If host defenses are intact, antagonism between two antibiotics may have little significance. However, if host defenses are compromised, the consequences can be dire.

Tetracycline and macrolides, including erythromycin, and clindamycin are

bacteriostatic and broad spectrum.

Sulfonamides are

bacteriostatic antibacterial agents, which inhibit bacterial synthesis of folic acid. These drugs are often used for urinary tract infections. Nursing considerations reference administration, techniques to decrease adverse effects, monitoring for allergic reaction, and patient education needs were discussed.

Erythromycin, the prototype of the macrolide antibiotics, is a

bacteriostatic drug that inhibits bacterial protein synthesis.

Success of antibiotic requires that the antibiotic

be present at the site of infection in an effective concentration for a sufficient time.

When conditions demand that we start therapy in the absence of laboratory data, it is essential that samples of exudates and body fluids be obtained for culture

before initiation of treatment; if antibiotics are present at the time of sampling, they can suppress microbial growth in culture and can thereby confound identification.

Surgery- When antibiotics are given for prophylaxis, they should be given

before the surgery. If the procedure is unusually long, dosing again during surgery may be indicated. As a rule, postoperative antibiotics are unnecessary. For most operations, a first-generation cephalosporin (e.g., cefazolin) will suffice.

Bleeding.Two cephalosporins—cefotetan and ceftriaxone—can promote

bleeding. Monitor prothrombin time, bleeding time, or both. Parenteral vitamin K can correct abnormal prothrombin time. Observe patients for signs of bleeding; if bleeding develops, discontinue the drug. Exercise caution in patients with a history of bleeding disorders and in patients receiving drugs that can interfere with hemostasis (anticoagulants; thrombolytics; antiplatelet drugs, including aspirin and other NSAIDs).

Intravenous.- Techniques for IV administration are

bolus injection, slow injection (over 3 to 5 minutes), and continuous infusion. The prescriber's order should specify which method to use; request clarification if the order is unclear.

Tetracyclines are

broad-spectrum, bacteriostatic antibiotics that inhibit bacterial protein synthesis.

Aminoglycosides are nephrotoxic

but renal injury is usually reversible.

Conjugation is a process

by which extrachromosomal DNA is transferred from one bacterium to another. To transfer resistance by conjugation, the donor organism must possess two unique DNA segments, one that codes for the mechanisms of drug resistance and one that codes for the "sexual" apparatus required for DNA transfer. Together, these two DNA segments constitute an R factor (resistance factor).

Tetracyclines form insoluble chelates with

calcium, iron, magnesium, aluminum, and zinc. Accordingly, they must not be administered with calcium supplements, milk products, iron supplements, magnesium-containing laxatives, and most antacids.

Bacteriostatic drugs

can slow bacterial growth but do not cause cell death. When a bacteriostatic drug is used, elimination of bacteria must ultimately be accomplished by host defenses (i.e., the immune system working in concert with phagocytic cells).

Surgery-Prophylactic use of antibiotics can decrease the incidence of infection in certain kinds of surgery. Procedures in which prophylactic efficacy has been documented include

cardiac surgery, peripheral vascular surgery, orthopedic surgery, and surgery on the GI tract (stomach, duodenum, colon, rectum, and appendix).

Carnitine Deficiency.-Cefditoren is excreted in combination with carnitine and can thereby lower carnitine levels. Do not give cefditoren to patients with pre-existing

carnitine deficiency or with conditions that predispose to carnitine deficiency.

Absorption of oral fluoroquinolones can be reduced by

cationic compounds, including iron salts, zinc salts, sucralfate, aluminum- or magnesium-containing antacids, calcium supplements, and calcium-containing foods (i.e., milk and milk products). Instruct patients to take these cationic compounds at least 6 hours before or 2 hours after their fluoroquinolone.

Drugs That Promote Bleeding. Drugs that interfere with hemostasis—anticoagulants, thrombolytics, and antiplatelet drugs (including aspirin and other NSAIDs)—can intensify bleeding tendencies caused by

cefotetan and ceftriaxone. Avoid these combinations.

Cephalosporins- Allergic Reactions.Hypersensitivity reactions are relatively common. Rarely, life-threatening anaphylaxis occurs. Avoid cephalosporins in patients with a history of

cephalosporin allergy or severe penicillin allergy. If penicillin allergy is mild, cephalosporins can be used with relative safety. Instruct the patient to report any signs of allergy (e.g., skin rash, itching, hives). If anaphylaxis occurs, administer parenteral epinephrine and provide respiratory support.

Erythromycin Adverse interaction Erythromycin can antagonize the antibacterial actions of

clindamycin and chloramphenicol. Concurrent use of erythromycin with these agents is not recommended.

When two drugs bind to the same site on plasma albumin what happens?

coadministration of those drugs produces competition for binding. As a result, binding of one or both agents is reduced, causing plasma levels of free drug to rise. In theory, the increase in free drug can intensify effects. However, since the newly freed drug usually undergoes rapid elimination, the increase in plasma levels of free drug is rarely sustained or significant unless the patient has liver problems that interfere with drug metabolism, or renal problems that interfere with drug excretion.

Because the same aminoglycoside dose can produce very different plasma levels in different patients, monitoring serum levels is

common. Peak levels must be high enough to cause bacterial kill; trough levels must be low enough to minimize toxicity to the inner ears and kidneys.

Aminoglycosides -Minimizing Adverse Interactions If interstitial fibrosis or renal tubular necrosis develops

damage to the kidneys may be permanent.

Intramuscular-Make IM injections

deep into a large muscle. Intramuscular injections are frequently painful; forewarn the patient. Check the injection site for induration, tenderness, and redness—and notify the prescriber if these occur.

The success of the therapy is indicated by the

disappearance of infectious organisms from post-treatment cultures. Cultures may become sterile within hours of the onset of treatment (as may happen with urinary tract infections), or they may not become sterile for weeks (as may happen with tuberculosis).

Attempted Treatment of Viral Infection-The majority of viral infections—including mumps, chickenpox, and the common cold

do not respond to currently available drugs. Hence, when drug therapy of these disorders is attempted, patients are exposed to all the risks of drugs but have no chance of receiving benefits.

Although most drug-food interactions concern drug absorption or drug metabolism, food may also (rarely) have a direct impact on

drug action. For example, foods rich in vitamin K (e.g., broccoli, brussels sprouts, cabbage) can reduce the effects of warfarin, an anticoagulant. This occurs because warfarin inhibits vitamin K-dependent clotting factors. Accordingly, when vitamin K is more abundant, warfarin is less able to inhibit the clotting factors, and therapeutic effects decline.

Dosages of antibiotics should be adjusted to produce

drug concentrations that are equal to or greater than the MIC for the infection being treated. Drug levels 4 to 8 times the MIC are often desirable.

To decrease resistance and development of superinfections

drug sensitivity testing is done. This identifies which antibiotic the microbe is susceptible to, which increases the likelihood the drug will kill the microbe.

Antimicrobial therapy refers to use of

drugs that have the ability to kill or suppress microorganisms that could cause infections.

Hyperkalemia.- High doses of IV potassium penicillin G may cause hyperkalemia, possibly resulting in

dysrhythmias or cardiac arrest. Monitor electrolyte and cardiac status.

Three oral tetracyclines—tetracycline—should be administered on an

empty stomach.

Drugs can alter all three phases of renal excretion

filtration, reabsorption, and active secretion. Example: By doing so, one drug can alter the renal excretion of another. Glomerular filtration can be decreased by drugs that reduce cardiac output: A reduction in cardiac output decreases renal perfusion (blood flow), which decreases drug filtration at the glomerulus, which in turn decreases the rate of drug excretion. By altering urinary pH, one drug can alter the ionization of another and thereby increase or decrease the extent to which that drug undergoes passive tubular reabsorption. Finally, competition between two drugs for active tubular secretion can decrease the renal excretion of both agents.

Trimethoprim is contraindicated in patients with

folate deficiency. If giving TMP/SMZ, it may be important to assess for megaloblastic anemia. This type of anemia is characterized by erythrocytes that have a larger-than-normal size (elevated mean cell volume [MCV]). When possible, the drug should be avoided during pregnancy and lactation.

Oral.-Advise patients to take oral cephalosporins with

food if gastric upset occurs. Instruct patients to refrigerate oral suspensions.

The interaction between calcium-containing foods and tetracycline antibiotics is a classic example of

food reducing drug absorption.

Whenever a parenteral penicillin is used, keep the patient under observation

for at least 30 minutes. If anaphylaxis occurs, treatment consists of epinephrine (subQ, IM, or IV) plus respiratory support.

Tetracyclines are first-choice drugs

for just a few infections, including those caused by Chlamydia trachomatis, rickettsia (e.g., Rocky Mountain spotted fever), H. pylori (i.e., peptic ulcer disease), B. anthracis (anthrax), Borrelia burgdorferi (Lyme disease), and M. pneumoniae.

Instruct the patient to take oral penicillins with a

full glass of water 1 hour before meals or 2 hours after. Penicillin V, amoxicillin, and amoxicillin/clavulanate may be taken with meals.

In addition to matching the drug with the bug and determining the drug sensitivity of an infecting organism, host factors when prescribing an antimicrobial drug must be considered. Two host factors

host defenses and infection site—are unique to the selection of antibiotics. Other host factors, such as age, pregnancy, and previous drug reactions, are the same factors that must be considered when choosing any other drug.

The principal adverse effects of trimethoprim are

hyperkalemia and possible birth defects.

Use moxifloxacin with great caution in patients with

hypokalemia or pre-existing QT prolongation and in those taking prodysrhythmic drugs.

Advise patients with penicillin allergy to wear some form of

identification (e.g., Medic Alert bracelet) to alert emergency healthcare personnel.

Vancomycin Baseline Data-The prescriber may order tests to determine the

identity and drug sensitivity of the infecting organisms. Take samples for culture before initiating treatment.

When an inducing agent is taken with another medicine, the dosage of the other medicine may need adjustment. For example

if a woman taking oral contraceptives were to begin taking phenobarbital, induction of drug metabolism by phenobarbital would accelerate metabolism of the contraceptive, thereby lowering its level. If drug metabolism is increased enough, protection against pregnancy would be lost. To maintain contraceptive efficacy, dosage of the contraceptive should be increased. Conversely, when a patient discontinues an inducing agent, dosages of other drugs may need to be lowered. If the dosage is not reduced, drug levels may climb dangerously high as rates of hepatic metabolism decline to their baseline (noninduced) values.

Hemolytic Anemia.-Cephalosporins can promote

immune-mediated hemolytic anemia. If hemolytic anemia develops, the cephalosporin should be discontinued. Blood transfusions may be given as needed.

Aminoglycosides.-When present in high concentration, penicillins can

inactivate aminoglycosides (e.g., gentamicin). Do not mix penicillins and aminoglycosides in the same IV solution.

Tetracycline and macrolides

including erythromycin, are bacteriostatic.

Duration of therapy depends on a number of variables

including the status of host defenses, the site of the infection, and the identity of the infecting organism. It is imperative that antibiotics not be discontinued prematurely. Accordingly, patients should be instructed to take their medication for the entire prescribed course, even though symptoms may subside before the full course has been completed. Early discontinuation is a common cause of recurrent infection, and the organisms responsible for relapse are likely to be more drug resistant than those present when treatment began.

Erythromycin Adverse interaction -Drugs that inhibit CYP3A4 (e.g., verapamil, diltiazem, HIV protease inhibitors, azole antifungal drugs) can

increase erythromycin levels, thereby posing a risk of QT prolongation and sudden cardiac death. People using these drugs should not use erythromycin.

In certain cases, a combination of two antibiotics may be less effective than one of the agents by itself

inducing antagonism between the drugs. Antagonism is most likely when a bacteriostatic agent (e.g., tetracycline) is combined with a bactericidal drug (e.g., penicillin). Antagonism occurs because bactericidal drugs are usually effective only against organisms that are actively growing. Hence, when bacterial growth has been suppressed by a bacteriostatic drug, the effects of a bactericidal agent can be reduced. If host defenses are intact, antagonism between two antibiotics may have little significance. However, if host defenses are compromised, the consequences can be dire.

Oseltamivir (an antiviral agent) may be employed for prophylaxis against

influenza.

The sulfonamides and trimethoprim act by

inhibiting bacterial synthesis of folic acid.

Erythromycin is generally safe. However, combined use of erythromycin with

inhibitors of CYP3A4 increases the risk of QT prolongation and sudden cardiac death.

Interactions that occur at the same receptor are almost always

inhibitory.

Selective toxicity is the ability of a drug to

injure a target cell or an organism without causing damage to surrounding cells or the host. These drugs can kill the organism without causing harm directly to the patient.

Aminoglycosides can cause irreversible

injury to sensory cells of the inner ears, resulting in hearing loss and disturbed balance.

Nursing considerations during administration of sulfonamides include

instructing patients to take with a full glass of water and drink 8 to 10 glasses of water per day to avoid crystalluria, complete full course of treatment, avoid sun exposure due to photosensitivity, stop drug and notify provider immediately with rash due to risk of allergy or Steven's Johnsons syndrome, or any signs of symptoms of blood dyscrasias, including sore throat, fever, pallor, easy bruising or bleeding.

Penicillin- Effects Resulting From Incorrect Injection.Take care to avoid

intra-arterial injection or injection into peripheral nerves because serious injury can result.

Antibiotic

is a chemical that is produced by one microbe and has the ability to harm other microbes. Under this definition, only those compounds that are actually made by microorganisms qualify as antibiotics. Drugs such as the sulfonamides, which are produced in the laboratory, would not be considered antibiotics under the strict definition. In contrast, an

Early discontinuation of antibiotics

is a common cause of recurrent infection, and the organisms responsible for relapse are likely to be more drug resistant than those present when treatment began.

Superinfection

is defined as a new infection that appears during the course of treatment for a primary infection. New infections develop when antibiotics eliminate the inhibitory influence of normal flora, thereby allowing a second infectious agent to flourish. When there is normal flora that contains a resistant organism, the antibiotic will selectively promote the growth of that specific resistant flora. Although the antibiotic promotes the overgrowth of resistant flora, it kills off sensitive strains, thus facilitating the survival of the resistant flora. Although there is selective overgrowth of the normal flora with resistance, there is still a decrease in the inhibitory effects of the sensitive flora.

antimicrobial drug

is defined as any agent, natural or synthetic, that has the ability to kill or suppress microorganisms. Under this definition, no distinction is made between compounds produced by microbes and those made by chemists. From the perspective of therapeutics, there is no benefit to distinguishing between drugs made by microorganisms and drugs made by chemists.

An additive response

is one in which the antimicrobial effect of the combination is equal to the sum of the effects of the two drugs alone.

A potentiative interaction (also called a synergistic interaction)

is one in which the effect of the combination is greater than the sum of the effects of the individual agents. A classic example of potentiation is produced by trimethoprim plus sulfamethoxazole, drugs that inhibit sequential steps in the synthesis of tetrahydrofolic acid.

Never combine two or more drugs in the same container unless what is established

it has been established that a direct interaction will not occur.

The goal of antimicrobial therapy is to

kill microbes that cause an infection

Nursing considerations include close monitoring of

laboratory drug peak levels 30 minutes following IV administration and trough levels one hour prior to next dose in single daily dosing. Additional monitoring includes renal function tests (creatinine clearance, BUN, and urine output) and patient education to notify nurse or provider with any ototoxicity symptoms of tinnitus, high-frequency hearing loss, persistent headache, nausea, unsteadiness, dizziness, or vertigo. The provider needs to be notified immediately, and the drug stopped.

a combination of two antibiotics may be

less effective than one of the agents by itself, inducing antagonism between the drugs.

High doses of tetracyclines can cause severe

liver damage, especially in pregnant and postpartum women who have renal impairment.

The first rule of antimicrobial therapy is to

match the drug with the bug. Hence, whenever possible, the infecting organism should be identified before starting treatment. If treatment is begun in the absence of a definitive diagnosis, positive identification should be established as soon as possible so as to permit adjustment of the regimen to better conform with the drug sensitivity of the infecting organism.

When treating infection, the therapeutic objective is to produce

maximal antimicrobial effects while causing minimal harm to the host

Antibiotic therapy is often used prophylactically to prevent

microbial infections.

The two principles of antimicrobial therapy focus on the

microbial susceptibility to drugs and the clinical usage of antimicrobials.

The quickest, simplest, and most versatile technique for identifying microorganisms is

microscopic examination of a Gram-stained preparation. Samples for examination can be obtained from exudate, sputum, urine, blood, and other body fluids.

As a rule, patients with a history of penicillin allergy should not receive penicillins again. If previous reactions have been

mild, a cephalosporin (preferably oral) may be an appropriate alternative. However, if severe immediate reactions have occurred, cephalosporins should be avoided too.

Monitoring Antimicrobial Therapy-Antimicrobial therapy is assessed by

monitoring clinical responses and laboratory results. The frequency of monitoring is directly proportional to the severity of infection. Important clinical indicators of success are reduction of fever and resolution of signs and symptoms related to the affected organ system (e.g., improvement of breath sounds in patients with pneumonia).

Tetracyclines adverse effects- Fungal overgrowth may occur in the

mouth, pharynx, vagina, and bowel. Inform patients about symptoms of fungal infection (vaginal or anal itching; inflammatory lesions of the anogenital region; black, furry appearance of the tongue), and advise them to notify the prescriber if these occur. Superinfection caused by Candida can be managed by discontinuing the tetracycline or by giving an antifungal drug.

conjugation frequently confers

multiple drug resistance. This can be achieved, for example, by transferring DNA that codes for several different drug-metabolizing enzymes. Hence, in a single event, a drug-sensitive bacterium can become highly drug resistant.

Myasthenia Gravis.- Fluoroquinolones can exacerbate

muscle weakness in patients with myasthenia gravis and, hence, should not be used in patients with a history of the disorder.

Superinfection is a

new infection that develops during the course of treatment for a primary infection. For example, a patient is receiving antibiotics for a respiratory infection, but develops Clostridium difficile.

It is imperative that antibiotics

not be discontinued prematurely. Accordingly, patients should be instructed to take their medication for the entire prescribed course, even though symptoms may subside before the full course has been completed.

it is the microbe that becomes drug resistant

not the patient.

Assess the patient with regard to medications during

nursing history and continue the assessment during and after medication administration.

Assessment of the patient receiving medications begins with what

nursing history.

The etiology of the problem directs what

nursing interventions

Drugs that inhibit PGP will have

opposite effects.

Routes-Eight cephalosporins are given only

parenterally (IM or IV), nine are given only orally, and one—cefuroxime—is given orally and parenterally.

Erythromycin has an antimicrobial spectrum similar to that of

penicillin G and, hence, can be used in place of penicillin G in patients with penicillin allergy.

The risk of ototoxicity is related primarily to

persistently elevated trough drug levels rather than to excessive peak levels.

Aminoglycosides Administration- When possible, adjust the dosage on the basis of

plasma drug levels. When using divided daily doses, draw blood samples for measuring peak levels 1 hour after IM injection and 30 minutes after completing an IV infusion. When using a single daily dose, measuring peak levels is unnecessary. Draw samples for trough levels just before the next dose (when using divided daily doses) or 1 hour before the next dose (when using a single daily dose).

Aminoglycosides are highly

polar polycations. As a result, they are not absorbed from the GI tract, do not cross the blood-brain barrier, and are excreted rapidly by the kidneys.

Identifying High-Risk Patients Tetracyclines are contraindicated in

pregnant women and in children younger than 8 years and should be avoided in women who are breastfeeding.

When drugs are combined with IV solution, what frequency happens

produces precipate

Although the use of multiple antibiotics is usually associated with

promoting drug resistance, there is one infectious disease—tuberculosis—in which drug combinations are employed for the specific purpose of suppressing the emergence of resistant bacteria.

For individuals who have had severe rheumatic endocarditis, lifelong

prophylaxis may be needed.

Aminoglycosides disrupt

protein synthesis and cause rapid bacterial death.

Aminoglycosides, like gentamicin, inhibit

protein synthesis in susceptible strains of gram-negative bacteria. These drugs are reserved for use in serious infections because of potentially serious adverse effects. Monitor for ototoxicity, renal toxicity, and peak and trough levels.

Spontaneous mutations produce

random changes in a microbe's DNA. The result is a gradual increase in resistance. Low-level resistance develops first. With additional mutations, resistance becomes greater. As a rule, spontaneous mutations confer resistance to only one drug.

superinfections are more likely in patients

receiving broad-spectrum agents. Because superinfections are caused by drug-resistant microbes, these infections are often difficult to treat.

Calcium and Ceftriaxone.-Combining calcium with ceftriaxone can form potentially fatal precipitates. To avoid harm, don't

reconstitute powdered ceftriaxone with calcium-containing diluents, and don't mix reconstituted ceftriaxone with calcium-containing solutions. In patients other than neonates, ceftriaxone and calcium-containing solutions may be administered sequentially, provided that the infusion line is flushed between infusions. Do not give IV ceftriaxone to neonates who are receiving IV calcium or to neonates who are expected to receive IV calcium.

Dosage Dosage for all fluoroquinolones, oral or IV, should be

reduced in patients with significant renal impairment.

Aminoglycosides Administration- In patients with renal impairment, the dosage should be

reduced or the dosing interval increased.

Tetracycline should not be given to patients with

renal failure.

Use all fluoroquinolones with caution in patients with

renal impairment and in patients age 60 and older, patients taking glucocorticoids, and patients who have undergone a heart, liver, or kidney transplantation.

Vancomycin- Identifying High-Risk Patients Exercise caution in patients with

renal impairment.

Sulfonamide Exercise caution in patients with

renal impairment. Sulfonamides may cause significant hemolysis if prescribed to patients with G6PD deficiency.

Ciprofloxacin is used to treat

respiratory, urinary tract, and GI infections, along with the preferred drug for preventing inhaled anthrax.

Aminoglycosides are antibiotic

s used primarily against aerobic gram-negative bacilli.

Treatment of fluoroquinolone

sensitive infections.

If the patient receives several drugs, offer them-

separately so that if one is refused or dropped, positive identification can be made and the drug can be recorded or replaced.

The combination product TMP/SMZ inhibits

sequential steps in bacterial folic acid synthesis and therefore is much more powerful than TMP or SMZ alone.

Vancomycin- Therapeutic Goal-Treatment of

serious infections, including CDI, infection with MRSA, and serious infections with susceptible organisms in patients allergic to penicillins.

Identifying High-Risk Patients- Penicillins should be used with extreme caution, if at all, in patients with a history of

severe allergic reactions to penicillins, cephalosporins, or carbapenems.

Adverse Effect- Phototoxicity Fluoroquinolones increase the risk of

severe sunburn, characterized by burning, erythema, exudation, vesicles, blistering, and edema. Advise patients to avoid sunlamps and to use a sunscreen and protective clothing when outdoors. Discontinue fluoroquinolones at the first sign of phototoxicity (e.g., burning sensation, redness, rash).

Antimicrobial prophylaxis is indicated following exposure to organisms responsible for

sexually transmitted diseases (e.g., syphilis, gonorrhea).

Dosage- Dosages for all cephalosporins—except ceftriaxone—should be reduced in patients with

significant renal impairment.

Tetracycline and demeclocycline must be used with great caution in patients with

significant renal impairment.

Milk-Protein Hypersensitivity. Cefditoren tablets contain

sodium caseinate, a milk protein. Do not give cefditoren to patients with milk-protein allergy. The drug is safe in patients with lactose intolerance.

Sodium Loading.-High IV doses of sodium penicillin G can produce

sodium overload. Exercise caution in patients under sodium restriction (e.g., cardiac patients, those with hypertension). Monitor electrolytes and cardiac status.

The principal adverse effects of TMP/SMZ are like those caused by

sulfonamides alone (i.e., hypersensitivity reactions, hemolytic anemia, kernicterus, and renal injury) and trimethoprim alone (hyperkalemia and birth defects).

Because they are broad-spectrum antibiotics, tetracyclines can cause

superinfections, especially C. difficile-associated diarrhea (CDAD) and overgrowth of the mouth, pharynx, vagina, or bowel with Candida albicans.

Prophylactic use of antimicrobial drugs includes

surgery, bacterial endocarditis, and neutropenia.

Omission of Surgical Drainage-Antibiotics may have limited efficacy in the presence of foreign material, necrotic tissue, or exudate. Hence, when appropriate

surgical drainage and cleansing should be performed to promote antimicrobial effects.

Instruct the patient to complete the prescribed course of treatment, even though

symptoms may abate before the full course is over.

Clindamycin Nursing considerations include

taking oral medication with a full glass of water on an empty stomach, one hour before, or two hours after meals. Children under 8 and pregnant women should not take tetracycline due to teeth staining. Patients taking tetracycline should not consume milk, calcium, iron, magnesium, or antacids products. Instruct patients to always complete full course of antibiotics, assess and teach signs and symptoms of adverse effects of severe diarrhea and superinfections, avoid sunlight, and risk of CDAD.

Tetracyclines can stain developing

teeth and therefore should not be given to pregnant women and breastfeeding women or children under 8 years old.

Children and pregnant women cannot take

tetracyclines. These drugs can cause superinfections, including C. difficile diarrhea (CDAD). Nursing education on administration and when to notify a health care provider is important.

.If a precipitate appears when drugs are mixed together what should happen to solution

that solution should be discarded.

Selective toxicity is defined as

the ability of a drug to injure a target cell or target organism without injuring other cells or organisms that are in intimate contact with the target.

Data that the nurse collect may lead to

the development of several nursing diagnoses related to medication administration.

Use of antibiotics promotes

the emergence of drug-resistant microbes. Please note, however, that although antibiotics promote drug resistance, they are not mutagenic and do not directly cause the genetic changes that underlie reduced drug sensitivity. Spontaneous mutation and conjugation are random events whose incidence is independent of drug use. Drugs simply make conditions favorable for overgrowth of microbes that have acquired mechanisms for resistance.

The more that antibiotics are used

the faster drug-resistant organisms will emerge. Not only do antibiotics promote the emergence of resistant pathogens, they also promote the overgrowth of normal flora that possesses mechanisms for resistance. Because drug use can increase resistance in normal flora and because normal flora can transfer resistance to pathogens, every effort should be made to avoid the use of antibiotics by individuals who do not actually need them (i.e., individuals who do not have a bacterial infection). Because all antibiotic use will further the emergence of resistance, there can be no excuse for casual or indiscriminate dispensing of these drugs.

the usual objective of antibiotic treatment is not outright kill of infecting organisms Rather

the goal is to suppress microbial growth to the point at which the balance is tipped in favor of the host.

Host defenses consist primarily of

the immune system and phagocytic cells (macrophages, neutrophils).

Aminoglycosides -Minimizing Adverse Interactions The trough serum level is

the lowest level between doses. It occurs just before administration of the next dose.

Although inhibition of drug metabolism can be beneficial, as a rule inhibition has undesirable results. That is, in most cases, when an inhibitor increases the level of another drug. What happens

the outcome is toxicity.

Improper Dosage-Like all other medications, antibiotics must be used in the right dosage. If the dosage is too low

the patient will be exposed to a risk of adverse effects without benefit of antibacterial effects. If the dosage is too high, the risks of superinfection and adverse effects become unnecessarily high.

Severe allergic reactions are more common with

the penicillins than with any other family of drugs. As a rule, patients with a history of severe allergy to the penicillins should not receive them again. The exception is treatment of a life-threatening infection for which no suitable alternative is available. In addition to the penicillins, other antibiotics (sulfonamides, trimethoprim, erythromycin) are associated with a high incidence of allergic responses. However, severe reactions to these agents are rare.

To prevent inhibition, when it is necessary to prescribe both an isoenzyme inhibitor along with a drug metabolized by the same isoenzymes (i.e., the substrate). What happens

the provider will prescribe the substrate at a lower dose. Still, because individual responses vary, a nurse should be alert for possible adverse effects. Unfortunately, because the number of possible interactions of this type is large, keeping track is a challenge. The safest practice is to check for drug interactions in one of the reliable software applications that are widely available.

To be effective, an antibiotic must be present at

the site of infection in a concentration greater than the MIC

If drug A inhibits the metabolism of drug B what happens?

then levels of drug B will rise. The result may be beneficial or harmful. The interaction of cobicistat (a strong CYP3A4 inhibitor) with atazanavir (an expensive drug used to treat HIV infection) provides an interesting case in point. Because cobicistat inhibits CYP3A4 (the CYP isoenzyme that metabolizes atazanavir), if cobicistat is combined with atazanavir, the plasma level of atazanavir will rise. Thus inhibition of CYP3A4 allows us to achieve therapeutic drug levels at lower doses, thereby greatly reducing the cost of treatment—a clearly beneficial result.

If drug A and drug B are both toxic to the same organ

then taking them together will cause more injury than if they were not combined.

Ciprofloxacin and ofloxacin can increase

theophylline levels, thereby posing a risk of toxicity, including seizures. Monitor theophylline levels and reduce the dosage as indicated.

Erythromycin Adverse interaction-Erythromycin can increase the half-lives and plasma levels of several drugs. When erythromycin is combined with

theophylline, carbamazepine, or warfarin, patients should be monitored closely for toxicity.

Grapefruit juice can inhibit the metabolism of certain drugs

thereby raising their blood levels. The effect is sometimes quite remarkable. In one study, coadministration of grapefruit juice produced a 406% increase in blood levels of felodipine [Plendil], a calcium channel blocker used for hypertension. In addition to felodipine and other calcium channel blockers, grapefruit juice can increase blood levels of lovastatin [Mevacor], cyclosporine [Sandimmune], midazolam [Versed], and many other drugs (Table 6.2). This effect is not seen with other citrus juices, including orange juice.

Thrombophlebitis.-Intravenous cephalosporins may cause

thrombophlebitis. To minimize this reaction, rotate the injection site and inject cephalosporins slowly and in a dilute solution. Observe the patient for phlebitis, and change the infusion site if phlebitis develops.

narrow-spectrum drugs are generally preferred

to broad-spectrum drugs.

Various laboratory tests are used to monitor treatment. Serum drug levels may be monitored for two reasons

to ensure that levels are sufficient for antimicrobial effects and to avoid toxicity from excessive levels.

The risk of nephrotoxicity is related to the

total cumulative dose and elevated trough levels.

Drug-food interactions sometimes increase

toxicity. The most dramatic example is the interaction between monoamine oxidase (MAO) inhibitors (a family of antidepressants) and foods rich in tyramine (e.g., aged cheeses, yeast extracts, Chianti wine). If an MAO inhibitor is combined with these foods, blood pressure can rise to a life-threatening level. To avoid disaster, patients taking MAO inhibitors must be warned about the consequences of consuming tyramine-rich foods and must be given a list of foods to strictly avoid.

Antibiotics can be used in combination to

treat mixed infections, prevent resistance, decrease toxicity, and increased antibacterial action.

Preadministration aminoglycosides- Parenteral Therapy

treatment of serious infections caused by gram-negative aerobic bacilli. One aminoglycoside—gentamicin—is also used (in combination with vancomycin or a beta-lactam antibiotic) to treat serious infections caused by certain gram-positive cocci, namely Enterococcus species, some streptococci, and Staph. aureus.

For young women with recurrent urinary tract infection, prophylaxis with

trimethoprim/sulfamethoxazole may be helpful.

Fluoroquinolones, such as ciprofloxacin, inhibit

two bacterial enzymes needed for DNA replication and cell division, which provides the drug a broad-spectrum affect against most gram-negative and gram-positive bacteria.

Misuses of antibiotics include primarily use with

viral infections, treatment of fever of unknown origin or lack of bacterial diagnosis, and improper dosing.

Ciprofloxacin and ofloxacin can increase

warfarin levels, thereby posing a risk of bleeding. Monitor prothrombin time and reduce warfarin dosage as indicated.

Before sensitivity testing can be done

we must first identify the microbe so that we can test for sensitivity to the appropriate drugs.

The only situation in which fever, by itself, constitutes a legitimate indication for antibiotic use is

when fever occurs in the severely immunocompromised host. Because fever may indicate infection and because infection can be lethal to the immunocompromised patient, these patients should be given antibiotics when fever occurs—even if fever is the only indication that an infection may be present.

When should you Record medication administration

while or immediately after the patient takes the medication.

Ceftriaxone is contraindicated for neonates

who are receiving (or expected to receive) IV calcium.

Fluoroquinolones are contraindicated in patients

with a history of myasthenia gravis.

Neutropenia-Severe neutropenia puts individuals at high risk of infection. There is some evidence that the incidence of bacterial infection may be reduced through antibiotic prophylaxis. However, prophylaxis may increase the risk of infection

with fungi: By killing normal flora, whose presence helps suppress fungal growth, antibiotics can encourage fungal invasion.

Erythromycin administration Inform patients using erythromycin ethylsuccinate and enteric-coated formulations of erythromycin base that they may take these drugs

without regard to meals.

Should you Remain with the patient and make sure that the medication is taken

yes