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NSG124 Pharmacology Study Test Plan EXAM 2 Unit 2 Module 5 & 6 Antimicrobial Identify subcategories: 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. Some agents, called narrow-spectrum antibiotics, are active against only a few species of microorganisms. In contrast, broad-spectrum antibiotics are active against a wide variety of microbes. 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. Therapy with 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. In certain cases, a combination of two antibiotics may be less effective than one of the agents by itself, inducing antagonism between the drugs.
Location NSG124.05.01.01 Antimicrobial Basics Antibiotic and antimicrobial drug: the formal definitions of these words are not identical
Student Notes *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. *An 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.
NSG124.05.01.02 Antibiotic Dosing, Duration, & Rational for Combination Therapy: 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. 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.
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. 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. 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.
* Prophylactic use: 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). Misuses of antimicrobial: a) Use in the absence of appropriate surgical drainage. b) antimicrobial therapy administered without adequate bacteriologic information *Attempted Treatment of Viral Infection The majority of viral infections—including mumps, chickenpox, and the common cold—do not respond to currently available drugs. *Treatment of Fever of Unknown Origin Although fever can be a sign of infection, it can also signify other diseases, including hepatitis, arthritis, and cancer. Unless the cause of a fever is a proven infection, antibiotics should not be employed.
NSG124.05.01.03 *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. *Treatment in the Absence of Adequate Bacteriologic Information As stressed earlier, proper antimicrobial therapy requires information on the identity and drug sensitivity of the infecting organism. *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.
Monitoring antimicrobial *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). * 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 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).
Introduction to Penicillins NSG124.05.02.01 Broad vs Narrow: The most useful classification of penicillins is based on an antimicrobial spectrum. When classified this way, the penicillins fall into four major groups: (1) narrow-spectrum penicillins that are penicillinase sensitive, (2) narrow-spectrum penicillins that are penicillinase resistant (antistaphylococcal penicillins), (3) broad-spectrum penicillins (aminopenicillins), and (4) extended-spectrum penicillins (antipseudomonal penicillins). Penicillin Action, Use, & Resistance Penicillins weaken the cell wall, causing bacteria to take up excessive amounts of water and rupture. As a result, penicillins are generally bactericidal. However, it is important to note that penicillins are active only against bacteria that are undergoing growth and division.
Penicillins weaken the cell wall by two actions: (1) inhibition of transpeptidases and (2) disinhibition (activation) of autolysins. **Penicillin Class: Narrow-spectrum penicillins: penicillinase sensitive: Drug: Penicillin G, Penicillin V Clinically Useful Antimicrobial Spectrum: treptococcus species, Neisseria species, many anaerobes, spirochetes, others **Penicillin Class: Narrow-spectrum penicillins: penicillinase resistant (antistaphylococcal penicillins) Drug: Nafcillin, Oxacillin, Dicloxacillin Clinically Useful Antimicrobial Spectrum: Staphylococcus aureus.
**Penicillin Class: Broad-spectrum penicillins (aminopenicillins) Drug: Ampicillin, Amoxicillin. Clinically Useful Antimicrobial Spectrum: Haemophilus influenzae, Escherichia coli, Proteus mirabilis, enterococci, Neisseria gonorrhoeae **Penicillin Class: Extended-spectrum penicillin (antipseudomonal penicillin) Drug: Piperacillin. Clinically Useful Antimicrobial Spectrum: Same as broadspectrum penicillins plus Pseudomonas aeruginosa, Enterobacter species, Proteus (indole positive), Bacteroides fragilis, many Klebsiella
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Side Effects and Toxicities: NSG124.05.02.02 x2 Severe: Inadvertent intra-arterial injection can produce severe reactions—gangrene, necrosis, sloughing of tissue—and must be avoided. Mild: If the penicillin allergy is mild, the use of cephalosporins is probably safe. Drug to Drug Interaction: Aminoglycosides. For some infections, penicillins are used in combination with an aminoglycoside (e.g., gentamicin). By weakening the cell wall, the penicillin facilitates access of the aminoglycoside to its intracellular site of action, thereby increasing bactericidal effects. Unfortunately, when penicillins are present in high concentrations, they interact chemically with aminoglycosides and thereby inactivate the aminoglycoside. Accordingly, penicillins and aminoglycosides should never be mixed in the same IV solution. Rather, they should be administered separately. Once a penicillin has been diluted in body fluids, the potential for inactivating the aminoglycoside is minimal.
Penicillin Action, Effect, Toxicity, Allergy, & Interactions Penicillin G is the least toxic of all antibiotics and among the safest of all medications. Other reactions include pain at sites of IM injection, prolonged (but reversible) sensory and motor dysfunction following accidental injection into a peripheral nerve, and neurotoxicity (seizures, confusion, hallucinations) if blood levels are too high. Inadvertent intra-arterial injection can produce severe reactions—gangrene, necrosis, sloughing of tissue—and must be avoided.
Penicillin reactions are classified as immediate, accelerated, and delayed. Immediate reactions occur 2 to 30 minutes after drug administration; accelerated reactions occur within 1 to 72 hours; delayed reactions occur within days to weeks. Immediate and accelerated reactions are mediated by immunoglobulin E (IgE) antibodies.
Nursing Considerations Related to Penicillin NSG124.05.02.03 Key points: Penicillin is bactericidal. *Advise patients with penicillin allergy to wear some form of identification (e.g., Medic Alert bracelet) to alert emergency healthcare personnel. *Instruct outpatients to report any signs of an allergic response (e.g., skin rash, itching, hives). Summary: Penicillin agents are bactericidal and are beta-lactam antibiotics. Many are resistant, and many patients are allergic. Broad spectrum, extended spectrum, and penicillins combined with a beta-lactamase inhibitor formation increase therapeutic action of penicillins and decrease resistance. Renal function must be closely monitored while patients receive penicillin and should not be combined with aminoglycosides. Review 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. Hyperkalemia: High doses of IV potassium penicillin G may cause hyperkalemia, possibly resulting in dysrhythmias or cardiac arrest. Monitor electrolyte and cardiac status. Effects Resulting from Incorrect Injection: Take care to avoid intraarterial injection or injection into peripheral nerves because serious injury can result. Minimizing Adverse Interactions: Aminoglycosides: When present in high concentration, penicillins can inactivate aminoglycosides (e.g., gentamicin). Do not mix penicillins and aminoglycosides in the same IV solution.
Penicillins
Preadministration Assessment Therapeutic Goal Treatment of infections caused by sensitive bacteria. Baseline Data The prescriber may order tests to identify the infecting organism and its drug sensitivity. Take samples for microbiologic culture before starting treatment. In patients with a history of penicillin allergy, a skin test may be performed to determine current allergic status. 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. Routes Penicillins are administered orally, IM, and IV. Before giving a penicillin, make sure the preparation is appropriate for the intended route. Dosage Doses for penicillin G are prescribed in units (1 unit equals 0.6 mg). Doses for all other penicillins are prescribed in milligrams or grams. Administration During IM injection, aspirate to avoid injection into an artery. Take care to avoid injection into a nerve.
Cephalosporin, Carbapenems, Vancomycin **The cephalosporins, carbapenems, and vancomycin are also antibacterial agents which inhibit the cell wall synthesis of bacteria, and by disrupting the cell wall, they cause bacterial lysis and death. **Cephalosporins and carbapenems are both beta-lactam antibiotics like penicillin. **Carbapenems are beta-lactam antibiotics that have very broad antimicrobial spectra— although none is active against MRSA. Four carbapenems are available: imipenem, meropenem, ertapenem, and doripenem. With all four, administration is parenteral. To delay emergence of resistance, these drugs should be reserved for patients who cannot be treated with a more narrow-spectrum agent.
Therapeutic Uses: The cephalosporins are broad-spectrum bactericidal drugs with a high therapeutic index. Cephalosporins can be useful alternatives for patients with mild penicillin allergy. Adverse Reactions: **Cephalosporins may cause pain at sites of IM injection; patients should be forewarned. Rarely, cephalosporins may be the cause of pseudomembranous colitis due to colonic overgrowth with Clostridium difficile. If this superinfection develops, the cephalosporin should be discontinued and, if necessary, oral vancomycin should be given. **Practically all cephalosporins are eliminated by the kidneys; excretion is by a combination of glomerular filtration and active tubular secretion. One cephalosporin—ceftriaxone—is eliminated largely by the liver. Consequently, dosage reduction is unnecessary in patients with renal impairment. ** Two cephalosporins—cefotetan and ceftriaxone—can cause bleeding tendencies. The mechanism is reduction of prothrombin levels through interference with vitamin K metabolism.
Amoxicillin Amoxicillin/clavulanate Ampicillin Ampicillin/sulbactam Dicloxacillin Nafcillin Oxacillin Penicillin G Penicillin V Piperacillin Piperacillin/tazobactam
Except where indicated otherwise, the implications here apply to all members of the penicillin family. 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. Instruct the patient to complete the prescribed course of treatment, even though symptoms may abate before the full course is over.
**Vancomycin [Vancocin] is the most widely used antibiotic in U.S. hospitals. Principal indications are C. difficile infection (CDI), MRSA infection, and the treatment of serious infections with susceptible organisms in patients allergic to penicillins. The major toxicity is renal failure. **Unlike most other drugs discussed here, vancomycin does not contain a beta-lactam ring. **Like the beta-lactam antibiotics, vancomycin inhibits cell wall synthesis and thereby promotes bacterial lysis and death. However, in contrast to the beta-lactams, vancomycin does not interact with PBPs. Instead, it disrupts the cell wall by binding to molecules that serve as precursors for cell wall biosynthesis. **Absorption from the GI tract is poor. Hence, for most infections, vancomycin is given parenterally (by slow IV infusion). Oral administration is employed only for infections of the intestine, mainly CDI.
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Summary of Major Nursing Implications: NSG124.05.03.02 (x3) Pre-administration: The prescriber may order tests to determine the identity and drug sensitivity of the infecting organism. Take samples for culture before initiating treatment. Implementation: administration: Advise patients to take oral cephalosporins with food if gastric upset occurs. Instruct patients to refrigerate oral suspensions. Ongoing evaluations and interventions: Monitor for indications of antimicrobial effects (e.g., reduction in fever, pain, or inflammation; improved appetite or sense of well-being).
Nursing Considerations for Cephalosporin, Carbapenems, Vancomycin *Monitor for indications of antimicrobial effects (e.g., reduction in fever, pain, or inflammation; improved appetite or sense of well-being). report any signs of allergy (e.g., skin rash, itching, hives) *Two cephalosporins— cefotetan and ceftriaxone—can promote bleeding. Monitor prothrombin time, bleeding time, or both. Parenteral vitamin K can correct abnormal prothrombin time.
Cephalosporins are contraindicated for patients with a history of allergic reactions to cephalosporins or of severe allergic reactions to penicillins. Ceftriaxone is contraindicated for neonates who are receiving (or expected to receive) IV calcium. 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.
Therapeutic Uses NSG124.05.04.01 Adverse effects: Tetracyclines irritate the GI tract. As a result, oral therapy is frequently associated with epigastric burning, cramps, nausea, vomiting, and diarrhea. These reactions can be reduced by giving tetracyclines with meals—although food may decrease absorption. Therapeutic effects: Disorders for which they are first-line drugs include (1) rickettsial diseases (e.g., Rocky Mountain spotted fever, typhus fever, Q fever); (2) infections caused by Chlamydia trachomatis (trachoma, lymphogranuloma venereum, urethritis, cervicitis); (3) brucellosis; (4) cholera; (5) pneumonia caused by Mycoplasma pneumoniae; (6) Lyme disease; (7) anthrax; and (8) gastric infection with H. pylori. Patient education: Advise patients to avoid prolonged exposure to sunlight, wear protective clothing, and apply sunscreen to exposed skin. Notify the prescriber if diarrhea occurs. Can cause discoloration of deciduous and permanent teeth. Tetracyclines are used topically and orally for severe acne vulgaris. Beneficial effects derive from suppressing the growth and metabolic activity of Propionibacterium acnes, an organism that secretes inflammatory chemicals. Tetracyclines are eliminated by the kidneys and liver. All tetracyclines are excreted by the liver into the bile. After the bile enters the intestine, most tetracyclines are reabsorbed.
Tetracycline, Macrolide, and Clindamycin The macrolides are broad-spectrum antibiotics that inhibit bacterial protein synthesis. They are called macrolides because they are big. Erythromycin is the oldest member of the family. Clindamycin: Hypersensitivity rash is common. Clostridium difficile associated diarrhea (CDAD) is a toxic adverse effect. Inhibits protein synthesis and treats anaerobic infections outside the CNS. Tetracyclines: Do not administer to children under 8 years of age, pregnant or lactating women. Broad-spectrum antibiotic that suppresses bacterial growth by inhibiting protein synthesis. Administer 1 hour before or 2 hours after ingesting of milk products; iron, calcium, magnesium supplements or antacids.
Clindamycin [Cleocin, Dalacin C] can promote severe CDAD, a condition that can be fatal. Clindamycin is active against most anaerobic bacteria (gram positive and gram negative) and most gram-positive aerobes. Gram-negative aerobes are generally resistant. Because of its efficacy against gram-positive cocci, clindamycin has been used widely as an alternative to penicillin. C. difficile–associated diarrhea (CDAD), formerly known as antibioticassociated pseudomembranous colitis, is the most severe toxicity of clindamycin. The cause is superinfection of the bowel with C. difficile, an anaerobic gram-positive bacillus. Patients should promptly report any diarrhea to their healthcare provider. Other Adverse Effects. Diarrhea (unrelated to CDAD) is relatively common. Hypersensitivity reactions (especially rashes) occur frequently. Hepatotoxicity and blood dyscrasias (agranulocytosis, leukopenia, thrombocytopenia) develop rarely.
Therapeutic use: The principal use for parenteral aminoglycosides is treatment of serious infections due to aerobic gram-negative bacilli. Primary target organisms are P. aeruginosa and the Enterobacteriaceae (e.g., E. coli, Klebsiella, Serratia, P. mirabilis). One aminoglycoside—gentamicin—is now commonly used in combination with either vancomycin or a beta-lactam antibiotic to treat serious infections with certain gram-positive cocci, specifically Enterococcus species, some streptococci, and Staphylococcus aureus. The aminoglycosides used most commonly for parenteral therapy are gentamicin, tobramycin, and amikacin. Adverse effects: The aminoglycosides can produce serious toxicity, especially to the inner ears and kidneys. The inner ears and kidneys are vulnerable because aminoglycosides become concentrated within cells of these structures. Ototoxicity; Nephrotoxicity;
NSG124.05.05.01 Aminoglycoside Pharmacology are a group of natural and semisynthetic antibiotics, which are classified as bactericidal drugs, are very potent and capable of potentially serious toxicities. The drugs are used primarily against aerobic gram-negative bacilli. They disrupt the protein synthesis of bacteria and cause rapid bacterial death. However, due to the toxicity risks for inner ears and kidney, their use is limited. The drugs must be administered intravenously (parenterally) because they are not absorbed by the GI tract.
Patients on aminoglycoside therapy should be monitored for ototoxicity. The first sign of impending cochlear damage is high-pitched tinnitus (ringing in the ears). Ototoxicity is largely irreversible. Accordingly, if permanent injury is to be avoided, aminoglycosides should be withdrawn at the first sign of damage (i.e., tinnitus, persistent headache, or both).
Summary of Nursing Implications NSG124.05.05.02 Preadministration assessment: 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. 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. Implementation: Administration: Aminoglycosides must be given parenterally (IV, IM) to treat systemic infections. Intravenous infusions
Nursing Considerations Aminoglycoside Ongoing Evaluation and Interventions * Monitoring Summary Monitor aminoglycoside levels (peaks and troughs), inner ear function (hearing and balance), and kidney function (creatinine clearance, BUN, and urine output). * Aminoglycosides can damage the inner ears, causing irreversible impairment of hearing and balance. Monitor for ototoxicity, using audiometry in high-risk patients. Instruct
Intramuscular and Intravenous: Gentamicin, tobramycin, amikacin, kanamycin. Oral: Neomycin, paromomycin. Topical: Gentamicin, neomycin, tobramycin. 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.