NURS 323 PHARM Quiz 2 Study Guide Complete & Graded A

NURS 323 PHARM Quiz 2 Study Guide Chapters reviewed: 48, 49, 52, 53, 54, 56, 57, 58, 64, 65, 66, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 87, 88, 89, Antibiotics Review terminology: - 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. As applied to antimicrobial drugs, selective toxicity indicates the ability of an antibiotic to kill or suppress microbial pathogens without causing injury to the host. Selective toxicity is the property that makes antibiotics valuable. pp651 (in other words, if antibiotics were as harmful to the host as they are to infecting organisms- these drugs would have no therapeutic utility. 3 examples of how to achieve selective toxicity these include: 1. Disruption of the Bacterial Cell Wall • Unlike mammalian cells, bacteria are encased in a rigid cell wall. The protoplasm within this wall has a high concentration of solutes, making osmotic pressure within the bacterium high. Several families of drugs such as penicillins and cephalosporins weaken the cell wall and, hence, promote bacterial lysis. Because mammalian cells have no cell wall, drugs directed at this structure do not affect humans. 2. Inhibition of an Enzyme Unique to Bacteria • The sulfonamides represent antibiotics that are selectively toxic because they inhibit an enzyme critical to bacterial survival but not to our survival. Specifically, sulfonamides inhibit an enzyme needed to make folic acid, a compound required by all cells, both mammalian and bacterial. Because we can use folic acid from dietary sources, sulfonamides are safe for human consumption. In contrast, bacteria must synthesize folic acid themselves, because unlike us, they cannot take folic acid from the environment hence, in order to meet their needs, bacteria first take up para-aminobenzoic acid (PABA), a precursor of folic acid and then convert the PABA into folic acid. Sulfonamides block this conversion. Because mammalian cells do not make their own folic acid, sulfonamide toxicity is limited to microbes. 3. Disruption of Bacterial Protein Synthesis • In bacteria, as in mammalian cells, protein synthesis is completed by ribosomes. However, bacterial and mammalian ribosomes are not identical, and hence we can make drugs that disrupt function of one but not the other. As a result, we can impair protein synthesis in bacteria while leaving mammalian proteins synthesis untouched. - culture and sensitivity test pp. 658 o The quickest, simplest and most versatile technique for identifying microorganisms is microscopic examination of Gram-stained preparation- this can be obtained by obtaining samples for examination such as exudate, sputum, urine, blood, and other bodily fluids. o Another new method known as Polymerase chain reaction (PCR) test or nucleic acid amplification test, can detect very low titers of bacteria and viruses. Testing is done by using an enzyme—either DNA polymerase or RNA polymerase. Microbes that can be identified with a PCR test include: C. Difficile, S. aureus, mycobacterium tuberculosis, neissseria gonorrhoeae, chlamydia trachomatis, and helicobacter pylori, and important viral pathogens such as: HIV (human immunodeficiency virus). Compared with Gram-staining, PCR test are both more specific and more sensitive. - mechanisms of resistance o bacterial resistance to antibiotics, which may be innate (natural and inborn) or acquired over time. As a rule, antibiotics resistance is associated with extended hospitalization, significant morbidity, and excess mortality. Organisms for which drug resistance is currently a serious problem include Enterococcid faecium, Staphylococcis aureus, Enterobacter species, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiealla species, and Clostridiodies difficile (C. difficile). o Microbes have four basic mechanisms for resisting drugs. • They can DECREASE the concentration of a drug at its site of action. • ALTER the structure of drug target molecules • PRODUCE a DRUG ANTAGONIST • CAUSE DRUG INACTIVATION o Spontaneous Mutation 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. o 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. o one that codes for the mechanisms of drug resistance o and one that codes for the “sexual” apparatus required fir DNA transfer. Together these two DNA segments constitute an R factor (resistance factor). o In contrast to spontaneous mutation, 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. o 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 will, hence, facilitate survival of the microbe that is drug resistant. In addition, 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. o Which antibiotics promote more resistance? ▪ All antimicrobial drugs promote the emergence of drug-resistant organisms. However, some agents are more likely to promote resistance than others. Because BROAD-SPECTRUM antibiotics kill more competing organisms than do Narrow-spectrum drugs, BROAD-SPECTRUM agents do the most to facilitate emergence of resistance. - CYP3A4 pp. 457-459 CYP3A4 are reversible inhibitors and are competitive inhibitors. These are enzymes that can be both reversible and irreversible. Don’t consume Grapefruit! Inhibitors of CYP3A4 such as Ketoconazole, itraconazole, erythromycin, cimetidine, saquinavir, ritonavir, grapefruit juice can SUPPRESS the metabolism of SILDENAFIL, thereby increasing its level. These combinations should be used with caution. It is metabolized in the liver. This the most common metabolic enzyme involced in drug interactions. Metabolizes approx. 50% of drugs o Tadalafil – Is CONTRAINDICATED FOR USE WITH NITRATES IR a blockers (Except tamsulosin [Flomax]). As with sildenafil and vardenafil, CYP3A4 Inhibitors can cause levels of tadalafil to rise. To avoid toxicity, men taking CYP3A4 inhibitors, should limit tadalafil dosage to 10mg every 72 hours. - CYP450 o Group of enzymes that are metabolized in the liver, but also located in the lungs, intestines, and kidneys. - disulfiram-like effect pp. 670—is very dangerous and is brought on by accumulation of acetaldehyde secondary to inhibition of aldehyde dehydrogenase. CEFAZOLIN & CEFOTETAN can induce a state of alcohol intolerance. Patients using these cephalosporins MUST NOT CONSUME ALCOHOL IN ANY FORM WHILE TAKING THESE MEDICATIONS. - Note—Cefotetan, cefazolin, and ceftriaxone—can promote bleeding!! Therefore, caution is needed when if these drugs are combined with other agents that promote bleeding such as anticoagulants, thrombolytics, nonsteroidal anti-inflammatory drugs NSAIDs, and other antiplatelet agents. - Superinfection – is defined as a new infection that appears during the course of treatment for a primary infection. An example of a superinfection is new infections develop when antibiotics eliminate the inhibitory influence of normal flora, thereby allowing a second infectious agent to flourish. A common example of superinfection is the development of a vaginal Candida infection in a female treated with a broad-spectrum antibiotic for a urinary tract infection. Because broad-spectrum antibiotics kill more normal flora than do narrow-spectrum drugs, superinfections are more likely in patients who are receiving broad-spectrum agents. pp. 655 - cross-sensitivity- pp. sensitivity to one substance that renders as individual sensitive to other substances of similar chemical structure. Cross sensitivity has been reported commonly among various B lactam antibiotics and sulfonamides. Ex. Patientrs allergic to one penicillin should be considered allergic to all other penicillins. - cross-resistance—antibioric resistance is associated with extended hospitalization, significant morbidity, and excess mortality. Remember that the microbe becomes drug resistant not the patient. It corresponds to resistance to all the antibiotics belonging to the same class due to a single mechanism. The more active the drug, the lower the level of resistance. Review labs: - WBC—4,500- to 11,000—having a low wbc count can be serious it increases the chances of developing a potentially life- threatening infection. High white blood count can indicate physical or emotional stress. People with particular blood cancers may also have high white blood cell count. - Neutrophil—1.5 to 8.0 High levels indicate infections most likely caused by a bacterial infection. Low counts of fewer than 500 microliters, normally lives in a person’s mouth, skin, and gut can cause serious infections. - Lymphocytes—1,000 to 4,800 in children is 3,000 to 9,500 (usually, high or low count can be a sign of disease) a low lymphocyte count means that your body is fighting infection. Infections can be caused by viruses, fungi, parasites, or bacteria. Just like high lymphocyte count, blood levels indicate your body is dealing with an infection or other inflammatory condition. Most often, a temporarily HIGH lymphocyte count is normal effect of your body’s immune system working. Sometimes lymphocyte levels are elevated because of a serious condition like leukemia. - Basophil—0 to 3 (a low basophil count is called basopenia). It can be caused by infections, severe allergies, or an overactive thyroid gland. - Eosinophil—30 to 350 – when you have high levels is called a type of disease-fighting white blood cell. This condition most often indicates a parasitic infection, and allergic reaction or cancer. You can have high levels of eosinophils in your blood or in tissues at the site of an infection or inflammation. Review drugs (mechanism of action, indication, adverse effects, and which patients to avoid): o Penicillins • Mechanism of action: Penicillins weaken the cell wall, causing bacteria to take up excessive amounts of water and rupture. As a result, penicillins are generally bactericidal. Penecillins weaken the cell wall by two actions: 1. Inhibition of transpeptidases and 2. Disinhibition (activation) of autolysins, transpetidases are enzymes critical to cell wall synthesis. • Indication/therapeutic use: treatment of infections caused by sensitive bacteria. Samples for microscopic culture to identify the infecting organism. Monitor for indications of antimicrobial effects- reduction of fever, edema, pain, and inflammation. Renal impairment can cause penicillins to accumulate to toxic levels. Monitor function in patients with renal disease. • Adverse effects: pain at sites, seizures, confusion, and hallucinations. Inadervent intra-arterial injection, can produce severe reactions such as gangrene, necrosis, and sloughing of tissue. • Which patients to avoid: peniciilins should be used with extreme caution in patients with a history of severe allergic reactions to penicillins, cephalosporins, or carbapenems. For patients with prior allergic responses, a skin test may be ordered to assess current allergy status. Sodium penicillin G should be used with caution in patients who have sodium-restricted diets. • Penicillins are the most common cause of drug allergy. Patients who receive penicillins experience an allergic reaction. Severity can range from a minor rash to life-threatening anaphylaxis. Although prior exposure to penicillins is required for an allergic reaction, responses may have been exposed to penicillins produced by fungi or to penicillins present in foods of animal origin. Because of cross sensitivity, patients allergic to one penicillin should be considered allergic to all other penicillins. In addition, a few patients display cross sensitivity to cephalosporins (Rosenthal & Burchum, 2021). If at all possible, patients with penicillin allergy should not be treated with any member of the penicillin family. The use of cephalosporins depends on the intensity of allergic response: if the penicillin allergy is mild, the use of cephalosporins is probably safe; however, if the allergy is severe, cephalosporins should be avoided (Rosenthal & Burchum, 2021). Individuals allergic to penicillin are encouraged to wear a medical identification bracelet to alert health care personnel to their condition. Penicillins 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 of drug administration; and delayed reactions occurs within days to weeks. Immediate and accelerated reactions are mediated by immunoglobin E (IgE) antibodies. Anaphylaxis is an immediate hypersensitivity reaction (Rosenthal & Burchum, 2021). o Cephalosporins (differences between generations) pp. 669 o Mechanism of action: Cephalosporins are B-lactam antibiotics similar in structure and actions to the penicillins. These drugs are bactericidal, often resistant to B-lactamases, and active against a broad spectrum of pathogens. Their toxicity is low. Cephalosporins are most effective against cells undergoing active growth and division. o First generation cephalosporins – are destroyed by B-lactamases o Second generation cephalosporins – Are less sensitive to destruction o Third, fourth, and fifth generation of cephalosporins – are highly resistant. Ceftaroline, a fifth-generation cephalosporin, has demonstrated activity against methicillin-resistant Staphylococcus aureus (MRSA). ▪ Absorption—because of poor absorption from the gastrointestinal (GI) tract, many cephalosporins are administered parenterally (by the intramuscular IM, or intravenous IV route). Only one can be administered orally and by injection Cefuroxime. o Indication: ▪ First generation: Gram positive like Staphylococci or streptococci- preferred use in patients with mild penicillin allergy, surgical prophylaxis, spectrum is narrow. ▪ Second generation: Gram positive and gram negative like Haemophilus influenzae, Klebsiella, pneumococci, and staphylococci- preferred used in patients who have otitis, sinusitis, and respiratory tract infections (these are broader than first and second generations. ▪ Third generation: Gram negative like Pseudomonas aeruginosa, Neisseria gonorrhoeae, and klebsiella, serratia. Preferred use in Meningitis ▪ Fourth generation: Gram negative like Pseudomonas aeruginosa preferred use in Hospital acquired pneumonia and complicated intra-abdominal and urinary tract infections ▪ Fifth generation: Gram Positive like METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS Preferred use in MRSA- associated infections. o Adverse effects: Serious adverse effects are rare. But if severe, immediate reactions such as bronchospasm and anaphylaxis. Cephalosporins are well tolerated and known as one of the safest groups of antimicrobial drugs. Hypersensitivity reactions are the most frequent adverse effects. Maculopapular rash that develops several days after onset of treatment is most common side effects. ▪ If during the course of treatment, signs of allergy appear such as urticaria, rash, hypotension, and difficulty breathing, the cephalosporin should be discontinued IMMEDIATELY. o Which patients to avoid: Patients with kidney disease as this drug is eliminated by the kidneys. Dosages of cephalosporins must be reduced. Ceftriaxone however- Is eliminated by the liver, therefore, dosage reduction is unnecessary in patients with renal impairment. o Patients with a history of cephalosporin allergy should NOT be given these drugs. Cephalosporins should NOT be given to patients with a history of severe reactions to penicillins. o Tetracyclines pp.676 o Mechanism of action: they are broad-spectrum antibiotics available for systemic therapy. These tetracyclines suppress bacterial growth by inhibiting protein synthesis. o Indication: all seven tetracycline are similar in structure, antimicrobial actions, and adverse effects. The only difference is pharmacokinetic. These include: tetracycline, demeclocycline, doxycycline, eravacycline, omadacycline, sarecycline, and minocycline. Disorders for which they are FIRST-line drugs include: Rickettsial diseases such as Rocky mountain spotted fever, typhus fever, Q fever, and infections caused by Chlamydia trachomatis (trachoma, lymphogranuloma venereum, urethritis, cervicitis, brucellosis, cholera, pneumonia caused by Mycoplasma pneumoniae, lyme disease, anthrax, and gastric infection with H. pylori. o Also, treatment of tetracycline is for people who have acne and periodontal disease. o Adverse effects: GI upset, effects on bonoes and teeth, superinfection, hepatoxicity, renal toxicity o Which patients to avoid: Tetracyclines should NOT be used in children under 8 years old, pregnant women should avoid d/t fetal harm. Breast feeding women should also avoid medication and older adults as tetracyclines can interact with drugs, including digoxin. Tetracyclines can increase digoxin levels, and increase INR levels by altering vitamin K- producing flora in the gut. o Advise patients to use sunscreen to exposed skin as these medications increases the sensitivity of the skin to ultraviolet light. o Tetracyclines should not be administered together with calcium supplements, milk products, iron supplememts, magnesium-contining laxatives, amd most antacids. o Tetracyclines – should be administered at least 1 hour before or 2 hours after ingestion of chelating agents. o Sulfamethoxazole: intermediate acting sulfonamide, usually used in combo with trimethoprim. Need proper hydration. o Sulfadiazine: short acting sulfonamide, need hydrate to prevent renal damage. o Topical sulfonamides: not used routinely because of high chance of hypersensitivity. Sulfacetamide used for conjunctivitis, corneal ulcer. Don’t use if allergic to sulfa. Silver sulfadiazine and mafenide used for 2nd-3rd degree burns. o Trimethoprim (TMP)/sulfamethoxazole (SMZ) o Mechanism of action: 80% of urinary tract pathogens are susceptible, resistance is low. Can be used for UTIs, otitis media, bronchitis, shigellosis, and pneumonia caused by P. jirovecci (watch out for AE), GI infections. Don’t use if pregnant or lactating. o Indication: o Adverse effects: stevens-johnson, blood dyscrasias (hemolytic anemia thrombocytopenia, etc.), kernicterus, renal damage, hyperkalemia, birth defects, megaloblastic anemia (those w folate deficiency)/, CNS effects, ppl w aids are susceptible to AE. Proper hydration is key, labs. o Which patients to avoid: avoid the meds as if taking alone, can intensify bone marrow suppression w pt taking methotrexate, hyperkalemia. o Sulfonamides pp.689 o Mechanism of action: they suppress bacterial growth by inhibiting the synthesis of tetrahydrofolate, a derivative of folate. In the absence of tetrahydrofolate, bacteria are unable to synthesize DNA, RNA, and proteins. o Indication: Principal indication for these drugs is the treatment of UTIs. The infections associated with UTIs are mainly due to Escherichia coli, a bacterium that is usually sulfonamide sensitive. Of the sulfonamides available, sulfamethoxazole (in combination with trimethoprim) is generally favored. o Adverse effects: hypersensitivity reactions such as rash, drug fever, and photosensitivity. The most severe hypersensitivity response is Stevens-johnson syndrome, a rare reaction with a mortality rate of about 25%. Symptoms include widespread lesions of the skin and mucous membranes combined with fever, malaise, and toxemia. To minimize the risk for severe reactions, sulfonamides should be discontinued immediately if skin rash of any sort is observed. Hematologic effects hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Red cell lysis can produce fever, pallor, and jaundice; patients should be observed for these signs. In addition, to hemolytic anemia, sulfonamides can cause agranulocytosis, leukopenia, thrombocytopenia, and very rarely, aplastic anemia. o Which patients to avoid: Patients who have a history of severe hypersensitivity to chemically related drugs. Infants younger than 2 months should not be given medication d/t to Kernicterus (a disorder in newborns caused by a desposition of bilirubin in the brain. Pregnant patients after 32 weeks gestations should not be given these medications and also mothers who are breastfeeding. o Drug to drug interactions: Sulfonamides can intensify the effects of warfarin, phenytoin, and sulfonylurea-type oral hypoglycemics such as glipizide and glyburide. o Clindamycin pp. 680 o Mechanism of action: They bind to the 50s subunit of bacterial ribosomes and thereby, inhibits protein synthesis. o Indication: Because of its efficacy against gram-positive cocci, clindamycin has been used widely as an alternative to penicillin. This drug does not cross the blood-brain barrier. Clindamycin is the FIRST-CHOICE severe group A streptococcal infection and for GAS GANGRENE (an infection caused by C. perfringens). o Adverse effects: CDAD (Clostridium difficile-associated diarrhea), formerly known as Antibiotic-associated pseudomembranous colitis, which is the most severe toxicity of clindamycin. The cause is superinfection of the bowel with C. Difficile. o Black box warning: Clindamycin can cause potentially fatal C. diff diarrhea; patients should promptly tell the providers of any diarrhea when taking this med. o Which patients to avoid: o Linezolid – has five approved indications: 1. infections caused by VRE, 2. Hospital-acquired pneumonia caused by S. aureus (methicillin-susceptible and methicillin-resistant strains) or S. pneumoniae (penicillin-susceptible strains only) 3. Community associated pneumonia (CAP) caused by S. Pneumoniae (penincillin-susceptible strains only). 4. Complicated skin and skin structure infections caused by S. aureus, streptococcus pyogenes, or streptococcus agalactiae. 5. Uncomplicated skin and skin structure infections caused bu S, aureus or S. pyogenes. o Adverse effects: Diarrhea, nausea, and headache, more Serious adverse effects are neuropathy and myelosuppression. o Patient to avoid this medication: patients who are diagnosed with Phenylketonuria. CBC should be done weekly, special attention is needed in patients who have preexisting condition of myelosuppression, those taking other myelosuppressive drugs and those receiving linezolid for more than 2 weeks. o Drug interactions: MAO (monoamine oxidase) posing a risk for hypertensive crisis. SSRIs can increase the risk of serotonin syndrome, patients using SSRIs such as paroxetine (Paxil, pexeva), Duloxetine (Cymbalta), should NOT take linezolid. o Tedizolid (Sivextro) – Has the same effects as Linezolid. Tedizolid was the second oxazolidinone antibiotic approved after linezolid. This drug is effective to treating MRSA as well as other bacterial skin and soft tissue infections caused by MRSA, methicillin-sensitive S. aureus (MSSA), S. pyogenes, S. agalactiae, Streptococcus anginosus group (including Streptococcus anginosus, streptococcus intermidius, and streptococcus constellatus), and E. fecalis. o Adverse effects: vomiting, diarrhea, nausea, dizziness, and headache. More serious adverse effects are neuropathy, and myelosuppression. o Fluoroquinolones pp. 711-712 o Mechanism of action: active against a broad spectrum of bacterial pathogens and may be administered by the oral or intravenous route. o Indication: Ciprofloxacin approved for a wide variety of infections such as the respiratrory tract, urinary tract, Gastrointestinal GI tract, bones, joints, skin, and soft issues. Also, Ciprofloxacin is the preferred drug for preventing anthrax in people who have inhaled anthrax spores. o Adverse effects: Tendon injury/ tendon rupture o Which patients to avoid: Patients younger than 18-year-olds, this prescription is not prescribed. This causea tendon injury. Tendon injury is reversible if diagnosed early, fluoroquinolones should be discontinued at the first sign of tendon pain, swelling, or inflammation. In addition, patients should refrain from exercise until tendinitis has been ruled out. Also, patients with a history of myasthenia gravis should also NOT receive this drug. o Sulfasalazine pp. o Mechanism of action: o Indication: used to treat inflammatory bowel disease, RA. o Adverse effects: GI reactions but enteric coat help, dermatologic reactions (rash, SJS and toxic epidermal necrolysis but rare), hepatitis/bone marrow suppression but rare. Do CBC, platelet count. o Which patients to avoid: those with sulfa allergy. o Macrolides pp. 678 o Mechanism of action: Broad-spectrum antibiotics that inhibit bacterial protein synthesis. They are called macrolides because they are big. Erythromycin is the oldest member of the family. The new macrolides (azithromycin and clarithromycin) are derivatives of erythromycin. o Indication: first-choice treatment for Corynebacterium diphtheriae and may be used as an alternative to penicillin G in patients with penicillin allergy. Accordinlgly, erythromycin is the treatment of choice for ACUTE DIPHTHERIA and for eliminating the diphtheria state. Several infections respond EQUALLY well to macrolides and tetracyclines. Both are drugs of first choice for certain chlamydial infections such as urethritis, cervicitis, and for pneumonia caused by Mycobacterium pneumoniae. o Adverse effects: epigastric pain, nausea, vomiting, and diarrhea. QT prolongation and sudden cardiac arrest therefore posing a risk for torsades de pointes, a potentially fatal ventricular dysrhythmia. When combined with CYP3A4 inhibitor, there is a fivefold risk for sudden cardiac death. o Which patients to avoid: pts should avoid this medication if they are currently taking calcium channel blockers such as verapamil, and diltiazem, azole antifungal drugs such as ketoconazole, itraconazole, CYP3A4 inhibitors, HIV protease inhibitors such as ritonavir, saquinavir, and nefazodone (antidepressant). o Metronidazole (Flagyl) pp. 713 o Mechanism of action: is used to treat protozoal infections and infections caused by obligate anaerobic bacteria. Note that Metronidazole is lethal to anaerobic organisms only. To exert bactericidal effects, metronidazole must first be taken up by cells and then converted into its active form; only anaerobes can perform the conversion. o Indication: infections of the CNS, abdominal organs, bones, and joints. Metronidazole is used for treatment of C. Difficile infection. In addition, this medication is also used for prophylaxis in surgical procedures associated with a high risk for infection by anaerobes such as colecteral surgery, abdominal surgery, gynecologic surgery. It is also used in combination with a tetracycline and bismuth subsalicylate to eradicate Helicobacter pylori in people with peptic ulcer disease. o Adverse effects: tendon rupture o Which patients to avoid: contraindicated in patients with a history of MS (Myathenia gravis). Renal impairment, and pts who are over 60 years old and patients taking glucocorticoids. o Daptomycin (Cubicin) pp. 713-714 o Mechanism of action: This drug inserts itself into the bacterial cell membrane and thereby forms channels that permit efflux of intracellular potassium (and possibly other cytoplasmic ions). Loss of intracellular ions has two effects. First, it depolarizes the cell membrane, second, it inhibits the synthesis of DNA, RNA, and proteins, thereby causing cell death. Daptomycin, is active only against gram-positive bacteria. The drug cannot penetrate the outer membrane of gram-negative bacteria and hence cannot harm them. Daptomycin is rapidly. Bactericidial to staphylococci (including methicillin-and vancomycin-resistant S. aureus and methicillin-resistant Staphylococcud epidermis), enterococci (including vancomycin-resistant Enterococcus faecium and Enterococcus faecalis), streptococci (including penicillin-resistant Streptococcus pneumoniae), and most other aerobic and anaerobic gram-positive bacteria. As a rule, daptamycin is more rapidly bactericidal than either vancomycin, linezolid, or quinupristin/dalfopristin. o Indication: it is good for two uses: 1. Blood stream infections including endocarditis with S. aureus and 2. Complicated skin and skin structure infections caused by susceptible strains if the following gram-positive bacteria: S. aureus (including methicillin-resistant strains), Streptococcus pyogenes, streptococcus agalactiae, streptococcus dysgalactiae subspecies equisimilis, and E. faecalis (Vancomycin-susceptible strains only). Daptomycin SHOULD NOT BE USED TO TREAT COMMUNITY- ACQUIRED PNEUMONIA (CAP). o Adverse effects: Constipation, nausea, diarrhea, injection-site reactions, headache, insomnia, and rash. Myoppathy (muscle injury), muscle pain and weakness in association with increased levels of creatinine phosphokinase (CPK)- A marker for muscle injury. o Which patients to avoid: people who are on HMG-CoA reductase inhibitors should suspend using them while daptomycin is being used. o Vancomycin pp. 673-674 o Mechanism of action: ▪ As in the case of the B-lactam antibiotics, vancomycin inhibits cell wall synthesis and therefore, promotes bacterial lysis and death. However, in contrast to the B-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. VANCOMYCIN is only active against GRAM-POSITIVE bacteria. The drug is especially active against S. aureus and Staphylococcus epidermidis, including strains of both species that are methicillin-resistant. Other susceptible organisms include streptococci, penicillin-resistant pneumococci, and C. difficile. ▪ Take samples for culture to determine the identity and sensitivity of the infecting organism. o Indication/therapeutic use: ▪ Principal indication is for C. Difficile (CDI), MRSA, and treatment for serious infections with susceptible organisms in patients allergic to penicillins. ▪ Vancomycin should be reserved for serious infections. This agent is the drug of choice for infections caused by MRSA OR S. EPIDERMIDIS. Most of strains of these bacteria are still sensitive to vancomycin. NOTE THAT VANCOMYCIN IS ALSO THE DRUG OF CHOICE FOR SEVERE CDI (C. Difficile), but not for MILD CDI. This drug is also employed as an alternative to penicillins and cephalosporins to treat severe infections like staphylococcal and streptococcal endocarditis in patients who are allergic to B-lactam antibiotics such as penicillin. ▪ Vancomycin DOES NOT CONTAIN A B-lactam ring. ▪ Oral administration is used ONLY for infections of the INTESTINE, MAINLY CDI (c. diff) ▪ Monitor for indications of antimicrobial effects, including reduction in fever, pain, edema, and inflammation. ▪ Vancomycin should be monitored during IV administration o Adverse effects: ▪ Renal toxicity ▪ To minimize risk, trough serum levels should be no greater than needed. If significant kidney damage develops, as indicated by 50% increase in serum creatinine level, vancomycin dosage should be reduced. ▪ RAPID INFUSION can cause red man syndrome, characterized by flushing, rash, pruritus, urticaria, tachycardia, and hypotension. o Which patients to avoid: ▪ Use with caution in patients who have renal impairment. o Telavancin: pp.675 o Is ONLY approved for IV therapy complicated skin and skin structure infections caused by susceptible strains of the following gram-positive organisms: S. aureus (including methicillin-sensitive and methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, and Enterococcus fecalis (but only vancomycin-sensitive strains). o Adverse effects: most common adverse effects are taste disturbance, nausea, vomiting, and foamy urine. Red man syndrome is associated by rapid infusion rate of administration. o Black box warning: ▪ When used to treat hospital-acquired or ventilator-associated bacterial pneumonia in patients with a creatinine clearance of less than 50 ml/min, has been associated with increased mortality compared with vancomycin. ▪ Telavancin can prolong the QT interval. Telavancin SHOULD NOT BE GIVEN TO PATIENTS HIGH RISK INCLUDING THOSE WITH CONGENITAL LONG-QT SYNDROME, Uncompensated heart failure, severe left ventricular hypertrophy and those that use other QT Drugs. o Aztreonam—Aztreonam (Azactam and Cayston) belongs to a class of B-lactam antibiotics known as monobactams. These agents contain a B-lactam ring, but the ring is not fused with a second ring. o Mechanisms of action: ▪ Aztreonam binds to PBP3; therefore, as with most B-Lactam antibiotics, the drug inhibits bacterial cell wall synthesis and thus, promotes cell lysis and death. The drug does not bind to PBPs produced by anaerobes or gram-positive bacteria. o Indication/therapeutic use: ▪ Aztreonam has a narrow antimicrobial spectrum, being active only against gram-negative aerobic bacteria. Susceptible organisms include Neissseria species, H. influenzae, P. aeruginosa, and Enterobacteriaceae such as E. coli, Klebsiella, Proteus, Serratia, Salmonella, and Shigella. Aztreonam is highly resistant to B-lactamase and therefore, is active against many gram-negative aerobes that produce them. The drug is NOT active against gram-positive bacteria and anaerobes. o Adverse effects: ▪ Most common effects are pain and thrombophlebitis at the site of injection. o Which patients to avoid: There is little cross-allergenicity with them, hence aztreonam appears to be safe for patients with allergies to other B-Lactam antibiotics. o Fosfomycin (Monurol)—is a unique antibiotic approved for single-dose therapy in women with uncomplicated urinary tract infection such as acute cystitis. Caused by E. Coli or E. faecalis. The drug kills bacteria by disrupting synthesis of the peptidoglycan polymer strands that compose the cell wall. o Adverse effects: o Common adverse effects include: diarrhea, headache, vaginitis, and nausea. It may also cause: abdominal pain, rhinitis, drowsiness, dizziness, and rash. o NOTE: Fosfomycin dosing may be done with or without food. Symptoms of cystitis should improve in 2 to 3 days. If symptoms fail to improve, additional doses will not help but will increase the risk of side effects. o Aminoglycosides pp. 683 o Mechanism of action: disrupt the bacterial protein synthsis. These drugs bind to the 30s ribosomal subunit, causisng 1. Inhibition of protein synthesis, 2. Premature termination of protein synthesis, and 3. Production of abnormal proteins secondary to misreading of the genetic code. The aminoglycosides are bactericidal. Cell kill is concentration dependent. Meaning the higher the concentration the more rapidly the infection will clear. o Indication: 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 Enterobacteriacea (e.g., Ecoli, Klebsiella and Serratia species, P. mirabilis). ▪ Topical therapy- treat infections of the eye and ears. Gentamicin and tobramycin can treat eye infections. Neomycin can treat infections of the eye and ear see chpt 87 & 89. o Adverse effects: serious toxicity to the inner ears (ototoxicity) and kidneys. Black box warning: neurotoxicity and ototoxicity in neurotoxicity may also include numbness, tingling, muscle twitching, and seizures. The first sign of impending cochlear damage is high-pitched tinnitus. Ototoxicity is largerly irreversible, if permanent injury is to be avoided, aminoglycosides should be withdrawn at the first sign of damage such as tinnitus, persistent headache, or both). o Which patients to avoid: Renal impairment as it can cause ototoxicity and more renal damage. o Gentamicin pp.686-687 o Indication: treats serious infections caused by aerobic gram-negative bacilli. Primary targets are P. aeruginosa and the Entero- bacteriaceae such as E. Coli, Klebsiella and serratia species, P. mirabilis o Adverse effects: kidneys and inner ears o Which patients to avoid: renal impairment, preexisting hearing impairment, and those receiving ototoxic and nephrotoxic drugs. o Tobramycin: is similar to Gentamycin with respect to uses, adverse effects, and interactions. This drug is more active than gentamicin against P. aeruginosa but LESS active against enterococci and Serratia species. See table 74.2 o Tobramycin is used for patients with Cystic Firosis. Tombramycin may also cause C. difficile associated diarrhea (CDAD). o Amikacin: has two outstanding features 1. It is active against the broadest spectrum of gram-negative bacilli 2. It is the least vulnerable to inactivation by bacterial enzymes. o In hospitals where resistance to gentamicin and tobramycin is common, amikacin is the preffered agent for intial treatment of infections caused by aerobic gram-negative bacilli. Review diseases (pathophysiology, signs and symptoms, complications, and first-line treatment): o Clostridium difficile/ C. difficile or CDI pp.673 o Pathophysiology: Gram-positive, spore forming, anaerobic bacillus that infects the bowel. Injury results from the release of two toxins: toxins A & B. o Signs/Symptoms: ab