Objective 4.2 Part 1 Antimicrobials EDITED 2024 Student PDF

Antimicrobial Agents PHARMACOLOGY PN 1290 WINTER 2024 OBJECTIVE 4.2 Learner Objectives 4.2.1 Describe the purpose of commonly used antimicrobial agents. 4.2.2 Discuss the therapeutic and adverse effects of commonly used antimicrobial agents. 4.2.3 Discuss examples of commonly used antimicrobial agen...

Antimicrobial Agents PHARMACOLOGY PN 1290 WINTER 2024 OBJECTIVE 4.2 Learner Objectives 4.2.1 Describe the purpose of commonly used antimicrobial agents. 4.2.2 Discuss the therapeutic and adverse effects of commonly used antimicrobial agents. 4.2.3 Discuss examples of commonly used antimicrobial agents. 4.2.4 Describe the monitoring of therapeutic levels of antimicrobials. 4.2.5 Discuss common drug interactions related to antimicrobial agents. 4.2.6 Discuss nursing interventions when administering these medications across the lifespan. Microorganisms are everywhere, both on the external environment of our bodies and on the internal environment of our bodies Microorganisms may be helpful or harmful to people Microbial Infection The healthy person is able to resist infectious microbes because of physical barriers (skin, cilia of the resp. system) and physiological barriers (gastric acid, antibodies) Every major class of microbes contains organisms that can infect people – bacteria, viruses, fungi, and protozoa Antimicrobial Agents Aka anti-infective agents Prescription required One of the most commonly prescribed meds Classified according to the type of pathogen they are attacking antibiotics, antifungals, antiparasitics and antivirals What is it? A chemical that will help get rid of living microorganisms that are pathogenic to the client. Microbial Infection A person will require an antiinfective when a pathogen is present Prior to prescribing, the physician will have to determine what microorganism or pathogen is present Bacteria are a large domain of single-celled, prokaryotic micro-organisms; come in a wide range of shapes and characteristics; requires further testing to determine appropriate treatment Fungi (or Fungus-singular) are a member of a large group of eukaryotic organisms which include yeast and molds; live and feed on other organisms A Virus is a small infectious agent that can replicate only inside the living cells of organisms Parasites are organisms, protozoa or worms that live on or in another organism; lives off that organism as well Bacteria Bacteria are classified based on the following; Shape Coccus (circular/spherical) Bacillus (Rod shape) Spirillum (spiral) Grouping Diplo (pair) Strept (chain) Staphyl (cluster) O2 requirements Aerobes (require O2 for life) Anaerobes (do not require O2 for life) Gram staining Gram pos or gram neg (Next slide) Response to antibiotics/antibacterials Bacteria Another important classification of bacteria is “gram positive” or “gram negative” Classed through gram stain procedure. Gram + organisms stain purple, Gram – organisms stain red Very useful in guiding choice of therapy used Gram + organisms have a thick cell wall & thick outer layer Gram – organisms have a cell wall structure that is more complex – a smaller outer capsule, a peptidoglycan layer and two cell membranes (inner & outer) These differences typically make Gram – infections harder to treat Bacterial Infections When normal host defences are compromised, a person becomes susceptible to infection Once the microorganisms enter the body, multiply and overwhelm the hosts defence system, clinical infection is visible Classic S/S of infection: fever, chills, sweating, redness, pain, swelling, fatigue, increased WBC, & formation of pus Not all will exhibit S/S of infection (older people/immunocompromised) To help the body combat infection, antibiotic therapy is often required Antibiotics are most effective when combined with natural host defences Health Care-Associated Infections Community-acquired infection Infection acquired by a person who has not recently (past year) been hospitalized or had a medical procedure Health care-associated infection (Nosocomial infection) Infection a patient acquires during the course of receiving treatment for another condition in a health care facility (Occurs at least 48 hours after admission) One of top 10 causes of death in Canada Tend to be more difficult to treat & resistant to traditional therapies Most commonly acquired through direct contact (IV equipment, catheters, dialysis equipment, etc.) Over 70% are preventable Handwashing is most important activity Use of disinfectants (bactericidal) and antiseptics (bacteriostatic) are also useful Empiric Therapy: Selection of an antibiotic that can best kill microorganisms known to be the most common causes of infection Principles of Antibiotic Therapy Prior to initiating treatment, a specimen should be collected for C&S (Culture & Sensitivity) C&S will identify the causative organism and determine what therapies work best to fight it (takes 48-72 hours) Definitive Therapy: AKA Targeted therapy. Antibiotic therapy is tailored to treat the identified organism by using the most narrow spectrum & least toxic drug based on C&S results Prophylactic Therapy: Antibiotics used to prevent infection (i.e. prior to surgery) Patients should be monitored for therapeutic efficacy and adverse effects A therapeutic response to therapy includes a decrease in S/S of infection compared to baseline findings Antibiotic Therapy A Subtherapeutic response occurs when the S/S do not improve. Adverse reactions can also occur Allergic, ototoxicity, neurotoxicity, hepatotoxicity, etc. Superinfections can occur when bacteria reduce or eliminate normal bacteria that are needed to maintain normal function. When these bacteria are absent, other opportunistic bacteria occupy and infect C. difficile, Candida albicans (yeast infections), Antibiotic Therapy Resistance Overuse or unnecessary use can result in: Patients expecting a prescription every time they are ill (antibiotics are not effective on viral infections) The weaker organisms being killed, leaving only the stronger and more resistant organisms Exposing organisms to antibiotics that did not kill them has led them to become resistant or a “sugerbug” Ex: MRSA Not finishing a course of antibiotics can also result in resistance Antibiotics Classified into broad categories based on their chemical structures Most common categories are: Sulfonamides, Penicillins, Cephalosporins, Carbapenems, Macrolides, Quinolones, Aminoglycosides, & Tetracyclines Also classified by: Antibacterial spectrum (broad vs. narrow) Potency (strength) Toxicity (produce adverse bodily effects r/t poisonous qualities) Pharmacokinetic properties (ADME) Mechanism of action (How they work/What they do) Mechanisms of Action The four most common MOAs of antibiotic action are: Interference with bacterial cell wall synthesis Interference with protein synthesis Interference with replication of DNA Antimetabolite action that disrupts critical reactions inside the bacterial cell Antibiotics Bactericidal antibiotics that kill the bacteria Bacteriostatic antibiotics that do not kill the bacterial, they limit or slow the growth of the bacteria Since most antimicrobials have activity against only one type of microbe, antibiotics are only effective against bacteria, and do not work against viral, parasitic or fungal infections May be given in conjuncture with other type of anti-infectives to limit the possibility of a secondary infection or if a mixed infection is present Antibiotics PART 1: SULFONAMIDES, PENICILLINS, CEPHALOSPORINS, MACROLIDES, & TETRACYCLINES Antibiotics: SULFONAMIDES Sulfonamides were one of the first groups of drugs used as antibiotics Many compounds, but only sulfamethoxazole combined with trimethoprim is commonly used (i.e. sulfatrim, Septra) MOA: Bacteriostatic – inhibit bacterial growth by inhibiting folic acid synthesis needed for cell growth and function Do not affect cells that require exogenous folic acid sources (human cells). Therefore, does not affect folic acid in people Indications: Broad spectrum. Used against both gram + & - bacteria, reaches high concentration in the kidney prior to elimination Treat acute and chronic UTIs, otitis media, ulcerative colitis, prophylaxis bowel surgery, etc. Antibiotics: SULFONAMIDES Contraindications Interactions Pregnant women at term, Infants younger than 2 months Known allergy Celebrex should not be used in those with sulfonamide allergy Potentiate (enhances) the effects of hypoglycemics, toxic effects of Dilantin, and anticoagulation effects of warfarin Nursing implications Educate about sun exposure Take on empty stomach Hydrate well Administer complete prescription Monitor for side effects Intake & Output (excreted by kidneys) Adverse Effects: SULFONAMIDES Headache Allergic reaction “Sulfa allergy” (delayed onset) Fatigue Dizziness Vertigo Tinnitus, hearing loss Insomnia Anorexia, GI upset Stomatitis Urine problems Photosensitivity (w/ exposure to sunlight) Antibiotics: BETA LACTAM Commonly used medications Have a beta-lactam ring that is part of the chemical structure Includes four Major subclasses: Penicillins, Cephalosporins, Carbapenems, & Monobactams MOA: Inhibit the synthesis of the bacterial peptidoglycan cell wall Some bacteria produce the enzyme Blactamase which produces resistance to the antibiotic, therefore these drugs may be given with B-lactamase inhibitors (i.e. Amoxicillin – Clavunate) Beta Lactam Antibiotics: PENICILLIN Safe antibiotics, generally well tolerated Developed by Sir Arthur Fleming (1928), derived from fungus (mould) Divided into four groups, based on structure & spectrum (Table 43.3 pg. 699) Natural penicillins, Penicillinase resistant, Amniopenicillins (broad), Extended spectrum penicillins MOA: Bactericidal – interferes with the building of bacterial cell walls; causes weakening, leads to cell walls bursting Indications: Most gram positive bacteria, UTIs, STIs, pneumonias, prophylaxis. Natural pens not able to kill gram neg bacteria. Extended spectrum pens have great coverage of gram pos and neg (i.e. Piperacillin/tazobactam) Contraindications: Known drug allergy Interactions: More pg. 701 Table 43.5 Beta Lactam Antibiotics: PENICILLIN Antacids reduce absorption Enhance anticoagulants Decrease oral contraceptive effectiveness Nursing Implications: Best taken on an empty stomach (Except PenV; amoxicillin) Monitor cross sensitivity with other drugs (Cephalosporins) Blood work monitoring Monitor for superinfections Mouth care (opportunistic yeast infections) Adverse Effects: PENICILLIN Urticaria Pruritus Angioedema GI upset Hypersensitivity Blood dyscrasias Stomatitis Phlebitis Superinfections Furry tongue Glossitis Pain at site Antibiotics: CEPHALOSPORINS Semisynthetic medications, widely used in clinical practice Structurally and pharmacologically related to penicillin Look for prefix – ceph or cef Five generations – each effective against a broader spectrum of bacteria. In general the coverage of gram – increases with each successive generation MOA: Bactericidal – weakens the bacteria by interfering with building blocks of cell wall; making them defective and unstable Indications: Have broad spectrum activity against gram + & - organisms or anaerobic bacteria (2nd gen only) Serious infections like bacteremia, septicemia, LRTI, joint/bone infections, Antibiotics: CEPHALOSPORINS First Generation cephalosporins: Inhibits the growth of most gram positive cocci and a mild effect on some gram negative microbes Ex: Keflex (cephalexin), Ancef (cefazolin) Second Generation cephalosporins: Has an improved ability to fight a greater number of gram negative microorganisms than the 1st generation; only generation to cover anaerobic microorganisms Ex: Mefoxin (ceftoxitin), Ceclor (cefaclor) Third Generation cephalosporins: More effective at inactivating beta-lactamase (an enzyme bacteria uses to build protection from antibiotics) Ex: Rocephin (ceftriaxone), Claforan (ceftotaxime) Fourth Generation cephalosporins: Even broader spectrum and longer duration against bacterial enzymes produced to destroy penicillins. Used as adjunct to prolong the life and action of the penicillins; more effective at eliminating organisms that have built a resistance to earlier generations. Ex: Maxipime (cefepime) Fifth Generation cephalosporins: Broad spectrum and covers gram-positive (including MRSA) and gram-negative organisms Ex: ceftaroline fosamil Antibiotics: CEPHALOSPORINS Contraindications: Cross sensitivity with penicillin allergies Interactions: pg. 706 Table 43.7 Alcohol can cause flushing, tremors, dyspnea, increased HR and decreased BP Increased risk of bleeding with anticoagulants Probenecid may decrease excretion of drug Nursing Implications: Monitor S/S of GI upset; give with food/milk Monitor BM’s Ensure labs are being monitored Intake and Output Rotate sites for administering Ensure suspensions are refrigerated Most cannot be given GI route as they are not absorbed Adverse Effects: CEPHALOSPORINS GI upset Anemia Headache, dizziness, malaise, fever Superinfections esp in gut Nephrotoxicity Hypersensitivity Nephrotoxicity (esp older adults) Increase risk of bleeding with other anticoagulants Route complications Antibiotics: Carbapenems Broadest antibacterial action of any antibiotics to date MOA: Bactericidal and inhibit cell wall synthesis Reserved for complicated body cavity and connective tissue infections in acutely ill hospitalized patients Must be infused over 60 minutes May cause drug-induced seizure activity This risk can be reduced with proper dosage. Examples: imipenem/cilastatin (Primaxin®) Used for treatment of bone, joint, skin, and soft tissue infections; many other uses Cilastatin inhibits an enzyme that breaks down imipenem. Small cross sensitivity with penicillin allergies Large group of antibiotics that first became available in the 1950s. Often considered a safe first choice with uncomplicated infections Antibiotics: MACROLIDES MOA: Mainly bacteriostatic – weakening the bacteria by preventing protein synthesis. Can be bactericidal in high concentrations to some bacteria. Indications: Alternative to penicillin allergies/resistance. Used for Streptococcus bacteria, chlamydia, gonorrhea, whooping cough, skin infection, URTI, & c. diff HP-pack for H.pylori EX: erythromycin, azithromycin, & clarithromycin Azithromycin & clarithromycin are the most common – have a longer duration of action which allows them to be given less often and produce milder GI upset. Antibiotics: MACROLIDES Contraindications: Known allergy Interactions: Adverse Effects: Reduce efficacy of oral contraceptives Highly protein bound and metabolized in the liver, may compete with other medications for metabolization causing prolonged drug and potential toxic effects (i.e. warfarin, carbamazepine, etc.) Very few – mild GI & Superinfections (Table 43.8 pg. 706) Nursing Implications: Hydrate well May be chewable tablet form, educate Consistent administration Avoid grapefruitreduces metabolism Antibiotics: TETRACYCLINES MOA: Bacteriostatic agents, broad spectrum – interferes with the bacteria’s ability to make protein Indications: Not the number one choice. Mainly used for UTI, STI, URI, pneumonia, Lyme disease. Used as an alternative when patient has allergies to other abx. Contraindications: Known allergy, pregnancy, & children under 8, known liver disease Examples: Vibramycin (doxycycline), Newest form is Tygacil (tigecycline) only used when other treatments unavailable, effective against resistant bacteria Interactions: Antacids, dairy products, calcium – can decrease absorption of abx. Can potentiate effects of oral anticoagulants Antibiotics: TETRACYCLINES Nursing Implications: Monitor out of date medications Educate about potential interactions Take with empty stomach Avoid dairy Binds to Ca, Mg, and Al ions-avoid administration in children younger than 8 and pregnant/lactating women Adverse Effects: TETRACYCLINES Relatively safe Effects are often dose related GI upset Photosensitivity Stomatitis; sore throat Teeth discoloration Vertigo Superinfections (if long term use) Yeast infections due to alterations of the GI flora (GI, thrush, vaginal) Antibiotics PART 2: AMINOGLYCOSIDES, FLUOROQUINOLONES, & OTHER DRUGS This section focuses on more intense antibiotics used to treat serious and harder to treat infections Intense Antibiotics Majority of these medications are given via parenteral routes These antibiotics can treat organisms that are resistant to one or more classes of antimicrobial drugs (multidrug-resistant organisms) Multidrug-resistant organisms are one of the world’s top health problem. These include – MRSA (Methicillin resistant staphylococcus aureus), VRE (Vancomycin-resistant enterococcus), ESBL (Extended-spectrum B-lactamases), and KPC (Klebsilla pneumonia carbapenemase) Antibiotics: Aminoglycosides Several routes available but not given orally because of poor oral absorption, best if given parenterally Very potent antibiotics with serious toxicities Kill mostly gram-negative bacteria, some gram-positive bacteria Three most common: gentamicin, tobramycin, amikacin Serum levels of these drugs routinely monitored Dosages adjusted to maintain optimal levels that maximize drug efficacy and minimize the risk for toxicity…known as Therapeutic Drug Monitoring Have narrow therapeutic range; lowest and highest acceptable drug levels are not far apart Dosage is calculated based on the patient’s weight Blood levels will be monitored and dosage changes made accordingly (peak-trough) Can be used for eyes, skin, or ears but is best when given parenterally if needed for systemic infections; poor oral absorption Antibiotics: AMINOGLYCOSIDES Blood level monitoring very important in prescribing; these drugs need to have a serum level at least 8 times higher than the minimum inhibitory concentration (MIC) which is the measurement used to determine the lowest concentration of drug needed to kill a standard amount of bacteria Usually given in adjunct with other antibiotics (synergistic effect) Has a postantibiotic effect (PAE) which is a time frame in which bacterial growth suppression occurs after short-term antibiotic exposure Antibiotics: AMINOGLYCOSIDES MOA: Bactericidal – weakening the bacteria by limiting the production of protein Indications: Used to treat aerobic gram – infections such as E.Coli, Pseudomonas; used to sterilize bowel before surgery, UTIs, Wound infections, TB Also used as adjunct therapy because of synergistic effects and post antibiotic effects Contraindications: Allergy, Pregnancy & lactation Examples: gentamycin, tobramycin, & amikacin Antibiotics: AMINOGLYCOCIDES Interactions: Nursing Implications: Increases risk of nephrotoxicity if used with vancomycin Ototoxicity increases if used with aspirin, furosemide, and ethacrynic acid Vitamin K production can be reduced due to disturbances of the normal gut flora Can potentiate warfarin toxicity Monitor for side effects related to toxicity; kidney functions Weigh daily Intake and output Vitals Ensure full course is taken Take at scheduled times with plenty of fluids Need to monitor serum levels and adjust dose accordingly to minimize toxicity but maximize efficacy; therapeutic drug monitoring Adverse Effects: AMINOGLYCOSIDES Nephrotoxicity (kidney) Ototoxicity (ears)..particularly w/ gentamycin); permanent damage Severe damage to CNVIII which in turn can damage the ears Neurotoxicity MOA: Potent bactericidal; act by interfering with bacterial DNA synthesis Antibiotics: QUINOLONES aka Fluoroquinolones Indications: Effective against most gram – pathogens, and some gram +, broad spectrum Most are excreted through the kidney unchanged, making them very effective in treating complicated UTIs Used as alternatives to other antibiotics when treating resp, GI, gyne, skin, and soft tissue infections, and STIs Very effective oral absorption as well Contraindications: Not suitable for children under 18, may affect cartilage development, pregnancy Examples: ciprofloxacin (Cipro), levofloxacin (Levaquin) Interactions: Antibiotics: QUINOLONES Antacids and ferrous sulphate reduce absorption Minerals and multivitamins decrease absorption Increase action of warfarin Avoid caffeine can increase anxiety and cause tachycardia Dairy reduces quinolone absorption Nursing Implications: Monitor signs and symptoms Keep patient hydrated, to promote excretion Monitor ECG Educate Monitor safety Advise about proper medication times if on potential interacting drugs Probably tolerated better if taken w/ food CNS = dizziness, light headedness, insomnia GI = GI upset (n, v, d, c ), thrush INTEG = rash, flushing, pruritus, urticaria EYES = Photosensitivity Adverse Effects: QUINOLONES Superinfections Tendinitis and tendon rupture tinnitus Renal insufficiency Joint pain Neuropathy ECG changes-prolonged QT interval More commonly with long time use Table 44.4 pg. 720 Antibiotics: Honorable mentions VANCOMYCIN One of the most powerful antibiotics MOA: Bactericidal – inhibits the building of bacterial cell wall Use in caution with people with kidney function issues Interactions: Can increase toxicity of other antibiotics, multiple drug and diluent incompatibilities Indications: Severe gram + infections; MRSA. NOT active against gram -, fungi, or yeast Vancomycin Adverse Effects: Frequent but minor flushing “red man syndrome” Hypotension Increased doses can cause nephrotoxicity and ototoxcity Nursing Implications: Given slowly (to reduce incidence of flushing and hypotension) Not absorbed very well in GI tract Monitor blood levels of drug, particularly trough levels Because it is excreted rapidly by the kidneys, monitor kidney functions Proper handwashing crucial!!! Nursing Process & Antibiotics Assessment Allergies, history of illness, lab results, intake&output, check for contraindications, medication history for interactions, ethnocultural and developmental variations, assess patient’s willingness to learn, C&S reports Diagnosis Ex: Inadequate knowledge r/t lack of information about disease process and medication regime Planning Set goals – patient will remain adherent to therapy regimen for full duration of treatment – patient is free of S/S of infection with negative C&S reports at end of antibiotic therapy Nursing Process & Antibiotics Implementation: General nursing interventions that apply to antibiotics include the following: Give oral antibiotics within recommended time frames with fluids/foods as indicated All medication is to be taken as specifically order, in full and at appropriate time frames Doses are not to be omitted or doubled up Do not take oral antibiotics the same time as antacids, iron/calcium supplements, or laxatives NHP are only to be used if there are no known interactions Continuously monitor for hypersensitivity reactions If there are signs of a reaction, STOP drug immediately, contact HCP, and monitor Obtain C&S PRIOR to initiating first dose of abx if possible Evaluation Monitor goals/outcomes, therapeutic & adverse effects Monitor patient S/S Antibiotic Therapy Case Study Page 712 Rahul has been a resident of a complex continuing care facility since experiencing a left-sided stroke 5 years ago. Currently, his cardiovascular status and cerebrovascular status are stable. However, he has had a productive cough and a low grade fever for 2 days. After physical assessment and chest radiographic examination, the health care provider diagnoses him with pneumonia of the left lower lobe of the lung. The health care provider orders: piperacillin/tazobactam sodium 2.25 G IV q8h theophylline 300mg PO q12h Maalox 30ml PO BID prn Ibuprofen 400mg PO q6h prn He also takes: warfarin 2mg PO daily at 1800 1. Explain the rationale behind the use of tazobactam sodium with piperacillin. 2. What assessments does the nurse need to undertake prior to starting the antibiotic? 3. What concerns or drug interactions should the nurse be aware of with the use of pipercillin/tazobactam and the other medications ordered for Rahul? 4. What parameters should be monitored to determine whether the antibiotic is working? Explain. Critical Thinking Activities 1.The nurse is reviewing a patient’s medications that are due this morning and note the following orders: doxycycline 200mg PO daily at 0800 Multivitamin with iron 1 tablet PO daily at 0800 Maalox 30ml PO BID What would be the priority action of the nurse when considering administering these medications together? 2.The nurse is reviewing the orders for a patient who has been admitted for treatment of pneumonia. The antibiotic orders include an order for penicillin. However, when the patient is asked about his allergies he lists “penicillin” as one of them. What will be the nurse’s next action?