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Antimicrobial Drugs
For Pharmacology NURS 422
| Term | Definition |
|---|---|
| Basic Principals of Antimicrobial Therapy | - Used to treat infectious diseases - Up to 30% of all hospitalized patients receive antimicrobials - Modern antimicrobials were developed in the 1930's & 1940's - Significantly reduced morbidity and mortality from infection |
| Antimicrobial Agent | Any agent that has the ability to kill or suppress microorganisms |
| Four Main Classes of Antimicrobials | - Antibiotics - Antifungals - Antivirals - Antiprotozoals |
| Bacteriostatic | Inhibits growth of bacteria - Immune system gets rid of infectious agent |
| Bacteriocidal | Kills bacteria directly |
| Colonization | HARMLESS inhabitation of skin and mucous membranes by pathogens |
| Symbiosis | Relationship with host Protective; Established colonies prevent outgrowth of harmful organisms |
| Microbiome | Collection of microbial organism and genetic information at a given site (i.e: gut microbiome, vaginal microbiome, buccal microbiome, etc) |
| Resident Flora | Usually bacteria; re-colonizes quickly if disturbed |
| Opportunistic Infections | When normal flora becomes pathogenetic when immune system is compromised |
| Superinfection | Infections due to treatment for another infection; usually antibiotic resistant |
| Dysbiosis | Breakdown of homeostasis of the microbiome, promoting the growth of detrimental microbiota I.e: Overgrowth of Staphylococcus aureus bacteria, leading to a staph infection |
| Fungal Infections | Large eukaryotes with thick cell walls - Resistant to antibiotics Single-celled fungi = yeasts Multi-celled fungi = molds Disseminated through environment. Reproduce by forming spores (detach from parent cell, germinates elsewhere,) |
| Mycoses | Infections CAUSED by fungi |
| Subcutaneous Mycoses | Fungi introduced into subcutaneous tissue during trauma |
| Systemic Mycoses | CAN CAUSE DEATH Inhalation of dust that contains fungus. Tends to be more serious *Usually happens if host immune system is compromised |
| Amphotericin B | SYSTEMIC MYCOSES ANTIFUNGAL PROTOTYE 'Amphoterrible' Treats a broad spectrum of fungi and some protozoa (NO BACTERIA) |
| Amphotericin B MOA | Fungicidal or fungistatic depending on dose/susceptibility Fungicidal = immunocompromised patients. Binds to sterols in fungal cell membrane. Increases permeability, allowing K+ to enter cell, thus reducing cell viability = stops/prevents reproduction |
| Amphotericin B Administration | MUST be given IV in 5% dextrose or NS over 2-6 hours due to poor absorption in GI tract Given in hospital because its highly toxic |
| Amphotericin B Adverse Effects | Infusion reactions = 1-3 hours AFTER administration (Fever, Chills, Nausea, Rigors, Headache due to release of pro-inflammatory cytokines) Pretreat w/ Tylenol, antiemetic, and diphenhydramine |
| Amphotericin B Adverse Effects (Cont.) | Hypokalemia - Need K+ Supplements Bone Marrow Suppression = Anemia NEPHROTOXICITY (occurs in ALL pts) = Dose dependent. Infuse 1 L of NS BEFORE administration. Monitor creatinine levels. Avoid other nephrotoxic drugs |
| Fluconazole | ANTIFUNGAL - SUBCUTANEOUS MYCOSES "-azole" = most common antifungal IV, PO with food, topical |
| Fluconazole Uses | Localized candida infections (UTI/Oral thrush) Systemic Candidiasis (If not too severe) **Suppression of cryptococcal meningitis in HIV after Ampho B |
| Fluconazole MOA | !!! Similar to Ampho !!! Binds to sterols in fungal cell membrane. Increases permeability, allowing K+ to enter cell, thus reducing cell viability = stops/prevents reproduction |
| Fluconazole Adverse Effects | USUALLY WELL-TOLERATED Skin rash, GI effects (eat small, frequent meals) Hepatotoxicity = Monitor hepatic enzyme levels Prolongation of QT Interval Monitor renal function weekly w/dosage reduction if renal toxicity occurs |
| Bacteria: Gram NEGATIVE Cell Envelope | THREE LAYERS Thin cell wall and an additional outer membrane that is hard to penetrate |
| Bacteria: Gram POSTIVE Cell Envelope | TWO LAYERS Relatively thick cell wall that is easily penetrated |
| Selective Toxicity | The ability of antibiotics to target specific microbes without harming the host |
| How is selective toxicity achieved? | Bacterial Cell Wall Disruption Inhibition of bacterial-specific enzymes Disruption of bacteria protein synthesis |
| Antibiotic Therapy | Prophylactic Therapy Empiric Therapy Definitive Therapy |
| Prophylactic Therapy | Drugs given to PREVENT infection rather than to treat an infection. I.e: Before dental procedures |
| Empiric Therapy | Antibiotic therapy for patients before causative organism is positively identified I.e: Before engaging with partner with an STI |
| Definitive Therapy | Drugs to TREAT an established infection by an identified pathogen with susceptibility results I.e: After gram stain & sensitivity testing |
| Selection of Antibiotics | Identify organism w/gram staining Drug sensitivity w/ culture and sensitivity test |
| How are antibiotics ruled out? | Allergy Inability to penetrate the site of infection Patient variables (How sick are they?) Host defenses Age Pregnancy/Lactation Previous allergic reactions Genetic Factors |
| Peak | Highest concentration that a given drug can achieve in the bloodstream Usually 1 hour after administration, but varies form drug to drug |
| Trough | Lowest concentration of drug in blood stream Drawn before dose is given. |
| Peak and Trough levels are CRITICAL for what drugs? | Aminoglycosides, Vancomycin, some antifungals Usually drawn up after 3rd or 4th dose |
| Penicillin | BETA-LACTAM ANTIBIOTICS - GETS INSIDE BACTERIUM Active against a variety of bacteria - widely used Principal adverse effect: allergic reaction Beta-lactam ring in structure Family: Cephalosporins, aztreonam, imipenem, meropenem, ertapenem |
| Penicillin MOA | Binds to penicillin binding PROs Weakens cell wall, causing bacteria to take in water and rupture Active ONLY against bacteria undergoing growth and division Bactericidal |
| Bacterial Resistance | Inability of penicillin to reach its target Inactivation of penicillin by bacterial enzymes (beta lactamases, penicillinase) Production of PBP that have low affinity for PCN- Mutated over time to prevent penicillin penetration (MRSA) |
| PBP | Penicillin Binding Proteins |
| Beta-Lactamases | MECHANISM OF BACTERIAL RESISTANCE Enzymes that render antibiotics with beta-lactam rings inactive. Bacteria can produce a large variety of these enzymes for penicillin |
| Classification of Penicillins | Narrow Spectrum (Penicillinase-Sensitive & Penicillinase-Resistant) Broad Spectrum Extended-Spectrum |
| Benzylpenicillin (Penicillin G) | NARROW-SPECTRUM PENICILLIN PROTOTYPE (PELICILLINASE SENSITIVE) Bactericidal to most GRAM POSTIVE bacterial and some gram negative (Generally ineffective to gram negative) |
| Benzylpenicillin Uses | Streptococcal Infections (Staph pharyngitis, gas gangrene, syphilis) |
| Benzylpenicillin Administration | IM or IV (For emergencies) |
| Penicillin Allergies | LEAST toxic of all antibiotics Common cause of drug allergies (0.4-7% of patients) Assess for allergy in each patient - Mild: Consider a cephalosporin - History of Anaphylaxis: AVOID penicillin & cephalosporin |
| Penicillin Allergy Reaction Types | Immediate (2-30 mins) Accelerated (1-72 hours) Late (Days to weeks) |
| Anaphylaxis S/S | Laryngeal Edema (Swelling of airway) Bronchoconstriction Severe Hypotension |
| Penicillin Drug Interactions | Aminoglycosides (i.e: Gentamicin) = Promotes action/Increases risk of toxicity. High concentrations of penicillin will inactivate aminoglycosides. Never administer in same IV solution Probenecid: Delays renal excretion, increases toxicity |
| Nafcillin Oxacillin Dicloxacillin | NARROW-SPECTRUM PENICILLINASE-RESISTANT PENICILLINS All IV dosing except Dicloxacillin (Oral) Ineffective against Methicillin-resistant staphylococcus aureus (MRSA) Effective against penicillinase-producing staphylococcus |
| MRSA | Methicillin-Resistant Staphylococcus Aureus Causes most staph infections GRAM POSITIVE, common in nose and mouth Resistant to ALL penicillinase-resistant PCNs |
| Ampicillin (Pricipen) Amoxicillin (Amoxil, DisperMox, Moxatag, Trimox) | BROAD-SPECTRUM PENICILLINS Ampicillin - Given oral, IV Amoxicillin- Very common, better for oral dosing |
| Ampicillin | Amoxicillin MOA | Same MOA as PCN G, but is also effective against some gram negative bacilli (E.Coli) (Weakens cell wall, causing bacteria to take in water and rupture Active ONLY against bacteria undergoing growth and division) |
| Ampicillin | Amoxicillin Adverse Effects | Rash, Diarrhea |
| Overcoming Beta-Lactamase-Mediated Resistance | Using Beta-Lactamase Inhibitors Clavulanic Acid: PROTOTYPE Extends antimicrobial spectrum when combined with a beta lactamase sensitive antibiotic Minimum Toxicity; SE related to penicillin |
| Amoxicillin/Clavulanic Acid (Augmentin) | BETA-LACTAMASE INHIBITOR |
| Cephalosporins | 1st Generation - 5th Generation Most widely used class of antibiotics (Progressing from 1st to 5th) Increased activity against Gram Negative bacteria and anaerobes Increased resistance to destruction by beta-lactamases Increased ability to reach CSF |
| Cephalosporins MOA | Binds to PBP to disrupt cell wall synthesis, causes cell lysis Most effective against cells undergoing active growth and division ALL bactericidal, low toxicity, administered IM or IV. Poorly absorbed in GI tract, few are given orally. |
| 1st Generation Cephalosporins | Cefazolin (Ancef, Kefzol) Best against GRAM POSTIVE bacterium For prophylaxis/otitis, sinusitis, pneumonia, abdominal infection |
| 2nd Generation Cephalosporins | Cefuroxime (Zinacef) | Cefaclor (Ceclor) For prophylaxis/otitis, sinusitis, pneumonia, abdominal infection |
| 3rd Generation Cephalosporins | Ceftriaxone (Rocephin) | Cefoperazone (Ceforbid) Preferred therapy for several infections INCLUDING C.Diff Highly active against gram-negative organisms |
| 4th Generation Cephalosporins | Cefepime (Maxipime) Able to penetrate CSF Broad-spectrum antibiotic |
| 5th Generation Cephalosporins | Ceftaroline (Teflaro) Effective against MRSA/VRSA |
| Cephalosporin Adverse Effects | Hypersensitivity (Most Common) Allergy (1% cross-reactivity w/ penicillins) Bleeding: Cefotetan & Ceftriaxone (Interferes with Vit. K metabolism - Reduces prothrombin levels) |
| Cephalosporin Drug Interactions | Probenecid - Delays renal excretion Alcohol - Disulfiram reaction w/ some 1st & 2nd generation drugs (projectile vomiting) Calcium & Ceftriaxone - In same tubing can form possibly fatal precipitates |
| Vancomycin (Vancocin, Vancoled) | GLYCOPEPTIDE ANTIBIOTIC Also called "Drug of last resort" |
| Vancomycin Indications | For SEVERE infections. Only active against GRAM POSITIVE bacteria because it is VERY toxic |
| Vancomycin Uses | Used against MRSA or Staphylococcus aureus, S. epidermidis Oral dose used for Clostridium Difficile (C.Diff) if metronidazole is ineffective Pneumococcal, streptococcal infections |
| Vancomycin MOA | Inhibits cell wall synthesis. Binds to molecules that help build cell wall, thus inhibiting the process. Promotes bacterial lysis (cell wall breakdown) and bacterial death |
| Vancomycin Adverse Effects | RENAL FAILURE: Do not use with other nephrotoxic drugs (i.e: NSAIDS). Monitor creatinine levels. Goal trough levels w/ most infections: 10-15 mg/L Serious infections: 15-20 mg/l **Dose-Dependent |
| Vancomycin Adverse Effects (Cont.) | Ototoxicity: Rare & Reversible. Long-term treatment increases risk. REDMAN SYNDROME - If given rapidly, may see flushing, rash, pruritis, tachycardia, hypotension. INFUSE SLOWLY OVER 1 HOUR OR LONGER |
| Drugs that Inhibit Protein Synthesis | Tetracyclines (Bacteriostatic) Macrolides (Bacteriostatic) Other Bacteriostatic Agents Aminoglycosides (Bactericidal) |
| Tetracycline | BROAD SPECTRUM BACTERIOSTATIC ANTIBIOTIC |
| Tetracycline Indications | Rickettsial disease (I.e: Rocky mountain fever, typhus), Chlamydial disease, brucellosis, cholera, pneumonia (mycoplasma), Lyme Disease, anthrax, H.pylori, acne (topically/orally), periodontal disease |
| Tetracycline MOA | Binds to the 30S ribosomal subunit on bacteria to stop bacterial protein synthesis. Take on EMPTY stomach. |
| Tetracycline Adverse Effects | Permanent discoloration on teeth, can inhibit Ca+ absorption over time, suppresses bone growth (increases risk of osteoporosis) Photosensitivity GI (C.Diff)/Hepatotoxicity Renal Impairment - Avoid in renal patients (Might be given low dose) |
| Tetracycline Interactions | Chelate formation Absorption decreases if given with milk products, calcium supplements, iron supplements, magnesium containing laxatives, antacids (Al, MG), Digoxin |
| Tetracycline Contraindications | Do not use in pregnancy or children less than 8 years old |
| Erythromycin (Ery-tab) | BROAD SPECTRUM BACTERIOSTATIC MACROLIDES Works against GRAM NEGATIVE bacteria and pneumonia best. Used when allergic to penicillin |
| Erythromycin Indications | Whooping cough (B.Pertussis), Acute diphtheria (Corynebacterium diphtheria), chlamydial infections, M. pneumonia |
| Erythromycin MOA | Binds to the 50S ribosomal subunit on bacteria to stop bacterial protein synthesis. |
| Erythromycin Adverse Effects | GI Effects Superinfection of the bowel Thrombophlebitis QT Prolongation/Sudden Cardiac Death |
| Erythromycin Interactions | Food (Taken on an empty stomach), warfarin, carbamazepine, theophylline, chloramphenicol, clindamycin, antiarrhythmics, antifungals, HIV-antivirals |
| Clindamycin (Cleocin) | LINCOSAMIDE BACTERIOSTATIC ANTIBIOTIC Famous for the WORST C.Diff Active against most anaerobic bacteria (gram positive and negative) |
| Clindamycin Indication | Only for certain anaerobic infections located outside the CNS |
| Clindamycin MOA | Inhibits protein synthesis |
| Clindamycin Adverse Effects | Can induce SEVERE antibiotic-associated Clostridium Difficile associated diarrhea (can be fatal) Superinfection in bowel Profuse watery diarrhea, abdominal pain, blood and mucous in stool. |
| Gentamicin (Garamycin) | AMINOGLYCOSIDE BACTERIALCIDAL ANTIBIOTIC NARROW SPECTRUM |
| Gentamicin Indications | Used to treat SERIOUS infections caused an aerobic gram negative bacilli (Pseudomonas, aeruginosa, E.Coli, Klebsiella, Serratia, Proteas mirabilis) **Combined with other antibiotics for Rx of gram positive infections |
| Gentamicin MOA | Inhibits protein synthesis by binding to 30s Ribosomal subunit Cell kill is concentration dependent (small dose = bacteriostatic. Large dose = bactericidal) |
| Gentamicin Adverse Effects | Ototoxicity, Nephrotoxicity |
| Gentamicin Nursing Consideration | Monitor Serum Levels Dosing: Single large dose daily or 2-3 smaller dosage This procedure is common; the same aminoglycoside dose can produce very different plasma levels in different patients |
| Gentamicin Nursing Consideration (Cont.) | IMPORTANT Peak levels must be high enough to kill bacteria. Trough levels must be low enough to minimize toxicity. Stop at the FIRST sign of ototoxicity (ringing in the ears) because condition is irreversible. |
| Pharmacotherapy for UTI | 80% of infections are related to gram negative (E.coli) bacteria. 10-15% of gram positive cocci |
| Pharmacotherapy for UTI: LOCATION | Upper - Serious Infection in the KIDNEY Acute Pyelonephritis Acute Bacterial prostatitis Lower: BLADDER infection Acute Cystitis - Bladder Acute Ureteral Syndrome |
| Pharmacotherapy for UTI: INFECTION TYPE | Isolated Unresolved Recurrent Complicated vs. Uncomplicated |
| Drugs that Inhibit Folic Acid & DNA Synthesis | Sulfonamides & Trimethoprim |
| Sulfonamides & Trimethoprim | BROAD SPECTRUM ANTIBIOTICS Oral treatment of choice for UTI Used as: Trimethoprim-Sulfamethoxazole Bacteriostatic Used in: Acute cystitis, long-term prophylaxis against recurrent infection, acute pyelonephritis (mild), acute bacterial prostatitis |
| Trimethoprim-Sulfamethoxazole Uses | Uncomplicated urinary tract infection Pneumocystis carinii GI Infections IV, IM, or PO administration. Excreted in urine |
| Trimethoprim-Sulfamethoxazole MOA | Inhibits sequential steps in bacterial folic acid synthesis, making it more powerful than TMP or SMZ alone |
| Trimethoprim-Sulfamethoxazole Adverse Effects | Mild GI Disturbances Hypersensitivity Reactions: rash, photosensitivity, SJS (Rare) Hemolytic Anemia in G6PD Deficiency (DO NOT give this drug to these patients) Kernicterus (Newborns) Cystalluria (Rare w/ newer preparations and hydration) |
| Fluoroquinolones | Bacteriocidal Common broad-spectrum antibiotic Effective against aerobic gram positive & some gram negative Rare risk of tendon damage (Avoid in children) Mild SE |
| Fluoroquinolones Interactions | Absorption REDUCED by: Al & Mg antacids Fe & Zn Salts Sucralfate Milk & Dairy products |
| Fluoroquinolones Drugs | **Ciprofloxacin (Cipro) 2nd Gen Norfloxacin (Noroxin) Ofloaxin (Floxin) Levofloxacin (Tavanic, Levaquin) - 3rd Gen Trovafloxacin - 4th gen |
| Ciprofloxacin (Cipro) | BROAD SPECTRUM ANTIBIOTIC |
| Ciprofloxacin Indications | Active against most gram negative bacteria, some gram positive UTI, GI, Respiratory Infections, Bone, Skin, anthrax prevention Used in serious infections Complicated UTI (Gram negative E.Coli) High rates of resistance, so not used in staph infections |
| Ciprofloxacin MOA | Inhibits two bacterial enzymes needed for DNA replication and cell division. Bacteria cannot reproduce or replicate. Bactericidal |
| Ciprofloxacin Route | IV & PO. Avoid in children younger than 18 (except in cases of complicated UTI, post-anthrax inhalation) |
| Ciprofloxacin Adverse Effects | Mild GI **CNS Effects (Dizziness, confusion esp. in elderly) Phototoxicity; Severe sunburn Tendon rupture in elderly, esp. if on glucocorticoids & w/ heart, lung, kidney transplants Increased risk of C.Diff & Candida infections |
| Ciprofloxacin Contraindications | Avoid cationic compounds such as calcium, zinc, dairy products, and others for 6 hours before or 2 hours after cipro dose. |
| Fosfomycin (Monurol) | MISCELLENOUS ANTIBIOTIC Newest agent in the USA |
| Fosfomycin Uses | Single dosing (3 gm) in uncomplicated UTIs (acute cystitis) Symptoms usually improve in 2-3 days, but if not, giving another dose has no effect but will increase side effects |
| Fosfomycin MOA | Bactericidal Inhibits bacterial cell wall synthesis, causes bacterial lysis and death. |
| Fosfomycin Adverse Effects | Diarrhea Headache Vaginitis |
| Urinary Tract Antiseptics | Nitrofurantoin (Furadantin, Macrodantin) Methenamine (Mandelamine) Nalidixic acid (NegGram) Cinoxacin (Cinobac) |
| Urinary Tract Antiseptics (Cont.) | Second choice drugs - UTIs only Concentrated in urine against common pathogens Ineffective in blood and tissues Bacteriostatic in LOW doses. Bactericidal in HIGH doses May be used as prophylaxis against recurrent infections |
| Antimycobacterial Agents | **Isoniazid (Hydra) - Bacteriostatic/Bactericidal **Rifampin (Rifadin) - Bactericidal Pyrazinamide (Tebrazid) Ethambutol (Myambutol) |
| Isoniazid (Hydra) | ANTITUBERCULAR ANTIBIOTIC Used in active and latent TB 1st line drug - great efficacy, low toxicity, easy to use, high patient acceptance & affordability |
| Isoniazid MOA | Inhibits synthesis of mycolic acid (the main component in mycobacterial wall) **Prodrug |
| Isoniazid Adverse Effects | Hepatotoxicity, Peripheral Nephrotoxicity CNS Effects: Seizures, Dizziness, Ataxia |
| Isoniazid Drug Interactions | Inhibits P450 isozymes - Interacts with a number of drugs including anticonvulsants |
| Rifampin (Rifadin) | ANTITUBERCULAR ANTIBIOTIC BROAD SPECTRUM Also 1st line for TB |
| Rifampin Indications | TB & Leprosy |
| Rifampin MOA | Inhibits protein synthesis by suppressing RNA Synthesis |
| Rifampin Adverse Effects | Hepatitis, discoloration of body fluids |
| Protozoa | Single-celled eukaryotes; free living & parasitic I.e: Malaria, Toxoplasmosis, Leishmaniasis, African Sleeping Sickness, Giardiasis |
| Antimalarial Drugs | Chloroquine Quinine Quinidine Primaquine |
| Antiprotozoal Drugs | Metronidazole (Flagyl) |
| Metronidazole (Flagyl) | ANTIPROTOZAL ANTIBIOTIC |
| Metronidazole Indications | Drug of Choice for symptomatic intestinal amebiasis, & systemic amebiasis, giardiasis and trichomoniasis (Anaerobic infections: intraabdominal, skin-related, gynecologic, bacterial septicemia, bone and joint, CNS, lower respiratory tract, endocarditis) |
| Metronidazole MOA | Interacts with DNA causing stand breakage, resulting in impairment of DNA function *Prodrug converted to active form in anaerobic cells only) |
| Metronidazole Adverse Effects | Nausea Headache Neurologic Injury SJS Dry Mouth **Metallic Taste in mouth **Darkened urine |
| Metronidazole Drug Interactions | Alcohol - Disulfiram-Like reaction (Projectile vomiting) Warfarin, phenytoin, lithium, cyclosporine, tacrolimus, rifampin, etc. |
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