Antimicrobial Therapy Basics PDF

Antimicrobial Therapy Basics Antibiotic Mechanisms of Action Antibiotic Spectrum Antibiotics can inhibit or kill target cells by affecting: Narrow = affect few microbes *preferred*...

Antimicrobial Therapy Basics Antibiotic Mechanisms of Action Antibiotic Spectrum Antibiotics can inhibit or kill target cells by affecting: Narrow = affect few microbes *preferred* Broad = affect many microbes *resistance risk* 1. Cell walls (causing lysis) 2. Enzyme action (suppressing growth) 3. Protein synthesis 4. Nucleic acid synthesis Resistance Superainfection Resistance supports continued bacterial growth. Suprainfections = secondary infection Rapid microbe division makes resistance more troubling. Antibiotics (especially broad) impact many Antibiotics (regardless of type) selectively kill sensitive microbes (including “good” ones). With less microbes, resulting in survival/expansion of “the rest” (yikes!) competition (less flora), secondary infections can take over. Resistome = all resistance genes Acquired Resistance = gene not previously present Common superinfections: Innate Resistance = resistant gene present in chrom. C Diff Environmental Resistance = nonpathogenic resistance Oral Candidiasis Clinical Resistance = pathogenic resistance Vaginal Candidiasis MDR = multiple drug resistance (BAD!) Influences on resistance: Inappropriate prescribing Non-prescription use (ex: Asia) Antibacterial cleaning products Food production (ex: prevention in overcrowded pens) Bactericidal Antibiotics Bacteriostatic Antibiotics These antibiotics kill growing microbes. These antibiotics suppress the growth of microbes. Antibiotic Classes: Antibiotic Classes: 1. Penicillins 1. Tetracyclines 2. Cephalosporins 2. Macrolides 3. Carbapenem 3. Lincosamides 4. Vancomycin 4. Aminoglycosides Many antibiotics have beta lactam rings (often with attached R groups) that bind to Beta Lactam Ring proteins in the microbe and work to disrupt the cell wall. These are enzymes in the microbe that can break down the antibiotic’s beta lactam ring Beta Lactamase (Result = inactivation of antibiotic = NOOOO!!!) ***Note: penicillinase is the name for beta lactamase in in microbes treated with penicillins This stops the breakdown of B-Lactam ring. Use with p-ase sensitive drugs Beta Lactamase “Nothing’s ever gonna break me down!” Inhibitors Ampicillin + sulbactam Amoxicillin + clavulanic acid Ticarcillin + clavulanic acid Piperacillin + tazobactam Ceftazidime + avibactam  Penicillins MOA Inhibits Cell Wall B-Lactam Ring + R group 1. Binds to penicillin binding protein Structure 2. Inhibits cross bridge formation (transpeptidase) 3. Osmotic lysis Most Gram + (cocci & bacilli) Activity Gram - spirochete Gram - Cocci Allergy Adverse GI probs Effects Neuromuscular sensitivity (overdose) Kidney function (overdose) Aminoglycosides (synergic) Other Oral contraceptives (won’t work) (Interactions) Probenecid (↑ penicillin) Tetracyclines (↓ effectiveness) Penicillin Drugs (-cillin) Penicillin G (IV) P-ase sensitive Streptococcus, neisseria, anaerobes, spirochetes Penicillin V (PO) Methicillin (X) Narrow Nafcillin (IV) Staphylococcus aureus P-ase resistant Oxacillin (IV/PO) Dicloxacillin (PO) Ampicillin (IV) H. Influenzae, E coli, proteus mirabilis, enterococci, Extended Amoxicillin (PO) streptococci, N. gonorrheae Spectrum Ticarcillin (IV) (Same as above) + pseudomonas aeruginosa, Piperacillin (IV) enterobacter, proteas, bacteroides, fragilis, klebsiella  Cephalosporins MOA Inhibits Cell Wall B-Lactam Ring + R1 group 1. Binds to penicillin binding protein Structure 2. Disrupts wall synthesis 3. Osmotic lysis Broad Spectrum! Activity **Some can cross BBB Allergy Adverse Bleeding (2nd/3rd) Effects ↑ acetaldehyde with alcohol Calcium deposits (ceftriaxone) 1st Generation (susceptible to B-lactamases) 2nd Generation Other 3rd Generation (classifications) 4th Generation 5th Generation Cephalosporin Drugs (Cef-) Cefazolin (IV) Surgical prophylaxis 1st Gen Cephalosporin (PO) UTI/mild soft tissue infection Both = allergy alternative Cefuroxime (IV/PO) Upper respiratory infection/H. Influenza, pneumonia 2nd Gen Cefoxitin (IV) Abdominal surgery prophylaxis Cefotetan (IV) Abdominal surgery prophylaxis Cefdinir (PO) Cefixime (PO) 3rd Gen Ceftriaxone (IV/IM) Cefotaxime (IV/IM) Ceftazidime (IV/IM) 4th Gen Cefepime (IV/IM) Meningitis, febrile neutropenia, pneumonia 5th Gen Ceftaroline (IV) MRSA Warning: Continued use = C Diff Risk!  Carbapenems MOA Inhibits Cell Wall B-Lactam Ring 1. Binds to penicillin binding protein Structure 2. Inhibits cell wall 3. Causes Lysis Broad! Gram + and - wall penetration Activity Use = severe infections! Penetrates all tissue + CSF! GI probs Adverse Hypersensitivity Effects Suprainfections (because it’s broad!) Seizures Carbapenem Drugs (-penem) Imipenem (IV/IM) Severe hospital infections Meropenem*** ***Common carbapenem Ertapenem Doripenem  Vancomycin MOA Inhibits Cell Wall B-Lactam Ring + R group Structure 1. Binds to d-alanyl & d-alanine sites 2. Inhibits transglycosylation NARROW! Gram + Activity Aero/anaerobic *Some* CSF activity Hypersensitivity (Red man!) Adverse Thrombophlebitis Effects Oto/Nephro TOXICITY Synergic with aminoglycosides Other Slow GI absorption = slow infusion necessary Vancomycin Vancomycin (IV/PO) MRSA, C. Diff, Meningitis VANCO is a heavy lifter!  Tetracyclines Inhibits ribosomal protein synthesis MOA 1. Transported into cell 2. Inhibits tRNA binding to mRNA (prevents amino acid addition on peptides) Broad! (bacteriostatic) Activity G+/G- GI probs Photosensitivity Adverse vestibular/hepatic/renal toxicity Effects Skeletal growth depression (Pediatric/Preg. use = BIG NO!) Dental effects (staining) Cations/antacids (↓ effect) Other Wide distribution (CNS) Incorporated into skin/teeth/bones Tetracyclines (-cycline) Short Acting Tetracycline ***Malaria Proph. Leptospirosis RM spotted fever Trachoma Intermediate Demeclocycline Lyme Disease Acne Acting Doxycycline Anthrax Peptic Ulcer Disease Cholera Periodontal Disease Long Acting Minocycline Syphilis ***Lots of resistance!!  Macrolides ***Penicillin alternative Inhibits ribosomal synthesis MOA 1. Binds to RNA 2. Inhibits peptidyltransferase (enzyme that forms peptide bonds) G+/G- Legionella Activity Myco. pneu. Chlamydiae GI distress QT prolongation Adverse Jaundice Effects Auditory impairment Thrombophlebitis Susceptible to gastric acid (needs coating) Other No CSF impact ½ Life = 1.5 hours (erythromycin) Macrolides (-mycin) ***No Grapefruit Erythromycin (IV/PO) Pneumonia, pertussis/diphtheria, juice! chlamydia, endocardial prophylaxis Azithromycin (IV/PO) Respiratory infections, peptic ulcers, Fewer - effects toxoplasmosis Clarithromycin (PO) Dental prophylaxis Dirithromycin (PO)  Lincosamides MOA Inhibit ribosomal protein synthesis Anaerobic infections Activity Beta-lactam resistant microbes GI problems Ab. pain Adverse Glossitis Effects Stomatitis Esophagitis C DIFF!!!!! ALL ROUTES! 🙂 Affects gut bacteria for 2+ weeks (C Diff… 😳) Other Clindamycin cross placenta (not BBB) Penetrates bone/tissue Lincosamides (Lin-) Clindamycin (all) Lung Abscesses Aspiration Pneumonia Lincomycin (all) Refractory bone infections Pelvic infections  Aminoglycosides Inhibition of RNA synthesis MOA → bactericidal inhibitor of protein synthesis = premature termination of synthesis Pseudomonas aeru. Activity E coli Myco tuberculosis Ototoxicity (otic fluid) Adverse Nephrotoxicity (proximal tubule) Effects Peripheral neuropathy headaches/dizziness IV/IM for systemic infection Oral for GI local infections Other No BBB and no eye action Rapid excretion Aminoglycosides (AG/NT/S) Amikacin Neomycin Gentamicin Tobramycin Streptomycin (TB)  Sulfonamides Folic Acid Synthesis Inhibition MOA 1. Inhibit Successive steps of folic inhibition → inhibits bacterial nucleotides Allergies Crystalluria Adverse Hemolytic anemia (liver damage) Effects Stevens-Johnson Syndrome (blisters - ouch!) photosensitivity Lag before onset Other Lots of drug interactions (displaced by Aspirin/Nsaids) Sulfonamides (Sulfa-) Sulfisoxazole Ear infections Eye Infections Sulfamethoxazole UTIs Short Acting Traveller’s Diarrhea “Ears, Eyes, UTI’s, Sulfamethizole diarrhea, burns, and meningi…” Sulfadiazine Burns (topical) + toxoplasmosis Long Acting Sulfadoxine Malaria combo Note: Sulfonamides led to the Food, Drug, and Cosmetic act after the elixir poisoning that killed many! Note: Sulf-Trimethoprim combos penetrate the CNS and increase anticoagulant effect  Fluoroquinolones Blocks DNA synthesis MOA 1. Blocks DNA gyrase in G- & topoisomerase in G+ BROAD! Anaerobic bacilli Cocci Activity Mycoplasma pneu. Legionella Chlamydia Myco TB Nausea Headache Ab pain Adverse Dizziness Effects Photophobia Long QT Tendonitis Taste Well absorbed Other 1st - 4th generations Fluoroquinolones (-floxacin) UTI Norfloxacin Broad Ciprofloxacin spectrum! Levofloxacin Used for typhoid, Lomefloxacin resistant TB, Ofloxacin pneumonia, reproductive tract Gram + Gemifloxacin infections, & UTIs infections Sparfloxacin Gram + & Moxifloxacin antianaerobicInf ections  Metronidazole MOA Enters cell and destroys DNA helical structure Broad! Activity Only obligate anaerobes (like C DIFF!) Parasitic diseases (“-iasis” infections) Cramps GI problems Adverse Metallic taste Effects Oral thrush Neuropathy Tachycardia with alcohol Oral/IV Other ½ Life = 8-10 hours Red/brown urine Metronidazole = use for C DIFF!