Intro to Antibiotics By: Alaina Darby

Outline Intro to Antimicrobials Overview Specific Things to Remember Helpful Tips for the Test Practice Questions

Intro to Antimicrobials Overview

Antibiotic vs Antimicrobial Antibiotics Produced by a microorganism Most of the older antimicrobials can be classified as antibiotics and are, therefore, classified as antibiotics and antimicrobials Example: penicillin Antimicrobials Antibiotics are a subset of antimicrobials Antimicrobials inhibits growth or kills microorganisms Many newer antimicrobials are not natural products, so they are antimicrobials but not antibiotics

Terms Gram stain Selective toxicity Post-antibiotic effect (PAE) Bactericidal Bacteriostatic Spectrum Biofilm Synergy

Concentration vs Time-Dependent Killing Concentration-dependent Cmax/MIC Cmax is the peak concentration Kills at high concentration but doesn’t really matter as much how long they are at the high concentration Can have longer dosing intervals These have a long PAE Example: aminoglycosides Time-dependent T>MIC Has to be above the MIC for an extended period of time but really high concentrations don’t usually increase killing Can give smaller doses more frequently If you are giving the drug IV, then a continuous infusion is good Has little to no PAE Example: vancomycin

Choosing Antibiotics DIAGNOSIS!! Specificity/Spectrum Bactericidal/Bacteriostatic PAE Site of infection Other factors at the site of infection Host factors

Site of action A (aminoglycosides) T (tetracyclines) Helpful memory aid: Think about the stock market. When you play the stock market, you want to buy low and sell high. There are 2 subunits of the ribosome – 50S and 30S. So… A smart person buys AT 30 and CELS for 50. AT: A (aminoglycosides) T (tetracyclines) CELS: C (clindamycin/chloramphenicol) E (erythromycin/other macrolides) L (linezolid) S (streptogramins)

Resistance Intrinsic vs Acquired Mechanisms Intrinsic: already present Acquired: mutation or transmission of genes Mechanisms Receptor alteration Decreased transport into microorganism Increased export (e.g. tetracyclines) Inactivation (e.g. beta-lactams, aminoglycosides) Alternative metabolic pathways (e.g. TMP/SMX) Defect in activation (e.g. metronidazole, 5-flucytosine)

Specific Things to Remember Important points for certain bugs and drugs. Specific Things to Remember

Metabolism/Excretion Almost everything that works on the cell wall is renally excreted. Almost everything that works anywhere else is metabolized.

Spectrum Gram negatives only Pseudomonas MRSA Anaerobes VRE Aztreonam Pseudomonas Cefepime Ceftazidime Piperacillin/Tazobactam (Zosyn) MRSA Vancomycin Ceftaroline Linezolid Streptogramins Daptomycin Anaerobes Clindamycin Metronidazole VRE Linezolid Streptogramins (faecium only) Daptomycin Cephalosporines DO NOT treat enterococcus!

Adverse Effects Almost everything can cause GI disturbances Aminoglycosides Nephrotoxicity Ototoxicity Tetracyclines Dental discoloration Photosensitivity Fluroquinolones Tendon ruptures Penicillins (and sometimes Cephalosporins) Hypersensitivity Clindamycin C. difficile infection Chloramphenicol Gray baby syndrome Telithromycin QT prolongation Sulfonamides Hypersensitivity Hematologic (G6PD deficiency) Kidney stones Metronidazole Disulfram-like reaction Isoniazid Liver failure

Drug Interactions Tetracyclines Macrolides Rifampin Ca2+ chelation Strong CYP inhibitors Especially erythromycin Exception: azithromycin Rifampin Induces everything

Helpful Tips for the Test Some fun memory aids for you!

Clindamycin has good activity in the bone Clindamycin has good activity in the bone. (That was a question my P1 year!) Tigecycline is hepatically and renally excreted… Tigers poop and pee a lot. (I didn’t come up with that.) TMP/SMX treats… T: Tree (respiratory) M: Mouth (GI tract) P: Pee (genitourinary) S: Syndromes (AIDS… like PCP) CefTAZidime and cefEPIme are the only cephalosporins that are EPIc enough to TAZe Pseudomonas. Quinolones are a “flock of sinners” (-floxacins) that gyrate (DNA gyrase) their hips at night (photosensitivity). They dance and party so much that their tendons rupture and they have heart problems (QT prolongation).