Antibiotics: A Comprehensive Guide PDF

# Antibiotics: A Comprehensive Guide ## Penicillins ### Antipseudomonal penicillin - Ureidopenicillin (No longer available as a single agent) - Penetrate cell wall of pseudomonas (Unlike aminoampicillin) - Additional adverse effects: Thrombocytopenia - Susceptible to beta lactamases - Main uses: N...

# Antibiotics: A Comprehensive Guide ## Penicillins ### Antipseudomonal penicillin - Ureidopenicillin (No longer available as a single agent) - Penetrate cell wall of pseudomonas (Unlike aminoampicillin) - Additional adverse effects: Thrombocytopenia - Susceptible to beta lactamases - Main uses: None only pipericillin in combination with tazobactam ### Penicillin Drug Development - Natural PCNs - Anti-staph PCNs - Aminopenicillins - Antipseudomonal PCNs - Penicillin/Beta-Lactamase Inhibitor Combinations ### Penicillin/Beta-Lactamase Inhibitor Combinations - Piperacillin/Tazobactam (Zosyn®) - Ampicillin/Sulbactam (Unasyn®) - Amoxicillin/Clavulanate (Augmentin®) - Used for Streptococci, MSSA, enterococci - Better Gram negative rod coverage than parent drugs alone - Anaerobes - Amp/sulbactam and amox/clav are not active vs. Pseudomonas - Susceptibility to one = susceptibility to ALL antistaphylococcal beta-lactams - Leads to good empiric coverage for nosocomial organism - Used for GI infections, abscess ## Cephalosporins ### 1st generation cephalosporin - Cefalozin - Cephalaxin - Cefadroxil - Elimnated renally - Useful for MSSA, streptococci and gram negative rods ### 2nd generation cephalosporin - Cefuroximine - Cefoxitin (Anaerobic activity) - Cefotaten (Anaerobic activity) ### 3rd generation cephalosporin activity - Decreased antistaph activity - Better antistrep activity ### 4th generation cephalosporin activity - Cefepime - Eliminated renally - Cefimine - Cefopodoimine ### Anti-MRSA Cephalosporin - Useful for MRSA and MSSA, strep, Gram neg rod - Not useful for Pseudomonas - Susceptible to beta lactamase ## Cephalosporin/beta-lactamase Inhibitor Combinations - They kill the really resistant bacteria Pseudomonas aeruginosa, Klebsiella pneumonia ## Carbapenems - Imipenum/cilastin, meropenum, Ertapenum - Renally eliminated - Imipenum has higher seizure ## Monobactam - Aztreonam - Only active against GNR including pseudomonas - Renally eliminated - Not cross-reactive with other beta-lactam allergies, except ceftazidime and cefiderocol - Gram-negative infections in patients with allergies to other beta-lactam ## Carbapenem/Beta-lactamase Inhibitor Combinations - Agents: meropenem-vaborbactam, imipenem- (cilastatin)-relebactam - As meropenem and imipenem, plus activity ## Glycopeptides - Vancomycin - Mechanism of action: bind to terminal of D-ala-D-ala chain of peptidoglycan halting cell wall synthesis - Poor bioavailability - Widely distributed, eliminated renally - Gram positive aerobes and anaerobes including MRSA - Do NOT kill beta-lactam susceptible staphylococci as quickly as beta-lactams - Mainly used for MRSA infections - Beta lactams kill MSSA better than Glycopolypeptide - Adverse effects: Vancomycin infusion syndrome (not an allergy) red man syndrome - Nephrotoxicity and ototoxicity - Used for MRSA and Gram positive infections with severe beta ### Lipoglycopeptide(s) - Telavancin (skin/skin, pneuomina from gram positive structure) - Oritavancin (skin/skin infection) - Dalbavancin (same as Dificile) ## Fosfomycin - Mechanism of action: inhibits monomer production - Bactercidal - Renally eliminated - Moderately bioavailable - Attacks Pseudomonas, staph, enterococci ## Cyclic Lipopeptide - Daptomycin - Mechanism of action: inserts into cell membrane of Gram-positive organisms, leading to cation leak, depolarization, and cell death - Bactericidal - Poorly absorbed - Inactive in lung - Excreted renally - Attacks: Gram positive aeroboc anaerobes including MRSA and VRE ## Rifamycins - Dif: Blocks transcription - Bacteriacidal - Cre: Rifampin, Rifabutin, Rifapentine, Rifaximin - Broad Gram-positive and Gram-negative - Mycobacteria - Strong inducers of CYP450, an enzyme system that metabolizes many drugs - Adverse effects: rash, hypersensitivity, hepatotoxicity - Discolors secretions orange-red - Rifapentine has an extended t½ - Rifaximin is not absorbed ## Protein Synthesis Inhibitors - All inhibit translation or transcription, leading to cessation of protein synthesis - Most are bacteriostatic - Against most bacteria ### Aminoglycosides - Gentamicin, Tobramycin, Amikacin, Neomycin, Streptomycin, Plazomicin - Mechanism of action: inhibit translation by binding to 16S rRNA of 30S ribosomal subunit, causing misreading and leading to cell death - Bactericidal - Low bioavailability - Renal elimination - Short half lives - Excellent activity vs. ## Macrolides - Erythromycin - Clarithromycin - Azithromycin - Mechanism of action: inhibit translation by binding 23s rRNA of 50S subunit of ribosome - Bacteriostatic - Achive high intracellular concentrations - Highly bioavailable ### Gl disturbances (N/V/D) - Particularly with higher doses, rash - Drug interactions: - Erythromycin, clarithromycin inhibitors of CYP 450 system - Azithromycin = almost no interaction potential - Resistance due to efflux pump - Uses for pneumonia,URTIS ### Lincosamides - Azithr - Elimin - Strept - includ - Mechanism of Action: Inhibits translation by binding to 50S subunit of bacterial ribosomes - Bacteriostatic - Active against staphylococci (including some MRSA) and streptococci, anaerobes (but not C. difficile) - Adverse effects: C. difficile infection, diarrhea, abdominal pain, nausea, rash - Main uses: SSTIs, anaerobic infections, acne (topical) - Resistance due to - altered target site - some GNR ## Tetracycline - Minocycline, doxycycline - Inhibit translation by binding reversibly to 16S rRNA of 30S ribosomal subunit, blocking tRNA - from binding ribosome- mRNA complex - Bacteriostatic - Active against: Staphylococci including many MRSA - Some strep ### Other Tetracyclines - Tigecycline, Eravacycline, Omadacycline - Modified tetracyclines that have an expanded spectrum - Poor absorption (omadacyline- moderate) - Very high distribution– low plasma concentrations - Long Half life - Most hepatic elimination - Covers many GNR and GPC - Includes VRE and MRSA - Good anaerobic coverage - Do NOT cover Pseudomonas or Proteus sp. - AEs: tigecycline significant ### Nitroimidazoles - Metronidazole, Tinidazole - MOA: interacts with DNA, leading to loss in DNA structure and strand breakage - Bactericidal ## Oxalidinones - Linezolid, Tedizolid - Mechanism of action: binds to 23S rRNA of 50S subunit, preventing protein synthesis by blocking formation of 70S initiation complex - Bacteriostatic - Highly bioavaillible ### Elimination - Linezolid- Dual hepatic metabolism (not via CYP450) and renal elimination - Tedizolid- Hepatic elimination - Linezolid is a weak, reversible inhibitor of monoamine oxidase - Be somewhat cautious of antidepressants when taking linezolid - Gram-positive aerobes – staphylococci (including MRSA), streptococci (including PCN- resistant strains), enterococci (including VRE) ### Adverse effects: - Possibility of serotonin syndrome with some drugs - Bone marrow suppression, particularly thrombocytopenia ## Fluoroquinolones - Drugs include: Ofloxacin, Ciprofloxacin, Levofloxacin, Moxifloxacin, - Mechanism of action: bind DNA gyrase (topo II) or topoisomerase IV, leading to DNA breaks - Bactericidal - Highly bioavailable - “Respiratory FQs” (aka Antipneumococcal FQs) - Have good activity vs. S. pneumoniae - Levofloxacin, moxifloxacin, gemifloxacin, delafloxacin, gatifloxacin - NOT ciprofloxacin, ofloxacin, earlier FQs - Ciprofloxacin used in pneumonia caused by GNR - Largely renally excreted, except moxifloxacin (hepatic) and gemifloxacin (dual) - Activity variable between drugs - All active vs Enterobacterales, atypical organisms - Ciprofloxacin, levofloxacin, and delafloxacin are active vs. P. aeruginosa - Ciprofloxacin has poor Gram-positive activity - Treatment failures with streptococci and staphylococci ### Resistance - Common in P. aeruginosa and S. aureus - Uncommon in streptococci - Very high in E. coli in some parts of the world and country - Adverse effects: lower seizure threshold, N/V/D, photosensitivity, arthropathy, QTc prolongation - Elderly: mental status changes - Absorption reduced drastically with concomitant multivalent cations