Antibiotics - Dr D O\'Brien PDF

Preview

Summary

Dr D O'Brien...

Description

ANTIBIOTICS β-Lactams   

Penicillin’s Cephalosporins Carbapenems

MOA  β-Lactam ring binds covalently and irreversibly on penicillin binding protein of bacteria o PBP responsible for building bacterial cell wall  Bacterial cell wall is disrupted, and cell lysis occurs Side effects  Hypersensitivity (type I) o Pruritus, flushing, urticaria, angioedema, wheezing, laryngeal oedema, hypotension +/- anaphylaxis PK/PD  Penetrate well into inflamed tissues  Penetration into non inflamed meninges is poor, but penetrates inflamed meninges well

Penicillin’s Benzylpenicillin (penicillin G)  IM or IV only o Broken down by stomach acid  Penetration to brain poor o Except inflamed meninges  Resistance is caused by production of β-lactamases (penicillinases) Organisms capable of resistance o S. aureus o E. coli o Pseudomonas aeruginosa o N. gonorrhoeae o Bacillus o Proteus Phenoxymethylpenicillin (penicillin V)  Oral admin Flucloxacillin  Orally or IV  Use declining due to increasing incidence of MRSA  Contraindications: o Pts with history of hepatic dysfunction due to flucloxacillin  Drug interaction with warfarin o Reduces concentration Broad spectrum penicillin’s

ANTIBIOTICS Inactivated by β-lactamase’s Broadened gram -ve coverage Ampicillin Amoxicillin o Ampicillin with added OH group  Increases oral absorption o Orally and IV o Pts with EBV given amoxicillin, 60% will develop a rash Co-amoxiclav  Amoxicillin + beta-lactamase inhibitor (clavulanic acid) o Effective against penicillinase producing organisms  Associated with cholestatic jaundice    

Cephalosporins *all have increased risk of C. difficile  Same MOA as penicillins First Generation: Cefazolin  Active against MSSA  Once daily IV with probenecid Cephalexin  Oral Cefuroxime  2nd generation  IV and oral  Inactive against enterococci, listeria, pseudomonas aeruginosa and MRSA Cefotaxime and ceftriaxone  3rd generation  Iv only  Hydrolysed and become inactive by ESBLs, ampC beta lactamases and carbapenemases  Associated with biliary pseudolithiasis  Fatal reaction in neonates  Therefore cefotaxime used in children Ceftazimide  Activity against pseudomonas aeruginosa  IV only  Hydrolysed and become inactive by ESBLs, ampC beta lactamases and carbapenemases

Glycopeptides Vancomycin

ANTIBIOTICS     

Bind rapidly and irreversibly to the cell walls of susceptible bacteria inhibiting cell wall synthesis – lysis of the cell occurs Vancomycin resistant enterococci spreading globally VRSA and vancomycin intermediate s. aureus o Still rare Only penetrates CSF during inflammation Side effects o Red man syndrome – flushing, itch, tachycardia, hypotension  If rapidly infused  Due to histamine release o Nephrotoxicity

Aminoglycosides Inhibit bacterial protein synthesis o Bind to and inhibit bacterial 30s ribosomal subunit  Parenteral admin only Gentamicin  Side effects o Ototoxicity  Penetrates into perilymph, vestibular and cochlear tissue  Deafness/vestibular damage o Nephrotoxicity  Acute tubular necrosis  Renal failure 

Macrolides  



Inhibit protein synthesis by binding irreversibly to the bacterial 50s ribosomal subunit Side effects: o QT prolongation o Arrhythmias o GI disturbances o Hepatotoxicity o Erythromycin can cause thrombophlebitis when administered IV o Erythromycin and clarithromycin inhibit CYP450 metabolism of warfarin, phenytoin  Can lead to toxic accumulation Azithromycin has greater activity against H influenzae than erythromycin but is less effective against gram +ve bacteria

Quinolones  

Bactericidal Bind to complex of DNA with each of 2 enzymes that are essential for DNA replication

ANTIBIOTICS



o DNA gyrase – gram -ve o DNA topoisomerase IV – gram +ve Side effects: o Tendon injuries o Peripheral neuropathy o QT prolongation o C. difficile infection

Metronidazole  Prodrug – activated by reduction of nitro group  Oral/parenteral/topical  Bactericidal  Extensively metabolised by the liver o Reduce dose in liver disease  Side effects o Increases warfarin levels o Inhibits alcohol dehydrogenase

Tetracyclines   

Binds to the 30s subunit of a ribosome inhibiting protein synthesis Bacteriostatic Side effects o GI disturbances o Photosensitivity o Binds to calcium causing tooth discolouration...