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Cell wall synthesis Beta Lactams: Inac%vate transpep%dases (penecillin binding proteins) that link pep%doglycan strands Penicillins Natural Penecillins Penecillin G Penecillin V Streptocooci, syphillis Neiserria IV or PO Penecillinase resistant Cloxacillin (Methecillin) main agent used in Canada Streptococci, MSSA IV or PO no dose adjustment in renal failure Aminopenicillins Amoxicillin Ampicillin Streptococci, Enterococoi and some gram –ve (E.coli) IV or PO Ureidopenicillins Azlocillin Piperacillin Mazlocillin More gram-­‐ve spectrum including Pseudomonas Streptococci enterococci No Staph IV only! Clavulanic acid and tazobactum block beta lactamase and extend spectrum Cephalosporins 1st GeneraIon Cefazolin Used in skin, so= %ssue, bone infec%ons and surgical prophylaxis Staph, Strep, E.coli IV only! Cephalexin PO only 2nd GeneraIon Cefuroxime Adds Haemophilus PO or IV 3rd GeneraIon Cefixime PO Strep (NO Staph) Gram –ve (No Pseudomonas) Cefotaxime IV CeJriaxone IV Strep (some) MSSA Haemophilus, Neisseria, enteric gram –
ves (NO pseudo) CeJizidime IV Pseudomonas Strep (NO Staph) Protein Synthesis Glycopep;des Carbapenems Vancomycin IV Blocks D-­‐alanyl Broadest D-­‐alanine cross spectrum linking an%bio%cs Resistance by available acquiring gene cassete that Imipenem IV hanges crooss MSSA, Strep, linking by Enterococcus, alanine to lysine enterics Only Gram +ve Pseudomonas, including anaerobes enterococcus Seizures in MSSA and MRSA presence of For C.difficile it is renal failure or given orally for CNS disease intraluminal pathogen Meropenem IV CSF penetra%on Same as in presence of imipenem some inflama%on Pseudomonas Renal failure may be usse at high sensiIve to one dises No seizure risk Drug monitoring: CBC Ertapenem IV and renal Broad func%on spectrum no required Pseudomonas Once a day Side effects: Neutropenia Inters%%al nephri%s Liver dysfunc%on (elevated AST ALT) Seizures at high doses C. Difficile coli%is is selected by most Beta lactams 10-­‐15% allergy to penecillin Aminoglycosides: act against 30S ribosome Gentamicin IV (TOP) Tobranycin IV (TOP) Enteric Gram –ves including Pseudomonas Synergis%c ac%vity in gram posi%ve treated with beta lactams. Renal Excre%on (dose adjust) Nephrotoxicity and Ototoxicity Tetracycline: reversibly bind to 30S Gram +ve, Gram –ve, Mycoplasma Ricke]sia, Chylmydia, spirochetes, anaerobes Skin rash, photosensi%vity stained teeth and bones Macrolides: reversibly binds to 50S subunit Gram +ve and non enteric gram –ve, Chylamydia and mycoplasma, Mycobacterium avium complex Erythromycin Not o=en used GI upset, drug interac%ons, Cholesta%c hepa%%ts Clarithromycin: PO drug interac%on through P450, less GI upset Azithromycin: prolonged half life less drug interac%ons Clindamycin PO IV: mechanism of ac%on same as macrolides. Used for skin so= %ssue infec%on Anaerobic coverage Linezolid: IV PO Totally synthe%c acts against 50S specific use for resistant gram +ve MRSA and vancomycin resitant enterococcus in blood skin or lung Expensive, significant toxici%es and interac%ons (Bone marrow suppression, thrombocytopenia, peripheral and op%c neuri%s, Interac%ons with MAOI inhibi%ors to cause serotoning syndrome) Nucleic acid synthesis Quinolones: act against DNA gyrase subunits A and B and topo IV, damages DNA and results in cell death Norfloxacin, ciprofloxacin PO Gram –ve (poor gram +ve) only oral agent effec%ve against Pseudomonas Levofloxacin, Moxifloxacin IV PO Strep and gram-­‐ve coverage, chylamydia, mycoplasma, legionella, mycobacteria Renal clearance need dose adjustment (except moxifloxacin which is cleared hepa%c) Trimethioprim Sulphamethoxazole: blocks bacterial folic acid synthesis Staph, gram –ve coverage (poor against Step and ineffec%ve against Pseudomonas), MRSA Pneumocys%s jirovecii Metronidazole: PO IV: Undergoes reduc%ve ac%va%on a=er entry into cell with toxic intermediate products An%anaerobic and an%parasi%c Toxicity: CNS, GI hepta%c metallic taste furry tongue alcohol inteolerance. Poten%ate warfarin an%coagula%on by lowering Vit K produc%on by killing anaerobes Legend Bacteriosta;c Bacteriocidal Route of administra;on Suscep;ble bacteria Other Info Deoxycholate Amphotericin B: IV Binds to ergosterol in fungal cell membrane and causes ion channel leaks and cell death An;fungal Triazoles: inhibit regosterol biosynthesis and CP450 enzymes in fungal resp chain -­‐ Fluconazole Typically used fro candidiasis -­‐ Voriconazole used fro aspergillus -­‐ Itraconazole -­‐ Posaconazole Exhinocandins: (caspofungin, micafungin, anidulafungin) IV Non-­‐
compe%%ve inhibi%on of 1,3-­‐B-­‐glucan synthesis in fungal cell wall used in aspergillus