Antibiotics 101

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Antibiotics 101. Puja Van Epps 1/20/14. Beta-lactams. Core PCN structure. Core Cephalosporin structure. Beta-lactams. Beta-lactamases are enzymes produced by some bacteria that provide resistance against beta lactams through hydrolysis of the β- lactam ring. Natural Penicillins. - PowerPoint PPT Presentation

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  • Antibiotics 101Puja Van Epps1/20/14

  • Beta-lactamsCore PCN structureCore Cephalosporin structure

  • Beta-lactams

    Beta-lactamases are enzymes produced by some bacteria that provide resistance against beta lactams through hydrolysis of the -lactam ring

  • Natural Penicillins

    Bicillin L-A (Penicillin G benzathine) IM onlyPenicillin G (IV)Penicillin V = PO

  • Natural Penicillins- Spectra

    GroupsImportant OrganismsGram PositiveGroup A/B/C/G strepS. pneumoniae* viridans streptococci gr.*, Strep milleri*Enterococcus (feacalis>faecium)Gram NegativeNeisseria meningitidis*Pasteuralla multocida Haemophilus ducreyi

    AnaerobesActinomycesClostridial sp.PeptostreptococcusFusobacteriumOtherTreponema pallidum

  • Natural Penicillins

    Bicillin: Primary, secondary, latent and late latent syphillisPCN G: Neurosyphillis; systemic infection due to susceptible bacteria (Streptococci)PCN V: Group A strep pharyngitis

  • Anti-staphylococcal PenicillinsNafcillin, oxacillin, methicillin, dicloxacillin (PO) Penicillinase is a specific type of -lactamase, showing specificity for PenicillinsFirst -lactamase to be identified; PCN R in S. aureusMajor Uses: Methicillin-susceptible S. aureus or Coagulase Negative Staph; PCN-susceptible strains of StreptococciNo gram negative activity

  • Aminopenicillins

    Ampicillin/amoxicillin; Augmentin (Amox-Clav); Unasyn (Amp-Sulbactam)Amp/amox Great for susceptible streps and enterococcus; very limited GN activity; cover anaerobesAddition of Clavulanate or Sulbactam enhances Gram negative activity No activity against MSSA without the beta-lactamase inhibitor.

  • Aminopenicillins

    Important holes in coveragePseudomonas sp.Atypical gram negatives mycoplasma pneumoniae, chlamydia pneumoniae, legionella sp. Enterobacter sp.If susceptible Ampicillin is the DOC for Enterococcus and Listeria

  • Anti-Pseudomonal PenicillinsTicarcillin, Ticar-Clav, Piperacillin, Pip-TazoGenerally good gram positive, gram negative and anaerobic coverage

    Ticarcillin and Piperacillin without their beta-lactamase inhibitor DO NOT cover MSSA

    Important holes in coverage: MRSA (ESBL+, KPC+, or other resistant GN)

    Stenotrophomonas maltophilia Ticar-Clav is second line, Pip/Tazo does not cover.

  • Cephalosporins5 generations, increasing gram negative coverage with each generation

  • First Generation CephalosporinsCefadroxil, Cephalexin (PO)Cefazolin (IV)

    Gram PositiveGroup A, B, C, G StrepStrep pneumoViridans strepMSSAGram NegativeE. coli, Klebsiella sp., Proteus mirabilis

    AnaerobesNo activity

  • First Generation CephalosporinsImportant holes in coverage MRSA, Enterococcus, Pseudomonas, anerobes

  • Second Generation Cephalosporins

    Cefuroxime (IV, PO), Cefotetan (IV), Cefoxitin (IV)In addition to the coverage of 1st generation - H. influenzae, M. catarrhalis, Neisseria sp., and anearobic coverage (variable)Important holes in coverage: - MRSA, Enterococcus, Pseudomonas

  • Third Generation Cephalosporins

    Ceftriaxone, Cefotaxime, Ceftazadime (IV)Cefixime, Cefdinir (PO) In general less active against gram-positive aerobes than previous generations, but have greater activity against gram-negativesCefotaxime and Ceftriaxone have the best gram + coverage in the groupOnly Ceftazadime covers Pseudomonas

  • Third Generation Cephalosporins

    Major holes in coverage - Enterococcus, MRSA, Pseudomonas (except Ceftazidime), +/- Acinetobacter, ListeriaCeftazidime crosses BBB, Ceftriaxone in inflamed meninges

  • Fourth Generation CephalosporinsCefepime (IV)

    gram-positives: similar to first generationgram-negatives: broad, including PseudomonasMajor holes: MRSA, poor anaerobic coverage, listeriaCrosses BBB

  • Fifth Generation CephalosporinCeftaroline (IV)Major advantage: - MRSAMajor holes in coverage: - Pseudomonas, enterococcus and anaerobesCAP, SSTI

  • Cephalosporin ReviewAntipseudomonal Ceftazadime and CefepimeAnti-MRSA Ceftaroline Anti-Enterococcal None (Ceftaroline has in-vitro activity against E. faecalis) Enterobacter sp. can develop resistance to cephalosporins during treatment, therefore not the treatment of choice

  • Carbapenems

    Ertapenem, Doripenem, Imipenem, MeropenemBroadest spectrum of activity Have activity against gram-positive and gram-negative aerobes and anaerobesBacteria not covered by carbapenems include MRSA, VRE, MR coagulase-negative staphAdditional ertapenem exceptions: Pseudomonas, Acinetobacter, Enterococcus

  • Carbapenems

    Major holes in coverage: - Atypicals (Legionella, Mycoplasma) , MRSA, VRE, Stenotrophomonas maltophilia, KPC+

    Ertapenem does not cover: - Pseudomonas, Acinetobacter, Enterococcus

  • Monobactam

    Aztreonam: binds preferentially to PBP 3 of gram-negative aerobesNo gram positive or anaerobic activity Major uses Hospital acquired infections in patients with anaphylaxis to any beta lactams (does not have cross reactivity)Important gram neg holes: Acinetobacter, ESBL+, KPC+

  • Fluoroquinolones Ciprofloxacin, Levofloxacin, MoxifloxacinBroad spectrum of activity, excellent bioavailability, tissue penetrationCipro has poor gram + coverageDisadvantages: resistance, expense, C diffAdvantages: Atypical coverage, Antipseudomonal (Cipro, Levo)

  • AminoglycosidesGentamicin, Tobramycin, Amikacininhibit protein synthesis by irreversibly binding to 30S ribosome, bactericidalFor gram + use in combination with cell wall agentsBroad spectrum gram neg coverage including Pseudomonas and AcinetobacterAlso have mycobacterial coverage

  • Aminoglycosides adverse effectsNephrotoxicityNonoligouric renal failure from damage to the proximal tubulesUnderlying CKD, Age, other nephrotixins, duration, high troughsOtotoxicity8th cranial nerve damage - vestibular and auditory toxicity; irreversible Related to duration of therapy (>2wks)

  • MacrolidesClarithromycin, Erythromycin, AzithromycinInhibit protein synthesis by reversibly binding to the 50s ribosomal unit

  • MacrolidesGram-Positive Aerobes Clarithro>Erythro>AzithroGram-Negative Aerobes Azithro>Clarithro>ErythroNo activity against any Enterobacteriaceae or PseudomonasAnaerobes activity against upper airway anaerobesAtypical Bacteria ExcellentAlso cover Mycobacterium avium complex, Campylobacter, Borrelia, Bordetella, Brucella.

  • Anti-MRSA drugs

  • VancomycinInhibits synthesis and assembly of the second stage of peptidoglycan polymersGram-positive bacteria: excellent coverageMajor uses: MRSA, MSSA (in PCN all), PCN R streptococci No activity against gram-negatives or anaerobesIf MIC to Vancomycin in MRSA is 2, Do not use

  • VancomycinRed-Man Syndromeflushing, pruritus, rashrelated to rate of infusionresolves spontaneously may lengthen infusion

    NOT AN ALLERGY

  • DaptomycinLipopeptide; binds to components of the cell membrane and causes rapid depolarization, inhibiting intracellular synthesis of DNA, RNA, and proteinMajor uses - SAB, Right-sided IE caused by S. aureus, VREIndicated for SSTI, R sided IE

    Do not use for lung infections including MRSA PNA pulmonary surfactant inhibits Daptomycin

  • LinezolidBinds to the 50S ribosomal subunit near the surface interface of 30S subunit causes inhibition of 70S initiation complex which inhibits protein synthesisActive against wide range of Gram + bacteria, limited to no Gram negative or anearobic activityMajor uses MRSA, VRE. Major problem thrombocytopenia with prolonged use (>2wks), bacteriostatic (cidal against Enterococcus)

  • TigecylineBinds to the 30S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis. Broad spectrum of activity including - MRSA, VRE, gram negatives (including resistant GN)Major holes- The 3 Ps Pseudomonas, Proteus and doesnt get in the urine Indicated for complicated SSTI, intra-abdominal infections, CAPMajor problems: GI issues, and shown to have increased mortality in serious infections monotherapy only as a last resort.

  • Clindamycin

    Inhibits protein synthesis by binding exclusively to the 50S ribosomal subunit Major uses - MRSA (some isolates), anaerobic coverage

  • Clindamycin

    A positive D test indicates the presence of macrolide-inducible resistance to clindamycin produced by an inducible methylase that alters the common ribosomal binding site for macrolides, clindamycin

  • Tetracylines Doxycyline, MinocylineGood gram pos, neg and anaerobic coverageMajor uses MRSA, anti-malarial prophylaxis, rickettsial infections, Borrelia burgdorferi

  • Trimethoprim, TMX-SulfaInhibit various steps within the folic acid biosynthetic pathwayGood gram pos and gram neg coverage (CA-MRSA)Important uses: Pneumocystis, Stenotrophomonas maltophilia, NocardiaMajor holesPseudomonas, anaerobes

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