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Antibiotic Usage
Antibiotic Usage
Antibiotic Usage
Intracellular: 2/3
Extracellular: 1/3
Plasma: 1/4
Interstitial fluid: 3/4
Pharmacodynamics vs pharmacokinetics
Bactericidal vs bacteriostatic
o Cidal for deep-seated infections but inflammation results
o Static better for slow-growing bacteria
Time (beta lactams) vs Concentration (fluoroquinolones, aminoglycosides)
o AUC/MIC: depends on concentration, vancomycin, fluoroquinolones,
aminoglycosides
o Time/MIC: time dependent, beta lactams. t/MIC >40%correlated with
survival
o Peak/MIC: concentration dependant, extended interval
aminoglycosides, Peak/MIC > 8 clinical cure, less toxicity!
Cell wall
o Penicillin, cephalosporins, carbapenems, vancomycin
DNA synthesis
o Metronidazole
DNA gyrase
o Fluorquinolones
RNA polymerase
o rifampin
Protein synthesis inhibitors
o 50s: macrolides, clindamycin, linezolid
o 30s: Tetracycline, aminoglycoside
Beta lactams: inhibit cell wall synthesis by binding to PBP in wall membrane,
prevent linking, autolytic
Fight beta-lactamase inhibitors (clavulanic acid, tazobactam) to combat
resistance!
Allergies: Allergy to R chain of penicillins so cephalosporins usually ok 99%
o I: IgE, anaphylaxis, within 1h
o II: cytotoxic: IgG, IgM: hemolytic anemia and other blood stuff >3d
o III: immune complex: serum sickness: 1-2weeks
o IV: T-cell mediated: contact dermatitis, rashes, >3d
Penicillin
o Penicillin: streptococci: Bacterial pharyngitis, endocarditis
o Cloxacillin: MSSA: bacteremia, endocarditis, bone/joint infection
o Piperacillin/tazobactam: gram + and -, pseudomonas, anaerobes:
febrile neutropenia, intraabdominal, polymicrobial, sepsis unknown
source
Cephalosporin: no activity vs enterococci or MSSA, increasing gm- activity
with generations, 4th gen have broad gm+ and activity.
o Cephalexin: MSSA, beta hemolytic strep: SSTI
o Ceftriaxone: Strep, gm-, Ecoli
o Ceftazidime: pseudomonas aeruginosa
Carbapenem (last gun)
o Meropenam: ampC producing citrobacter spp: for post trauma/surgical
menigitis, polymicrobial infections, pseudomonas, broad spectrum.
Glycopeptides/Lipopeptides: activity against gm+ and beta-lactam resistant (MRSA).
Bactericidal. Vanco is slow acting because long distribution phase. PO vanco not
systemically absorbed so only use for C diff. Daptomycin inactivated by lung
surfactant so not effective for pneumonia. Vanco troughs 30min pre dose, ensure
are between 15-20mg/L.
Vancomycin:
o Inhibition of bacgterial cell wall synthesis, early phase of beta-lactams
o Gm+ enterococci, MRSA, coag neg staph
Lipopeptides: Daptomycin
o Distrupt cell membrane
o Calcium dependent to enter cells, disrupts DNA/RNA/protein synthesis
Aminoglycosides: inhibit 30S, bactericidal, renal elimination, nephrotoxicity
Gentamicin:
o gm-, pseudomonas, synergy vs strep and enterococci w/
bacteremia/endocarditis, with beta lactam or vancomycin
o for Drug resistant UTI, gm -,
Macrolide inhibit 23s ribosome in 50S subunit
Active vs intracellular organisms, bacteriostatic
Azithromycin long half life, vs mycoplasma, chlamydophilia, legionella, M
catarrhalis, C trachomatis, mycobacterium avium complex
For MAC tx in HIV, combo with beta lactam for CAP, STI