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125 Cards in this Set
- Front
- Back
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with time-dependence, bactericidal activity continues as long as serum concentrations are _____
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>MBC (minimum bactericidal concentration)
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enzyme that catalyzes the cross-linking of peptidoglycan layer
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transpeptidase
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bactericial activity of beta lactams: concentration _____ and time _____
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independent
dependent |
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B-lactams: mech of action
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inhibits transpeptidation rxn which is the final step in peptidoglycan synthesis
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activity of B-lactam against a gram neg bacteria depends on what 3 things:
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ability to penetrate outer membrane
beta-lactamase sensitivity intrinsic ability to bind to penicillin-binding proteins |
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vancomycin: mech of action
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acts on 2nd stage of cell wall synthesis by inhibiting the utilization of lipid intermediates in PDG synth
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vancomycin: concentration____ and time_____
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independent
dependent |
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bacitracin: mech of action
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bactericidal for gram pos
inhibits the dephosphorylation step, preventing regeneration of the lipid carrier |
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polymyxin B: mech of action
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bactericidal for gram-neg
nonspecific for cell membranes of any type....highly toxic |
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daptomycin: mech of action
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binds to bacterial membranes and causes rapid depolarization of the membrane, results in cell death
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daptomycin: only activity is vs ____
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aerobic gram +
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bacterial ribosomal subunits are ___ and ___
mammalian subunits are ___ and ___ |
30S and 50S
40S and 60S |
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aminoglycosides: concentration ____
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dependent
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aminoglycosides: bactericidal or static? mech of action?
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bacteriocidal
interacts with 30S subunit receptor protein (inhibits protein synth) |
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tetracyclines: bacteriocidal or static? mech of action?
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static
binds to 30S unit prevents chain elongation |
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chloamphenicol: bacteriocidal or static? mech of action?
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static
binds to 50S inhibits peptidyl transferase, prevents chain elongation by inhibiting peptide bond formation |
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macrolides: give some examples
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erythromycin
azithromycin clarithromycin |
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macrolides: bacteriocidal or static? mech of action?
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static
binds reversibly to 50S subunit P site inhibits translocation by preventing proper association of the peptidyl-tRNA chain with its binding site....prevents chain elongation |
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douching is ___
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BAD
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clindamycin: mech of action
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binds to 50S unit
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quinupristin/dalfopristin: mech of action
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binds irreversibly to diff sites on the 50S unit
inhibits translocation of mRNA at the elongation step |
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linezolid: bacteriocidal or static? mech of action?
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static
binds to 50S unit |
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sulfonamides: class? bacteriocidal or static?
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nucleic acid synthesis inhibitors
static |
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sulfonamides: mech of action
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structural analogs of PABA
compete with PABA for binding to the enzyme dihydropteroate synthetase |
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trimethoprim: bacteriocidal or static? mech of action?
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static
competitive inhibitor of dihydrofolate reductase (inhibit nucleic acid synthesis) |
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SMZ-TMP: mech of action
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sequential blockade of folic acid synthesis results in synergism
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rifampin: bactericidal or static? mech of action
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bactericidal
selective toxicity to bacterial RNA polymerase |
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quinolones: cidal or static? mech of action?
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cidal
inhibit DNA gyrase resulting in inhibition of DNA replication |
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nitrofurantoin: cidal or static? mech of action?
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cidal
enzymatic reduction of nitrofurans produces produces toxic intermediates which cause DNA strands to break |
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metronidazole: bacteriocidal for ____ bacteria
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anaerobic
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metronidazole: mech of action
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nitro group is reduced to reactive intermediates by bact enzymes which destroy DNA
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beta lactams that are resistant to beta-lactamases
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nafcillin
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drugs that inactivate beta lactamase
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clavulanate potassium
sulbactam sodium tazobactam sodium |
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aztreonam: resistant to most ___
ineffective vs ____ |
beta-lactamases
ineffective vs MRSA |
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what is the broadest spectrum beta-lactam
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imipenem
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major mechanism of vancomycin resistance
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acquired resistance
enzymes produce a modified PDG side chain to which vanc cannot bind |
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aminoglycoside resistance mechanism
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enzymatic inactivation
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mechanism of chloramphenicol resistance
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production of chloram acetyltransferase which inactivates the chloram
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most common resistance mechanism to macrolides
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altered ribosomal proteins
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rifampin resistance mechanism
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altered DNA-dependent RNA polymerase
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fluoroquinolone resistance mechanism
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mutations in the gene coding for DNA gyrase
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sulfonamide resistance mechanism
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production of increased PABA
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trimethoprim resistance mechanism
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altered dihydrofolate reductase which is TMP-insensitive
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MRSA is also called
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hospital acquired MRSA
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MRSA: mechignism of action
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modified PBP2a confers reduced affinity for beta-lactams
all beta lactams ineffective |
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DOC for bacteremia associated with MRSA
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IV vancomycin
also IV daptomycin |
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DOC for infective endocarditis associated with MRSA
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IV vancomycin
also IV daptomycin |
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DOC for pneumonia associated with MRSA
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IV vancomycin
also linezolid |
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DOC for osteomyelitis associated with MRSA
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IV vancomycin
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DOC for meningitis associated with MRSA
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IV vancomycin
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DOC for vancomycin-intermediate resistant S. aureus
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linezolid
daptomycin |
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1s line therapy for acute OM
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high dose amoxicillin
high risk groups should receive amoxicillin/clavulanate 14:1 high dose |
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acute OM: alternative agents
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if urticaria/anaphylaxis did not occur: cefuroxime axetil
if did occur: azithromycin if pt is allergic to beta lactams and pen resistant s pneumoniae: clindamycin |
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meningitis DOC
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penicillin or ampicillin may be used for susceptible strains
for empiric therapy, initiate with 3rd gen cephalo AND vancomycin until susceptibility is determined |
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2nd most common bacterial cause of nosocomial urinary tract and surgical wound infx
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enterococci
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2 major enterococcal pathogens
which has higher resistance rate? |
e. faecalis
e. faecium (higher) |
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risk factors for acquisition of VRE
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previous vancomycin use
immunosuppression use of indwelling catheters |
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with VRE, its best to reserve po vancomycin for _____
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antibiotic associated pseudomembranous colitis
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DOC for non-VRE infections
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penicillin or ampicillin
alt: vancomycin for penicillin allergy |
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non-VRE enterococcal bacteremia suggested therapy
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combination of penicillin or ampicillin plus an aminoglycoside
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DOC for VRE with high level penicillin resistance
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linezolid
daptomycin |
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community acquired MRSA is typically susceptible to what 3 drugs
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TMP-SMX
clindamycin tetracycines |
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what is the most common cause of skin/soft tissue infections in the ER
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comm acquired MRSA
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what are the 2 naturally occuring penicillins
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G and V
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penicillin G and V: good activity vs ____ but sensitive to ____
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gram pos
beta lactamase |
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nafcillin features
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penicillinase resistant
narrow spectrum of activity vs gram pos inactive vs gram neg |
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ampicillin and amoxicillin: class? susceptible to ____, increased activity vs ____
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aminopenicillin
beta lactamase gram neg |
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ticarcillin w/clavulanate, piperacillin, piperacillin w/tazobactam: class? sensitive to? highest activity vs ____, active vs _____
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antipseudomonal
staphylococcal penicillinases gram neg pseudomonas |
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90% of penicillin elimination is via ____
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tubular secretion
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penicillin G and V are DOC for what bacteria
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groups A (pyogenes) and B (agalactiae) streptococci
viridans streptococci t. pallidum |
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penicillin G is DOC for pneumonia caused by _____
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penicillin sensitive s. pneumoniae
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DOC for meningitis
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ampicillin
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DOC for Lyme dz during pregnancy and young children
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amoxicillin (preferred over doxy)
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DOC for septicemia, pneumonia, and intra-abdominal sepsis caused by p. aeruginosa
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piperacillin
ticarcillin |
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most useful combo for monotherapy of potential polymicrobial infx
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ampicillin/sulbactam
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type III allergic rxn to penicillin:
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serum sickness is most common
interstitial nephritis |
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type IV allergic rxn to PCN
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contact dermatitis
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interstitial nephritis is most common with what penicillin
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methicillin
but also has occurred with penicillin G and ampicillin |
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bleeding abnormalities are most common with what PCN
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ticarcillin
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penicillin V and ampicillin should be eaten with food or on empty stomach?
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empty stomach
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cephalosporins: all are ineffective vs ______ (with one exception)
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enterococci
Listeria MRSA (except ceftaroline) |
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1st gen cephalo: similar to? most active against?
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ext spectrum aminopenicillins
gram pos |
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2nd gen cephalo: comparison to 1st gen? activity against g+ and g-?
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broader spec but more resistant to beta lactamase
good activity against g+ increased activity against g- |
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3rd gen cephalo: gram+ and - activity? how resistant to beta lactamase?
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highest g- activity
lowest g+ activity highest resistance to beta lactamases |
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preferred drug class beta-lactamase producing H. influenza meningitis
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3rd gen cephalo (ceftriaxone, cefotaxime)
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what 3rd gen cephalo is an antipseudomonal
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ceftazidime
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what cephalo generations have the best CSF penetration
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3rd
virtually zero for 1st and 2nd |
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cephalo elimination: what drug blocks its tubular secretion
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probenecid
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1st gen cephalo: ineffective vs ________ (6)
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b. fragilis
h. flu Listeria MRSA PRSP enterococci |
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what 1st gen cephalo is used for surgical prophylaxis
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cefazolin
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DOC combo for parenteral therapy of PID
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cefoxitin/doxycycline
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cefoxitin has excellent activity vs ____ and ____
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anaerobes
facultative g- bacilli |
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DOC for empirical therapy of s. pneumoniae meningitis
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cefotaxime or ceftriaxone
+ vancomycin |
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cefotaxime and ceftriaxone: DOC for what 2 conditions
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beta lactamase producing H flu meningitis
empirical therapy of s. pneumoniae meningitis |
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DOC for gono genital tract infx due to penicillinase-producing n. gonorrhea (PPNG)
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ceftriaxone
combined with doxy or azithro for chlamydia coverage |
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the only orally administered 1st line option for uncomplicated gonorrhea
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cefixime
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what beta lactam has the highest activity vs pseudomonas
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ceftazidime
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DOC for empiric drug therapy of neutropenic fever
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cefepime (4th gen ceph)
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cephalosporins: ADR
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allergic rxns most common
hematological rxns (hypoprothrombinemia) disulfiram rxn - when alcohol is ingested w/in 48-72 hrs after dosing with a cephalo |
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aztreonam: activity vs g+ aerobes and anaerobes
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NO activity
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clinical use of aztreonam
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g- aerobes
not indicated for meningitis |
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imipenem/cilastatin: mech of action
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bactericidal, broad spec beta lactam
highly resistant to beta lactamase active against ESBL (ext spec beta lactamase) producing organisms |
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cilastatin: competitive inhibitor of ____? prevents what?
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renal dihydropeptidase
prevents renal metabolism of imipenem, blocking production of a nephrotoxic metabolite |
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imipenem/cilastatin: active against ____
ineffective against ____ |
broad spec antibacterial against gram+ and - aerobes and anaerobes
ineffective vs MRSA and VRE |
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DOC for neutropenic fever
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imipenem/cilastatin
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imipenem/cilastatin: ADRs
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seizures
CNS disorders renal disease |
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meropenem: not degraded by ____ so does not require ____
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renal dehydropeptidase
cilastatin |
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vancomycin: bacteriostatic vs ____, synergistic bactericidal when combined with an _____, ineffective against ____
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enterococci
aminoglycoside gram-, mycobacteria, anaerobes (bacteroides), intracellular organisms (rickettsia, chlamydia) |
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vancomycin: how is it eliminated
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glomerular filtration of unchanged drug
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vancomycin: DOC for what 8 conditions
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septicemia, pneumonia, wound infx caused by MRSA
septicemia, infected prosthetic devices caused by MRSE meningitis, ocular infx caused by s. pneumo (in combination with ceftriaxone) enterococcal endocarditis (in combination with aminoglycoside) |
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vancomycin: ADRs
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rapid IV causes massive histamine release
pruritus with macular rash, flushing ototoxicity and nephrotoxicity |
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bacitracin: features
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bactericidal for gram+ but too nephrotoxic to be used systemically
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fosfomycin: first anti-infective agent to be approved as single dose tx for ____
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UTIs
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first anti-infective agent to be approved as single dose tx for UTIs
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fosfomycin
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polymyxin B: effective against ____, no activity against ____
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gram- bacilli
gram+, anaerobes, and fungi |
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drug of last choice for life threatening pseudomonas infx
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polymyxin B
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polymyxin B: ADRs
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neurotoxicity: paresthesias, dizziness, vertigo
nephrotoxicity: azotemia, increased SCr, acute tubular necrosis |
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daptomycin: mech of action
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binds to bact membranes and cause rapid depol, leads to inhibition of protein, RNA, and DNA synth
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daptomycin: indications
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complicated skin infx, including MRSA
DOC for vancomycin-intermediate and vanco-resistant s. aureus alternative for e. faecalis/faecium DOC for VRE: bacteremia, systemic infx, endocarditis |
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DOC for VRE (bacteremia, systemic infx, endocarditis)
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daptomycin
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daptomycin: dosing
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IV infusion over 30 min qd x 7-14 days
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daptomycin: ADRs
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increased incidence of myopathy
potential DI with statins |
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telavancin: mech of action
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inhibits cell wall synth
disrupts membrane barrier fxn |
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telavancin: indications
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complicated skin and skin structure infx
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telavancin: ADRs
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pregnancy test required (use is avoided unless benefits outweigh risks)
infusion-related reactions prolongs the QTc interval |
