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187 Cards in this Set
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classification of antimicrobials: inhibit cell wall synthesis (5) |
1. penicillins 2. cephalosporins 3. carbapenems 4. monobactams (aztreonam) 5. vancomycin |
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classification of antimicrobials: alter nucleic acid metabolism (2) |
classification of antimicrobials: alter nucleic acid metabolism 1. Rifamycins 2. Quinolones |
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classification of antimicrobials: inhibit protein synthesis (8) |
classification of antimicrobials: inhibit protein synthesis 1. chloramphenicol 2. tetracyclines 3. glycycycline (tigecycline) 4. macrolides 5. clindamyin 6. streptogramins (quinupristin/dalfopristin) 7. oxazolidinones (lineozolid) 8. aminoglycosides |
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classification of antimicrobials: inhibit folate metabolism |
1. trimethoprim 2. sulfonamides |
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classification of antimicrobials: miscellaneous |
classification of antimicrobials: miscellaneous 1. metronidazole 2. daptomycin 3. polymyxin/colistin |
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protein synthesis: what are the two phases |
1. transcription 2. translation |
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protein synthesis: transcription |
protein synthesis: transcription: DNA transferred to a complementary sequence of RNA nucleotides by RNA polymerase |
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protein synthesis: translation list the three phases |
1. initiation 2. elongation 3. termination |
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protein synthesis: translation initiation |
protein synthesis: translation initation: mRNA + fmet/tRNA + 30S subunit |
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protein synthesis: translation elongation |
protein synthesis: translation elongation
amino acids added to growing polypeptide dictated by mRNA |
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protein synthesis: translation termination |
protein synthesis: translation termination polypeptide released and messenger/ ribosome/ tRNA complex dissociates (70s yields 70S and 50S) |
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protein synthesis inhibitors: aminoglycosides |
blocks the initiation of translation and causes the misreading of mRNA
works on 30S |
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protein synthesis inhibitors: tetracyclines |
blocks the attachment of tRNA to the ribosome
works on 30S |
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protein synthesis inhibitors: terptogramins |
each interferes with a distinct step of protein synthesis
works on 50S |
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protein synthesis inhibitors: macrolides |
prevents the continuation of protein synthesis
works on 50S |
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protein synthesis inhibitors: chloramphenlocol |
prevents peptide bonds from being formed
works on 50S |
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protein synthesis inhibitors: lincosamides |
prevents the continuation of protein synthesis
works on 50S |
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protein synthesis inhibitors: oxazolidinones |
thought to interfere with the initiation of protein synthesis
works on 50S |
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tetracyclines name 3 tetracylines |
1. tetracycline 2. doxycyline 3. minoclycline |
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are tetracyclines bateriostatic or bacteriocidal? what is the spectrum of tetracycline?
what is the 1st line for lyme disease? |
tetracyclines are bacteriostatic spectrum: relatively narrow - some gram +, some gram - - S. pneumoniae, H. influenzae, gonococci, meningococci, E. coli - rickettsiae, chlamydiae, mycoplasma
1st line for lyme disease is tetracycline |
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tetracyclines: pharmacokinetics absorption |
- oral absorption is incomplete, except for minocycline and doxycyline (90% bioavailablity) - for oral, decrease absorption by multivalent cations (aluminum, calcium, magnesium, iron, zinc- containing products) - chelation (binding) of divalent and trivalent cations by teracycline - milk products too |
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tetracyclines: pharmacokinetics distribution |
widely distributed, including CSF (even without inflammation) |
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tetracyclines: pharmacokinetics elimination |
primary route of elimination tetracycline = renal (60% unchanged) minocycline = liver metabolism, renal excrtion deoxyclycline = inactivated in the GI tract, excreted in feces
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which drugs accumulate in kidney disease? |
tetracycline and minocycline accumulate in kidney disease |
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which med is preferred in patients with kidney dysfunction? |
doxycycline |
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tetracyclines safety what is the pregnancy category? list the adverse effects |
- pregnancy category D (as in DON'T) - ADE GI irritation photosensitivity liver toxicity kidney toxicity fanoconi syndrome permanent brown discoloration of teeth vestibular toxicity (minocycline >> doxycycline) wear sunscreen |
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tetracyclines safety: Fanconi sydrome |
- toxic effect on proximal renal tubules - n/v, polyuria, polydipsia, proteinuria, acidosis, glycosuria, aminoaciduria from outdated tetracycline |
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tetracyclines safety: permanent brown discoloration of teeth |
- deposition of drug in teeth and bones - avoid in children up to 8 years old |
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tigecylcine (tygacil) example of drug is it bacteriostatic or bacteriocidal? what is the spectrum?
do you use it as a first line drug? |
glycylcycline (minocycline derivative) - bacteriostatic
spectrum: gram + including MRSA and VRE
gram - including: enterobacteriaceae A. naumannii (but increasing resistance) S maltophilia
Anaerobes including B. fragilis Mycobacteria
this is not a first line drug |
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tigecycline (tygacil) pharmacokinetics what pregnancy category is tegecycline? |
IV only large volume of distribution (~8 L/kg), low mean blood levels 0.62 + or - 0.09 mcg/mL elimination through feces via biliary excretion
pregnancy category D |
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tigecycline (tygacil) ADE |
- similar to tetracyclines - high incidence of nausea/vomiting 30-35% of patients experience n/v - hepactic toxicity possible
if we do not store this medication properly then it breaks down. this medication is known to interfere with teeth and bone development including adult teeth when given as a child |
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macrolides list some examples (3) |
- azithromycin - clarithromycin - erythromycin |
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marcolides: mechanism of action what does it inhibit? is it bacteriostatic or bacteriocidal? |
- inhibit RNA dependent protein synthesis via binding to 50S ribosome - inhibit translocation of aminoacyl transfer-RNA and inhibit polypeptide synthesis - bacteriostatic at normal doses and bacteriocidal at for some organisms at high concentrations
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macrolides: mechanism of resistance |
bacteria are resistant often because of the overuse of z-packs - associated with frequent use +/- high dose - alteration/mutation of ribosomal subunit (high-level) - active efflux pump (low- level) - possible corss- resistance with clindamycin
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macrolides: spectrum of activity |
includes gram + and gram - erythromycin is similar to PCN in spectrum against streptococci but is NOT reliable against staphylococci
clarithromycin/azithromycin have improved activity against some gram negatives including: - H influenzae - neisseria sp. M. catarrhalis, B. burgdorferi, H pylori
- added activity against chlamydia, mycoplasma, legionella ("atypicals") - mycobacteria ("MAC") |
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macrolides: pharmacokinetics |
- absorption: erythromycin base destroyed by gastric acid, enteric coated or esterified - distribution: widely distributed, except CSF - hepatic metabolism |
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macrolides: erythromycin IV form: GI intolerance: drug - drug interactions with CYP450 inhibitor: excretion: prolonged tissue levels: |
macrolides: erythromycin IV form: yes GI intolerance: yes drug-drug interactions with CYP450 inhibitor: yes excretion: biliary prolonged tissue levels: no |
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macrolides: clarithromycin IV form: GI intolerance: drug - drug interactions with CYP450 inhibitor: excretion: prolonged tissue levels: |
macrolides: clarithromycin IV form: no GI intolerance: less drug - drug interactions with CYP450 inhibitor: yes excretion: CYP450/renal prolonged tissue levels: No |
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macrolides: azithromycin IV form: GI intolerance: drug - drug interactions with CYP450 inhibitor: excretion: prolonged tissue levels: |
macrolides: azithromycin IV form: yes GI intolerance: less drug-drug interactions with CYP450 inhibitor: Yes/no excretion: biliary/fecal prolonged tissue levels: yes |
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macrolides: clinical uses |
- respiratory tract infections - chalmydia trachomatis (STD) azithromycin - MAC (mycobacteria) in patients with HIV - H. pylori (peptic ulcer disease) (clarithromycin) - option in pCN allergic patients |
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macrolides: clinical uses respiratory tract infections |
- most are active against gram + like group A streptococci, S. pneumoniae, atypicals - clarithromycin and azithromycin have improved activity against some gram negatives (ie sinusitis, bronchitis, pneumonia) - hospitalization patients use erythromycin and azithromycin |
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macrolides safety: pregnancy categories erythromycin/ azithromycin clarithromycin |
macrolides safety: pregnancy categories erythromycin/ azithromycin category B clarithromycin category C |
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macrolides safety: ADE |
- GI intolerance - cardiac arrhythmias - clarithromycin in community acquired pneumonia and acute COPD - clarithromycin: metallic taste - cholestatic hepatitis - ototoxicity |
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macrolides safety: ADE GI intolerance |
macrolides safety: ADE GI intolerance -GI upset, diarrhea erythromycin is motilin-receptor agonist other two may too |
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macrolides safety: ADE cardiac arrhythmias |
- QT prolongation erythromycin, clarithromycin >>> azithromycin - when combined with azole antifungals it prolongs QTc |
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macrolides safety: ADE CAP and acute COPD |
- with acute exacerbation COP increases cardiovascular events and acute coronary syndrome events - with community acquired pneumonia, increase of cardiovascular events |
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macrolides safety: ADE erythromycin lactobionate injection |
thrombophlebitis - use 0.9% NS only - avoid dextrose (or use Neut) - concentration dependent
sodium load/ fluid overload (b/o dilution for above) |
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macrolides safety: drug interactions |
erythro > clarithro > azithro interactions - new information on azithro interactions - erythro/clarithro: potent inhibitors of CYP3A4 (and 1A2)
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macrolides safety: drug interactions erythro/clarithro |
potent inhibitors of CYP3A4 (and 1A2) - warfarin - simvastatin - carbamazepine, phenytoin - some benzodiazepnes - cyclosporine, tacrolimus |
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cindamycin: mechanism of action is it bacteriostatic or bactericidal? |
binds to the 50S subunit and prevents transpeptidation
bacteriostatic |
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cindamycin: spectrum of activity |
gram positive and anaerobic organisms only - streptococci, staphylococci (methicillin-susceptible strains) - fusobacterium, peptostreptococcus, peptococcus, C. perfringes, B. fragilis (but increasing resistance) |
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cindamycin: clinical uses |
- skin/soft tissue infections - dental (staph and strep) - option for PCN- allergic patients - bacterial vaginosis - acne |
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cindamycin: pharmacokinetics |
- nearly completely absorbed - distributes well, except CSF - > 90% protein bound - extensive liver metabolism |
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cindamycin: pregnancy category |
cindamycin is pregnancy category B |
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cindamycin: adverse effects |
the gamut of GI effects, often diarrhea and lots of stools that lead to pseudomembranous colitis
make sure to ask the patient about GI bc you do not want it progressing |
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linezolid (zyvox) what class is it in? is it bacteriostatic or bactericidal? |
linezolid (zyvox) belongs to the oxazolininone class
lizeolid (zyvox) is bacteriostatic |
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linezolid (zyvox): mechanism of action
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- binds to 23S component of 50S ribosomal subunit - inhibits formation of initiation complex |
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linezolid (zyvox): mechanism of resistance |
single point mutation in 23S component of 50S ribosomal subunit
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linezolid (zyvox): pharmacokinetics |
- completely absorbed when administered orally (100% bioavailability) - widely distributed, including CSF - primarily undergoes non-enzymatic oxidation to two metabolites (~70%)
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linezolid (zyvox): spectrum of activity |
gram + organisms only - streptococci, staphylococci (including MRSA), enterococci (including VRE) - listeria monocytogenes - mycobacteria |
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linezolid (zyvox): clinical uses |
resistant gram positive infections like MRSA and VRE skin/ soft tissue infections, respiratory infections, bacteremia/ sepsis
save this medication for organisms you need to treat |
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linezolid (zyvox): - pregnancy category - ADE |
pregnancy category C adverse effects - bone marrow suppression - weak MAO inhibitor |
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linezolid (zyvox): ADE bone marrow suppression |
- thrombocytopenia (about 2 weeks out) - anemia, leukopenia |
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linezolid (zyvox): ADE weak MAO- inhibitor |
- avoid tyramine containing foods (certain wines and cheeses) - potential for interaction with adrenergic and sertonergic agents (may cause serotonin syndrome) - flushing, increase BP, increase HR, sweating/ increase temperature, dilated pupils
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aminoglycosides list examples (5) |
1. gentamicin 2. tobramycin 3. amikacin 4. neomycin 5. streptomycin |
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aminoglycosides: mechanism of action |
- inhibits protein synthesis by binding to the 30S ribosome - diffuse through porins of outer membrane, but transport across inner membrane depends on electron transport (energy-dependent process) |
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aminoglycosides: mechanism of action inhibits protein synthesis |
inhibits protein synthesis by binding to the 30S ribosome misread DNA producing nonfunctional proteins - polyribosomes split apart, unable to synthesize protein - result = increase in AG transport, increase disruption of bacterial cytoplasmic membranes = eventual cell death |
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aminoglycosides: mechanism of action diffuse through porins |
diffuse through porins of outer membrane, but transport across inner membrane depends on electron transport (energy- dependent process)
- rate limiting and can be blocked or inhibited by divalent cations, reduced pH and anerobic conditions (think: gunky lower respiratory infection)
- transport may be facilitated by penicillins and vancomycin
increase doses to penetrate these areas |
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aminoglycosides: mechanism of resistance |
- inactivation by microbial enzyme - failure to penetrate intracellularly - target: lower affinity of the drug for the bacterial ribosome |
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aminoglycosides: mechanism of resistance inactivation by microbial enzymes |
- most common - genes that encode aminoglycoside- modifying enzymes
note: amikacin is not inactivated by the same enzymes that render the others inactive |
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aminoglycosides: spectrum of activity |
- aerobic gram negative organisms only including P. aeruginosa - gram positive activity limited to combination therapy (combined with cell wall- active agent to achieve synergy) |
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aminoglycosides: clinical uses |
- gram negative coverage (including P. aeruginosa) - gram positive infections at low doses for synergy |
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aminoglycosides: clinical uses gram negative coverage |
- alternative in PCN- allergic patients - respiratory tract infections, UTIs, skin/soft tissue infections, bacteremia/sepsis, intra-abdominal infections - used in combo with other agents (except UTIs) |
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aminoglycosides: clinical uses gram positive coverage |
gram positive infections at low doses for synergy - staphylococci, enterococci (endocarditis) - NOT alone |
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aminoglycosides: pharmacodynamics |
1. rapidly bactericidal 2. concentration- dependent killing increased killing with higher concentrations peak/MIC ratios are important 3. post antibiotic effect (PAE): bacteria fail to grow despite concentrations below the MIC
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aminoglycosides: pharmacokinetics what kind of kinetics? absorption |
linear kinetics absorption: - primarily given IV - poorly absorbed by GI tract - rapidly absorbed after IM administration (painful) - may see these used as inhalation
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aminoglycosides: pharmacokinetics distribution |
- distribution limited - ~25% of lean body weight - low concentrations in respiratory secretions, CSF |
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aminoglycosides: pharmacokinetics elimination |
via kidneys dose adjust in patients with kidney dysfunction |
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aminoglycosides: safety pregnancy category? ADE? |
pregnancy category D adverse effects - nephrotoxicity (8-26%) - ototoxicity - neuromuscular blockade (rare)
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aminoglycosides: safety neprhotoxicity |
- elevated trough concentrations - risk: cumulative dose, duration, elderly - often reversible |
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aminoglycosides: safety ototoxicity |
- largely irreversible - risk: dose and duration, concomitant ototoxins |
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aminoglycosides: safety neuromuscular blockade (rare) |
- inhibition of presynaptic release of acetylcholine and blockage of postsynaptic receptor sites of acetylcholine - associated with anesthesia or the administration of other neuromusuclar blocking agents, rapid infusion |
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aminoglycosides dosing: therapeutic drug monitoring |
- narrow therapeutic index - interpatient variability in concentration - "therapeutic" levels associated with improved response - peaks: efficacy - troughs: toxicity |
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aminoglycosides dosing: administration |
- dose based on lean or adjusted body weight - infuse standard interval dose (EIA) over 60 min
endotoxin- like reactions (shaking, chills, and fever) with EIA dosing |
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aminoglycosides dosing and rational for extended - interval |
aminoglycosides have a concentration- dependent killing - post antibiotic effect - tissue penetration - negligible troughs (undetectable) potentially reduce toxicity (renal accumulation is saturable) - little to no ototoxicity - easier to monitor |
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aminoglycosides dosing and rational for extended - interval what are the two methods? |
- conventional dosing - extended interval dosing |
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aminoglycosides extended - interval dosing exclusion criteria |
exclude patients from aminoglycoside extended-interval dosing if they have - renal dysfunction - pregnancy - elderly - dialysis - endocarditis/ gram- positive synergy - severe fluid overload states - extensive burns |
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aminoglycoside conventional dosing: when do you take peaks and troughs? |
therapeutic drug monitoring is very important - peaks 30 minutes after end of an infusion - troughs - prior to dose |
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aminoglycoside conventional dosing: gram-negative pneumonia desired peaks: desired toughs: |
aminoglycoside conventional dosing: gram-negative pneumonia
desired peaks: 7-9 mcg/mL desired toughs: < 2 mcg/ mL |
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aminoglycoside conventional dosing: gram-negative sepsis, other desired peaks: desired toughs: |
aminoglycoside conventional dosing: gram-negative sepsis, other desired peaks: 5-7 mcg/mL desired toughs: < 2 mcg/mL |
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aminoglycoside conventional dosing: UTI, gram positive synergy desired peaks: desired toughs: |
aminoglycoside conventional dosing: UTI, gram positive synergy desired peaks: 3-5 mcg/mL desired toughs: < 1 mcg/ mL |
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amikacin desired peaks: desired toughs: |
amikacin higher end of range for life threatening infections desired peaks: 20-30 mcg/mL, life threatening infections 25-30 mcg/mL desired toughs: 5-10 mcg/mL |
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aminoglycoside conventional dosing: for EIA |
aminoglycoside conventional dosing: for EIA
draw 1 level 8 - 12 hours after the infusion is completed the refer to graph |
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which of the following protein synthesis inhibitors requires dose adjustment in a patient with acute renal failure?
A. azithromycin B. clindamycin C. linezolid D. Gentamicin |
D. Gentamicin |
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quinolones: mechanisms of action |
targets DNA gyrase and topoisomerase IV |
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quinolones: mechanisms of action what happens when topoisomerases are inhibited? |
topoisomerases are the enzymes responsible for supercoiling DNA (DNA gyrase)
when quinolones inhibit topoisomerase IV they interfere with replicated DNA separation into daughter cells which is required for normal transcription and replication |
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quinolones: mechanism of resistance (3) |
1. alteration in DNA gyrase or topoisomerase enzymes 2. alterations in membrane permeability 3. Active efflux pump |
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quinolones: spectrum of activity (4) |
1. gram negative organisms (enterobacteriaceae, ciprofloxacin, and levofloxacin active against P. aeruginosa) 2. newer agents active agents (levoflaxacin, moxiflocacin) active against Streptococcus pneumoniae 3. Moxifloxacin also has some anaerobic activity 4. activity against "atypicals" |
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quinolones: pharmacodynamics |
- concentration- dependent - bactericidal |
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quinolones: pharmacokinetics absorption |
quinolones: pharmacokinetics absorption - well absorbed after oral administration (> 95%) - impaired absorption with mutivalent cations (same as tetracyclines) |
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quinolones: pharmacokinetics distribution |
- widely distributed - high tissue levels |
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quinolones: pharmacokinetics elimination |
- prodeominantly renal, but can be mixed moxifloxacin predominantly metabolized by liver - differ in half lives- ciprofloxacin (~4 hrs), levofloxacin (~8 hrs), moxifloxacin (~12 hrs)
cipro is taken 2-3 times daily while other are 1x daily |
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quinolones: clinical uses |
- option in PCN- allergic patients (but not for simple infections) - skin/soft tissue infections (levofloxacin, moxifloxacin) - UTI, prostatitis - intra-abdominal infections, febrile neutropenia - respiratory tract infections (pneumonia, bronchitis, sinusitis) - traveler's diarrhea |
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why are quinolones not ideal agents for skin/ soft tissue infections? |
quinolones are broad spectrum and are too broad for simple skin infections |
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quinolones clinical uses: intra-abdominal infections, febrile neutropenia
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quinolones clinical uses: intra-abdominal infections, febrile neutropenia - often in combintation with other agents (metronidazole) - increased resistance of B. fragilis to moxifloxacin |
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quinolones clinical uses: respiratory tract infections (pneumonia, bronchitis, sinusitis) |
quinolones clinical uses: respiratory tract infections (pneumonia, bronchitis, sinusitis)
- hospital- associated (cirpofloxacin, levofloxacin) - community associated (levofloxacin, moxifloxacin) including S. pneumoniae, inappropriate prescribing of cipro for CAP |
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is it appropriate to prescribe cipro for CAP? |
NO cipro does not cover CAP |
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quinolones safety: what pregnancy category? list some ADEs make sure to include the BBWs and allergies |
quinolones are pregnancy category C ADE: - rashes, photosensitivity - arthropathy (joint disease), tendonitis (BBW) - increased liver enzymes - QT prolongation (moxi "prototype"/control) - CNS side effects: dizziness, hallucinations, delirium, seizures - GI: nausea, vomiting, associated with C diff - allergic reaction: glottic angioedema (life threatening, if this happens never give it to the pt again)
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which drug is a prototype of QT prolongation? |
moxifloxacin causes QT prolongation and is used to compare other drugs |
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quinolones drug interactions how much time should be between administration? |
oral: aluminum, magnesium, calcium containing antacids, calcium supplements, iron, sucralfate, dairy, tube feeds (multivalent cations)
- administrations should be separated by 2 hours
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how do folic acid inhibitors work? |
inhibitors interfere with two steps in synthesis of DNA and RNA is required as a cofactor. inhibiting action of folic acid & therefore synthesis cannot go through
- sulfonamids are structural analogs and competitive antagonists of PABA - trimethoprim prevents reduction of dihydrofolate to tetrahydrofolate |
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trimethoprim/ suflamethoxazole (bactrim) what is the spectrum of activity? |
- trimethoprim is similar in spectrum to sulfamethoxazole
gram positives: S. aureus, streptococci (not group A strep) gram negatives: - moraxella catarrhalis, e. coli, p. mirabilis, B. cepacia, N. gonorrhoeae, S. maltophilia - actinomyces, chlamydia, toxoplasmosis, P. jiroveci (PCP) - NO activity vs. Pseudomonas aeruginosa and Bacteroides spp. - resistance is common |
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trimethoprim/ suflamethoxazole mechanism of action |
- SMX inhibits dihydropteroate > inhibits dihydrofolic acid production - TMP inhibits dihydrofolate reductase > blocks dihydrofolic acid going to tetrahydrofolic acid > limits DNA synthesis
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trimethoprim/ suflamethoxazole: mechanism of resistance |
- more slowly with combo vs. each individual component - SMX: usually plasmid mediated w/ gram negative, enzyme mutation - TMP: chromosomal, some plasmid |
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trimethoprim/ suflamethoxazole (bactrim): pharmokinetic/pharmodynamic |
- good oral absorption - good tissue penetration; CNS w/o decent w/o inflammation - some hepatic metabolism (> SMX) - renally (> TMP) excreted via filtration and tubular decretion |
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trimethoprim/ suflamethoxazole (bactrim): common usage |
- UTIs, prostatitis, skin CA- MRSA - PCP pneumonia - GI infections (eg. salmonella, traveler's disease) - stenotrophomonas |
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trimethoprim/ suflamethoxazole (bactrim): ADE |
- caution with folate deficiencies - hypersensitivity (cough, SOB, pulmonary infiltrates) - bone marrow suppression, heme abnormalities - hepatotoxicity; pancreatitis - renal impairment (intersitital nephritis) - derm: rash steven- johnson should be discontinued at the first appearance of skin rash or any sign of adverse reaction
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metronidazole (flagyl) how does it work? |
metronidazole enters a bacterium where, via the electron transport protein ferrodoxin, it is reduced. The drug then binds to DNA and DNA breakage occurs
toxic metabolite |
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metronidazole (flagyl) mechanism of action what is the ONLY kind of bacteria that it covers? what kind of killing does it have? |
- undergoes an intracellular chemical reduction, a mechanism unique to anaerobic metabolism
- reduced metronidazole is cytotoxic interacts with DNA to cause a loss of helical structure, strand breakage resultant inhibition of nucleic acid synthesis = cell death
only provides anaerobic coverage renally eliminated as an ACTIVE metabolite
concentration- dependent killing |
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metronidazole (flagyl) PK/PD |
- good oral bioavailablity, for C. diff it's available in IV or oral - hepatic metabolism - renal elimination of active metabolite
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metronidazole (flagyl) spectrum |
anaerobic bacteria only |
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metronidazole (flagyl) pharmacology |
- IV/PO: excellent oral bioavailability - good distribution including CSF (45%) - liver metabolized (50%) with metabolites renally excreted |
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metronidazole (flagyl) pharmacology, liver metabolism |
live metabolized 50% with metabolites renally excreted - dose adjustment in patients with liver disease - dose adjustment in patients with severe kidney failure not yet on dialysis |
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metronidazole (flagyl) pregnancy category? |
pregnancy category B |
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metronidazole (flagyl) ADE |
systemic, oral or IV - CNS (ataxia, dysarthria, dizziness, confusion, excitation, depression, seizures) - peripheral neuropathy (has to do with time of exposures, doses, etc) - GI, metallic taste - disulfiram- like reaction (must avoid alcohol) - darkened/brownish urine
pt should never be on both oral and IV at the same time |
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metronidazole (flagyl) common causes |
- anaerobic infections - C. difficile colitis - parasitic infections - vaginosis, trichomoniasis, amebiasis |
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which of the following have anti- anaerobic activity A. ampicillin/sulbactam B. Metronidazole C. Clindamycin D. A & B only E. all of the above (A, B, & C) |
E. Ampicillin/sulbactam, metronidazole, clindamycin all have anti-anaerobic activitiy |
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daptomycin (cubicin) give an example describe the mechanism of action |
cyclic lipopetide mechanism of action - binds bacterial membrane = loss of membrane potential plus inhibition of protein, DNA, and RNA synthesis - calcium- dependent binding and insertion of lipophilic tail into gram positive cytoplasmic membrane - ion leakage and collapse of organism leads to cell death
works on gram positive only: MRSA, VRE pokes holes in the wall & destroys integrity reserve drug, not first line |
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daptomycin (cubicin) time or concentration dependent? bactericidal or bacteriostatic? |
concentration dependent bactericidal (including VRE) |
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daptomycin (cubicin) pharmacokinetics - IV, PO? - where does it not penetrate well? - how is it eliminated? - pregnancy category? |
- poorly absorbed orally (IV only) - protein binding: 92% protein bound, primarily albumin - Vd ~ 0.09 L/kg, poor penetration into lungs & CSF renal elimination
pregnancy category B |
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daptomycin (cubicin) ADE |
- myositis (increase creatine kinase (CK) ) - myopathy (weakness, pain, increased CPK) - peripheral nephropathy - N/V/D, constipation - dizziness, insomnia - injection site |
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daptomycin (cubicin) clinical use |
- alternative to vancomycin and/or linezolid for resistant gram- positive infection - not effective for pneumonia |
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vancomycin- resistant enterococcus sp. (VRE)
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- Enterococci are gram positive cocci (pairs/chains) - UTIs, wound infections, bacteremia, endocarditis - high level of antibiotic resistance - drug of choice depends on resistance ampicillin >> vancomycin >> quinupristin/dalfopristin, linezolid, daptomycin |
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pharmacodynamic parameters correlating to efficacy Beta lactams list the drugs within beta lactams pattern of activity PK-PD parameter |
beta lactams: PCN, cephs, cabapenems, monobactams pattern of activity: time-dependent killing PK-PD parameter: T > MIC |
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pharmacodynamic parameters correlating to efficacy
linezolid pattern of activity: PK-PD parameter: |
pattern of activity: time dependent killing PK- PD parameter: 24 hr AUC/ MIC |
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pharmacodynamic parameters correlating to efficacy
vancomycin pattern of activity: PK-PD parameter: |
pattern of activity: time dependent killing and prolonged persistent effects PK- PD parameter: 24 hr AUC/ MIC |
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macrolides clindamycin tetracyclines tigecycline
pattern of activity: PK- PD parameter: |
pattern of activity: time dependent killing and prolonged persistent PK- PD parameter: 24 hr AUC/ MIC |
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aminoglycosides metronidazole quinolones daptomycin |
pattern of activity: concentration dependent killing and prolonged persistent PK- PD parameter: peak/MIC 24 hr AUC/ MIC |
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common antibiotic choices made simple focus on gram negatives cefazolin cefurozime |
STIs, UTIs |
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common antibiotic choices made simple focus on gram negatives ceftriaxone |
CAP, SBP, meningitis |
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common antibiotic choices made simple focus on gram negatives ampicillin/sulbactam |
SSTIs, intra-abdominal, pneumonia |
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common antibiotic choices made simple focus on gram negatives piperacillin/tazobactam aminoglycosides (gent/tobra) leveofloxacin aztreonam
cefepime |
hospital- acquired infections cover P. aeruginosa |
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common antibiotic choices made simple focus on gram negatives imipenem meropenem doripenem Amikacin |
RESERVED for more resistant gram- negative infections Cover P. aeruginosa |
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common antibiotic choices made simple focus on gram negatives tigecycline |
RESERVED for very multi-drug resistant organisms |
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common antibiotic choices made simple focus on gram positive |
remember to look at the side |
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influenza - describe the virus - what is important for prevention? - what drugs are available |
influenza: RNA virus types A & B vaccine is important for prevention: prevention with antiviral agents when allergic to vaccine, outbreaks due to lack of vaccination or poorly matched strain drugs for prevention and treatment: - amatadine and rimantadine - neuramindase inhibitors |
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neuraminidase inhibitors list two and the way they're administered |
- oseltamivir (tamiflu) [PO] - zanamivir (relenza) [oral inhalation]
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neuraminidase inhibitors: mechanism of action |
- inhibit enzyme neuraminidase in influenza A and B - prevent release of new virions |
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neuraminidase inhibitors: clinical uses |
prevention treatment within 48 hours of onset of symptoms - decreased duration of fever and symptom ~30% - decreased severity and risk of complication ~40% - * > 48 hours on severe, complicated, progressive |
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neuraminidase inhibitors: oseltamivir (tamiflu) how old does the patient need to be? who do you take it? how is it eliminated? what are the ADEs? |
oseltamivir (tamiflu) - treatment for children 2 weeks or older; prophylaxsis for one year or older - oral prodrug that is rapidly hydrolyzed by the liver - eliminated unchanged in the urine - ADE: GI discomfort, n/v, take with food
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neuraminidase inhibitors: zanamivir (relenza) how old does the patient need to be? how is it eliminated? what are the ADEs? |
- treatment for a child 7 years or older, prophylaxsis 5 years or older - eliminated unchanged in the urine - ADE: respiratory tract irritation, bronchospasm (avoid in patients with asthma, COPD, or other lung disorders) - oropharyngeal/facial edema |
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how do you take zanamivir and what is the usual dose? |
5 mg/inhalation usual dose 10 mg |
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community acquired pneumonia (CAP) bacterial causes (4) |
- S. pneumoniae - H. influenzae, Staphylococcus aureus, gramnegative bacteria each 3-10% - atypical pathogens - pseudomonas, other in "repeat offenders", previous ventilator, co-morbidities |
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what is the leading cause of CAP? |
S. pneumoniae (20-60%) endemic areas of high macrolide resistance |
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CAP bacterial causes: atypical pathogens |
- including Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila penumoniae
"atypical" because may not produce classic symptoms eg skin rash w/ Mycoplasma, No sore throat w/ legionella; blood streaked phlegm, abdominal pain, diarrhea w/ Legionella |
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CAP treatment options IDSA/ATS guidelines what are the two categories of outpatient patients? |
- outpatient: previously healthy; no risk factors drug- resistant for S.pneumoniae (DRSP) - outpatient w/ comorbidities |
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CAP treatment options IDSA/ATS guidelines outpatient: previously healthy; no risk factors drug resistant for S. pneumoniae (DRSP) |
- macrolide (azithro, clarithro, erythromycin) - doxycycline (weak recommendation) |
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CAP treatment options IDSA/ATS guidelines
outpatient with comorbidities list potential comorbidities list the potential meds to be used what's an important note? |
outpatient CAP with comorbidities could include chronic heart, lung, liver, or renal disease, DM, alcoholism, asplenia, maligancies, immunosuppressing conditions/ use of immunosuppressing drugs; use of antimicrobials within the previous 3 months, risk for DRSP
- respiratory/ antipneumococcal FQ (moxifloxacin, gemifloxacin, levofloxacin [750 mg]) - beta lactam (high dose amox or amox/clav; ceph alternatives; deoxy) plus a macrolide
NOTE: for patients without comorbidities BUT in areas of high DRSP consider employing the above regimen
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CAP treatment options IDSA/ATS guidelines what are the two categories for patients requiring hospitalization |
- for patient requiring hospitalization (non- ICU) - patient requiring hospitalization (ICU) |
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CAP treatment options IDSA/ATS guidelines patient requiring hospitalization (non ICU) |
- respiratory/ antipneumococcal FQ (levofloxacin, moxifloxacin) - cefotaxime/ ceftriazone + macrolide/ doxycycline |
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CAP treatment options IDSA/ATS guidelines patient requiring hospitalization (ICU) |
- beta lactam (ceftriaxone, cefotaxime, amp/sulbactam) + either IV azithromycin or an antipneumococcal FQ - if pseudomonas is a concern then use pip/tazo, imipenem, meropenem, cefepimean antipseudomonal agent + plus an antipseudomonal FQ (levo 750 mg or cipro 400 mg q8h) - if MRSA is a concern, add vanco or linezolid |
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Staphylococcus aureus is it gram positive or negative? list some examples of infections
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staphylococcus aureus gram positive cocci (in clusters) skin infections, pneumonia, meningitis |
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Staphylococcus aureus resistance |
- beta lactamase: penicillin/ ampicillin ineffective >> semiisthethic PCN (eg oxacillin), beta-lactamse INH combination (eg augmentin)
-mecA gene >> altered PCN binding protein = MRSA semisynthetic PCN ineffective >> vancomycin, linezolid |
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skin and soft tissue infections |
- involve any or all layers of the skin, subcutaneous fat, fascia, or muscle - classified by site of infection & causative organism - outcomes |
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skin and soft tissue infections outcomes |
mild SSTIs are often self limiting moderate to severe infections can progress if not treated appropriately - soft tissue infection in diabetics can lead to gangrene and loss of limb - necrotizing infection can be fatal |
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cellulitis define it list symptoms what causes it? |
- an acute inflammation of the skin and subcutaneous fat - symptoms: local tenderness, pain, swelling, warmth, erythema - often secondary to trauma or underlying skin lesion: insect bites, abrasions - often caused by S. aureus and S. pyrogenes (group A strep) |
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cellulitis: treatment for mild celluitis more severe cellulitis cellulitis for immunocompromised patients |
- mild cellulitis: local treatment, cleaning/irrigation with soap and water
- more severe celluitis: should be treated with oral antibiotics targeting gram positive organism. use dicloxacillin, cephalexin, cefprozil, clindamycin, TMP/SMX
- immunocompromised patients, systemic signs and symptoms (fever, increased pain, lymphadenopathy), and those not improving after 2 days on antibiotics require more aggressive therapy |
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emergence of CA-MRSA at risk behaviors/ populations |
at risk behaviors/ populations - prison systems - IV drug use - men having sex with men population - LTCF patients - sports teams - teens - military recruits - households - day care centers - horse farms and pets |
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emergency of CA- MRSA characteristics |
- methicillin R; erythro, clinda S - more virulent (vs. ha- MRSA) - tends to primarily be associated with SSTI but also reported as cause of bacteremia and sever pneumonia - tend to be PVL_ associated with necrotizing infection increased rate of abnormal CXR findings associated with secondary pneumonia associated with clots at bone/joint sites |
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CA-MRSA age: risk factors: infection site: resistance pattern: potential treatment options |
CA-MRSA age: children and younger adults infection site: SSTI (75%), occasionally BSI, OM, RTI resistance pattern: often only beta lactam resistant; frequently susceptible to TMP- SMX, clindamycin, tetracyclines and quinolones potential treatment options: clindamycin, TMP-SMX, minocycline, aminoglycosides, quinlones, vancomycin, linezolid, daptomycin, Q/D |
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HCA-MRSA age: risk factors: infection site: resistance pattern: potential treatment options |
HCA-MRSA age: older adults risk factors: recent/prolonged hospitalization or surgery, ECF, indwelling catheter, HD, recent antibiotics, MRSA exposure infection site: SSTI, RTI, UTI, BSI resistance pattern: frequently multidrug resistant potential treatment options: vancomycin, linezolid, daptomycin, Q?D, TMP- SMX, minocycline |
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new concerns in pediatric and adolescent population |
- unique host: healthy kids/ young people otherwise healthy w/o HA-MRSA risks - 50%+ MRSA infections are Ca-MRSA - 80% present with skin/soft tissue infections ie pustule, furuncles, carbuncles, "spider bite", necrotic lesions, abscesses, celluitis - family/ "social" hx: ease of transmission/ carriers - considerable variation in severity - abscesses must be drained promptly for both good outcome and diagnostic culture no swabbing |
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new concerns in pediatric and adolescent population considerable variation in severity |
- many without fever/systemic signs - severe infection (eg sepsis, [ necrotizing] pneumonia, etc or systemic findings or comorbidities (diabetes, congenital heart disease, etc) should be hospitalized |
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antimicrobial selection - what dictates IV vs PO? |
severity, site and local resistance pattern/available agents will dictate IV vs. PO plus choice based on allergy, toxicity |
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antimicrobial selection CA-MRSA consideration |
- CA-MRSA is resistant to beta lactams and freequently resistant to erythromycin and quinolones
erythro-R may incude clinda-R such that after clinda exposure, isolates may become clind-R (check via D-test that should be negative)
if there's increased risk for community acquired MRSA prevelance the TMP/SMX, clindamycin (depends on local susceptibility), doxycycline (>8 years old) |
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antimicrobial selection when should you question the use of beta lactams? |
question the use of beta lactams if local CA-MRSA is low |
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antimicrobial selection if life-threatening infection, then you |
hospitalize and - vanco and nafcillin + gentamicin for synergy - some add rifampin instead of gent |
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antimicrobial selection if resolution/response is slow/inadequate |
- consider need for additional drainage - consider additional/ alternative therapy |
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urinary tract infections |
- fever, flank pain, urinary urgency/frequency, heme + urine - symptoms differ in infant/s young adults/children/ elderly - complicated vs. uncomplicated: men are always complicated - presence of microorganism in the urinary tract that cannot be accounted for by contamination - lower tract infection: urethritis, cystitis, prostitis, epididymitis - upper tract infection: pyelonephritis - most common organism is E coli HIGH ampicillin resistance |
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UTI treatment options |
- TMP/SMX - nitrofurantoin (cystitis) - tetracyclines - ampicillin + gentamicin - quinolone - cephalosporins - aztreonam - amplicillin/ sulbactam, piperacillin/ tazobactam - carbapenems |
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what kind of bacteria is possible with a UTI? |
P. aeruginosa is possible with risk factors |
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why is a UTI more complicated for men than it is for women? |
men have to get the bacteria to retrograde much further so it's harder for them to get an UTI
look for other reasons than just bacterial infection like women |
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what the most common UTI bacteria for women? |
e. coli |
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acute uncomplicated cystitis and pyelonephritis in women
cystits what medications should you prescribe? |
- nitrofuratonin 100 mg BID x 5 days -TMP/SMX 160/800 mg (DS) BID x 3 days - fosfomycin 3 g single dose - fluoroquinolones (levo, cipro) are highly efficacious in 3 day regimens; propensity for collateral damage - beta- lactams 3-7 day regimes (amox/clav, cefdinir, cefaclor, cefpodoxime-proxetil) are alternatives
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acute uncomplicated cystitis and pyelonephritis in women
cystits nitrofuratonin 100 mg BID x 5 days |
- minimal resistance, propensity for collateral damage - efficacy comparable to 3 days of TMP/SMX |
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acute uncomplicated cystitis and pyelonephritis in women
cystits -TMP/SMX 160/800 mg (DS) BID x 3 days |
- efficacy as assess in numerous clinical trials - if local resistance rates for pathogen are less than 20% or if the infecting strain is known to be susceptible |
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acute uncomplicated cystitis and pyelonephritis in women
acute pyelonephritis what medications should you prescribe? |
- oral cipro |
