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90 Cards in this Set
- Front
- Back
What are some conditions which effect Vd?
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Spinal cord injury, Liver disease associated with low albumin and/or ascites, Neonates, Burns (initial phases), Acute and chronic renal failure, Severe edema, Peritonitis, Critical illness (ICU patients)
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What are some conditions which effect Cl?
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Cystic fibrosis, Spinal cord injury, Neonates, Burns, Renal dysfunction/failure, Dialysis
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What are some risk factors with aminoglycoside use associated with nephrotoxicity?
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Cmin concentrations > 2 mg/L, cumulative dose; duration of therapy (especially >10 days); dehydration; previous aminoglycoside therapy; female sex; liver disease (cirrhosis, biliary disease); concurrent nephrotoxins; advanced age; previous underlying renal dysfunction
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What class of antibiotic is vancomycin?
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glycopeptide
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What is the spectrum of activity for vancomycin?
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gram positive bacteria ONLY!! Good activity against Staphylococcus aureus (including MRSA), S. epidermidis and other coagulase-negative staphylococci, and streptococci, Active against most Enterococcus species, Activity includes most Gram-positive anaerobes including Clostridium spp
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Where does vancomycin bind for it's MOA?
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vancomycin binds to the D-alanyl-D-alanine terminus of cell wall precursors
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What is the primary change causing vancomycin resistance?
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change of D-alanyl-D-alanine to D-alanyl-D-lactate (this is the primary Mechanism present in vancomycin-resistant enterococci (VRE), particularly E. faecium (VREF)
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What organism is vancomycin used to treat when administered orally?
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Clostridium diff.
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What dosage has recent data shown to be significant for increased risk of vancomycin induced nephrotoxicity?
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>=4 gm/day
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What are possible adverse effects of vancomycin?
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nephrotoxicity, ototoxicity, rash/pruritis, hypersensitivity reactions (ranging from rashes to anaphylaxis), phlebitis and injection site reactions, neutropenia/thrombocytopenia (rare)
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What other drugs increase risk of nephrotoxicity when administered concommitantly w/ vancomycin?
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mycophenolate, aminoglycosides, amphotercin B, cisplatin, cyclosporine
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What class of drug is telavancin?
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telavancin is a lipoglycopeptide, Similar to vancomycin but not exactly; Inhibits cell wall synthesis; also affects bacterial cell membrane function
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What is the spectrum of activity for telavancin?
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telavancin has excellent activity against Gram-positive organisms including MRSA, MRSE, VRE
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What two ways does telavancin cause concentration dependant bacteriocidal activity?
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through inhibition of cell wall synthesis and disruption of bacterial membrane function
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What are the common SE's of telavancin?
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most common is altered taste (metallic or soapy), also foamy urine, N/V and headache
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What is the brand name of telavancin
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Vibativ
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What program helps track and monitor ADE's resulting from telavancin?
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Risk Evaluation and Mitigation Strategy (REMS) program in place due to pregnancy risk
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What tests does telavancin alter results for?
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telavancin can interfere with results of Prothrombin time (PT), International normalized ratio (INR), Activated partial thromboplastin time (aPTT)
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What class is daptomycin?
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daptomycin is a cyclic lipopeptide
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What is the MOA for daptomycin?
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daptomycin binds to gram-positive bacterial cell membrane by a calcium dependent insertion of the lipid tail; rapid depolarization of the cell membrane and efflux of K+ destroying the ion concentration gradient
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What patient population does daptomycin not work well in?
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daptomycin does not work well in patients who are hypocalcemic or patients with respiratory tract infections (daptomycin is inactivated by the lung surfactant)
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What pertinent drug/drug interaction is possible with daptomycin?
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daptomycin can have an increased risk of musculoskeletal toxicity or myopathy when taken concurrently with statins, so patients should be warned.
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What class of drugs is linezolid?
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linezolid is a Oxazolidinone
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What distinguishes linezolid from other antibiotics?
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Orally absorbed (compared to mostly IV only abx's) used for narrow spectrum Gram positive use; bacteriostatic
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What is the MOA for linezolid?
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linezolid inhibits an early step in bacterial protein synthesis; Prevents the formation of the tRNAfMet-mRNA-30S (or 50S) subunit ternary complex
prevents formation of 70S ribosome complex that initiates protein synthesis |
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What are potential SE's of linezolid?
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common GI and HA, elevated hepatic transaminases, reversible bone marrow suppression, taste alterations and tongue discoloration
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What distinguishes linezolid from other multi-drug resistant gram positive infection antibiotics?
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Only agent available both IV and PO for treatment of multidrug-resistant Gram-positive infections
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What is a potential drug interaction with linezolid?
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linezolid is a reversible monoamine oxidase inhibitor; Mild, reversible, and competitive inhibition of both MAO-A and MAO-B, Potential interaction with adrenergic and serotonergic agents
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What is the spectrum of activity and general clinical use for linezolid?
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Good activity against MRSA, MRSE, other Gram-positive organisms, Clinically effective, widely used for VRE, Considered good alternative to vancomycin; Alternative agent for treating variety of serious Gram-positive infections including respiratory tract, skin/soft tissue, bone and joint infections
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What is Synercid?
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Quinupristin/Dalfopristin combination; a streptogramin antibiotic which inhibit bacterial cell growth by blocking bacterial protein synthesis
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What is the spectrum of activity of Synercid?
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Primarily active against only Gram-positive organisms, Good activity against Staphylococcus aureus (including MRSA), S. epidermidis and other coagulase-negative staphylococci, and streptococci, Active against certain Enterococcus species, including vancomycin-resistant E. faecium (VREF), Not active against E. faecalis
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What is the MOA of Synercid?
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The main target of Synercid is the 50S bacterial ribosome.
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What is the most common resistance to Synercid?
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plasmid mediated target modification is the most important mechanism of bacterial resistance, Causes resistance to quinupristin by methylation of common binding sites
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What are possible SE's of Syncercid?
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phlebitis (must be administered via central line), arthralgias/myalgias, elevated hepatic enzymes, HA, N/V
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What are potential drug/drug interactions with Synercid?
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Synercid significantly inhibits CYP 3A4, so other drugs metabolized w/ CYP 3A4 pathway may need adjustment
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What are the atypical bacteria?
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legionella, mycoplasma, chlamydias
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What is the MOA for the tetracyclines?
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Drugs reversibly bind primarily to the 30S ribosomal subunit; Block binding of the aminoacyl-transfer RNA to the acceptor site on the messenger RNA-ribosome complex
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Describe resistance to tetracycline drugs?
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Decreased accumulation of drug due to decreased influx, or acquisition of an energy-dependent efflux mechanism, Mutations of ribosomal binding site also common, Resistance often chromosomal and constitutive, but may also be plasmid-mediated, resistance generally for all (except minocycline)
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What is an important counseling point for tetracycline drugs?
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should be taken on empty stomach, due to significantly altered absorption with food and/or dairy products
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Of the tetracyclines, which drug undergoes a substantial amount of hepatic metabolism?
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minocycline is the only tetracycline to undergo significant hepatic metabolism
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Which of the tetracyclines has the highest rate of renal clearance?
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tetracycline is 60-70% or more cleared renally
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What is the spectrum of activity for tetracyclines?
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Gram + aerobes: intrinsic activity against streptococci and staphylococci, including some strains of MRSA and VRE; Best activity against MRSA: Minocycline > Doxycycline >> others; Gram - aerobes: active against wide range of bacteria but limited by PK considerations; urinary concentrations sufficient for treating UTI due to E. coli and other enteric bacteria; Systemic use usually reserved for treatment of “unusual” infections, e.g. tularemia, plague, Anaerobes: Originally active against many anaerobes, but resistance now limits use; Atypicals: Good activity, especially against Chlamydia
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What are potential ADE's of tetracyclines?
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phototoxicity, deposition in bone and teeth, and hypersensitivity reactions (rare), gastric discomfort, hepatotoxicity, CNS SE's, superinfections (Candida especially)
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What are possible drug interactions with tetracycline?
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tetracyclines have potential for interacting with drugs/foods containing di-/tri-valent cations; warfarin (increased bleeding risk), and oral contraceptives
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What class of drugs is tigecycline?
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tigecycline is a glycylcycline antibiotic
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What is the MOA for tigecycline?
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Inhibits bacterial protein synthesis by binding to 30S ribosomal subunit
Prevents synthesis, elongation of peptide chains |
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What are the important bacteria covered by tigecylin's spectrum of activity?
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Highly active against Gram-positive bacteria; Staphylococcus aureus (including MRSA); S. epidermidis (including MRSE), Most streptococci; Enterococci (including VRE), Excellent activity against many Gram-negative organisms, including nosocomial strains, Enterobacteriaceae, Citrobacter, Acinetobacter, Stenotrophomonas, Poor activity against Pseudomonas aeruginosa, Excellent activity against clinically relevant anaerobes
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What is colistin?
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Colistimethate / Colistin(Polymyxin E) is a large cyclic polypeptide which is bacteriocidal and acts as a cationic detergent
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What is the primary method of elimination for colistin?
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colistin is 65-60% eliminated unchanged in the urine, and must be dose adjusted in renal impairment
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What are the adverse effects of colistin?
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nephrotoxicity in 30-35% of patients, CNS toxicity, rash and pruritis, GI, hypersensitivity rxns, and superinfections (C. diff.)
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What is the spectrum of activity for colistin?
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Activity limited to primarily Gram-negative aerobes
Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter species |
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What is the general infusion rate of vancomycin?
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vancomycin is generally infused over 90 minutes. IM administration is also contraindicated due to extreme pain and potential for muscle necrosis
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Describe the volume of distribution for vancomycin?
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vancomycin follows a two compartment model; Vd of the central compartment is approximately 0.2 - 0.6 L/kg, with an distribution half-life of approximately 20 minutes, vanco is also 50% protein bound
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What is the total body clearance and half-life of vancomycin?
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total body clearance is approximately 0.7 x CrCL and half-life is usually 6-8 hours (depending on renal function)
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What other factors increase a patient's risk of vancomycin induced nephropathy?
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Combination therapy with aminoglycosides, Other concurrent nephrotoxins, Increased age, Previous underlying renal dysfunction, Prolonged, elevated Cmin concentrations ( > 15 mg/L)
Doses > 4 grams/day |
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What is the estimated Vd of vancomycin?
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estimated Vd for vancomycin is 0.7 L/kg (based on TBW, but may also use ADW)
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When are peak concentrations drawn for vancomycin?
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peak concentrations for vancomycin are generally drawn one hour after the end of the infusion to avoid taking a sample during the distribution phase
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What are the common aminoglycosides?
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tobramycin, gentamicin, netilmicin, and amikacin
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What drugs are considered to be concentration dependent?
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aminoglycosides, fluoroquinolones, metronidazole, ketolides, daptomycin, telavancin
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What drugs are considered to be time dependent?
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penicillins, cephalosporins, monobactams, carbapenems, macrolides, clindamycin, oxazolidinones, azithromycin, vancomycin
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If a drug is a concentration dependent drug, what dosing schedule is optimal?
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large single daily dose would be more optimal for a concentration dependent drug
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If a drug is time dependent, what dosing schedule would be optimal?
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time dependent drugs are more effective given smaller doses multiple times daily to maintain drug exposure for the longest possible time
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What is the most common and most clinically relevant resistance to beta lactams?
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Destruction of antibiotic by β-lactamases is by far the most common and most clinically relevant
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What is the most important beta-lactamase produced in gram positive bacteria?
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penicillinase is the most important beta-lactamase produced in S. aureus
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What are examples of plasmid mediated constitutive beta-lactamase producers for gram negative bacteria?
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Haemophilus influenzae, Moraxella catarrhalis, E. coli, Klebsiella pneumoniae, Proteus mirabilis
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What are examples of chromosomally mediated inducible beta-lactamase producers in gram negative bacteria?
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Serratia spp., Pseudomonas aeruginosa, Acinetobacter spp., Citrobacter spp., Enterobacter spp. (SPACE organisms)
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What are the TEM-1, TEM-2, SHV-1
lactamases? |
Most common plasmid-mediated β-lactamases in gram-negative bacteria; Often constitutive; Extended-spectrum cephalosporins (2nd, 3rd, & 4th-generations) resist hydrolysis by these beta-lactamases; β-lactamase inhibitors (e.g., clavulanate, tazobactam) protect parent β-lactam compounds and provide improved activity
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What are ESBL's?
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extended spectrum beta- lactamases; Hydrolyze extended-spectrum cephalosporins (including 3rd- and 4th-gen. cephs) and aztreonam; Carbapenems and cephamycins are spared; Usually inhibited by β-lactamase inhibitors (e.g. clavulanate, tazobactam)
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What is meant by "stable derepression" for beta-lactamase producing bacteria?
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hyperproduction, or Permanent production of large amounts of -lactamase independent of antibiotic exposure, caused by mutation in repressor genes which would normally regulate & decrease expression of the enzymes
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What is a more common and important form of resistance for beta-lactamase producing gram positive bacteria?
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resistance to beta-lactams through altered PBP's (penicillin binding proteins) and may produce either low-level or high-level resistance
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What mechanism of resistance plays an important role in the multidrug resistance of P aeruginosa and Acinetobacter?
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efflux pumps
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What is the most important and clinically relevant mechanism of resistance for aminoglycosides?
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Aminoglycoside-modifying enzymes; Acetyl-, phosphoro-, and adenyltransferases; Significant effects on MIC; Major mechanism of clinically relevant resistance
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What is the most clinically important mechanism of resistance for fluoroquinolones?
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Chromosomal mutations in DNA gyrase and topoisomerase IV most clinically important; Gram-negative bacteria
gyrA mutations major gyrB mutations minor Gram-positive bacteria parC mutations major parE mutations minor |
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What forms of bacterial resistance are most common and important for macrolides and ketolides?
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efflux accross cell membrane is the most common, but alterations of the ribosomal binding site through ribosomal methylation is the most important mechanism of resistance
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What is the most important form of resistance for vancomycin?
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resistance to vanco is uncommon, but can happen through alterations in synthesis of cell wall precursors
D-alanyl-D-alanine --> D-alanyl-D-lactate |
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What are hVISA and VRSA?
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heteroresistand vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus; both are considered non-susceptible
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What are the most clinically important and the most common resistance to have developed in S. aureus?
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penicillinase is the most common resistance, but alterations to PBP's is the most clinically important
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What antibiotics are effective against MRSA?
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vancomycin, linezolid, quinupristin/dalfopristin, daptomycin, telavancin, tigecycline; community-aquired- minocycline, TMP/SMX, clindamycin
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What is the definition of Community-Associated Methicillin-Resistant S. aureus (CA-MRSA)?
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MRSA specimen obtained outside hospital setting or within 48 hours after hospital admission; No clinical culture with MRSA in previous 6 months; None of the following within 1 year before infection:
Hospitalization, Admission to nursing home, SNF, or hospice, Surgery, Hemodialysis, Patient without permanent indwelling catheters or medical devices |
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What are some of the common characteristics of CA-MRSA?
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Presence of SCCmec type IV
Mobile DNA cassette containing the gene that encodes for methicillin resistance (mecA) and other genes necessary for integration into the bacterial chromosome; Presence of gene encoding Panton-Valentine Leukocidin (PVL) toxin, an important virulence factor; Lack of plasmids encoding for multidrug resistance, as is typical of hospital–acquired strains |
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What is the primary mechanism of clinically relevant clindamycin resistance (in CA-MRSA)?
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Primary mechanism of clinically relevant clindamycin resistance is ribosomal methylation; Strains capable of expressing erm gene may be either constitutive (MLSBc) or inducible (MLSBi) phenotypes
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What test is used with CA-MRSA to determine the presence of clindamycin resistance?
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the "D" test
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What are important mechanisms of resistance for Streptococcus pneumoniae?
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alterations in PBP's resulting in either low- or high-level resistance; Ribosomal methylation --> macrolides, clindamycin
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Of the aminoglycosides, what are the most effective for treatment of P. aeruginosa?
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amikacin is best, then tobramycin, then gentamicin for P. aeruginaso
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What is the therapeutic range for severe systemic infections or pneumonia when dosing aminoglycosides?
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8-10 mg/L for gentamicin is appropriate therapeutic range for severe systemic infections or pneumonia
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What is the therapeutic range for less severe systemic infections when dosing aminoglycosides?
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6-8 mg/L for tobramycin is appropriate therapeutic range for less severe systemic infections
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What is the therapeutic range for urinary tract infections when dosing aminoglycosides?
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4-6 mg/L for netilmicin is appropriate therapeutic range for UTI's
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What is the therapeutic range for amikacin?
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25 - 30 mg/L (severe systemic infections, pneumonia);
20 - 25 mg/L (other infections |
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What are the Cmin concentrations recommended for aminoglycosides?
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<2mg/L is recommended for Cmin concentrations of gentamicin, tobramicin, and netilmicin;
<10mg/L is recommended Cmin for amikacin |
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What is the general loading dose for aminoglycosides?
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2 mg/Kg is (using ibw, ADW, or TBW)
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