Ios 10 Exam 2

Front 1

What are some conditions which effect Vd?

Back 1

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)

Front 2

What are some conditions which effect Cl?

Back 2

Cystic fibrosis, Spinal cord injury, Neonates, Burns, Renal dysfunction/failure, Dialysis

Front 3

What are some risk factors with aminoglycoside use associated with nephrotoxicity?

Back 3

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

Front 4

What class of antibiotic is vancomycin?

Back 4

glycopeptide

Front 5

What is the spectrum of activity for vancomycin?

Back 5

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

Front 6

Where does vancomycin bind for it's MOA?

Back 6

vancomycin binds to the D-alanyl-D-alanine terminus of cell wall precursors

Front 7

What is the primary change causing vancomycin resistance?

Back 7

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)

Front 8

What organism is vancomycin used to treat when administered orally?

Back 8

Clostridium diff.

Front 9

What dosage has recent data shown to be significant for increased risk of vancomycin induced nephrotoxicity?

Back 9

>=4 gm/day

Front 10

What are possible adverse effects of vancomycin?

Back 10

nephrotoxicity, ototoxicity, rash/pruritis, hypersensitivity reactions (ranging from rashes to anaphylaxis), phlebitis and injection site reactions, neutropenia/thrombocytopenia (rare)

Front 11

What other drugs increase risk of nephrotoxicity when administered concommitantly w/ vancomycin?

Back 11

mycophenolate, aminoglycosides, amphotercin B, cisplatin, cyclosporine

Front 12

What class of drug is telavancin?

Back 12

telavancin is a lipoglycopeptide, Similar to vancomycin but not exactly; Inhibits cell wall synthesis; also affects bacterial cell membrane function

Front 13

What is the spectrum of activity for telavancin?

Back 13

telavancin has excellent activity against Gram-positive organisms including MRSA, MRSE, VRE

Front 14

What two ways does telavancin cause concentration dependant bacteriocidal activity?

Back 14

through inhibition of cell wall synthesis and disruption of bacterial membrane function

Front 15

What are the common SE's of telavancin?

Back 15

most common is altered taste (metallic or soapy), also foamy urine, N/V and headache

Front 16

What is the brand name of telavancin

Back 16

Vibativ

Front 17

What program helps track and monitor ADE's resulting from telavancin?

Back 17

Risk Evaluation and Mitigation Strategy (REMS) program in place due to pregnancy risk

Front 18

What tests does telavancin alter results for?

Back 18

telavancin can interfere with results of Prothrombin time (PT), International normalized ratio (INR), Activated partial thromboplastin time (aPTT)

Front 19

What class is daptomycin?

Back 19

daptomycin is a cyclic lipopeptide

Front 20

What is the MOA for daptomycin?

Back 20

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

Front 21

What patient population does daptomycin not work well in?

Back 21

daptomycin does not work well in patients who are hypocalcemic or patients with respiratory tract infections (daptomycin is inactivated by the lung surfactant)

Front 22

What pertinent drug/drug interaction is possible with daptomycin?

Back 22

daptomycin can have an increased risk of musculoskeletal toxicity or myopathy when taken concurrently with statins, so patients should be warned.

Front 23

What class of drugs is linezolid?

Back 23

linezolid is a Oxazolidinone

Front 24

What distinguishes linezolid from other antibiotics?

Back 24

Orally absorbed (compared to mostly IV only abx's) used for narrow spectrum Gram positive use; bacteriostatic

Front 25

What is the MOA for linezolid?

Back 25

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

Front 26

What are potential SE's of linezolid?

Back 26

common GI and HA, elevated hepatic transaminases, reversible bone marrow suppression, taste alterations and tongue discoloration

Front 27

What distinguishes linezolid from other multi-drug resistant gram positive infection antibiotics?

Back 27

Only agent available both IV and PO for treatment of multidrug-resistant Gram-positive infections

Front 28

What is a potential drug interaction with linezolid?

Back 28

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

Front 29

What is the spectrum of activity and general clinical use for linezolid?

Back 29

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

Front 30

What is Synercid?

Back 30

Quinupristin/Dalfopristin combination; a streptogramin antibiotic which inhibit bacterial cell growth by blocking bacterial protein synthesis

Front 31

What is the spectrum of activity of Synercid?

Back 31

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

Front 32

What is the MOA of Synercid?

Back 32

The main target of Synercid is the 50S bacterial ribosome.

Front 33

What is the most common resistance to Synercid?

Back 33

plasmid mediated target modification is the most important mechanism of bacterial resistance, Causes resistance to quinupristin by methylation of common binding sites

Front 34

What are possible SE's of Syncercid?

Back 34

phlebitis (must be administered via central line), arthralgias/myalgias, elevated hepatic enzymes, HA, N/V

Front 35

What are potential drug/drug interactions with Synercid?

Back 35

Synercid significantly inhibits CYP 3A4, so other drugs metabolized w/ CYP 3A4 pathway may need adjustment

Front 36

What are the atypical bacteria?

Back 36

legionella, mycoplasma, chlamydias

Front 37

What is the MOA for the tetracyclines?

Back 37

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

Front 38

Describe resistance to tetracycline drugs?

Back 38

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)

Front 39

What is an important counseling point for tetracycline drugs?

Back 39

should be taken on empty stomach, due to significantly altered absorption with food and/or dairy products

Front 40

Of the tetracyclines, which drug undergoes a substantial amount of hepatic metabolism?

Back 40

minocycline is the only tetracycline to undergo significant hepatic metabolism

Front 41

Which of the tetracyclines has the highest rate of renal clearance?

Back 41

tetracycline is 60-70% or more cleared renally

Front 42

What is the spectrum of activity for tetracyclines?

Back 42

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

Front 43

What are potential ADE's of tetracyclines?

Back 43

phototoxicity, deposition in bone and teeth, and hypersensitivity reactions (rare), gastric discomfort, hepatotoxicity, CNS SE's, superinfections (Candida especially)

Front 44

What are possible drug interactions with tetracycline?

Back 44

tetracyclines have potential for interacting with drugs/foods containing di-/tri-valent cations; warfarin (increased bleeding risk), and oral contraceptives

Front 45

What class of drugs is tigecycline?

Back 45

tigecycline is a glycylcycline antibiotic

Front 46

What is the MOA for tigecycline?

Back 46

Inhibits bacterial protein synthesis by binding to 30S ribosomal subunit
Prevents synthesis, elongation of peptide chains

Front 47

What are the important bacteria covered by tigecylin's spectrum of activity?

Back 47

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

Front 48

What is colistin?

Back 48

Colistimethate / Colistin(Polymyxin E) is a large cyclic polypeptide which is bacteriocidal and acts as a cationic detergent

Front 49

What is the primary method of elimination for colistin?

Back 49

colistin is 65-60% eliminated unchanged in the urine, and must be dose adjusted in renal impairment

Front 50

What are the adverse effects of colistin?

Back 50

nephrotoxicity in 30-35% of patients, CNS toxicity, rash and pruritis, GI, hypersensitivity rxns, and superinfections (C. diff.)

Front 51

What is the spectrum of activity for colistin?

Back 51

Activity limited to primarily Gram-negative aerobes
Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter species

Front 52

What is the general infusion rate of vancomycin?

Back 52

vancomycin is generally infused over 90 minutes. IM administration is also contraindicated due to extreme pain and potential for muscle necrosis

Front 53

Describe the volume of distribution for vancomycin?

Back 53

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

Front 54

What is the total body clearance and half-life of vancomycin?

Back 54

total body clearance is approximately 0.7 x CrCL and half-life is usually 6-8 hours (depending on renal function)

Front 55

What other factors increase a patient's risk of vancomycin induced nephropathy?

Back 55

Combination therapy with aminoglycosides, Other concurrent nephrotoxins, Increased age, Previous underlying renal dysfunction, Prolonged, elevated Cmin concentrations ( > 15 mg/L)
Doses > 4 grams/day

Front 56

What is the estimated Vd of vancomycin?

Back 56

estimated Vd for vancomycin is 0.7 L/kg (based on TBW, but may also use ADW)

Front 57

When are peak concentrations drawn for vancomycin?

Back 57

peak concentrations for vancomycin are generally drawn one hour after the end of the infusion to avoid taking a sample during the distribution phase

Front 58

What are the common aminoglycosides?

Back 58

tobramycin, gentamicin, netilmicin, and amikacin

Front 59

What drugs are considered to be concentration dependent?

Back 59

aminoglycosides, fluoroquinolones, metronidazole, ketolides, daptomycin, telavancin

Front 60

What drugs are considered to be time dependent?

Back 60

penicillins, cephalosporins, monobactams, carbapenems, macrolides, clindamycin, oxazolidinones, azithromycin, vancomycin

Front 61

If a drug is a concentration dependent drug, what dosing schedule is optimal?

Back 61

large single daily dose would be more optimal for a concentration dependent drug

Front 62

If a drug is time dependent, what dosing schedule would be optimal?

Back 62

time dependent drugs are more effective given smaller doses multiple times daily to maintain drug exposure for the longest possible time

Front 63

What is the most common and most clinically relevant resistance to beta lactams?

Back 63

Destruction of antibiotic by β-lactamases is by far the most common and most clinically relevant

Front 64

What is the most important beta-lactamase produced in gram positive bacteria?

Back 64

penicillinase is the most important beta-lactamase produced in S. aureus

Front 65

What are examples of plasmid mediated constitutive beta-lactamase producers for gram negative bacteria?

Back 65

Haemophilus influenzae, Moraxella catarrhalis, E. coli, Klebsiella pneumoniae, Proteus mirabilis

Front 66

What are examples of chromosomally mediated inducible beta-lactamase producers in gram negative bacteria?

Back 66

Serratia spp., Pseudomonas aeruginosa, Acinetobacter spp., Citrobacter spp., Enterobacter spp. (SPACE organisms)

Front 67

What are the TEM-1, TEM-2, SHV-1
lactamases?

Back 67

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

Front 68

What are ESBL's?

Back 68

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)

Front 69

What is meant by "stable derepression" for beta-lactamase producing bacteria?

Back 69

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

Front 70

What is a more common and important form of resistance for beta-lactamase producing gram positive bacteria?

Back 70

resistance to beta-lactams through altered PBP's (penicillin binding proteins) and may produce either low-level or high-level resistance

Front 71

What mechanism of resistance plays an important role in the multidrug resistance of P aeruginosa and Acinetobacter?

Back 71

efflux pumps

Front 72

What is the most important and clinically relevant mechanism of resistance for aminoglycosides?

Back 72

Aminoglycoside-modifying enzymes; Acetyl-, phosphoro-, and adenyltransferases; Significant effects on MIC; Major mechanism of clinically relevant resistance

Front 73

What is the most clinically important mechanism of resistance for fluoroquinolones?

Back 73

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

Front 74

What forms of bacterial resistance are most common and important for macrolides and ketolides?

Back 74

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

Front 75

What is the most important form of resistance for vancomycin?

Back 75

resistance to vanco is uncommon, but can happen through alterations in synthesis of cell wall precursors
D-alanyl-D-alanine --> D-alanyl-D-lactate

Front 76

What are hVISA and VRSA?

Back 76

heteroresistand vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus; both are considered non-susceptible

Front 77

What are the most clinically important and the most common resistance to have developed in S. aureus?

Back 77

penicillinase is the most common resistance, but alterations to PBP's is the most clinically important

Front 78

What antibiotics are effective against MRSA?

Back 78

vancomycin, linezolid, quinupristin/dalfopristin, daptomycin, telavancin, tigecycline; community-aquired- minocycline, TMP/SMX, clindamycin

Front 79

What is the definition of Community-Associated Methicillin-Resistant S. aureus (CA-MRSA)?

Back 79

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

Front 80

What are some of the common characteristics of CA-MRSA?

Back 80

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

Front 81

What is the primary mechanism of clinically relevant clindamycin resistance (in CA-MRSA)?

Back 81

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

Front 82

What test is used with CA-MRSA to determine the presence of clindamycin resistance?

Back 82

the "D" test

Front 83

What are important mechanisms of resistance for Streptococcus pneumoniae?

Back 83

alterations in PBP's resulting in either low- or high-level resistance; Ribosomal methylation --> macrolides, clindamycin

Front 84

Of the aminoglycosides, what are the most effective for treatment of P. aeruginosa?

Back 84

amikacin is best, then tobramycin, then gentamicin for P. aeruginaso

Front 85

What is the therapeutic range for severe systemic infections or pneumonia when dosing aminoglycosides?

Back 85

8-10 mg/L for gentamicin is appropriate therapeutic range for severe systemic infections or pneumonia

Front 86

What is the therapeutic range for less severe systemic infections when dosing aminoglycosides?

Back 86

6-8 mg/L for tobramycin is appropriate therapeutic range for less severe systemic infections

Front 87

What is the therapeutic range for urinary tract infections when dosing aminoglycosides?

Back 87

4-6 mg/L for netilmicin is appropriate therapeutic range for UTI's

Front 88

What is the therapeutic range for amikacin?

Back 88

25 - 30 mg/L (severe systemic infections, pneumonia);
20 - 25 mg/L (other infections

Front 89

What are the Cmin concentrations recommended for aminoglycosides?

Back 89

<2mg/L is recommended for Cmin concentrations of gentamicin, tobramicin, and netilmicin;
<10mg/L is recommended Cmin for amikacin

Front 90

What is the general loading dose for aminoglycosides?

Back 90

2 mg/Kg is (using ibw, ADW, or TBW)