Lange Chapter 1

Question 1

what are the 3 genetic modifications leading to antimicrobial resistance?

Answer 1

conjugation (plasmid-pilus transfer R), transduction (transfer via bacteriopahges), transformation (uptake of naked DNA via transposon)

Question 2

what are the 3 major biochemical mechanisms for antimicrobial resistance?

Answer 2

degradation/modification of antibiotic, reduction in bacterial antibiotic concentration(inhibit abx entry, produce efflux pumps), modification of antibiotic target

Question 3

give an example of degradation/modification of antibiotic biochemical resistance?

Answer 3

beta lactamases

Question 4

give an example of interference with antibiotic entry biochemical resistance?

Answer 4

MRSA can develop thickened wall requiring higher vancomycin concentrations to inhibit bacterial growth (VISA)

Question 5

give an example of the production of efflux pumps for biochemical antibiotic resistance?

Answer 5

transposons pump out tetracycline, seen in many enteric bacteria.

Question 6

give an example of alteraction of cell wall precurors (modification of abx target)?

Answer 6

VRE. vancomycin requires to bind D-Alanine- D- alanine at the end of peptidogylcan cell wall precurors of gram positive bacteria. E.Faecium has vanA or vanB transposon that encodes D-alanine-D-Lactate.

Question 7

Give an example of changes in target enzyme/modification of abx target?

Answer 7

Pen and cephalosporins bind to Penicillin binding proteins (PBPs) in bacterial cell wall. Pen resistant strep pneumo has decreased PBPs decreasing ability to bind. MRSA has the same with low affinity PBP encoded by Mec A gene.

Question 8

what 2 parameters found to correlate with infectious cure ?

Answer 8

T>MIC and AUC/MIC

Question 9

what PK diameter associated with beta lactam success?

Answer 9

T>MIC of 50%

Question 10

what PK diameter associated with AUC/MIC?

Answer 10

aminoglycosides and FQ

Question 11

how can the development of resistance be prevented?

Answer 11

short courses of abx (<5 days), high doses of antibiotics to achieve high AUC/MIC ratios, 50-200 dependent on the organism

Question 12

what are the beta lactam antibiotics?

Answer 12

Penicillins, cephalosporins, and carbapenems.

Question 13

what are the key characteristics of beta lactam antibiotics?

Answer 13

all contain beta lactams, all bind to PBPs, all require bacterial growth for bacteriocidal action, and are antagonized bacteriostatic abx.

Question 14

what is the most common beta lactam toxicity?

Answer 14

allergic delayed and immediate hypersensitivity reactions

Question 15

beta lactam seizures?

Answer 15

PNC/imipenem in patients with renal dysfunction

Question 16

Common reaction associated with cephalosporins?

Answer 16

allegic reaction (all beta lactams), interfere with vitamin K causing increase PT time. Ceftriaxone is excreted by bile and can crystalize to form biliary sludge

Question 17

beta lactam nephrotoxicity?

Answer 17

think cephalosporin + aminoglycoside

Question 18

beta lactam toxicities in general?

Answer 18

allergic skin rash, anaphylaxis, phlebitis, seizure, cytopenias

Question 19

key points about ceftaroline?

Answer 19

increased affinity to PBP for MRSA and VISA, MSSA. Penetrates all body tissues including BBB and joint fluid. approved for CAP, soft tissue infections. Similar gram negative coverage to ceftriaxone

Question 20

Key points of azactam?

Answer 20

no cross reactivity with penicillins. Binds PBP of gram negative rods but not gram positive. Marketed as non-nephrotoxic replacement for AGs but no synergy with penicillins and does not treat strep viridans. Useful for treatment of pyelonephritis.

Question 21

Neoplastic causes of FUO?

Answer 21

Lymphoma (hodkin, Pel-Ebstein (cylical increase then decrease over 1-2 weeks), Leukemia, hypernephroma (hish ESR), hepatoma (cancer cells of liver), atrial myxoma

Question 22

Autoimmune causes of FUO?

Answer 22

SLE, Stills disease, hypersensitivity angiitis, PMR w/TA, PAN, MCTD, subacute thyroiditis

Question 23

what’s still disease?

Answer 23

high fevers, evanescent skin rash, leukocytosis, high ferritin, high ESR

Question 24

FUO in an AIDS patient in order of frequency?

Answer 24

mycobacterial infections, bacteria, CMV, PCP, toxoplasmosis, cryptococus, and histoplamosis.