Lange Chapter 1 Flashcards
what are the 3 genetic modifications leading to antimicrobial resistance?
conjugation (plasmid-pilus transfer R), transduction (transfer via bacteriopahges), transformation (uptake of naked DNA via transposon)
what are the 3 major biochemical mechanisms for antimicrobial resistance?
degradation/modification of antibiotic, reduction in bacterial antibiotic concentration(inhibit abx entry, produce efflux pumps), modification of antibiotic target
give an example of degradation/modification of antibiotic biochemical resistance?
beta lactamases
give an example of interference with antibiotic entry biochemical resistance?
MRSA can develop thickened wall requiring higher vancomycin concentrations to inhibit bacterial growth (VISA)
give an example of the production of efflux pumps for biochemical antibiotic resistance?
transposons pump out tetracycline, seen in many enteric bacteria.
give an example of alteraction of cell wall precurors (modification of abx target)?
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.
Give an example of changes in target enzyme/modification of abx target?
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.
what 2 parameters found to correlate with infectious cure ?
T>MIC and AUC/MIC
what PK diameter associated with beta lactam success?
T>MIC of 50%
what PK diameter associated with AUC/MIC?
aminoglycosides and FQ
how can the development of resistance be prevented?
short courses of abx (<5 days), high doses of antibiotics to achieve high AUC/MIC ratios, 50-200 dependent on the organism
what are the beta lactam antibiotics?
Penicillins, cephalosporins, and carbapenems.
what are the key characteristics of beta lactam antibiotics?
all contain beta lactams, all bind to PBPs, all require bacterial growth for bacteriocidal action, and are antagonized bacteriostatic abx.
what is the most common beta lactam toxicity?
allergic delayed and immediate hypersensitivity reactions
beta lactam seizures?
PNC/imipenem in patients with renal dysfunction
Common reaction associated with cephalosporins?
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
beta lactam nephrotoxicity?
think cephalosporin + aminoglycoside
beta lactam toxicities in general?
allergic skin rash, anaphylaxis, phlebitis, seizure, cytopenias
key points about ceftaroline?
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
Key points of azactam?
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.
Neoplastic causes of FUO?
Lymphoma (hodkin, Pel-Ebstein (cylical increase then decrease over 1-2 weeks), Leukemia, hypernephroma (hish ESR), hepatoma (cancer cells of liver), atrial myxoma
Autoimmune causes of FUO?
SLE, Stills disease, hypersensitivity angiitis, PMR w/TA, PAN, MCTD, subacute thyroiditis
what’s still disease?
high fevers, evanescent skin rash, leukocytosis, high ferritin, high ESR
FUO in an AIDS patient in order of frequency?
mycobacterial infections, bacteria, CMV, PCP, toxoplasmosis, cryptococus, and histoplamosis.
