Micellaneous Antibiotics

Question 1

Adverse effects to penicillins

Answer 1

Rash, hypersensitivity, diarrhea, cytopenia, renal impairment

Question 2

Pharmacokinetics of penicillins

Answer 2

Time-dependent (MIC most important for optimized killing). Short t1/2, so requires frequent dosing.

Question 3

Resistance mechanisms of penicillins

Answer 3

beta-lactamase, changes in outer membrane porins, altered penicillin binding proteins.

Question 4

Clinical use of natural penicillins

Answer 4

drug of choice for strep infections from pharyngitis to cellulitis to endocarditis, all stages of syphilis, gas gangrene from clostridia (combine w/ clindamycin to decr toxin production), periodontal infections, enterococcal infections.

Question 5

Clinical use of aminopenicillins

Answer 5

URIs and LRIs, but shifting to combinations w/ beta-lactamase inhibitors. Uncomplicated UTI, enterococcal infections.

Question 6

Clinical use of semi-synthetic penicillins

Answer 6

Drug of choice for non-MRSA/MRSE staph infections

Question 7

Clinical use of extended spectrum penicillins

Answer 7

pseudomonas infections, mixed infections w/ gram-negatives and enterococci

Question 8

Clinical use of penicillin/beta-lactamase inhibitor combinations

Answer 8

URI, LRI, head and neck infections, skin and soft tissue infections (cellulitis), animal and human bites (amoxicillin/clavulanic acid), intra-abdominal infections, nosocomial infections w/ pseudomonas (pip/tazo, ticar/clav)

Question 9

Pharmacokinetics of cephalosporins

Answer 9

Time-dependent killing, so maintain higher MIC w/ freq dosing.

Question 10

Resistance to cephalosporins

Answer 10

beta-lactamase production, changes in outer membrane porins, altered PBP. Cephalosporins are stable against beta-lactamase of Staph that would inactivate a penicillin/ amoxicillin.

Question 11

Adverse effects of cephalosporins

Answer 11

low toxicity: rash most common, cross-reactivity w/ penicillin, diarrhea.

Question 12

Clinical uses of 1st gen cephalosporins and name the two main ones.

Answer 12

Skin and soft tissue infections by strep and staph, perioperative antibiotic prophylaxis. PO 1st gen is cephalexin, IV 1st gen is cefazolin.

Question 13

Clinical uses of 2nd generation cefuroxime group cephalosporins

Answer 13

URIs, LRIs

Question 14

Clinical use of 2nd generation cephamycin group cephalosporins and name the main one

Answer 14

intra-abdominal and pelvic infections (UWHC formulary), cefoxitin.

Question 15

Clinical use of 3rd generation cephalosporins and the main ones.

Answer 15

Ceftriaxone for menigitis, gonorrhea, viridans strep endocarditis, intraabdomina (plus metronidazole), community-acquired pneumonia (also cefpodoxime). All treat UTIs. Ceftazadime for pseudomonas. Ceftriaxone is the main one.

Question 16

Clinical use of 4th generation cephalosporins and the main ones.

Answer 16

Nosocomial infections, febrile neutropenia, pseudomonas infections. Cefepime is the only one!

Question 17

Pharmacology of 3rd generation cephalosporins

Answer 17

Long t1/2 allows QD dosing, meningitis or CNS tx needs BID. Long term use associated with biliary sludging.

Question 18

Clinical use of 5th generation cephalosporins and the major ones.

Answer 18

Bacterial skin and soft tissue infections, community-acquired pneumonia, emerging role treating MRSA. Ceftaroline as only one!

Question 19

Pharmacodynamics and pharmacokinetics of carbapenems.

Answer 19

Time-dep killing, so keep MIC high for longer. PAY ATTENTION TO RENAL DOSE ADJUSTMENTS. Imipenem inactivated by dehydropeptidase 1 in the kidney brush border, so given w/ cilistatin. Ertapenem w/ a long t1/2, so QD dosing. Meropenem and imipenem can cross BBB.

Question 20

Resistance mechanisms of carbapenems

Answer 20

beta-lactamases (carbapenemases), altered porins, changes in PBP. In 2014, saw carbapenem-resistant enterobacteriaceae, most commonly Klebsiella pneumoniae carbapenemase.

Question 21

Adverse reactions to carbapenems

Answer 21

rash, hypersensitivity, cross reaction w/ penicillin. Imipenem can cause seizures if too high dosed (esp if renally impaired).

Question 22

Pharmacodynamics and pharmacokinetics of aztreonam

Answer 22

Time-dependent killing, so time above MIC important. Cleared renally. Can be safely used in pts w/ adverse rxn to penicillins and beta-lactams

Question 23

Mechanism of action of aztreonam

Answer 23

inhibition of cell wall synthesis

Question 24

Resistance mechanism of aztreonam

Answer 24

beta-lactamases

Question 25

Adverse effects of aztreonam

Answer 25

rash and hypersensitivity

Question 26

Clinical uses of aztreonam

Answer 26

Main use against gram-negative rods (pseudomonas) in cases of penicillin hypersensitivity. Can be used for other gram-negatives, but it rarely is.

Question 27

Mechanism of action of daptomycin

Answer 27

Binds bacterial membranes and causes rapid membrane depolarization. Loss of membrane potential leads to inhibition of protein and nucleic acid synthesis, leading to cell death.

Question 28

Pharmacology of daptomycin

Answer 28

Concentration-dependent killing. Long half-life for once-daily dosing. Inactivated by pulmonary surfactant so it can’t be used for treating pneumonia. IV only.

Question 29

Adverse reactions to daptomycin.

Answer 29

Rash and hypersensitivity are uncommon. Myopathy and elevated CK in 3% of pts.

Question 30

Clinical uses of daptomycin

Answer 30

Serious MRSA, VRE, and coag-neg staph infections, including bacteremias and endocarditis. Not for pneumonia.

Question 31

Mechanism of action of vancomycin

Answer 31

Binds D-alanyl-D-alanine portion of the peptide precursor, a crucial site of attachment preventing vital peptidoglycan polymerase and transpeptidation reactions. Prevents transglycolation so disaccharide can’t be added to peptidoglycan, leading to cell autolysis. A slow cidal antibiotic (takes longer than beta-lactams).

Question 32

Resistance mechanisms to vancomycin

Answer 32

Enterococcal resistance mediated by peptidoglycan percursor that has decreased affinity to vancomycin because it is a D-alanyl-D-lactate or D-alanyl-D-serine. 6 patterns of resistance: VanA- VanG. VRSA in 13 clinical isolates in the US since 2002, via the VanA gene. Other organisms w/ intrinsic resistance to vancomycin via peptidoglycan precursor changes.

Question 33

Pharmacology of vancomycin

Answer 33

Time-dependent killing with slow cidal activity. IV form fo systemic infections. Oral form isn’t well-absorbed, so high intraluminal levels in the colon make it good for treating C. diff. A large molecule, so it is difficult to get in the CNS but still is used for CNS infections. Dialysis can remove it, depending on the filter used. Trough levels helpful to guide dosing if renal impairment and with organisms w/ higher MIC values.

Question 34

Adverse reactions to vancomycin

Answer 34

neutropenia, renal impairment if combined with other nephrotoxins, “red man syndrome” of red rash and itching of face, neck, and upper chest w/ rapid infusion from histamine release (but not a true allergic reaction).

Question 35

Clinical use of vancomycin

Answer 35

MRSA and coag-neg staph serious infections, enterococcal infections resistant to ampicillin, S. pneumoniae in meningitis and severe pneumococcal infections w/ proven or high-risk of drug-resistant pneumococci, alternative for penicillin allergies, C. diff in oral form.