ID: abx pharmacology

MIC

lowest concentration at which bacteria is inhibited

MBC

lowest concentration at which bacteria is killed

lower MIC =

more pharmacologically active drug

host defense factors

\-skin and mucous membranes

\-elimination mechanisms

\-acidity of gastric acids

\-enzymes

\-gag reflex

\-airflow turbulence

\-cytokines

\-fever

functions of normal gut flora

\-digestion and absorption

\-stimulates immune system to maintain constant “priming”

\-provides protection against potentially pathogenic

four major mechanisms of resistance

target site modification

enzymatic inactivation of drugs

decreased penetration of cell wall or membrane

drug efflux

T or F: antimicrobials alone can cure infections

F

risk factors for development of resistance

\-overuse of antibiotics

\-use of broad spectrum abx

\-inappropriate drug dosing

inappropriate durations of therapy

vancomycin, televancin, dalbavancin, oritavancin spectrum

staph aureus (including MRSA)

coagulase-negative staph

strep (including resistant S. pneumoniae)

enterococcus

anaerobes: C. diff (PO vanc)

orita: VRE

what’s special about ortiavancin spectrum?

it covers VRE

vancomycin, televancin, dalbavancin, oritavancin MOA

cell wall inhibitors

vancomycin, televancin, dalbavancin, oritavancin Vd

vanc: medium

tele: low

Orita: medium-high

dalba: low-medium

vancomycin, televancin, dalbavancin, oritavancin PD

AUC/MIC

vancomycin, televancin, dalbavancin, oritavancin AE

\-erythema

\-nephrotox

\-ototox

\-hematologic

**televancin:**

CNS

metallic/soap taste

foamy urine

linezolid, tedizolid spectrum

staph (MRSA), strep, enterococcus

\-coagulase negative staph

\-resistant S. pneumoniae

\-VRE

\-myobacterium avium

\-abcessus

\-tuberculosis

\-nocardia

linezolid, tedizolid MOA

protein inhibitor

linezolid, tedizolid VD

medium: tiny particles penetrate all tissues

linezolid, tedizolid PD

AUC/MIC

linezolid, tedizolid AE

\-thrombocytopenia >14 days

\-anemia >28 days

\-lactic acidosis

\-peripheral neuropathy >28 days

\-optic neuropathy >28 days

\-serotonin syndrome

linezolid, tedizolid routes

Iv and PO

linezolid is mainly used for vanc resistant ______

enterococcus

linezolid monitoring

CBC

vitals

daptomycin spectrum

staph (MRSA), strep, enterococcus

\-coagulase-negative staph

\-MDR S. pneumoniae

\-VRE

Daptomycin MOA

cell wall inhibitor: irreversibly binds to cel membrane causing exodus of K+

Daptomycin Vd

low

stays in blood, goes to lungs but bound by surfactant

Daptomycin PD

peak/MIC

Daptomycin AE’s

\-myalgia

\-myositis

serious/rare:

\-rhabdo

\-renal failure

Daptomycin monitoring

SCr

creatine kinase

Daptomycin route

IV

linezolid and tidezolid route

IV and PO

vanc route

IV and PO

televancin route

IV

oritavancin route

IV Q week

dalbavancin route

IV Q week

PCN spectrum

strep

enterococcus

ampicillin/amoxicillin spectrum

gram+:

strep

enterococcus

gram-:

enterobacterales

haemophilius/moraxella

amox/clav spectrum

gram+

s. aureus MSSA

strep

enterococcus

gram-:

enterobacterales

haemophiliu/moraxella

anaerobes

Nafcillin/Dicloxacillin spectrum

s. aureus MSSA

strep

piperacillin/tazobactam spectrum

gram+

staph aureus MSSA

strep

enterococcus

gram-:

enterobacterales

pseudomonas\*

haemophilus/moraxella

anaerobes

1st gen cephs spectrum

gram+

staph aureus MSSA

strep

gram-:

enterobacterales

2nd gen cephs spectrum

gram+:

s. aureus MSSA

strep

gram-:

enterobacterales

haemophilus/moraxella

anaerobes: CEFOXITIN

3d gen cephs spectrum

\+:

s. aureus MSSA

strep

\-:

enterobacterales

pseudomonas: CEFTAZIDIME

haemophilus/moraxella

cefepime spectrum

\+:

s. aureus MSSA

strep

\-:

enterobacterales

pseudomonas

haemophiuls/moraxella

what is the only ceph that covers MRSA?

ceftaroline

ceftaroline spectrum

\+:

s. aureus MSSA and MRSA

strep

\-:

enterobacterales

haemophilus/moraxella

carbapenem spectrum

\+:

s. aureus

strep

enterococcus (not erta)

\-:

enterobacterales

pseudomonas (not erta)

haemophilus/moraxella

anaerobes

which carbapenem does NOT cover strep or psuedomonas?

ertapenem

monobactam aztreonam spectrum

\-: enterobacterales and pseudomonas

clindamycin spectrum

\+.:

s. aureus MSSA and MRSA

strep

anaerobes

metronidazole spectrum

anaerobes only

fluoroquinolones spectrum

\+:

s. Aureus (not cipro)

MRSA (dela only)

strep (not cipro)

entero dela only)

\-:

enterobacterales

pseudomonas (not moxi)

haemophilus/moraxella

anaerobes: moxi ONLY

atypicals!!

aminoglycoside spectrum

\-:

enterobacterales

pseudomonas

haemophilus/moraxella

macrolide spectrum

\+:

s. aureus MSSA

strep

\-:

enterobacterales (only GI)

haemophilus/moraxella

atypicals!!

TMP/SMX spectrum

\+:

s. aureus MSSA and MRSA

strep

\-:

enterobacterales

haemophilus.moraxella

rifampin spectrum

\+:

s. aureus MSSA and MRSA

strep

\-:

haempohilus/moraxella

atypicals

nitrofurantoin spectrum

\+:

s. aureus MSSA and MRSA

strep

enterococcus

\-:

enterobacterales

fosfomycin spectrum

\+:

s. aureus MSSA and MRSA

strep

enterococcus

VRE

\-:

enterobacterales

pseudomonas

Lefamulin spectrum

\+:

s. aureus MSSA and MRSA

strep

enterococus

VRE

\-:

haemophilus/moraxella

atypicals

B lactam MOA

cidal

inhibition of cell wall synthesis; inhibit last step in peptidoglycan synthesis

bind to PBP’s

major mechanisms of resistance in B lactams

\-enzymatic inactivation of drugs: B-lactamase enzymes

\-decreased affinity of antibiotic for PBP’s

\-decreased concentration of antibiotic at target site of activity

constitutive enzyme production

constant level of production

inducible enzyme production

expressed after exposure to antibiotic

what is drug of choice for extended spectrum B-lactamses?

carbapenems

describe B-lactam resistance through alterations in PBP’s

\-B-lactams cannot effectively bind to altered PBP’s

\-common in gram+

\-MRSA

what type of bacteria develop resistance through decreased membrane permeability?

gram-

when expressed alone, efflux pumps cause ______ level resistance to B-lactams

low

pen V route

oral

Pen G route

parenteral

penicillinase resistant penicilins

Dicloxacillin (PO)

Nafcillin (IV)

Nafcillin is primarily metabolized by ____

the liver

aminopenicillins

ampicillin (PO and IV)

amoxicillin (PO)

extended spectrum penicillin

piperacillin (usually used with tazobactam)

PCN adverse effects

\-more diarrhea with ampicillin

\-skin rash

\-interstitial nephritis and ATN

\-hepatic transaminase elevation

\-neutropenia, increased bleed times, thrombocytopenia, hemolytic anemia

\-CNS

\-hypokalemia

\-hypernatremia

\-C.dif and superinfection

PCN DDI’s

\-aminoglycosides (don’t mix or put in same IV line)

\-probencid (increased concentration of PCN)

type 1 reactions

\-immediate

\-anaphylaxis

\-IgE

\-2-20 mins after

type 2 reactions

\-IgG and IgM

\-blood issues

\-uncommon

\-reversible

type 3 reactions

\-1-3 weeks after

\-IgG: circulating drug-antibody complexes

\-serum sickness: rash, fever

\-resolve after d/c

type 4 reactions

\-delayed reaction

\-lymphocytes and macrophages

\-idiopathic: itching and maculopapular rashes

\-reversible

cross hypersensitivity: PCN and PCN

similar side chains: 20-40%

not similar:

cross hypersensitivity: PCN and ceph

1st gen: 3-4%

2nd gen:

cross hypersensitivity: PCN and carbapenem

cross hypersensitivity: PCN and aztreonam

0%

cross hypersensitivity: cephs and cephs

similar side chain:

cross hypersensitivity: cephs and carbapenems

cross hypersensitivity: cephs and aztreonam

0% (slight risk with ceftazidime)

cross hypersensitivity: carbapenems and cephs

cross hypersensitivity: carbapenems and carbapenems

100%

cross hypersensitivity: carbapenems and aztreonam

0%

cross hypersensitivity: aztreonam and aztreonam

100%

PCN-ceph with similar side chain cross hypersensitivity

20%

T or F: cefazolin’s side chain is similar to all PCN’s

F: cefazolin has a unique side chain

potentially cross reactive combos to memorize:

\-PCN, ampicillin, amoxicillin, and cephalexin

\-PCN and cefoxitin

\-cefotaxime, ceftriaxone, cefuroxime, ceftazidime, cefepime

\-ceftazidime and aztreonam

cephs: effects of the NMTT side chain

\-inhibition of vitamin K epoxide reductase (bleeding)

\-inhibition of aldehyde dehydrogenase (alcohol tox)

1st gen cephs

cephalexin

cefazolin (ancef)

2nd gen cephs

cefuroxime axetil - Ceftin (PO)

Cefuroxime - Zinacef (IV)

Cefoxitin - Mefoxin (IV)

3rd gen cephs

Cefdinir - Omnicef (PO)

Cefditoren pvoxil - spectracef (PO)

Ceftriaxone - Rocephin (IV)

Ceftazidime - Fortaz (IV)

which ceph has longer half life and can be given QD?

Ceftriaxone

4th gen ceph

Cefepime - Maxipime (IV)

5th gen ceph

Ceftaroline (Teflaro)

what’s special about ceftaroline?

first and only B-lactam to have activity against MRSA