Overview of antimicrobials Part I, J Kinder, DSA Flashcards
Goal of prophylactic therapy
prevent infection or prevent dangerous disease in those already infected
what is preemptive therapy
targeted therapy in high risk patients who are asymptomatic but have become infected
what is empiric therapy
provide antimicrobial therapy to a symptomatic patient without identification of infecting organism
what is definitive therapy
infecting organism is known
streamlined therapy based on susceptibility and duration
post Tx suppressive therapy
cover patient with antimicrobial therapy at lower dose when infection has not been completely eradicated and immunological or anatomical defect still present which lead to original infection
What is the most valuable immediate test for susceptibility of microbial agent
gram stain
What is MIC
minimum inhibitory [ ]
lowest [ ] of drug required to inhibit growth
disk diffusion method for determining suscebtibility can qualitatively measure what
susceptible or Resistant
not MIC
methods to determine MIC
dilution tests and optical diffusion
What is narrow specrum
antibacterial acts on single or limited group microorganisms
what is extended spectrum
active against gram + bacteria but also against significant number of gram - bacteria
what is broad spectrum
act on wide variety bacterial species (both gram + and -)
What is bacteriostatic
arrests growth and replication of bacteria
protein synthesis inhibitors
what is bactericidal
kills bacteria
types of bactericidal killing
[ ] dependent (inc [ ] inc killing)
time dependent )activity continues as long as serum [ ] above minimum bacterial [ ])
what common antibiotics are concentration dependent bactericidals
aminoglycosides and fluoroquinolone
what are common antibiotics that are time dependent bactericidals
B lactams and vanco
What are common antibacterial targets
cell wall synthesis cell membrane synthesis synthesis 30S and 50S ribosomal subunits nucleic acid metabolism function of topoisomerases folate synthesis
What are 2 factors assoc with antimicrobial R
evolution
clinical/environmental practices
What are the R mechanisms
- reduced entry of antibiotic
- enhanced export antibiotic
- release microbial enzymes that kill antibiotic
- alteration of microbial proteins that transform pro-drugs to the effective moieties
- alteration of target proteins
- development of alternative pathways to those inhibited by antibiotics
penicillin structure
thiazolidine ring connected to B-lactam ring attached to side chain
what determines susceptibility of penicillins
side chains
MOA of penicillins
inhibit transpeptidation reaction, last step in peptidoglycan synthesis
Penicillin binding proteins remove terminal D alanine
B lactams are analogs of D-ala D-ala so bind PBP and prevent their crosslinking
leads to cell autolysis
How does R happen to penicillins
structural differences in PBPs and dec PBP affinity for B lactams
active efflux pumps
drug destruction!!
inactivation by B lactamases
what are aminopenicillins used for
extended spectrum, usually given with B lactam inhibitor
What are the aminopenicillins
ampicillin (+/-sulbactam)
amoxicillan (+/-clavulanic acid)
Therapeutic use of aminopenicillins
URI (S pyogenes, S pneumoniae, H influenzae, sinusitis, otitis media, enterococcal infections)
What type of spectrum are anti-pseudomonal penicillins and what are they types
extended spectrum
ticarcillin (+/-clavulanic acid)
piperacillin (+/- tazobactam)
Therapeutic use of anti-pseudomonal penicillins
serious gram - infections, hospital acquired pneumonia, immunocompromised patients, bacteremia, burn infections, UTI
What are the adverse effects of anti-pseudomonals
allergic rxns, anaphylaxis, interstitial nephritis (rare), nausea, vomiting, mild-severe diarrhea, pseudomembranous colitis
cephalosporins have same MOA and R as what class of antibiotics
penicillins
cephalosporins do not have activity for what microbes
MRSA, listeria or enterococci
activity of 3rd generation cephalosporins
less active against gram +
more active against enterobacteriae
What drugs are 3rd generation cephalosporins
Ceftriaxone, ceftazidime
Tx use of 3rd generation cephalosporins
DOC serious gram - infections (Klebsiella, enterobacter, Proteus, Providencia, Serratia, Haemophilus)
ceftriaxone is DOC for what
all forms gonorrhea and severe lymes disease, meningitis
activity of 4th generation cephalosporins
extends spectrum beyond 3rd generation
serious hospitalized patients
What drugs are 4th generation cephalosporins
cefepime
Therapeutic use of cefepime
empiracal Tx of nosocomial infections
adverse effects cefepime
1% cross reactivity to penicillins, diarrhea, intolerance to alcohol
MOA and R carbapenems is similar to what other drug class
penicillins
spectrum of carbapenems
aerobic and anaerobic microorganisms, gram +, excellent against enterobacteriacae, PSeudomonas, Acinetobacter
Therapeutic uses of carbapenems
UTI, lower RTI, intra-abdominal, gynecological, SSTI, bone and joint infections
ALL IV or IM
what is beneficial about ertapenem
longer half life which allows for once daily dosing
Adverse effects of carbapenems
nausea/vomiting, seizures, HS
MOA glycopeptides
inhibits cell wall synthesis binding with high affinity to D alanylD alanine terminal
Unable to penetrate outer membrane gram - bacteria
Bacterial Resistance of glycopeptides
alteration of Dalanyl D alanine to D alanyl D lactate or serine
spectrum of glycopeptides
broad gram + coverafe inclusing MRSA, MRSE
all gram - and mycobacterium resistant
Therapeutic use of glycopeptides
osteomyelitis, endocarditis, MRSA, strep, enterococci, CNS infections, bacteremia,
orally for Clostridium difficile!
adverse effects glucopeptides
macular skin rash, chills, fever,rash
red man synfrome from rapid infusion
release of histamine from toxic effect vanco
ototoxicity and nephrotoxicity
