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128 Cards in this Set

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What are 5 abuses of antimicrobial chemotherapy?
1. Treatment of untreatable infections; 2. therapy of fever of unk origin; 3. improper dosage; 3. inappropriate use of chemotherapy alone; 4. poor drug selection due to lack of bacteriological info
What's goal of antibiotics?
To eliminate pathogen; keep normal flora; prophylaxis
Antibiotics are part of ?, which are part of ?
Antimicrobials; anti-infective agents
What is the most important characteristic of an ideal antimicrobial agent?
Demonstrate SELECTIVE toxicity
In addition to SELECTIVE toxicity, antimicrobials also have these 4 characteristics…
1. Not induce allergic RXN; 2. not destroyed, neutralized, or excreted too fast by host; 3. therapeutic dose is established @ site of infection; 4. pathogens do NOT develop resistance to them
What re 2 properties of antimicrobial agents?
1. Chemotherapeutic index (Bigger=Better); 2. clinical effectiveness depends on drug's maximal efficacy, NOT potency
What are 2 activities of antibiotics?
BacterioSTATIC; BacterioCIDAL
The 4 phases of bacterial growth are…
Lag phase; Log phase; Stationary phase; Death phase
What's the definition of an antibiotic?
Antibacterial agent that's natural, semi-synthetic, or synthetic.
In an immunocompromised individual, you must use what type of antibiotic?
BacterioCIDAL
What is post antibiotic effect?
Period where drug is no longer @ MIC but bacteria can't resume growth yet
What is the benefit of having post antibiotic effect?
Allows spacing out of doses, minimizes amount of drug given
What 4 factors determine if an antibiotic is CIDAL or STATIC?
1. Mechanism of action; 2. microbe's state of growth; 3. concentration of drug; 4. spectrum of activity
Narrow spectrum antibiotics target against what?
Either G+ or G- but NOT both
What is the benefit of narrow spectrum?
Very specific so lower risk of superinfections
Extended spectrum antibiotics target against what?
G+ AND G-
Broad spectrum antibiotics target against what?
G+ AND G- AND other microbes
The triad of interaction is between what?
Host; drug; pathogen
What are 3 ways to get selective toxicity?
1. Drug blocks vital pathway unique to microbe; 2. drug blocks vital RXN in microbe and host BUT /w greater effect on microbe; 3. drug blocks vital pathway in microbe and host BUT only microbe can convert the drug to active metabolite
What's the difference b/w location of b-lactamases in G+/- organisms?
G+: extracellular vs. G-: in periplasmic space
What's the difference b/w location of PBPs in G+/- organisms?
G+: plasma membrane vs. G-: inner membrane
How do polar antibiotics enter G- bugs?
Through porin channels in outer membrane
What are the 2 mechanisms of antibiotic resistance for G- bugs?
1. efflux pump; 2. absence of porins (both are in outer membrane)
What is the function of PBP?
Crosslinks peptidoglycan layers
What are the 3 mechanisms of acquired resistance?
1. drug fails to reach its target; 2. drug is not active (e.g. via b-lactamase); 3. altered target (e.g. vancomycin; methicilllin)
What are the 4 genetic mechanisms to acquired resistance?
1. mutation; 2. transduction; 3. transformation; 4. conjugation
? selects for the ? of ? organisms
ANTIBIOTICS selects for the OUTGROWTH of RESISTANT organisms
What are 4 ways to avoid developing antibiotic resistance?
1. use only when there's well established need; 2. select the best antibiotic for use based on results of bacteriologic tests; 3. effective concentration of sufficient periods; 4. use multiple drug therapy only when indicated
What are the 4 indications for combination antibiotics?
1. empirical therapy of severe infections of unk cause; 2. treat polymicrobial infections; 3. synergism; 4. prevent resistance
What are 3 potential results of combination antibiotics?
1. antagonism; 2. addition; 3. synergism
What are the 5 generalizations for cell wall synthesis inhibitors?
1. kills G+>>G-; 2. narrow or extended spectrum; 3. CIDAL; 4. poor penetration of BBB; 5. oral administration; renal clearance
What causes Red man syndrome and ototoxicity?
Vancomycin and teicoplanin
All cell wall synthesis inhibitors are narrow or extended spectrum except for ? and ? which are broad spectrum.
Fosfomycin and D-cycloserine
All cell wall synthesis inhibitors are CIDAL except for ?
D-cycloserine
All cell wall synthesis inhibitors are poor penetrators of BBB except for ?
D-cycloserine
What is Red man syndrome?
Side effect for taking vancomycin; flushing; hypotension=>shock
What are 2 mechanisms of resistance to vancomycin?
1. enterococci vanA, B, or C that alters pentapeptide so lowers affinity for drug; 2. S. aureus overexpresses D-ala-D-ala, the substrate
None
b-lactams block ?
What are the 4 generalizations of b-lactams?
1. block; 2. various routes, renal cleared, not metabolized; 3. allergic response w/ cross sensitization; 4. CIDAL for G+
The cell wall inhibitors include…
b-lactams only work when bugs are…
Actively synthesizing cell walls
All b-lactams have what common structural feature?
Ring w/ C-N bond that's cleaved by b-lactamase
The R group on b-lactams impart 4 specific properties:
1. acid stability; 2. binding to plasma protein i.e. availability in blood; 3. spectrum; 4. resistance to b-lactamase
The 4 ways to resist b-lactams include:
1. b-lactamase; 2. change PBP; 3. block access by altering protein S susceptible G- cocci; 4. efflux pump in susceptible G- cocci
What is the most common allergic RXN associated w/ b-lactams?
Delayed hypersensitivity w/ reversible rash
Which b-lactam associated allergic RXN is life threatening?
Acute
The spectrum of penicillins vary w/ what?
Group
Group 1 penicillin is ? spectrum.
Narrow, G+ aerobes
Group 2 penicillin works against?
Penicillinase producing S. aureus
Group 3 penicillin is ? spectrum.
Extended
What are 2 antibiotics used against pseudomonads?
Carboxypenicillins; ureidopenicillins
What is Stevens-Johnson syndrome?
Exfoliative foliculitis; skin sloughing off
Stevens-Johnson syndrome
Group 1 penicillin side effect; clindamycin side effect; sulfonamide side effect
Group 1 penicillin side effect and clindamycin side effect
Stevens-Johnson syndrome
Group 2 penicillin AND hepatic cleared
Nafcillin
Nafcillin
Group 2 penicillin AND hepatic cleared
P. aeruginosa
Ureidopenicillin
Ureidopenicillin
P. aeruginosa
Pt w/ infectious mononucleosis tend to get what?
Aminopenicillin rash
Aminopenicillin rash occurs in who?
Pt w/ infectious mononucleosis
What's the general 5 trends from 1st to 4th generation cephalosporins?
1. activity toward Gm- bacteria increases while that toward Gm+ organisms decreases;
2. less acid stable;
3. stability against b-lactamases improves with each successive generation;
4. activity against S. aureus decreases; anti-pseudomonal activity increases;
5. CNS penetration increases
None
The 3 types of penicillin allergic RXNs
Acute; allergic; delayed
cephalosporins against anaerobes
2nd generation cephalosporin
anatabuse effect is associated w/ what?
2nd & 3rd generation cephalosporins
What has the broadest spectrum of activity of all b-lactams?
Carbapenems
Carbapenems antagonize the bacterioCIDAL effects of what 2 drugs?
Penicillin and cephalosporin
How do carbapenems antagonize the bacterioCIDAL effects of penicillin and cephalosporin?
By inducing b-lactamases that inactivate them
What is the only b-lactam w/ no cross-reactivity to penicillin?
Aztreonam
If a pt. is allergic to penicillin, what is the only b-lactam you can give him?
Aztreonam
aztreonam is a ?
Monobactam
Only monobactam in US is ?
Aztreonam
Aztreonam spectrum
Narrow; G- aerobes
Narrow; G- aerobes
Aztreonam spectrum
4 main groups of b-lactams
Penicillin; cephalosporin; carbapenem; monobactam
What are the 3 b-lactamase inhibitors?
Clavulanic acid; sulbactam; tazobactam
Block 30S
Tetracyclines; aminoglycosides; spectinomycin
Block 50S
Macrolides; chloramphenicol; streptogramins; oxazolidinones; lincosamides
Block tRNA synthetase
Mupirocin
What's the most important mechanism for bacterial resistance to tetracyclines?
Increase efflux
2 factors that lower absorption of tetracyclines
Divalent and trivalent cations; increased pH
Tetracylcines shouldn't be given to pregnant women because
1. crosses the placenta; 2. accumulates in bone, dentine, and enamel of unerupted teeth
All tetracyclines renal cleared EXCEPT
Doxycycline; minocycline
Which 2 tetracyclines are indicated for renal failure (but not hepatic failure) pt?
Doxycycline; minocycline
Rickettsial diseases
Tetracyclines
Which 2 drugs will lead to pseudomembranous coilitis?
Tetracycline; clindamycin (a lincosamide)
What's the prototype aminoglycoside?
Streptomycin
Aminoglycosides and quinolones are ? dependent killing whereas cell wall synthesis inhibitors are ? dependent killing.
Aminoglycosides and quinolones are CONCENTRATION dependent killing whereas cell wall synthesis inhibitors are TIME dependent killing.
3 outcomes of aminoglycosides
1. no peptide; 2. partially formed peptide; 3. mutated peptide w/ wrong aa incorporation
The most important way to resist aminoglycosides is ?
Enzymatic inactivation of drug
What 5 drugs cause ototoxicity?
Vancomycin; aminoglycoside; quinine; salicylate; macrolide
macrolides
#NAME?
#NAME?
Macrolides
prototype macrolide
Erythromycin
erythromycin
Prototype macrolide
streptomycin vs spectinomycin
Streptomycin is the prototype aminoglycoside; spectinomycin is a group of protein synthesis inhibitors (blocker of 30S) like aminoglycosides and tetracyclines
Cross-resistance b/w 4 blockers of 50S
Macrolides; streptogramins; clindamycin; chloramphenicol
What 4 drugs bind to the same site on 50S and therefore will competitively inhibit each other?
Macrolides; streptogramins; clindamycin; chloramphenicol
None
MLS-Type B
Macrolide; lincosamide; type B streptogramin
Most important way to resist macrolides (MLS-Type B) is ?
Methylase (ermA, B, C) changes target ribosome
cholestatic hepatitis
Erythromycin estolate
Which is the only macrolide that does NOT inhibit P450 enzymes and cause drug interactions?
Azithromycin
Major way to resist chloramphenicol is ?
Acetyltransferases that modify drug
In pt who cannot use tetracycline, switch to what?
Chloramphenicol
2 side effects of chloramphenicol…
Aplastic anemia; gray baby syndrome
What is gray baby syndrome?
Side effect of chloramphenicol; infants w/ inadequate levels of liver enzyme glucuronyl transferase can't metabolize drug
Drugs that affect P450 enzymes
Macrolides (except azithromycin); chloramphenicol; streptogramin; NNRTIs
Streptogramins and synergisim
Quinupristin and dalfopristin, individually STATIC but together CIDAL
If use Synercid (quinupristin/dalfopristin) in pt w/ MLS-Type B resistance, then the antibiotic is bacterio?
STATIC because essentially using dalfopristin alone
-pristin
Streptogramin
None
type B streptogramin
Quinupristin
type A streptogramin
Dalfopristin
Streptogramins are used for
Vancomycin resistant G+ infections
If vancomycin resistant G+ infections, use
Streptogramin or Oxazolidinones
Methylase is induced by the use of ? but not by the use of ? and ?
MLS-Type B is induced by the use of ERYTHROMYCIN but not by the use of STREPTOGRAMIN and CLINDAMYCIN.
clindamycin
Lincosamide
lincosamide
Clindamycin
Treat osteomyelitis w/
Clindamycin
Synercid
quinupristin/dalfopristin
quinupristin/dalfopristin
Synercid
Pseudomonads are intrinsically resistant to what?
Trimethoprim-sulfamethoxazole
For concentration-dependent killers like aminoglycosides and quinolones, the AUC/MIC ratio for immunocompromised patients must be ? than that for immunocompetent patients.
At least 4x bigger
The fluoroquinolones used against G- (e.g. pseudomonas) are in what order?
Cipro>Levo>Moxi
The fluoroquinolones used against G+ (e.g. streptococci) are in what order?
Moxi>Levo>Cipro
What is the prototype for drug/prodrug antiviral combinations?
Acyclovir/valacyclovir