AGACNP Barkley Review Antibiotics exam with
solutions |2025|
Abx selective toxicity & mechanism of antibiotic action - ANSWER -Abx unique MOA
that makes them selectively toxic to bacteria
- ability to disrupt bacterial cell wall or inhibit cell wall synthesis
- lethal or nonlethal inhibition of bacterial protein synthesis
- inhibition of bacterial nucleic acid synthesis
- antimetabolites
DNA or RNA synthesis inhibitors - ANSWER -fluoroquinolones, rifampin
T/F: any antibiotic may promote resistance, but *broad spectrum* agents are the most
likely to cause it - ANSWER -True
Mechanisms of antibiotic resistance - ANSWER -1) production of drug-metabolizing
enzymes
2) decreased drug uptake
3) change in drug receptor w/ decreased binding of abx
4) synthesis of compounds that antagonize the antibiotic
Ways organisms become resistant to antibiotics - ANSWER -1) *spontaneous
mutation* - occurs only to one drug
2) *conjugation*
- mostly in GN bacteria, occur b/w normal flora & pathogens
-*R-factor* w/c is extra-chromosomal DNA encoding for resistance that is passed from
one bacteria to the next
- responsible for multiple-drug resistant bugs
CDC's campaign to prevent antimicrobial resistance - ANSWER -*Infection Prevention*
- vaccinate
- remove catheters
*Diagnose & Tx infections effectively*
- target the pathogen
- contact the experts
*Use ABX wisely*
- practice antimicrobial control
- use local data
- tx infection, NOT contamination or colonization
- know when to say "NO" to Vanco
- stop ABX when infection has cleared or unlikely a bacterial infection
*Prevent transmission*
,- isolate the pathogen
- break the chain of contagion
Who should receive ABX prophylaxis? - ANSWER -1) Select *surgical patients* -
cardiac, peripheral vascular, orthopedics, GI, GYN (hysterectomy)
2) *severely neutropenic*
3) pt at risk for *bacterial endocarditis*
4) pts w/ *recurrent UTIs, severe rheumatic endocarditis*
Indications for ABX combinations - ANSWER -1) *initial therapy for severe infection* -
until organism is ID'd
2) *mixed infections* - common in GI, pelvic, brain abscesses
3) *prevent emergence of resistance* - TB, HIV, certain parasites
4) *to decrease toxicity*
5) *to promote synergistic effect* - PCN + gentamicin, TMP-SMZ*
ABX combination disadvantages - ANSWER -1) increased risk of *adverse effects* like
allergy or toxicity
2) risk of *suprainfection* (ex. C. diff & yeast infection*
3) risk for *drug resistance*
4) increase *cost*
Cell wall synthesis inhibitors - ANSWER -PCN, cephalosporins, carbapenems,
aztreonam, vancomycin, fosfomycin, teicoplanin
Penicillins - ANSWER -- *inhibit transpeptidases necessary for cell wall synthesis* &
activate autolysis w/c cleave bonds in the cell wall.
- *target the PCN binding proteins (PBP) - PBP1 & PBP3 (crucial targets)
- *resistance* is d/t inability of drug to reach PBPs or enzymatic inactivation of the drug
- PCN resistant drugs produce beta-lactamase which cuts into the beta-lactam ring of
the drug which inactivates the ABX so the ABX is no longer become anti-infective.
•Allergic reactions (1-5%); Anaphylaxis (.004-.015%)
•Cross reaction - 3-7% PCN to Ceph
•Prolonged high dose = granulocytopenia, interstitial nephritis
Bacterial cell wall - ANSWER -Gram positive vs Gram negative
Gram negative has an outer membrane and gram positive does not w/c prevents PCN
from reaching PBPs (target molecules)
PCN: *Narrow-spectrum PCNase sensitive* - ANSWER -*PCN G, PCN V K*
useful for Strep, Neisseria, many anaerobes, & spirochetes
PCN: *Narrow-spectrum PCNase resistant* - ANSWER -*Nafcillin, Oxacillin*,
Cloxacillin, Dicloxacillin
,- useful for Staph aureus
PCN: *Broad-spectrum* - ANSWER -*Ampicillin, Amoxicillin*, Bicampicillin
- useful for H. flu, E. coli, P. mirabilis, N. gonorrheae, enterococci
susceptible to beta-lactamase
PCN: *Extended-spectrum* - ANSWER -- *Piperacillin*, Carbenicillin, Ticarcillin,
Mezlocillin
useful for H. flu, E. coli, P. mirabilis, N. gonorrheae, enterococci
*PLUS*
*pseudomonas*, enterobacter, proteus, *B. fragilis*, & Klebsi
susceptible to beta-lactamase
PCN side effects & toxicities - ANSWER -1) Pain at IM injection site - bec PCN is
thick/viscious
2) reactions to procaine & potassium - from the injection, not PCN itself
3) rare neurotoxicity
4) *ALLERGY* - can occur immediate (2-30 mins), accelerated (1-72h); late (days to
weeks)
*anaphylactic reactions occur w/ PCNs more than any other drugs*
*Incidence is 0.02% but mortality is 10%
Allergy is exposure dependent, NOT dose dependent.
What to do if pt has PCN allergy? - ANSWER -*AVOID PCNs ENTIRELY*
*mild allergy* - can give cephalosporin
*severe allergy or anaphylaxis* - avoid PCN & cephalosporin (5-10% cross-sensitivity)
Alternatives to PCN
- Vanco & erythromycin
*Life-threatening + NO abx alternatives, give PCN according to desensitization
schedule*
PCN Combined with a Beta-Lactamase Inhibitor - ANSWER --cillin/bactam
-cillin/clavulanate
limited toxicity; *great for Pseudomonas*
*Ampicillin + sulbactam (Unasyn)*
*Amox + clav (Augmentin)*
Ticarcillin + clav (Timentin)
, *Piperacillin + tazobactam (Zosyn)*
Cephalosporins - ANSWER -*widely used abx*
*beta-lactam abx that bind to PBPs*
resistance d/t beta-lactamases (bacteria makes them) w/c cleave open the drugs
•Allergic reactions (1-3%)
•Cefotetan - disulfiram-like reaction with EtOh and hemostasis (hypoprothrombinemia)
1st generation cephalosporins - ANSWER -*Cefazolin, cephalexin*
Use: *Gram- positive cocci*, Proteus mirabilis, E. coli, Klebsiella pneumoniae.
*Cefazolin used prior to surgery to prevent S. aureus wound infections*
2nd generation cephalosporins - ANSWER -* Cefoxitin, cefaclor, cefuroxime*
Use: GP w/ some GN, Haemophilus influenzae, Enterobacter aerogenes, Neisseria
spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens.
3rd generation cephalosporins - ANSWER -*Ceftriaxone, cefotaxime, ceftazidime*
Use: serious gram-negative infections resistant to other β-lactams.
*Ceftriaxone*—meningitis, gonorrhea, disseminated lyme disease
*Ceftazidime* —Pseudomonas
4th generation cephalosporins - ANSWER -*Cefepime* - broadest spectrum
Use: GN, GP, & Pseudo
Cephalosporins: side effects & toxicities - ANSWER -1) Allergy - *maculopapular rash
after several days (most common)*
2) increased *risk for bleeding* (cefotetan, cefmetazole, cefoperazone)
3) *thrombophlebitis w/ IV infusion*
4) *Alcohol intolerance* - disulfiram-like reaction (cefotetan, cefmetazole, cefoperazone)
Carbapenems - ANSWER -*Imipenem, meropenem*, ertapenem, doripenem,
avibactam
*Imipenem* is a broad-spectrum, β-lactamase- resistant carbapenem. Always
administered with cilastatin (inhibitor of renal dehydropeptidase I) to decrease
inactivation of drug in renal tubules
*Meropenem* - may be used for bacterial meningitis; but S/E - seizures
*Ertapenem - for acute pelvic infections, CAP, complicated GI, GU, SSTI*
*Doripenem - complicated intra-abd or complicated UTI*
*Avibactam* - used in combo w/ Ceftazidime for complicated intra-ab & UTI
Use: GPC, GNR, and anaerobes. Wide spectrum, but significant side effects *limit use
to life-threatening infections or after other drugs have failed.*