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Flashcards in Antibiotics 1 Deck (57):

host factors to consider

age, weight, organ function,signs and symptoms of infection, immune status, comorbid conditions, foreign bodies, living environment, travel, drug allergies, prior antibiotics


organism factors to consider

intrinsic resistance, propensity to acquire resistance during treatment, prior exposure to antibiotics, likelihood of organism being pathogenic, minimum inhibitory concentration (MIC), likelihood of infectious agent growing in culture


antimicrobial factors to consider

antimicrobial spectrum, clinical data, pharmacokinetics, synergy or antagonism with other agents, drug interactions, convenience, cost


gram negative organisms cell structure and function

outer membrane of LPS endotoxin, outer membrane proteins for attachment and virulence, porin protein-passive transport, thin cell wall, B lactamase in the periplasmic space


gram positive organisms cell structure and function

thick cell wall composed of NAM and NAG alternating. Cross linked by transpeptidase. Beta lactamase secreted outside the cell.


beta lactam mechanism of action

bind to penicillin-binding proteins. These proteins catalyze the polymerization of the glycan strand and cross linking between glycan chains.


mechanisms of resistance to beta lactam drugs

enzymatic destruction: beta lactamase (big deal in gram negative organisms)
reduced permeability: gram negative organisms can alter porin channels to limit entry
target site alteration: gram positive organisms can have low affinity binding of antibiotic to target PBPs


spectrum of activity for beta lactam drugs

lack activity against atypical organisms like mycoplasma pneumoniae, and chlamydophilia pneumoniae. lack activity against MRSA except for ceftaroline.


pharmacokinetics of beta lactam drugs

short half lives, 20 minutes to a few hours. widely distributed, CSF penetration variable. Liver metabolism. Renal excretion, but ceftriaxone is hepatobiliary.


time dependent killing and beta lactam drugs

bacterial killing is achieved when these drugs acylate PBPs. antibacterial effect requires a certain number of PBPs to be acylated to cause stasis or cidality. give more frequently and give as a continuous infusion. Want concentration > MIC for ~50% of the dosing interval.


side effects of beta lactam drugs

hypersensitivity reactions: anaphylaxis is rare, delayed hypersens can happen along with drug fever and acute interstitial nephritis. Seizures can happen with high doses in patients with renal dysfunction. Can cause N/V and diarrhea


natural penicillins spectrum

mostly gram-positive aerobic organisms. Streptococci, enterococcus. Can deal with oral anaerobes and clostridium, but not C. difficile. Can deal with gram negatives like N. meningitidis, as well as spirochetes like T. pallidum (syphilis). Is drug of choice for syphilis


natural penicillins clinical uses

odontogenic infections. streptococcal infections (pharyngitis, cellulitis, endocarditis, pneumococcal pneumonia). enterococcal infections. Syphilis.


natural penicillins pharmacokinetics

penicillin V is more acid stable than penicillin G, leading to better bioavailability. Widely distributed, renal elimination.


natural penicillin pharmacodynamics

T>MIC. can be given as continuous infusion to increase T > MIC and allow outpatient administration


anti-staphylococcal penicillin agents

oxacillin, nafcillin, dicloxacillin


anti-staphylococcal penicillin spectrum

MSSA (methicillin-susceptible Staphylococcus aureus) and streptococci


anti-staphylococcal penicillin clinical uses

primarily MSSA infection. can be used for skin and soft tissue infection, joint infection, bacteremia, and endocarditis. Superior to vancomycin for MSSA infection.


anti-staphylococcal penicillin adverse events

oxacillin: hepatotoxicity, neutropenia. Nafcillin: similar to oxacillin, but also have thrombophlebitis


anti-staph penicillin pharmacokinetics

dicloxacillin: 50% absorbed, decreased with food.
Oxacillin, nafcillin: 30 min half life, requires frequent dosing


aminopenicillin agents

ampicillin, amoxicillin


spectrum for aminopenicillins

similar to penicillin. ampicillin is a drug of choice for enterococci. used in listeria. Poor activity in enterobacteriaceae due to beta lactamases. combining with a B-lactamase inhibitor restores some susceptibility. Active against non B-lactamase producing haemophilus


clinical uses for aminopenicillins

amoxicillin: otitis media, upper and lower respiratory tract infections in kids, lyme disease.
IV Ampicillin: listeria, empirically in meningitis, enterococcal infection (drug of choice), used in conjunction with gentamicin for endocarditis


aminopenicillin pharmacokinetics

bioavailability: amoxi>ampicillin

amOxicillin = better Oral absorption


aminopenicillin adverse effects

GI irritation. Hypersensitivity: non-IgE rash (delayed), type 1 hypersensitivity due to potential for cross reactivity with cefadroxil and cefpozil


antipseudomonal penicillins agents

piperacillin, ticarcillin


extended-spectrum penicllin/B-lactamase inhibitor combos

ampicillin/sulbactam, amoxicillin/clavulanate, piperacillin/tazobactam, ticarcillin/clavulanate


extended-spectrum penicllin/B-lactamase inhibitor combos spectrum

B-lactamase inhibitor enhances activity against B-lactamase producing organisms. Gram positive: MSSA. Gram negative: enterobacteriaceae. Anaerobes: bacteroides, fusobacterium, prevotella. Retained activity against streptococci and enterococci.


which extended-spectrum penicllin/B-lactamase inhibitor combos are effective against pseudomonas aeruginosa?

only pip/taz and tic/clav


which extended-spectrum penicllin/B-lactamase inhibitor combos has poor activity against enterobacteriaceae?



what has activity against acinetobacter baumanni?



extended-spectrum penicllin/B-lactamase inhibitor combos clinical uses

mixed infections: intra-abdominal, diabetic foot, odontogenic, animal/human bites, aspiration pneumonia, nosocomial pneumonia (not amp/sulb or amox/clav due to lack of PsA activity)


extended-spectrum penicllin/B-lactamase inhibitor combos side effects

hypersensitivity reactions (IgE or delayed hypersensitivity reaction). GI (diarrhea common with clav). Interstitial nephritis. Blood dyscrasias are rare. pip/taz can cause thrombocytopenia and aplastic anemia


cephalosporins spectrum

generally more resistant to B lactamases than penicillins. resistant to penicillinases. susceptible to cephalosporinases. Ceftazidime and cefepime have activity against Pseudomonas aeruginosa. lack activity against MRSA and Enterococcus EXCEPT for ceftaroline. Lack activity against B. fragilis.


cephalosporin side effects

hypersensitivity reactions: kess common than with penicillins. 3rd and 4th gen have super low chance of cross-allergenicity with penicillins. GI: ceftriaxone causes biliary pseudolithiasis. Coagulopathy with cefamandole, cefotetan, cefoperazone. Disulfiram-like reaction with ethanol in cefamandole, cefotetan, and cefoperazone. CNS: seizure due to GABA inhibition


first-gen cephalosporin agents

cefazolin, cephalexin, cephadroxil.


first-gen cephalosporin spectrum

MSSA, streptococci. Some enteric GNRs. Activity against enterobacteriaceae unpredictable and shouldnt be assumed. Works on Proteus, E. coli, and Klebsiella pneumonia (PEcK)


first gen cephalosporin clinical uses

cefazolin: surgical prophylaxis, serious MSSA infections, non-purulent cellulitis, definitive therapy for UTI (based on culture results)

Cephalexin/cefadroxil: SSTI, UTI (based on culture results)


first-gen cephalosporin clinical side effects

hypersensitivity reactions: higher cross-reactivity rate with penicillin than higher generation cephalosporins. better tolerated than antistaphylococcal penicillins


first-gen cephalosporin pharmacokinetics

do not cross BBB!!! can't use to treat CSF infections


second-gen cephalosporin agents

cefuroxime, cefaclor, loracaref, cefprozil

cephamycins: cefoxitin, cefotetan

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second-gen cepahlosporin spectrum

gram-positive organisms: staphylococci, streptococci, less active than 1st gen cephalosporins. Gram-neg organisms: some enterobact, H. influenzae, m.catarrhalis, n.gonorrheae. anaerobes: cefoxitin and cefotetan.


what 2nd gen cephalosporin has common resistance in bacteroides?



second gen cephalosporin clinical uses

community acquired respiratory tract infections, gonorrhea, surgical prophylaxis. cefoxitin, cefotetan for colon surgery


third generation cephalosporin agents

cefotaxime, ceftriaxone, ceftazidime, cefdinir, cefpodoxime, ceftibutin, cefixime.

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third gen cephalosporin spectrum

extended activity against enterobacteriaceae. resistance is problematic. useful against streptococci, less active against staphylococci than 1st gen. ceftazidime active against pseudomonas, less active against streptococci and staphylococci.


ceftriaxone clinical uses

community acquired pneumonia, meningitis, complicated UTI, intra-abdominal infection, CSF lyme disease, streptococcal endocarditis, conoccoal infection and PID


ceftazidime clinical uses

definitive treatment of pseudomonas infections. no longer recommended as monotherapy for neutropenic fever. empiric treatment of post-neurosurgical meningitis.


third gen cephalosporin side effects

greater correlation with C. difficile infection than other drugs. development of resistant organisms. Ceftriaxone: concerns in neonates: biliary sludging, kernicterus, interaction with calcium containing solutions causing precipitation. use cefotaxime instead


third gen cephalosporin pharmacokinetics

widely distributed, effective penetration across BBB. ceftriaxone undergoes hepato-biliary and renal elimination: no dose adjustment required for renal dysfunction


fourth gen cephalosporin agent

cefepime. is a zwitterion, which permits rapid entry into outer membrane of gram-negative bacteria


4th gen cephalosporin spectrum

gram negative: excellent activity against enterobacteriaceae and pseudomonas. relative resistance to hydrolysis by B lactamase. gram positive: high affinity for PBPs of gram positive bacteria: MSSA, S. pneumoniae including strains relatively resistant to penicillin


4th gen cephalosporin clinical uses

geared towards nosocomial infections, particularly when pseudomonas is a concern. neutropenic fever. meningitis. nosocomial pneumonia. UTI


4th gen cephalosporin side effects

akinetic seizures, since it crosses BBB very easily


5th gen cephalosporin agent/chemistry

ceftaroline. possesses a side chain that mimicks a portion of the cell wall structure and acts as a trojan horse, allowing access to the PBP2a.


5th gen cephalosporin spectrum

gram positive: S. aureus, E. faecalis, S. pneumoniae.

gram negative: similar to 3rd gen cephalosporins. Lacks activity against pseudomonas


5th gen cephalosporin clinical uses

complicated skin and soft tissue infections. Approved for CAP. bacteremia (used with daptomycin).