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
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
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
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
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
a TAN-FACed PRO wrestler wearing a FOX FUR coat is driving your CAR
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.
i TRIed to FIX DINIR BUT i didnt have a DIME after TAX time. im one POD
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