Antibiotics 1 Flashcards
gram positive organisms have:
cell wall:
- 20-80 nm think (much thicker than gram-neg cell wall);
- has peptidoglycan (backbone with alternating subunits of N-acetylglucosamine and N-acetylmuramic acid with beta1to4 linkages), identical tetrapeptide side chains attached to NAM, identical peptide cross-bridges
gram negative organisms have
- outer membrane (semipermeable lipid bilyaer with phospholipids, lipoproteins, LPS, and proteins)
- porins
- surface proteins (work as enzymes, adhesins)
- periplasmic space (site of BETA-LACTAMASE)
- peptidoglycan cell wall (2-3 layers thick with 2-3 nm)
Beta lactams: structural features, MOA, mechs of resistance
- beta-lactam ring for antibacterial activity; look at side chain as well
- binds penicillin binding proteins (PBPs): PBPs catalyze polymerization of the glycan strand (transglycosylation) and the cross-linking b/w glycan chains (transpeptidation); with peptidoglycan precursor buildup autolysins are triggered
- think beta-lactamase (expressed outside of cell in gram positive, in periplasmic space for gram negatives); alteration in porin channels and beta-lactams can’t penetrate outer membrane of gram-neg bacteria; low affinity binding of antibiotic to target PBPs (MRSA alters PBP2a, S pneumoniae alters PBP2x and PBP2b)
Beta lactam characteristics:
- Prevent transpeptidation (cross-linking) of peptidoglycan layers in the cell wall by binding to penicillin-binding proteins
- Most with short half-lives (maybe 20 minutes)
- Time-dependent pharmacodynamics (T > MIC)
- Most eliminated via renal route (adjust with renal insufficiency)
- Hypersens reactions and GI effects!!
- Lacks activity against organisms w/o cell wall: Mycoplasma pneumoniae, chlamydophilia pneumoniae
- Exception for MRSA activity: CEFTAROLINE!!!
Natural Penicillin quick facts (Penicillin V and Penicillin G):
Spectrum: effective against non-beta-lactamase producing bacteria: think strep, and anaerobes (actinomyces, prevotella, Clostridium except difficile); select gram neg bacteria (Neisseria), Syphilis
Place in therapy: oral strep infection, non-purulent cellulitis, syphilis
SE’s: hypersens reaction, GI SE’s, seizures at high doses (particularly with renal dysfunction)
Antistaph penicillin quick facts (Oxacillin, Nafcillin, Dicloxacillin):
Spectrum: MSSA, strep;
Place in therapy: MSSA infection (better than vanco)
SE’s: Nafcillin with thrombophlebitis and neutropenia, oxacillin with hepatotoxicity and neutropenia;
PEARLS: bulky side chain shields beta-lactam ring from penicillinase, but too big to get entry into gram-neg cell)
Aminopenicillin quick facts (Ampicillin, amoxicillin)
Spectrum: strep, enterococci (ampicillin DOC here), LIsteria; some gram negs (proteus mirabilis, E coli, Listeria);
Place in therapy: amoxicillin (comm-acquired URTI’s), IV ampicillin (DOC for enterococcal infections), IV ampicillin (listeria meningitis), IV ampicillin with aminoglycosides (enterococcal endocarditis);
SE’s: hypersens rxn with non-IgE rash (type IV hypersens) and IgE rxn (type I hypersens)
Pearls: susceptible to effects of beta-lactamse produced by staph and other gram-neg organisms, and increased risk of cross-reactivity with cefadroxil and cefprozil due to identical side chain
Extended spec penicillin-beta-lactamase inhibitor combos (amp/sulbactam, amoxicillin/clavulanate, piperacillin/tazobactam, ticarcillin/clavulanate):
Spectrum: enhanced gram-neg acitivity (enterobacteriaceae), enhanced gram-positive activity (MSSA), anaerobes like B fragilis; retained activity against strep and enterococci;
Place in therapy: Pip/taz and ticar/clav active against nosocomial infections like pneumonia, intra-abdo infections, wounds (PSEUDOMONAS); amox/clav and amp/sulb against aniaml and human bites, URI’s, and diabetic foot infection;
SE’s: non-IgE rash, hypersens rxns, amox/clav with diarrhea, pip/taz: thrombocytopenia and interstitial nephritis
Cephalosporin characteristics:
- Generally more resistant to beta-lactamases than penicillins (susceptible to cephalosporinases)
- lacks activity against MRSA and enterococcus, EXCEPT ceftaroline (5th gen)
- Lacks activity against B fragilis
- can cause hypersens rxns similar to penicillins (some cross-reactivity with penicillin)
1st gen cephalosporin facts (cefazolin and cephalexin):
Spectrum: strep and MSSA, some gram-negatives (beta-lactamase limits gram-neg spectrum), NO ANAEROBES OR ENTEROCOCCI;
Place in therapy: definitive therapy based on cultures (E coli, kelb UTI and MSSA with cefazolin); surgical prophylaxis with cefazolin
SE’s: Less antigenic than penicillins, but more cross reactivity with them than other cephalosporins;
Misc: NOT for CSF infection
2nd gen cephalosporin (cefuroxime, cefaclor, loracarbef, cefprozil are true; cephamycins with cefoxitin and cefotetan):
Spectrum: true cephalosporins with better activity against S pneumoniae than first gen and better gram neg activity than first gen (H influenzae, N gonorrheae, some enterobacteriaceae); CEPHAMYCINS: better activity against E coli and kleb, and has ACTIVITY AGAINST ANAEROBES;
Place in therapy: true cephs for CA respiratory tract infections, and cephamycins mostly surgical prophylaxis colon surgery;
Pearls: DON’T USE against ESBL-producing enterobacteriaceae
3rd gen cephalosporin (cefotaxime, ceftriaxone, ceftazidime, cefdinir, cefpodoxime, ceftibutin, cefixime)
Spectrum: activity against enterobacteriaceae increased;
ceftriaxone and cefotaxime against S pneumoniae, H influenzae, M catarrhalis, but less active against MSSA than first gen, and
ceftazidime for P aeruginosa, with poor activity against gram-pos organisms (S pneumoniae, MSSA), and both with NO ACTIVITY AGAINST enterococcus or anaerobes;
Place in therapy: ceftriaxone (adults) and cefotaxime (infants): good for CAP, meningitis when S pneumoniae or H influenze, or good when enteric gram-negs are likely (intraabdo infections and UTI’s); ceftriaxone good for lyme;
ceftazidime and cefepime: nosocomial infections where Pseudomonas is a concern, and Ceftas with poor gram-positive activity;
Pearls: no renal dosing required for ceftriaxone: can get biliary sludging and Ca crystals with infants
4th gen cephalosporin (zwitterion cefepime):
Spectrum: excellent gram-neg activity including Pseudomnoas, better activity against gram pos organisms than ceftazidime; cefepime is piperacillin/tazobactam without anaerobic activity; NO ACTIVITY AGAINST enterococcus or anaerobes;
Place in therapy: nosocomial infections, monotherapy for febrile neutropenia, post-neurosurg meningitis, nosocomial pneumonia;
SE”s: similar to other beta lactams
5th gen cephalosporin (ceftaroline, ceftobiprole)
Spectrum: similar gram neg activity to ceftriaxone (NO PSEUDOMONAS), S aureus INCLUDING MRSA, some enterococcus activity (unlike the other cephalosporins), and STILL NO ACTIVITY AGAINST ANAEROBES);
Place in therapy: monotherapy for complicated skin and soft tissue infections;
Pearl: some reports of ceftaroline-resistant MRSA
Monobactam quick facts (Aztreonam):
Spectrum: gram negs including P aeruginosa, NO ACTIVITY AGAINST gram-pos and anaerobes; very similar to aminoglycosides;
Place in therapy: usually used in combo with other agents for nosocomial infections especially in patients with penicillin allergy or renal dysfunction;
Pearls: shares same side chain as CEFTAZIDIME (maybe allergic cross-reactivity)
