Cell Wall Active Antimicrobials Flashcards
1,3. Explain the mechanism of action B-lactams: penicillins and cephlosporins.
- penetrate cell wall (Gram neg- pass through the porin and gram + diffuse across the peptidoglycan) and bind to penciling binding proteins
- antibiotic inhibits transpeptidation so that peptidoglycan cross-linking doe snot occur; integrity of cell wall is lost
- leakage or inhibition of substance that normally acts to inhibit autolysis
note penicillins and cephalsporins are time-dependent killers meaning that time above MIC is the most important parameter for optimizing bacterial killing- frequent dosing
- Describe the major mechanisms by which bacteria develop resistance to cell wall active agents. (5)
enzyme activation (beta-lactamases or extended-spectrum beta lactamases [ESBL]) alteration in target site altered bacterial membrane efflux pumps (environmental?)
cephalosporins show low toxicity and limited cross-reactivity with penicillins
rash
diarrhea
- List the major adverse drug reactions associated with beta-lactam antimicrobials, vancomycin and daptomycin.
beta-lactams: rash/hypersensitivity, antibiotic associated diarrhea, cytopenias, renal impairment
- Discus the summarizing statements, part 1
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1,3. Explain the spectrum of activity of penicillin G and its formulations.
gram-positive: streptococci, most enterococci, most pneumococci, peptostretococcus, Listeria, Clostridia
Gram neg: pasturella, Neisseria meningitdis
Spirochetes: Treponema pallidum (syhpilis) and Borrelia species (Lyme disease)
DOC with streptococcal, syphilis
Gas gangrene, periodontal infection and enterococcal infections
Penicillin G is the intravenous formulation
Benzathine penicillin G is the IM form (low over weeks)
Penicillin VK is the oral formulation
1,3. Explain the spectrum of activity of amoxicillin and its formulations.
same spectrum of activity as penciling while adding some Gram negatives including most E.coli, Proteus mirablia dn Haemophilus
Upper and lower respiratory infections, uncomplicated UTI and enterococcal infections
DOC for nonMRSA/MRSE staph infection
Amoxicillin is the oral formulation
Ampicillin is used as the IV formulation
1,3. Explain the spectrum of activity of dicloxacillin and its formulations.
niche antibiotics for staphylococci; excellent activity against staphylococci and streptococci, no activity for gram neg, enteroccocci or anaerobes
dicloxacillin is the oral form (cellulitis)
oxacillin is the IV form (endocarditis or osteomyelitis)
1,3. Explain the spectrum of activity of extended spectrum penicillin and its formulations.
better activity against Gram negative aerobes and pseudomonas, more commonly use as a combo with beta-lactamase inhibitor
gram negative aerobes, pseudomas, some strep and staph, peperacillin covers enterococci
sued in pseudomas infections and mixed infections with gram negatives and enterococci
1,3. Explain the spectrum of activity of penicillin/beta-lactamase inhibitor and its formulations.
spectrum: S. aureus, E. coli, H. influenzae, Moraxella catarrhalis, Klesiella, Bacteroids and other anaerobes
Used: upper and lower respiratory tract infections, celulitis, animal and human bites, intra abdominal infections, nosocomial infections including pseudomonas (popular for outpatient infection and nosocomial infections)
oral: amoxicillin/clavulanic acid
IV: piperacillin/taxobactam
1,3. Explain the spectrum of activity of 1st generation cephalosporins and its formulations.
Gram positive cocci, E. coli and Klebsiella (widely used for Gram Positive skin and soft tissue infections due to strep or staph and pre-op prophylaxis)
cephalexin- oral
cefazolin- IV: used often for perioperative antibiotic prophylaxis
1,3. Explain the spectrum of activity of 2nd generation cephalosporins and its formulations.
cephamycins subgroup is only with significant amount of anaerobic activity
Cefuroxime group: 1st gen+ Haemophilus and Moraxella– used for upper and lower respiratory infections
Cephamycin group: 1st gen+ anaerobes and more gram neg.– used for intra abdominal and pelvic infections
cefoxitin- IV agent
1,3. Explain the spectrum of activity of 3rd generation cephalosporins and its formulations.
ceftriaxone- long half life, large spectrum
ceftriaxone- niche treating Pseudomonas infections (no meaningful gram positive activity
excellent gram neg. and streptococcal activity, DOC for N. gonrrhoeae (ceftriaxone) and pseudomonas (cetrazadime); can achieve excellent levels in CSF, used in management of meningitis
meningitis (ceftriaxone)
CAP (both)
UTI (all)
gonorrhea (ceftriaxone)
Pseudomonas (ceftazadime)
viridans strep endocarditis (ceftriaxone)
intra-abdominal (ceftriaxone + metronidazole for anaerobes)
1,3. Explain the spectrum of activity of 4th gen. cephalosporins and its formulations.
important drug for nosocomial infections including Pseudomonas
excellent Gram positive (of 1st gen), excellent Gram neg. (of 3rd gen, including Pseudomonas) but no coverage for anaerobes and no MRSA
used for nosocomial infections, febrile neutropenia and Pseudomonas
IV: Cefepime
1,3. Explain the spectrum of activity of ceftaroline and its formulations.
coverage of MRSA
excellent Gram pos., S. pneumonia, although activity against Gram negative and anaerobes is limited
used for SSTI and CAP
ceftaroline- IV
1,3. Explain the spectrum of activity of carbapenems and its formulations. Note the mechanism of action and adverse reactions.
broadest spectrum activity used for serious infections, critically ill patients and highly resistant organisms
mechanism: inhibition of cell wall synthesis, time dependent
most bacteria except MRSA, Enterococus faecium, Clostriudium difficult, stenotrophomonas and Burkholderia
excellent Gram pos. almost all Gram neg and anaerobes
(ertapenem does not cover pseudomonas or Acinetobacter, long half life)
meropenem: (IV) better gram neg activity, crosses BBB, good for pediatric meningitis)
**resistance through alterations in porins and changes in PBP, 2014 carbapenem resistant enterobacteriaceae
***pay close attention to renal dose adjustments
adverse effects: rash, hypersensitive, cross rxn with penicillins, imipenem (high dose seizures)
