L23 Cell Wall Inhibitors II Flashcards
Cephalosporins display variable susceptibility to beta-lactamase enzymes; which generation is most stable?
4th generation
First generation cephalosporins work best against ___; they also have good activity against a few ___.
Gram positive aerobes; Gram negative aerobes
Which Gram-positive bacteria are susceptible to first generation cephalosporins?
- Methicillin-susceptible S. aureus
- Penicillin-susceptible S. pneumoniae
- Group streptococci
- Viridans streptococci
Which Gram-negative bacteria are susceptible to first generation cephalosporins?
- P. mirabilis
- E. coli
- K. pneumoniae
PEK
Second generation cephalosporins contain what two types of antibiotic in addition to cephalosporins?
- Cephamycins
2. Carbacephemas
Second generation cephalosporins are slightly less active against ___, but more active against ___. The cephamycins also have activity against ___.
Gram-positive aerobes; Gram-negative aerobes; anaerobes
Which Gram-positive bacteria are susceptible to second generation cephalosporins?
- Methicillin-susceptible S. aureus
- Penicillin-susceptible S. pneumoniae
- Group streptococci
- Viridans streptococci
Which Gram-negative bacteria are susceptible to second generation cephalosporins?
- P. mirabilis
- E. coli
- K. pneumoniae
- H. influenzae
- Enterobacter spp. (some)
- Neisseria spp.
- M. catarrhalis
HENPEK
Which type of second generation cephalosporins have activity against anaerobes, and which anaerobes?
Cephamycins (cefoxitin, cefotetan, cefmetazole); Bacteroides fragilis
Third generation cephalosporins are less active against ___ aerobes, but have greater activity against ____ aerobes, including some beta-lactamase-producing strains.
Gram-positive; Gram-negative
Which third generation cephalosporins retain the best activity against Gram-positive aerobes, including PRSP?
Ceftriaxone and cefotaxime
Which Gram-negative bacteria are susceptible to third generation cephalosporins?
- P. mirabilis
- E. coli
- K. pneumoniae
- H. influenzae
- M. catarrhalis
- N. gonorrhoeae
- N. meningitidis
- Citrobacter sp.
- Enterobacter sp.
- Acinetobacter sp.
- Morganella morganii
- Serratia marcescens
- Providencia
- Salmonella sp.
- Shigella sp.
- Pseudomonas aeruginosa
Which third generation cephalosporins have activity against Pseudomonas aeruginosa?
Ceftazidime and cefoperazone
What is beneficial about fourth generation cephalosporins?
- Extended spectrum of activity (including Pseudomonas aeruginosa and beta-lactamase producing Enterobacter spp.)
- Stable against beta-lactamases; poor inducer of extended-spectrum beta-lactamase enzymes
What is the only fourth generation cephalosporin currently available?
Cefepime
What is beneficial about fifth generation cephalosporins?
Extended activity against respiratory pathogens (H. influenzae, S. pneumoniae, Moraxella, S. aureus) and Gram positive pathogens of SSSI (S. pneumoniae, MRSA)
What is ceftaroline used for?
- Community acquired bacterial pneumonia
2. SSSI
What is ceftolozane-tazobactam (Zerbaxa) used for?
Beta-lactam resistant GNRs including Pseudomonas; complicated intra-abdominal infections and UTI
Overall, cephalosporins are NOT active against which 6 bacteria?
- MRSA
- Enterococcus spp.
- Listeria monocytogenes
- Stenotrophomonas maltophilia
- Clostridium difficile
- Atypical bacteria, including Legionella
How are cephalosporins absorbed?
Oral cephalosporins are well-absorbed, but achieve lower serum concentrations than parenteral products.
How are cephalosporins distributed?
Widely into tissues and fluids; CSF concentrations achieved only with parenteral cefuroxime, 3rd, and 4th generation agents
How are cephalosporins eliminated?
Primarily eliminated unchanged by the kidney via glomerular filtration and tubular secretion
Which 2 cephalosporins are not eliminated by the kidney?
- Ceftriaxone (biliary)
2. Cefoperazone (liver)
Most cephalosporins have short elimination half-lives (< 2 hours), except for ___, which has a half-life of 8 hours.
Ceftriaxone
What are first generation cephalosporins used for clinically?
Skin and soft tissue infections, septic arthritis, osteomyelitis, endocarditis, surgical prophylaxis, UTIs, bacteremia
What are second generation cephalosporins used for clinically?
Sinusitis, otitis media, upper and lower respiratory tract infections, polymicrobial infections or surgical prophylaxis for abdominal surgery (cefoxitin, cefotetan)
Which second generation cephalosporin is no longer recommended for meningitis?
Cefuroxime
What are third generation cephalosporins used for clinically?
Bacteremia, pneumonia, complicated UTI, peritonitis, intra-abdominal infections, skin and soft tissue infections, bone and joint infections, meningiti
What is ceftriaxone used for?
Uncomplicated gonorrhea, CAP, PRSP, viridans strep endocarditis
What are fourth generation cephalosporins used for clinically?
Pneumonia, bacteremia, UTIs, skin and soft tissue infections, intra-abdominal infections, Gram-negative meningitis, febrile neutropenia
Which generations of cephalosporins cover Pseudomonas?
Third, fourth
What are fifth generation cephalosporins used for clinically?
Community acquired bacterial pneumonia, SSSIs
What is the incidence of hypersensitivity for cephalosporins; what is the cross-reactivity with penicillins?
5%; 5-15%
When can cephalosporins be used/not used with respect to allergy?
Okay to use if the reaction is rash or itching; do not use if there is an IgE-mediated reaction
Certain cephalosporins (cefamandole, cefotetan, cefmetazole, cefoperazone, moxalactam) have an MTT side chain, which can cause what 2 adverse effects?
- Hypoprothrombinemia (due to enzyme inhibition of vitamin K metabolism or reduction in vitamin K-producing bacteria in the GI tract
- Ethanol intolerance
What are the hematologic side effects of cephalosporins?
Leukopenia and thrombocytopenia
What are the GI side effects of cephalosporins?
Increased bili and C. diff. colitis
What are the 4 carbapenems currently available?
- Imipenem
- Meropenem
- Ertapenem
- Doripenem
What is the primary target of carbapenems?
PBP-2
What are the most broad spectrum agents available?
Carbapenems
Which bacteria are not covered by carbapenems?
- MRSA
- PRSP
- VRE
- Coag-negative staph.
- C. difficile
- Atypical bacteria
- S. maltophilia
Which carbapenems are best for treating Gram-positive aerobes?
Imipenem and doripenem
Which Gram-positive bacteria are susceptible to carbapenems?
- Methicillin-susceptible S. aureus
- Penicillin-susceptible S. pneumoniae
- Group streptococci
- Viridans streptococci
- Enterococcus faecalis
Which Gram-negative bacteria are susceptible to carbapenems?
- P. mirabilis
- E. coli
- K. pneumoniae
- H. influenzae
- M. catarrhalis
- N. gonorrhoeae
- N. meningitidis
- Citrobacter spp.
- Enterobacter spp.
- Acinetobacter spp.
- Morganella morganii
- Serratia marcescens
- Providencia
- Salmonella spp.
- Shigella spp.
- Pseudomonas aeruginosa
Which carbapenems are best for treating Gram-negative aerobes?
Meropenem and doripenem
Which carbapenem does not treat Pseudomonas aeruginosa?
Ertapenem
Which Gram-positive anaerobes are susceptible to carbapenems?
- Peptococcus spp.
- Peptostreptococcus spp.
- Veillonella
- Clostridiium spp. (not C. diff.)
Which Gram-negative anaerobes are susceptible to carbapenems?
- Bacteroides spp.
- Fusobacterium
- Prevotella spp.
How are carbapenems distributed?
Widely into body tissues and fluids
Which carbapenem penetrates the CSF best?
Meropenem
How are carbapenems eliminated?
Primarily by the kidney
Why can imipenem be nephrotoxic and what can be co-administered to help?
It undergoes hydrolysis by a dihydropeptidase enzyme in the renal brush border to a nephrotoxic metabolite; it is co-marketed with cilastin, a DHP inhibitor
What are the clinical uses of carbapenems?
Empiric therapy for hospital acquired infections such as respiratory tract infections, septicemia, intra-abdominal infections, skin and soft tissue infections, bone and joint infections, polymicrobial infections, infections due to beta-lactamase-producing organisms, febrile neutropenia (imip and mero), meningitis (meropenem)
What is the incidence of hypersensitivity of carbapenems?
3%
What are the CNS adverse effects associated with carbapenems?
Confusion, dizziness, hallucinations, seizures
What are risk factors for seizures when taking carbapenems?
Pre-existing CNS disorder, high doses, and renal insufficiency
What is the only monobactam currently available?
Aztreonam
What is the preferred binding site of monobactams when inhibiting cell wall synthesis?
PBP-3 of gram-negative aerobes
Which Gram-negative bacteria are susceptible to monobactams?
- E. coli
- K. pneumoniae
- P. mirabilis
- S. marcescens
- H. influenzae
- M. catarrhalis
- Enterobacter
- Citrobacter
- Providencia
- Morganella
- Salmonella
- Shigella
- Pseudomonas aeruginosa
What are the clinical uses of aztreonam?
UTIs, respiratory tract infections, meningitis, bacteremia, skin and soft tissue infections, and intra-abdominal infections due to susceptible gram-negative aerobes