Cephalosporins, Monobactams, Carbapenems - Fitzy lecture Flashcards Preview

Respiratory Medicine Midterm > Cephalosporins, Monobactams, Carbapenems - Fitzy lecture > Flashcards

Flashcards in Cephalosporins, Monobactams, Carbapenems - Fitzy lecture Deck (19):
1

General cephalosporin properties

MOA and resistance comparable to other B-lactams

variable degradation by b-lactamases

clearance (most) by renal excretion

All Generations 1-3 are ineffective and lack activity against:
-Listeria monocytogenes
-Legionella spp.
-Atypicals mycoplasma
-MRSA
-Enterococci

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First generation Cephalosporins

Cefazolin - parenteral, IV, IM
-Penetrates well into bone

Cephalexin - PO
-2x daily for pharyngitis

Cephradrine - parenteral and oral

Useful in gram + cocci, streptococci, staphylococcus aureus (not MRSA, MRSE, enterococci)

Surgical prophylaxis if skin flora likely pathogenic - soft tissue, skin infections due to S. aureus, S. pyogenes

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Second generation Cephalosporins

Cefoxitin - IV, IM
-anaerobes (B. fragilis)

Cefatetan - IV, IM
-anaerobes (B. fragilis)

Cefaclor - PO
-Serum-sickness (skin and joint adverse reactions) in pediatrics

Cefuroxime axetil - PO
-Poor substrate for B-lactamase

Less active against gram +
Enhanced activity in gram (-)
-E.coli, Klebsiella, H. influenzae, Moraxella cattharalis, Proteus spp.

If facultative gram - bacteria and anaerobes are likely pathogens
-intra-abdominal and gynecological sepsis, surgical prophylaxis for intraabdominal and colorectal surgery

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Third generation cephalosporins (parenteral)

Ceftriaxone - penicillin resistant N. gonorrhea, biliary clearance

Cefotaxime - Enters CSF, useful for meningitis due to H. influenzae, S. pneumoniae, N. meningitis

Cetazidime - pseudomonas aeruginosa

Cefaperazone - etOH intolerance

Enhanced activity in gram - rides, enteric organisms
comparable to 1st gen in S. aureus, S. pneumoniae, S. pyogenes

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Ceftriaxone

Long t1/2 - 8 hr, 1xday
Penetrates CSF and bone
biliary excretion

Penicillin resistant gonorrhea
Lyme disease involving CNS or joints
Meningitis due to ampicillin resistant H. influenzae and meningitis in children

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Cefotaxime

IV, IM
Penetrates CNS well
Renal elimination, tubular secretion

Bacterial meningitis from H. influenzae, S. pneumoniae, N. meningitides, gram - enteric bacteria

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Ceftazidime

active against P. aeruginosa when resistant to anti-pseudomonal penicillins or patient is allergic to pcn

give in combination with amino glycoside (tobramycin) for treatment of serious P. aeruginosa

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Fourth generation cephalosporins

Cefepime - IV, IM

Activity greater than cefotaxime against gram - bacteria, H. influenzae, N. gonorrhea, N. meningitidis

Excellent CSF penetration

Activity similar to ceftazidime against P. aeruginosa

Exerts gram + activity comparable to 1st gen combined with extended gram - activity of 3rd gen

Insensitive to many b-lactamase

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Cefepime

4th gen
+ charged quaternary ammonium --> better penetration through outer membrane of gram - bacteria and lower affinity than 3rd gen for chromosomal b-lactamases of gram - bacilli

as active against P. aeruginosa as ceftazidime, active against some ceftazidime-resistant isolates

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Cephalosporin hypersensitivity

Immediate hypersensitivity - anaphylaxis, bronchospasm, urticaria

Delayed - rash

1-2% of PCN allergy share hypersensitivity to cephalosporins

Avoid in its with recent, severe hypersensitivity run to PCN

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Disulfiram-like reaction for cephalosporins

Cefatetan and Cefoperazone inhibit aldehyde dehydrogenase

Results in nausea, flushing, HA when consuming etOH

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Cefotetan and cefaperazone adverse effect in Vit K

reduction in Vit K producing bacteria in GI tract

Hypoprothrombinemia and bleeding - caution in patients taking warfarin or with coagulation abnormalities

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Aztreonam

Parenteral IV, IM

Binds to PBP 3 of gram - rods (including P. aeruginosa)

Substitute for extended spectrum PCN or gen 3, 4 cephalosporins if contraindicated due to hypersensitivity (low cross-reaction)

Safe alternate for aminoglycosides in elderly or renal impaired

Synergistic with aminoglycosides

Not used alone in empirical therapy, narrow spectrum, not active against gram + ssp or anaerobes

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Carbapenems in empiric therapy

Broadest spectrum abx:
-gram +: E. faecalis, Listeria
-gram - : H. influenzae, N. gonorrhea, Enterobacteriaceae, P. aeruginosa
-anaerobes: B. fragilis

Not degraded by common b-lactamases

IV, penetrates tissues and fluid, including CNS with inflamed meninges

Cleared by glomerular filtration
-Imipenem metabolized by kidney to nephrotoxic metabolite

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Carbapenems Adverse Effects

Hypersensitivity and rash - caution with PCN allergy

CNS toxicity - seizures, confusion

Nephrotoxicity - imipenem - always used with cilastatin

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Imipenem/Cilastatin in nephrotoxic effect

Cilastatin: renal dipeptidase inhibitor, NOT a b-lactamase inhibitor

Imipenem - inactivated by dipeptidase enzyme in proximal tubule
-metabolite nephrotoxic

Cilastatin inhibition maintains imipenem and prevents nephrotoxicity

Given IV, IM

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Doripenem

IV, IM

complicated urinary tract and intra-abdominal infections

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Meropenem

IV, IM

Stable to human renal dehydropeptidase, administered without cilastatin

lower risk of seizures than imipenem-cilastatin

bacterial meningitis (>three months old) and intraabdominal infection

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Ertapenem

IV

Narrower spectrum of activity than imipenem or meropenem

active against most Enterobacteriaceae and anaerobes
less active than other carbapenems for P. aeruginosa, Acinetobacter, and Gram + bacteria -enterococci and penicillin- resistant pneumococci.