Cephalosporins, Monobactams, Carbapenems - Fitzy lecture

Question 1

General cephalosporin properties

Answer 1

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

Question 2

First generation Cephalosporins

Answer 2

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

Question 3

Second generation Cephalosporins

Answer 3

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

Question 4

Third generation cephalosporins (parenteral)

Answer 4

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

Question 5

Ceftriaxone

Answer 5

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

Question 6

Cefotaxime

Answer 6

IV, IM
Penetrates CNS well
Renal elimination, tubular secretion

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

Question 7

Ceftazidime

Answer 7

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

Question 8

Fourth generation cephalosporins

Answer 8

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

Question 9

Cefepime

Answer 9

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

Question 10

Cephalosporin hypersensitivity

Answer 10

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

Question 11

Disulfiram-like reaction for cephalosporins

Answer 11

Cefatetan and Cefoperazone inhibit aldehyde dehydrogenase

Results in nausea, flushing, HA when consuming etOH

Question 12

Cefotetan and cefaperazone adverse effect in Vit K

Answer 12

reduction in Vit K producing bacteria in GI tract

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

Question 13

Aztreonam

Answer 13

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

Question 14

Carbapenems in empiric therapy

Answer 14

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

Question 15

Carbapenems Adverse Effects

Answer 15

Hypersensitivity and rash - caution with PCN allergy

CNS toxicity - seizures, confusion

Nephrotoxicity - imipenem - always used with cilastatin

Question 16

Imipenem/Cilastatin in nephrotoxic effect

Answer 16

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

Question 17

Doripenem

Answer 17

IV, IM

complicated urinary tract and intra-abdominal infections

Question 18

Meropenem

Answer 18

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

Question 19

Ertapenem

Answer 19

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.