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CARBAPENEMs
Cephalosporin
semisynthetic antibiotics derived from cephalosporin C.
like penicillin.
exhibit their bacterial killing occurs by inhibiting cell
wall synthesis
they are selectively toxic with a wide margin of safety.
commonly classified into generations based on their
spectrum of activity.
The higher the generation, the more superior the
activity against gram negative organisms, and more
resistant to beta lactamases.
Pharmacokinetics
after oral administration, absorption differs greatly for
diff. cephalosporin's.
eliminated unchanged mainly through the kidneys by
GFR and tubular secretion except ceftriaxone, which is
eliminated by both renal and hepatic pathways, and
cefoperazone which is eliminated mainly by the
hepatobilliary route.
distribute well into body tissues and fluids, but
penetration into the CNS is poor except when meninges
are inflamed.
Cefazolin has poor penetration into the CNC and should
not be used for meningitis.
GENERATION
Prototype drugs
Useful spectrum
First
Cefazolin (IV)
Cephalexin (PO)
Cephalotin (IV)
Cephadrine(PO, IV)
Cefadroxil(PO)
Second
Cefuroxime(IV,PO)
Cefaclor (PO)
Cefamandole
Cefonicid
Cefprozil
Cefoxitin (IV,IM)
Third
Enterobacteriaceae, serratia,
Neisseria gonorrhea, less active
than 1st gen against gram
positive cocci
Fourth
Cefipime(IV, IM)
Ceftolozane (IV)
Cefpirome (IV)
*all cephalosporin's
have no activity
against enterococci
and listeria
*According to DOH, the resistance of 2nd gen rates for cefuroxime were: e.coli-20.3% kleb28.9%
Adverse Reaction
Adverse Effects
Frequency (%)
Hypersensitivity reactions
(cross react with penicillin's in 5-20%)
1-3
Hematologic
1-5
Diarrhea
2-5
1-7
20
Interstitial nephritis
rare
Adverse Effects
Hypersensitivity reactions such as rash, pruritus and
urticaria have been seen in 1-3% of pxs.
often prescribed for patients allergic to penicillin but cross
reactivity may occur in 2-30% of pxs.
Cephalosporins with the methylthiotetrazole side chain
(cefamandole, cefofetan) may produce coagulation
problems due to its inhibition of vitamin k dependent
carboxylase. This enzyme converts certain factors (II,VII, IX
and X) to their active form.
Ceftriaxone is associated with biliary sludging, biliary
pseudolithiasis and symptomatic obstructive biliary disease.
Serum sickness like disease has been described with the
intake of cefaclor.
DOSAGES OF COMMON
CEPHALOSPORINS
1 Generation:
st
2nd Generation:
Cefuroxime: neonates: 50-100mg/kg/day q12, children 75-150 mg/kg/day q8 max:6g/day
3rd Generation:
Cefixime: children: 8-10mg/kg/day q12-24hrs, mas 400mg/day
Ceftriaxone: >7days: 50-75mg/kg/dose q24hr, children 50-100mg/kg/day q24, max 4g/day
4th Generation:
Cefipime(IV): neonates: <14days: 30mg/kg/dose q12, children: 50mg/kg/dose q12 IV 20-30min
Carbapenems
these drugs have activity against gram-positive cocci
including most streptococci, staphylococci, although
variable activity against MRSA.
Carbapenems have moderate activity against
Enterococus faecalis but most E.faecium are resistant.
very active against many enterobacteriaceae,
pseudomonas aeruginosa, acinetobacter, anaerobic
bacteria including Bacteroides fragilis are susceptible to
carbapenems.
Carbapenems
DRUG
Gram Negative
Anaerobes
Meropenem
And Imipenem
S. aureus (MSSA
only),
S. agalactiae
S.pneumoniae
(including penicillin
resistant strains)
S.pyogenes
e.coli, h.influenza,
klebsiella,
M.catarrhalis,
Proteus mirabilis,
Pseudomonas
aeruginosa, including
ESBL producing org
Bacteroides sp.
Including fragilis
Clostridium spp.
Peptostreptococcus
spp.
Porphyromonas
Prevotella bivia
Ertapenem
S. aureus (MSSA
only),
S. agalactiae
S.pneumoniae
(including penicillin
resistant strains)
S.pyogenes
E.coli,
H.influenza (betalactamase negative
isolates)
K pneumoniae,
M.catarrhalis,
Proteus mirabilis,
Bacteroides sp.
Including fragilis
Clostridium spp.
Peptostreptococcus
Porphyromonas
Prevotella bivia
Pharmacokinetics
Imipenem is excreted in the urine and undergoes partial
metabolism in the kidneys.
Cilastatin does not affect serum concentrations of imipenem.
Meropenem and ertapenem are more stable, less likely to
induce seizures than imipenem.
Slightly more active against enterobacteriaceae and slightly
less active against gram positive bacteria.
Safety and efficacy of meropenem has been established in
pedia px and well as in px with CNS infection.
Ertapenem has poor activity to pseudomonas and
acinetobacter spp.
Adverse Effects
Carbapenems are indicated for: documented multidrug
resistant gram negative infectionn due to org proven or
suspected to be susceptible to carbapenems and
polymicrobial infections in which other agents have
insufficient activity or are contraindicated due to its
toxic potential.
Some adverse reactions include: diarrhea, nausea,
vomiting and skin rashes.
Toxic levels of imipenem in patients may produce
seizures.
*DOH resistance rats for imipenem: pseudomonas 13.5%, klebsiella 0.7% and
enterobacter-2.3%
Sources:
Philippine Pediatric Antibiotic Manual
Nelsons Textbook of Pediatrics 20th Ed.
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