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CEPHALOSPORINs

and
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)

Gram positive strep, s.aureus,


some gram negative organism

Second

Cefuroxime(IV,PO)
Cefaclor (PO)
Cefamandole
Cefonicid
Cefprozil

Cefoxitin (IV,IM)

Community acquired E.coli,


klebsiella, proteus, h.influenza,
m.catarrhalis, less active
against gram postitive bactreia

Added activity against


bacteroides fragilis

Third

Ceftriaxone (IV, IM)


Cefotaxime (IV)
Cefixime (PO)
Cefdinir (IV)
Cefpodoxime (IV)

Enterobacteriaceae, serratia,
Neisseria gonorrhea, less active
than 1st gen against gram
positive cocci

Ceftazidime (IV, IM)


Active against pseudomonas
aeruginosa

Fourth

Cefipime(IV, IM)
Ceftolozane (IV)
Cefpirome (IV)

Comparable to 3rd gen but more


stable to b-lactamases of gram
negative bacteria

*all cephalosporin's
have no activity
against enterococci
and listeria

1st Gen Cephalosporin

[Gram (+) strength: +

+++, Gram (-) strength: - ]


effective against gram (+) cocci, including b-lactamase
producing S.aureus and variability against gram (-) enteric bacilli.
No drug from this gen. will attain appreciable concentrations in
the CNS.
They are valuable in children who have non anaphylactic allergy
to penicillins.
used to treat staph. & strep. skin structure infections, bone and
joint infections, pharyngitis and uncomplicated community
acquired UTI cause by susceptible bacteria.
Cefazolin produces higher concentrations in blood than do the
other parenteral 1st gen drugs.
*According to DOH 2009, the resistances of 1st gen rates are: e coli-48.6%, klebsiella-53.4%,
enterobacter-85.3%

2nd Gen Cephalosporin

[Gram (+) strength: +++,

Gram (-) strength: + ]

Have similar or somewhat less activity against gram positive


cocci such as staph.aureus, streptococci.
Better activity against H.influ, M.catarrhalis, N.meningitides,
N.gonorrhea and some members of the enterobacteriaciae.
The cephamycins (cefoxin) are more active than are the 1st
or second gen ceph against gram negative enteric bacteria
and B.Fragilis, but they have poor activity against gram (+)
cocci.

*According to DOH, the resistance of 2nd gen rates for cefuroxime were: e.coli-20.3% kleb28.9%

3rd Gen Cephalosporin

[Gram (+) strength: +,

Gram (-) strength: +++]

potent against gram-negative enteric bacteria.


excellent activity against H.influ, M.catarrhalis,
N.meningitides, N.gonorrhea, Grp.A strep and pensusceptible pneumococci but relatively poor activity
against staph.
Ceftazidime and cefoperazone are the only 3rd gen with
activity against P.aureginosa.
Parenteral cephalosporin provide high concentrations of
drug in serum and adequate concentrations in the CSF.
*According to DOH the resistance rates for ceftriaxone were: e.coli-17.6%, klebsiella29.7%, enterobacter-27.4%, n.gonor-0% for ceftazidime resistance for P.aeruginosa was
15.4%

4th Gen Cephalosporin

[Gram (+) strength: -,

Gram (-) strength: ++++]

has activity against P. aeruginosa and retains good activity


against methicillin-susceptible staphylococcal infections
Sensitive to oxacillin-susceptible staphylococci, penecillinresistant strains of S.pneumonia, viridians streptococci and
most strains of enterobacteriaceae, including ESBLproducing strains of E.coli and k.pnuemoniae.
It is indicated for the parenteral treatment of LRT, urinary
tract, skin and skin structure, intraabdomonal infections as
well as empiric monotheraphy in pediatric patient with
cancer who have fever and neutropenia.
*According to DOH resistance rates for cefipime were: e.coli-21.4%, Klebsiella-14.3%, enterobacter-14.4%,
pseudomonas aeriginosa-11.2%.

Adverse Reaction

Adverse Effects
Frequency (%)

Hypersensitivity reactions
(cross react with penicillin's in 5-20%)

1-3

Hematologic

1-5

Diarrhea

2-5

Abnormal Liver function tests

1-7

Biliary Sludge (ceftriaxone)

20

Interstitial nephritis

rare

- Generally well tolerated by children.


- The usual reactions experienced are local, including
the pain at injection site or thrombophlebitis wen given
parenterally, and mild GI complaints when given orally.
- Drug fever has been associated as well as non-specific
antibiotic associated diarrhea.

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

Cefaclor: children >6mo: 20-40mg/kg/day q8, max 1g/day


Cefalexin: children: 25-50 mg/kg/day div q6-8hrs PO, max 4g/day
Cefazolin (IV): >7days: 20mg/kg/dose q8-12hr, children 50-100mg/kg/day q6-8, max 6g/day

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 (Imipenem-cilastatin, meropenem


and ertapenem)
Similar to other beta lactams, these drugs also inhibit
bacterial cell wall synthesis.
composed of a fused b-lactam ring and a five
membered ring system.
different from other b-lactams in being unsaturated and
containing carbon atom instead of the sulfur atom.
Of all the beta lactam antibiotics, carbapenems have
the broadest spectrum.
have a high affinity to penicillin binding proteins and are
not hydrolyzed by most b-lactamases.

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

Bacteria wher in Carbapenems have good activity


Gram Positive

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.

Cross reactions in penicillin allergic patients may


occur.
Candidemia may occur with prolonged use of
carbapenems.
Carbapenems are poorly absorbed from GI tract and
must be given parenterally.
Ertapenem has a longer serum half-life which allows
for dosing every 24hrs.
it is widely distributed in the body such as int tissue
fluids, bone and pleural fluid.
It reaches low concentrations in the CSF but increases
if the meninges are inflamed.

*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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