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Cephalosporin (1) -lactum antibiotics containing 7-aminocephalosporanic acid nucleus
Classification:Based on antibacterial activity
1stgeneration- good activity against gram
positive & relatively modest activity againstgram negative
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Cephalosporin (2)
2ndgeneration- increased activity against gramnegative
3rdgeneration- increased spectrum of activityagainst gram negative, but less active againstgram positive than 1stgeneration
4thgeneration- extended spectrum of activityagainst gram positive & negative
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Cephalosporin (3)
Generation Example Spectrum
FirstCephalexin
Cephalothin
Mostly gram positive
Few gram negative
Second CefuroximeCefaclor
Covers most gram negative
Third
Cefotaxime*
Ceftriaxone
Cefpodoxime proxetil*
Increased spectrum for gram
negative
Less active against gram
positive
FourthCefepime
CefpiromeExtended spectrum of activity
*Most active a ainst ram ositive or anisms in the rou
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Cefpodoxime proxetil
CONH
OCH3
C
H H
NH2N
N
S
CH2OCH
3
COOCHOCOOCH(CH3)2
O
SN
CH3
Methoxymethyl group improves theantibacterials activity against gram+ve
bacteria and increases the GI stability.
Methoxymino group
protects against
hydrolysis
by beta lactamases
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Cefpodoxime proxetil
3rdgeneration, extended spectrum, semi-synthetic, oral cephalosporins
Prodrug- active metabolite is cefpodoxime
Active against wide spectrum of gram positive &gram negative organisms
Stable against many -lactamases producingorganisms
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Mechanism of Action
Inhibition of bacterial cell wall synthesis
Binds to PBPs & inhibits transpeptidationreaction involved in final step in synthesis of
bacterial cell wall
Also binds to the inhibitor of murein hydrolase
which causes lysis of bacterial cell
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Spectrum of Activity (1)
Aerobic Gram-Positive microorganisms:
Staphylococcus aureus (including penicillinaseproducing & excluding MRSA)
Staphylococcus saphrophyticus
Streptococcus pneumoniae (excluding penicillin-
resistant)
Streptococcus pyogenes
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Spectrum of Activity (2)
Aerobic Gram-Negative microorganisms:
Escherichia coli
Klebsiella pneumoniae
Hemophilus influezae (including -lactamaseproducing)
Proteus mirabilis
Moraxella (Branhamella) catarrhalis
Neisseria gonorrhoeae ( including penicillinaseproducing)
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Comparison of antibacterial activity of
cefpodoxime
Organisms Cefpodoxime(MIC90mcg/mL)
Cefixime(MIC90 mcg/mL)
Cefaclor(MIC90 mcg/mL)
Gram Positive Organisms
Staph. aureus 2 32 8
Strep. pyogenes 0.02 0.13 0.25
Strep. pneumoniae 0.02 0.13 0.25
Strep. agalactae >0.12 0.28 32
Gram Negative Organisms
H. influenzae 0.25 0.25 16
M. catarrhalis 0.125 0.06 1
K. pneumoniae 0.125 0.5 8
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Pharmacokinetics
Rapidly absorbed from GIT & de-esterified to itsactive metabolite, cefpodoxime
Bioavailability 50%
Cmax= 1.4 mcg/mL (100 mg)2.3 mcg/mL (200 mg)
3.9 mcg/mL (400 mg)
T1/2 = 2.09 to 2.84
Plasma Protein Binding = 21-29%
Food enhances absorption
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Pharmacokinetics
Distribution:
Skin-blister fluid:
200 mg BD for 5 days-mean maximum concentration 1.6 mcg/mL
Tonsil tissue:100 mg single dose-0.24 mcg/mL at 4 hrs & 0.09 mcg/mL at 7 hrs
(exceed MIC90for S. pyogenes)
Lung tissue:
200 mg single oral dose- 0.63 mcg/mL at 3 hrs; 0.52 mcg/mL at 6 hrs &0.19 at 12 hrs (exceed MIC90for S. pneumoniae & H. influenzae)
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Pharmacokinetics
Metabolism:
Minimal metabolism of cefpodoxime
Most drug excreted in urine as intact (29-33%) & metabolites
Renal Failure:
Elimination reduced in sever renal impairment (Creatinine clearance
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Indications (1)
Treatment of infections caused by susceptiblestrains of microorganisms
Acute otitis media
Pharyngitis & Tonsillitis
Community-acquired pneumonia
Acute bacterial exacerbation of chronicbronchitis (AECB)
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Indications (2)
Acute, uncomplicated urethral & cervical gonorrhea
Acute, uncomplicated ano-rectal infections in women
Uncomplicated skin & skin structure infections (SSTIs)
Acute maxillary sinusitis
Uncomplicated urinary tract infections
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Contraindications
Patients with known allergy tocefpodoxime or cephalosporin group
Warnings:
Allergy to penicillin group of antibiotics
H/O severe antibacterial associateddiarrhea
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Precautions
Renal insufficiency
Prolonged use
Pregnancy & Lactation: Pregnancy category BUse only if clearly indicated
Paediatric: Safety & efficacy not established in
infants
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Drug Interactions
Antacids: High doses decreases
absorption of cefpodoxime
Probenecid: Decrease renal excretion of
cefpodoxime
Nephrotoxic drugs: Close monitoring of
renal function is advised
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Adverse Reactions
Well tolerated in various clinical trialsusing recommended dosage range (100-400 mg BD)
Most were transient & mild to moderate inseverity in clinical trials
Diarrhea
Nausea & Vomiting
Abdominal pain
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Dosage
Tablets administered with food to enhanceabsorption
Suspension may be given without regard food
Adult & Adolescents (>12 yrs)
100-400 mg BD for 5-14 days
Children (2 months to
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Children (2 months to
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Adult & adolescents (>12 yrs)
Type of InfectionTotal daily
dose
FrequencyDuration
(Days)
Pharyngitis &/or tonsilitis 200 mg 100 mg BD 5-10
Acute CAP 400 mg 200 mg BD 14
AECB 400 mg 200 mg BD 10
Uncomplicated gonorrhea 200 mg Single dose
SSTI 800 mg 400 mg BD 7-14
Acute maxillary sinusitis 400 mg 200 mg BD 5
Ucomplicated UTI 200 mg 100 mg BD 7
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Application of Switch Therapy
Structural similarity to parenteral antibiotic, Ceftriaxone
Hospital-acquired pneumonia
Pneumonia caused by Gram-negative bacilli
Sepsis of unknown origin
Sepsis caused by Gram-negative bacilli
Pyelonephritis
Arthritis caused by Gram-negative bacilli
J of Antimicrobial Chemotherapy1994;33:169-171
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Similar spectrum of activity (Gram positiveas well as gram negative)
Reduces need for IV administration
Early hospital discharge
Reduces cost of therapy
Step-Down therapy for Ceftriaxone
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Clinical Trial
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Cefpodoxime Vs Cefixime in lower
respiratory tract infections
Study design :Prospective, open label, comparative, multicentric
study
Mean age of recruitment :6 months12 years, (10 years) with LRTIs
Drug intervention :Cefpodoxime in 396 patients-5mg/kg
Cefixime in 380 patients,-4 mg/kg
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Comparison of MIC of Cefpodoxime and Cefixime
MIC (mcg/mL ) Cefpodoxime Cefixime
H. influenza 0.06-0.12 0.06
M. catarrhalis 0.12-0.25 0.12
S. pneumoniae 0.03 0.25
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Comparison of clinical out come
Cefpodoxime Cefixime
Clinical out come
Cure 61.3% 43%
Improvement 35.7% 43.8%
Clinical success 97.0% 86.8%
Failure 3.0% 13.2%
Bacterial out come
Eradication 93.4% 82.9%
Failure 6.6% 17.1%
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Comparison of clinical out come
0%
10%
20%
30%
40%
50%
60%
Excellent V.Good Good Fair Poor
Cefpodoxime
cefixime
Physicians global assessment
Ind ian Jou rnal of Pediatr ics ; Volume 71;2004
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0%
10%
20%
30%
40%
50%
60%
Excellent V.Good Good Fair Poor
Cefpodoxime
cefixime
Patients global assessment
Ind ian Jou rnal of Pediatr ics ; Volume 71;2004
Comparison of clinical out come
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Cefpodoxime Vs Ceftriaxone in
Community-acquired bronchopneumonia
Cefpodoxime Ceftriaxone
Dose 200 mg BD oral for10 days 1 gm/day I.M. for 10days
Clinical cure 98% 95%
Bacterialeradication
94.3% 97.4%
Zuck et al, 1990
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Comparison of Cefpodoxime Vs
Amoxicillin/Clavulanate
Study design :Multicentric, randomized, double blind, clinical study
Recruitment for study :229 children with acute Otitis media
Drug intervention:
Cefpodoxime proxetil -10mg/kg BD for 10 days Amoxicillin/clavulanate -40mg/10mg per kg TID for 10
days
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Bacteriological cure rate
Parameters Cefpodoxime Amoxicillin/
clavulanate
Cured 68% 65%
Improved 24% 23%
Failed 8% 13%
Recurrence
rate
24% 25%
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Adverse events
0%
5%
10%
15%
20%
25%
30%
35%
40%
cefpodoxime
Amoxycillin/cla
vulanate
Pediatric pharmacology and therapeutics. J.Pediatr.1992
Clinical efficacy for Cefpodoxime proxetil b.i.d. is
Equivalent to Amoxicillin/Clavulanate t.i.d. in AOM
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Conclusion
Cefpodoxime proxetil is well tolerated
Superior alternative to other third generation
cephalosporins
Expanded spectrum of activity
First line antimicrobial in pediatric patients ofLRTIs