2. Cefditoren is an advanced 3rd generation, broad spectrum
oral cephalosporin with unique structure
1994: Approval in Japan (Meiact by Meiji
Seika Pharma Co., Ltd.
2001: USFDA approved (Spectracef by Vansen
Pharma Inc)
2004: Approved in Spain (Meiact byTedec Meiji
Pharma)
2006: Approved in India (Zostum-O by Zuventus)
2018: Dry powder for suspension 100 mg/5 mL in
pediatric patients in India
2
3. Antibiotic Therapy in the Resistance Era:
the Need for New Molecules
• Rapidly growing menace of bacterial resistance to commonly
prescribed antibiotics
• Drug resistance: Gram +ve & Gram-ve bacteria is an important
challenge
• Extended-spectrum β-lactamases (ESBLs), ampC β-lactamases, &
carbapenemase-producing gram-ve bacteria
• Limited availability of effective drugs against resistant bacteria
Taneja N. Microbiol Insights. 2016 Mar 20;9:9-19.
4. Di Marco F. Eur Rev Med Pharmacol Sci. 2014;18(3):321-32.
5. Pivoxil group
Enhances oral bioavailability
Aminothiazolyl group
Enhanced gram –ve coverage
over Cefuroxime/ Cefpodoxime &
other oral Cephalosporin
Methylthiazolyl group
Improved gram positive coverage
Cefditoren Pivoxil: Unique Structure
1. Balbisi E.A. :Cefditoren, a New Aminothiazolyl Cephalosporin: Therapeutic Trials, Pharmacotherapy. 2002;22(10)
2. Mohanty S, Kapil A, Dhawan B, Das BK. Bacteriological and antimicrobial susceptibility profile of soft tissue infections from Northern India. Indian J
Med Sci [serial online] 2004 [cited 2007 Mar 9];58:10-15. Available from: http://www.indianjmedsci.org/text.asp?2004/58/1/10/8267
3. http://findarticles.com/p/articles/mi_qa3867/is_200412/ai_n9520670/print
7. Aerobic Gram-Positive Microorganisms Aerobic Gram-Negative Microorganisms
1. Staphylococcus aureus (methicillin-
susceptible strains, including β-
lactamase-producing strains)
2. Streptococcus pneumoniae
3. Streptococcus pyogenes
4. Streptococcus agalactiae
5. Streptococcus Groups C and G
6. Streptococcus, viridans group
(penicillin-susceptible & intermediate
strains)
1. H. influenzae
(including β-lactamase-producing strains)
1. H. parainfluenzae (including β-
lactamase-producing strains)
2. Moraxella catarrhalis (including β-
lactamase-producing strains)
3. E coli, klebsiella, enterobacter,
Serratia, proteus, Morganella
morganii etc.
Balanced Antimicrobial Spectrum
1. Wellington K. Drugs. 2004;64(22):2597-618.
2. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021222s013s016lbl.pdf
8. Giménez MJ, Aguilar L, Granizo JJ. Revisiting cefditoren for the treatment of community-acquired infections caused by
human-adapted respiratory pathogens in adults. Multidiscip Respir Med. 2018 Nov 2;13:40.
100 % Susceptibility against Penicillin Resistant Strains
10. In vitro antibacterial activity
(Antimicrobial Resistant Isolates in Southern Europe)
The ARISE project . Soriano et al. Int J. of Antimicrobial Agents 2004
CDTR is the oral -lactam with the highest intrinsicactivity against the most
prevalent bacterial respiratory pathogens
Soriano F. Antimicrobial susceptibility of Haemophilus influenzae, Haemophilus parainfluenzae and Moraxella catarrhalis isolated from adult patients with
respiratory tract infections in four southern European countries. The ARISE project. Int J Antimicrob Agents. 2004 Mar;23(3):296-9.
11. Intrinsic activity of Cefditoren Vs. Amoxicillin/clavulanic acid or Cefuroxime
High potency of Cefditoren against human-associated respiratory pathogens
Giménez MJ. Revisiting cefditoren for the treatment of community-acquired infections caused by human-adapted respiratory pathogens
in adults. Multidiscip Respir Med. 2018 Nov 2;13:40.
12. Cefditoren: Fastest Bactericidal
activity within 4 hr
Compared to Cefixime, Cefuroxime, Co-amoxiclav
Clarithromycin, Azithromycin, Erythromycin
Only Cefditoren showed
Significant
bactericidal activity
within 4 hr against
penicillin-resistant S.
pneumoniae
Significant
bactericidal activity
against β-lactamase -
ve (after 24 h) & + ve
strains of H.
influenzae (after 12 h)
Significant bactericidal
activity at 6 h against
β-lactamase + ve strains
of M. catarrhalis
(vs. cefuroxime at 12 h)
Dubois J. In vitro study of the post-antibiotic effect and the bactericidal activity of Cefditoren and ten other oral antimicrobial agents against upper
and lower respiratory tract pathogens. Diagn Microbiol Infect Dis. 2000 Jul;37(3):187-93.
13. Cefditoren Concentration remains above MIC for Longer duration :
Better Bacteria Killing compared to other antibiotics
Di Marco F. Eur Rev Med Pharmacol Sci. 2014;18(3):321-32.
14. 1. Stable in the presence of a variety of ß-lactamases: penicillinases &
cephalosporinases
2. Stable to hydrolysis by many plasmid-mediated β-lactamases, including TEM-1,
ROB-1, SHV-1, SHV-3, SHV-10, OXA-5, OXA-12, PSE-1, PSE-2, PSE-3, PSE-4,
SAR-1, HMS-1, con- CARB-4, LCR-1, TLE-1, and OHIO-1
Cefditoren:Stable to Hydrolysis by
β-lactamases
PBPs-Penicillin-binding proteins
ESBLs- Extended spectrum β-lactamases
Wellington K, Curran MP. Cefditoren pivoxil: a review of its use in the treatment of bacterial
infections. Drugs. 2004;64(22):2597-618.
14
Active against all
6 PBPs &
17 ESBLS
15. Streptococcus agalactiae in pregnant women: serotype and antimicrobial
susceptibility patterns over 5 years (Jan 2015 to Dec 2019) in Eastern
Sicily (Italy)
• Streptococcus agalactiae (Group B Streptococcus or GBS) represents the main
pathogen responsible for early- and late-onset infections in newborns
• Total of 3494 GBS were isolated from vaginal swabs of pregnant women (37-39 weeks),
as recommended by the Centers for Disease Control and Prevention
• All 3494 clinical isolates were susceptible to cefditoren and vancomycin.
• Resistance to penicillin, ampicillin, levofloxacin, clindamycin, and erythromycin
was observed in 6 (0.2%), 5 (0.1%), 161 (4.6%), 1090 (31.2%), and 1402 (40.1%) of
the strains, respectively
• Most of erythromycin-resistant GBS (1090/1402) showed the cMLSB phenotype, 276
the M phenotype, and 36 the iMLSB phenotype
• Our findings revealed a higher prevalence of serotype III and a relevant resistance rate,
among GBS strains, to the most frequently used antibiotics in antenatal screening
15
Genovese C. Eur J Clin Microbiol Infect Dis. 2020 Dec;39(12):2387-2396. Epub 2020 Jul 22.
17. Parameters
Absorption Cefditoren pivoxil absorbed from the gastrointestinal tract
and hydrolyzed to cefditoren by esterases
Bioavailability more with high fat meal than fasting state
Cmax 1.8 ± 0.6 μg/mL
Tmax 1.5 to 3 hours after dosing
Plasma Proteins
Binding
88% (primarily to human serum albumin)
Terminal half-life 1.6 ± 0.4 hours
Elimination Predominantly eliminated by the kidneys
Tissue concentration - Penetrate into bronchial mucosa, epithelial lining
fluid, skin blister fluid, tonsillar tissue
- Clinically relevant concentrations are achieved in these
tissues for ≈ 4 hours
Pharmacokinetics
Wellington K. Drugs. 2004;64(22):2597-618.
18. 18
Cefditoren: Absorption and Distribution
Bronchial
mucosa
Tissue conc as compared to serum conc of Cefditoren
54%
Epithelial
lining fluid
31%
Skin
blister
fluid
40–56%
Tonsil
tissue
12%
• Widely distributed & penetrates into bronchial mucosa, epithelial lining fluid, skin blister fluid,
tonsillar tissue, sinus mucosa, skin tissue, tooth extraction wound etc.
Clinically relevant concentrations are achieved in these tissues in almost 4 hrs
Wellington K. Cefditoren pivoxil: a review of its use in the treatment of bacterial infections. Drugs. 2004;64(22):2597-618.
19. Indications
USFDA , India Japan
1. Acute Bacterial Exacerbation
of Chronic Bronchitis
2. Acute sinusitis, Pharyngitis,
Tonsillitis, Laryngitis
3. Otitis media
4. Community-Acquired pneumonia
5. Uncomplicated Skin and Skin-
Structure Infections
• Respiratory tract infections
• Skin and Skin-Structure
Infections
• Burns and Surgical Wounds
• Dental infections
• Urinary tract infections
• Cholecystitis, Cholangitis
20. Among
3rd-generation oral
Cephalosporins
Cefditoren has
Most
balanced
spectrum
(gram+ ve & -
ve bacteria)
Highest
intrinsic
activity on
strept.
Pneumoniae,
(PEN-R strains
included)
The most
appropriate
option: When
switching from
parenteral to
oral therapy
can be included
among the 1st-
line treatments
of mild-
moderate
AECB
Delphi based Recommendations
By ITALIAN Panel of 70 Pulmonologists (2017)
due to the similar spectrum &
better intrinsic activity
Blasi F et al. J Chemother. 2017 Oct;29(5):274-286.
21. Japanese Guidelines
Recommendation in children
Japanese Guidelines for the Management of Respiratory
Infectious Diseases in Children recommend cefditoren
pivoxil as an initial antimicrobial therapy in children (2
months and older).
Uehara S. et al.Pediatrics International (2011) 53, 264–276.
22. CDTR PI- Cefditoren
pivoxil
Uehara S. et al.Pediatrics International (2011) 53, 264–276.
Cefditoren in children >2 months for Respiratory Infectious Diseases
Continued……
23. Type of Infection Dosage Duration(days)
Pharyngitis/Tonsillitis, Acute sinusitis, otitis
media, laryngitis
200mg BID
10
Uncomplicated Skin and Skin Structure
Infections
200mg BID
Acute Bacterial Exacerbation of Chronic
Bronchitis
400 mg BID
Community-Acquired Pneumonia 400 mg BID 14
Adult: Dosage & Administration
Recommended doses in children (2 months to 12 yrs )
3 mg/kg/dose, 3 times a day, after meals for 10 days
Can be increased up to 6 mg/kg/dose if needed,
Maximum daily dose: 200 mg, 3 times a day (600 mg / day)
24. Cefditoren: Special population
• Pregnancy
– Pregnancy Category B (USFDA)
– Animal studies: No teratogenicity, No toxicity
– No adequate and well-controlled studies in pregnant women
– Used during pregnancy only if clearly needed
• Nursing Mothers
– Cefditoren was detected in the breast milk of lactating rats.
– Caution should be exercised when cefditoren is administered to nursing women
25. Cefditoren- Place in Therapy
Dual Dimension
First line therapy
in treatment of
RTI, SSTI and UTI
Switch & Step Down
Therapy
Ideal for Switch over therapy:
1. Most appropriate option when switching from
parenteral therapy with 3rd-generation (cefoperazone,
cefotaxime, ceftriaxone ) to oral therapy
2. Due to the similar spectrum and better intrinsic activity
28. A Comparison of Cefditoren Pivoxil 8-12 mg/kg/day
and Cefditoren Pivoxil 16-20 mg/kg/day in Treatment of Children With
Acute Presumed Bacterial Rhinosinusitis (ARS)
• A Prospective, Randomized, Investigator-Blinded, Parallel-Group Study
• n=140 patients (aged 1-15 years) with a clinical diagnosis of uncomplicated ARS
• 72 received low dose (group I) and 68 received high dose Cefditoren Pivoxil (group II)
• Group I: 8-12 mg/kg/day
• Group II: 16-20 mg/kg/day
• Duration : 14 days
• Responses rate at day 14 in
• Groups I (Low dose) : 95.5% and
• Groups II (high dose) - 95.4%
• Most common treatment-related adverse events: diarrhea and vomiting
• Both low and high doses regimens of Cefditoren appeared a similar clinical outcome for
treatment in uncomplicated ARS in pediatric patients
2015 June
Poachanukoon O. Clin Exp Otorhinolaryngol. 2015 Jun;8(2):129-35
29. Efficacy of cefditoren in upper respiratory tract infections:
a pooled analysis of 6 clinical trials
• 6 Prospective, comparative, multi-centre and randomized Trials
Pharyngotonsillitis Studies
(N=1322)
randomized
Cefditoren 200 mg
BID for 5 to 10 day
N=666
Penicillin-V
250mg QID
or 400mg TID for 10
days
N=656
ITT (n=610)
PP (n=507) ITT (n=604)
PP (n=503)
Acute Sinusitis Studies
(N=1819)
randomized
Cefditoren
200 mg BID
for 10 day
N=637
Cefuroxime
250 BID 10
Days
Or
Amox-clav
N=642
ITT (n=603)
PP (n=565)
ITT (n=616)
PP (n=556)
Cefditoren 400
mg BID for 10
day
N=540
ITT (n=507)
PP (n=468)
Amoxicillin/clavulanate 875/125 mg bid 10 days OR
Amoxicillin/clavulanate 500/125 mg tid 10 days
Granizo JJ. Rev Esp Quimioter. 2008 Mar;21(1):14-21.
30. • S. pyogenes eradication was higher with cefditoren at end of therapy (EOT) (90.4% vs.
82.7%; p=0.002) and follow-up (84.7% vs. 76.7%; p=0.008)
• In pharyngitis clinical response were found (success rates: cefditoren 95.3 % vs
comparators 92.3%).
• No differences in sinusitis clinical response were found between CDN and comparators
Granizo JJ. Rev Esp Quimioter. 2008 Mar;21(1):14-21.
31. Efficacy and safety of cefditoren pivoxil in treatment of
respiratory infections
Li JT. Zhonghua Yi Xue Za Zhi. 2003 Mar 10;83(5):391-4.
N=199
cases of respiratory infections
Cefditoren 200 mg BID for 5 -14 day
• Total effective rate - 94.9%
• Causative bacteria -elimination rate -
96.7%
Mild diarrhea, nausea and vomiting,
and stomach discomfort, in 9 cases
(incidence rate of 4.5%)
• The resistance rate to cefditoren pivoxil of pathogens of respiratory infections and the
efficacy of cefditoren pivoxil show no difference from those tested 7 years ago
32. Cefditoren for 5 days Vs. amoxicillin for 10 days therapy against acute
tonsillopharyngitis in children due to group A β-hemolytic streptococci
Acute tonsillopharyngitis
(Group A β-hemolytic streptococci)
N= 112 children
Cefditoren pivoxil
for 5 days
Amoxicillin for
10 days
a. Clinical Efficacy: 100%
b. Bacterial Elimination Rate: 100%
c. Does not disturb the gut microbial
flora as compared to amoxicillin
(p = 0.0049)
Clinical Efficacy
a. Clinical Efficacy: 97.9%
b. Bacterial Elimination Rate: 100%
2011 June
Tsumura N. Jpn J Antibiot. 2011 Jun;64(3):179-90
33. Five-day oral cefditoren pivoxil vs 10-day oral amoxicillin for pediatric group A
streptococcal pharyngotonsillitis
• 258 children with pharyngotonsillitis caused by group A streptococcus , attending the
pediatric OPD of showa hospital (konan, Japan)
• Two Groups
•Oral cefditoren-pivoxil (3 mg/kg t.i.d. For 5 days) and
• oral amoxicillin (10 mg/kg t.i.d. For 10 days)
• Eradication was confirmed in
• cefditoren-pivoxil group- 99% (102/103)
• amoxicillin group- 100%
•No clinically significant adverse reactions
• Similar efficacy between cefditoren- for 5 days & amoxicillin for 10 days
2008 June
Ozaki T. J Infect Chemother. 2008 Jun;14(3):213-8.
34. Cefditoren pivoxil (CDTR-PI) for 5 days Vs. amoxicillin (AMPC) 10 day
• The advantages of short-term treatment includes
– A lower cost,
– Improvement in drug compliance,
– Decrease in the frequency of the occurrence of adverse reactions
– Decrease in the frequency of the appearance of drug-resistant strains,
– Alleviation of the psychological burden of patients and their parents
Continued…….
Shorter treatment period may make the cefditoren regimen preferable for the treatment
of acute tonsillopharyngitis in children
Tsumura N. Jpn J Antibiot. 2011 Jun;64(3):179-90
Ozaki T. J Infect Chemother. 2008 Jun;14(3):213-8.
35. Evaluation of the safety and efficacy of cefditoren pivoxil fine granules in pediatric patients
with laryngopharyngitis and tonsillitis caused by Streptococcus pyogenes
• 790 patients were enrolled in 147 institutions
•Of them, 734 and 718 patients were chosen for safety and efficacy analysis, respectively
• Children (9 months - 14 yrs) presenting with S. pyogenes
• Laryngopharyngitis (n=464) or
• Tonsillitis (n=254)
• Mean daily doses were ≥9 mg/kg and <13.5 mg/kg
• Clinical response rate -
• Laryngopharyngitis : 98.5%
• Tonsillitis: 98.4%
• Patients in which bacteriological response assessed,
•Strept. pyogenes eradication rate was 94.6% for laryngopharyngitis (194/205 pts) and
•92.4% (110/119 patients) for tonsillitis
• No serious adverse drug reactions were reported
2010 August
Kawamata et al. Jpn J Antibiot. 2010 Aug;63(4):299-311
36. Trial Study Design Key Results
Kawamata S. Jpn J
Antibiot. 2010
Jun;63(3):207-23.
Postmarketing study of
CDTR-PI in pediatric
patients with acute otitis
media
n=2144 patients
Across
305 medical institutions
Clinical efficacy of CDTR-PI- 93.5% (1831/1958 )
For each major resistant strain, the response rate
I. 88.0% for penicillin-intermediate S. pneumoniae
(PISP),
II. 90.1% for penicillin-resistant S. pneumoniae (PRSP),
and
III. 92.5% for β-lactamase negative ampicillin-resistant
H. influenzae (BLNAR),
while the bacterial eradication rate was
a. 85.7% for PISP,
b. 77.5% for PRSP, and
c. 81.8% for BLNAR
Most common ADR was diarrhea (1.30%)
38. Cefditoren versus levofloxacin in patients with
exacerbations of chronic bronchitis (AECB)
38
Open-label, randomized study
40 patients with AECB
(age 40–75 yrs)
Cefditoren 200 mg
twice a day for 5 days
(n = 20)
Levofloxacin 500 mg
once daily for 7 days
(n = 20)
Parameters Evaluated
• Reduction of inflammatory biomarkers
• Clinical and bacteriological response
• Safety
Blasi F. Ther Clin Risk Manag. 2013;9:55-64.
39. Clinical efficacy in the overall population, the cefditoren and levofloxacin arms at test of cure (TOC)
Levels of KL6 (A) and IL6 (B) and C-reactive protein (C) cefditoren and levofloxacin
arms at visit 1, 2 and TOC.Note: *P = 0.05 TOC vs visit 1
At the end of treatment (test-of-
cure, 6-9 days after drug
initiation), the clinical success
rate in the overall study
population was 78%; 80% in
cefditoren arm and 75% in
levofloxacin arm
• Inflammatory parameters were
significantly reduced at visit 1
were Krebs von den Lundgen-6
(KL-6) & interleukin-6 in the
cefditoren and levofloxacin
arms
• Cefditoren is associated with
a significant reduction of IL-6
and KL-6, two key mediators
of lung inflammation and
epithelial damage
Ther Clin Risk Manag. 2013;9:55-64.
40. Cefditoren-pivoxil versus cefuroxime-axetil in AECB
Randomized, double-blind, double-dummy,
parallel multicenter study
64 centers in Germany, Spain, Austria, Switzerland &
Italy
N=541 AECB patients
Cefditoren 200 mg
twice a day for 5 days
(n = 264)
Cefuroxime 250 mg
twice daily for 10 days
(n = 277)
Alvarez-Sala JL. Antimicrob Agents Chemother. 2006 May;50(5):1762-7.
41. At the end of treatment, exploratory analysis of the
a) Per-pathogen bacteriological response seen
– 72.8% (of 103 isolates) in the cefditoren-pivoxil arm
– 67.0% (of 94 isolates) in the cefuroxime-axetil group
b) Clinical success was obtained in
• 80 % in the cefditoren-pivoxil group
• 82.7% in the cefuroxime-axetil group
c) Cefditoren-pivoxil 5 day Vs. 10-day cefuroxime-axetil course
had similar success in AECB
d) Cefditoren has an advantage of shorter duration of
therapy
41
Results (Continued…….)
Alvarez-Sala JL. Antimicrob Agents Chemother. 2006 May;50(5):1762-7.
42. Cefditoren versus Clarithromycin in AECB
• Study design- double-blind, multicenter study
• Aim- Comparative efficacy of cefditoren with clarithromycin.
• Subjects- 743 adult outpatients with acute exacerbation of chronic bronchitis.
• Drug administration- 10-day course of either
– Oral cefditoren 200 mg twice/day or
– Clarithromycin 500 mg twice/day
Ramirez JA, Tucker RM, Bettis RB, Cyganowski M, Hunt BJ. Treating acute exacerbations of chronic bronchitis. J Resp Dis 2001;22(suppl 8):75-80.
Cefditoren Clarithromycin
Clinical cure rates, day 7-14 82% 83%
Eradication rates, day 7-14 74% 73%
Adverse effects 27% 35%
Results:
43. The efficacy of cefditoren pivoxil in the treatment of
lower respiratory tract infections
A pooled analysis of clinical trials with particular focus was the most common causative pathogens, S pneumoniae,
H influenzae, and M catarrbalis - A total of 1223 target pathogens were isolated before treatment
Summary of Phase III studies of cefditoren in patients with c lower respiratory tract infections
Cefditoren 200 mg Cefditoren 400 mg Comparators
Infection/Study No. of
Patients
Treatment
duration
No. of
Patients
Treatment
duration
No. of
Patients
Regimen
Community-acquired pneumonia (CAP)
ME 301
(study 1)
n=109 10 days n=110 10 days n=116 Amoxicillin/clavulanate 500/ 125 mg
TID for 10 day
CEF 970022
(study 2)
n=181 14 days n= 165 14 days n= 167 Cefpodoxime 200 mg BID for 14 day
CEF 970062
(study 3)
n=148 14 days n= 159 14 days n= 147 Amoxicillin/clavulanate 875/ 125 mg
BID for 14 day
Acute exacerbations of chronic bronchitis (AECB)
ME 303 (study 4) n=241 5 days n=244 Cefuroxime 250 mg BID for 10 day
CEF 970032 n=148 10 days n=144 10 days n=160 Cefuroxime 250 mg BID for 10 day
CEF 970052
(study 6 )
n=208 10 days n=198 10 days n=217 Clarithromycin 500 mg BID for 10
day
Granizo JJ. Clin Ther. 2006 Dec;28(12):2061-9.
44. Cefditoren 200 mg Cefditoren 400 mg Comparators
Infection/Study End of Therapy End of Therapy End of Therapy
Community-acquired pneumonia (CAP)
ME 301 (study 1) 87.2% 86.4% 92.2% (Amoxi/clav)
CEF 97002 (study 2) 90.5% 89.7% 92% (Cefpodoxime )
CEF 97006 (study 3) 88.0% 89.9% 90.3% (Amoxi/clav)
CAP overall 91.8 % 89.2 % 91.5%
Acute exacerbations of chronic bronchitis (AECB)
ME 303 (study 4) 82.2% 83.2% (Cefuroxime )
CEF 970032 87.9 % 95.5 % 89.4% (Cefuroxime )
CEF 970052 (study 6 ) 88.5 % 84.4% 98.9% (Clarithromycin )
AECB overall 85.8 % 91.3 % 87.1%
Overall (CAP + AECB) 87.1% 90.0 % 89.9 %
Clinical Outcome (% of responders) at the End of Therapy
Granizo JJ. Clin Ther. 2006 Dec;28(12):2061-9.
In addition to clinical response cefditoren was associated with high rates of
per-pathogen bacteriologic response among the main causative
pathogens in lower respiratory tract infection
45. Safety and Efficacy of Cefditoren in Acute Bacterial Exacerbation of
Chronic Bronchitis
Design: Randomized, double blind, Phase III study
Study groups
Outpatients with a history of recurrent productive cough & at least 2 symptoms of AECB
included in this study
Patients assigned to :
Cefditoren (CDTR) 200 or 400 mg BID for 10 days
Cefuroxime (CXM) 250 mg BID
Results
CDTR 200 mg and 400 mg BID provided effective and safe treatment for AECB
Most frequent treatment-related adverse events
CDTR 200 mg group: Diarrhoea
CDTR 400 mg and CXM 250 mg groups : Diarrhoea, nausea, & vaginal moniliasis
Bettis R. Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 711.
46. Cefditoren pivoxil versus cefpodoxime proxetil for community-
acquired pneumonia
• Multicenter, prospective, RCT, conducted in the US & S. Africa
• n = 851 patients with community-acquired pneumonia (CAP)
– Cefditoren 200 or 400 mg BID
– Cefpodoxime 200 mg BID 14 days
• Post treatment visit: 48 hours after completion of treatment
• 1 follow-up visit (7-14 days after completion of treatment)
RESULTS
van Zyl L. Cefditoren pivoxil versus cefpodoxime proxetil for community-acquired pneumonia: results of a
multicenter, prospective, randomized, double-blind study. Clin Ther. 2002 Nov;24(11):1840-53
46
Treatment group Cure Rates Overall eradication rates
Post treatment visit Follow-up visit Post treatment visit
Cefditoren 200 mg 90.5% (162/179) 88.4% (160/181) 88.7% (134/151)
Cefditoren 400 mg 89.7% (148/165) 87.2% (143/164) 89.9% (134/149)
Cefpodoxime 200 mg 92.2% (153/166) 90.4% (151/167) 95.7% (134/140)
Cefditoren has a role in the treatment of community-acquired pneumonia in ambulatory patients
47. Giménez MJ, Aguilar L, Granizo JJ. Revisiting cefditoren for the treatment of community-acquired infections caused by human-
adapted respiratory pathogens in adults. Multidiscip Respir Med. 2018 Nov 2;13:40.
Comparative efficacy of Cefditoren Vs. Amoxicillin/clavulanic acid
or Cefuroxime, Clarithromycin, Cefpodoxime
48. Cefditoren Vs. cefpodoxime against Streptococcus pneumoniae
• Pharmacodynamic parameters and bactericidal activity against Streptococcus
pneumoniae were investigated by simulating total and free serum
concentrations of cefpodoxime versus cefditoren.
• Total drug concentration Time >MIC against the penicillin-intermediate
(PISP) and resistant (PRSP) strains were 70.6% and 42.9% for
cefpodoxime, and 89.6% and 62.5% for cefditoren, respectively.
Echeverria O et al. Pharmacodynamics of simulated total versus free-drug serum concentrations of a low versus a high protein bound third-
generation oral cephalosporin (Cefpodoxime versus cefditoren) against Streptococcus pneumoniae. J Chemother. 2007 Jun;19(3):288-94.
48
49. Trial Study Design Sample Size Key Results
Tsumura N. Jpn J
Antibiot. 2011 Jun;
64(3):179-90.
Comparative efficacy
of cefditoren Pivoxil
(CDTR-PI) for 5
days vs. Amoxicillin
for 10 days
112 children of
acute
Tonsillopharyngitis
caused by β-
hemolytic
streptococci (GAS)
Clinical efficacy was 100% for CDTR-PI vs.
97.9% for amoxicillin
Bacterial elimination rate was 100% in both
groups
CDTR-PI does not disturb the GI microbial flora
compared with amoxicillin
CDTR-PI for 5 days is a useful option for the
treatment of acute tonsillopharyngitis in children
Ozaki T. J Infect
Chemother. 2008 J
un;14(3):213-8.
5-day oral
Cefditoren vs. 10-
day Amoxicillin
258 patients of
pharyngotonsillitis
Cefditoren (n): 103
Amoxicillin (n): 155
Eradication was confirmed in 99%
(102/103) of the cefditoren-pivoxil group
and 100% of the amoxicillin group.
Because the efficacy was similar
between cefditoren- for 5 days & amoxicillin
for 10 days, the shorter treatment period
may make the cefditoren regimen
preferable
Clinical Trials: Tonsillitis/Pharyngitis
50. Trial Study Design Sample Size Key Results
Kawamata S. Jpn
J Antibiot. 2010
Jun;63(3):207-23.
Postmarketing study
of CDTR-PI in
pediatric patients with
acute otitis media
2144 patients were
enrolled in 305
medical institutions.
Clinical efficacy of CDTR-PI- the response rate was
93.5% (1831/1958 patients)
For each major resistant strain, the response rate was
88.0% for penicillin-intermediate S. pneumoniae (PISP),
90.1% for penicillin-resistant S. pneumoniae (PRSP), and
92.5% for beta-lactamase negative ampicillin-resistant H.
influenzae (BLNAR), while the bacterial eradication rate
was 85.7% for PISP, 77.5% for PRSP, and 81.8% for
BLNAR
Most common ADR was diarrhea (1.30%)
Li JT. Zhonghua Yi
Xue Za
Zhi. 2003 Mar
10;83(5):391-4.
Clinical study: To
evaluate the efficacy
and safety of
cefditoren pivoxil in
treatment of
respiratory infections
199 cases of
respiratory infection
In adults
cefditoren Pivoxil
200 mg tablets
1. The total effective rate was 94.9%, and the
causative bacteria -elimination rate was
96.7%.
2. Clinical adverse events : moderate
diarrhea, mild nausea and vomiting were
seen in 9 cases.
3. Cefditoren pivoxil is effective and safe in
treatment of mild and moderate respiratory
infections.
Clinical Trials: Otitis media, Respiratory Infections
51. 51
Trial Study Design Sample Size Key Results
Blasi F et al.
Ther Clin Risk
Manag. 2013;9:55-
64.
Open-label,
randomized, study
Cefditoren 200 mg
twice a day for 5 days
vs. levofloxacin 500
mg once daily for 7
days
40 patients with
acute bronchitis
Clinical cure rate was 80% with
Cefditoren Vs. 75% with Levofloxacin
Cefditoren is associated with a
significant reduction of interleukin-6
and KL-6, two key mediators of lung
inflammation &epithelial damage
Echeverria O. J
Chemother. 2007 J
un;19(3):288-94.
Cefpodoxime
Vs.
Cefditoren
Against
Streptococcus
pneumoniae
strains
Total drug concentration Time >MIC
against the penicillin-intermediate
(PISP) and resistant (PRSP) strains were
- 70.6% and 42.9% for cefpodoxime, &
- 89.6% and 62.5% for cefditoren
respectively
52. Trial Study Design Sample
Size
Key Results
Alvarez-Sala JL.
Antimicrob Agents
Chemother. 2006
May;50(5):1762-7.
Randomized,
double-blind,
Cefditoren 200
mg BD 5 days vs.
Cefuroxime 250
mg BD for 10 days
541 patients
acute
bronchitis
Clinical success was obtained
in 79.9% of the 264 patients
included in the cefditoren and in
82.7% of the 277 patients in the
cefuroxime group
C Yong-ning, L De-
rong, Z Li et al. A
Clinical Trial of
Cefditoren Pivoxil in
the Treatment of the
Respiratory Infection.
West China Medical
Journal 2003-02
An open clinical trial
Cefditoren pivoxil
200mg P.O. twice a
day for 7-14 days
38 cases of
respiratory
infections
1. The results showed that the
clinical cure rates was 71.
11%, efficacy rates was
97.36%, respectively. The
clinical incidence of adverse
reactions was 2.3%.
2. Cefditoren pivoxil was
efficacy and safety in the
treatment of respiratory
infection.
53. Clinical Safety
1. Post-marketing surveillance evaluating safety >2000 children treated with
cefditoren (daily dose: 10.0 mg/kg with treatment period of 7 days), the incidence
of diarrhea, the most frequent adverse drug reaction, was (1.30%) 1
2. Study in children comparing cefditoren vs. amoxicillin/clavulanic acid for 10
days in the treatment of acute bacterial rhinosinusitis, the most frequent adverse
event was diarrhea (4.5% with cefditoren vs. 18.1% for amoxicillin/clavulanic
acid) (P = 0.02)2
1. Kawamata S. Jpn J Antibiot. 2010 Jun;63(3):207-23.
2. Barberán J. International Journal of General Medicine. 2012;5:455-464.
54. Balanced broad Spectrum: broad spectrum activity against Gram-positive
and Gram-negative bacteria
Excellent activity: against S. pneumoniae, S. pyogenes, MRSA, H.
influenzae (common upper respiratory tract pathogens)
Active against all 6 Penicillin-binding proteins (PBPs) & 17 Extended-
spectrum β-lactamases (ESBLs)
Achieves high concentrations in Tissue: Respiratory/bronchial mucosa,
tonsillar tissue, maxillary sinus mucosa, wound fluid & skin blister fluid
Cefditoren has 4, 8 & 16 folds lesser MIC compared to Amox-Clav,
Cefpodoxime, Cefuroxime & Cefixime
Ideal for Switch over therapy: Due to the similar spectrum with third-
generation cephalosporins and better intrinsic activity
Cefditoren
