Are there comparison data/studies on the efficacy of cefdinir versus cefpodoxime or cefuroxime?

Comment by InpharmD Researcher

Limited clinical data comparing the efficacy of cefdinir vs cefpodoxime or cefuroxime were identified. One RCT comparing cefdinir to cefuroxime for the treatment of patients with acute exacerbation of chronic bronchitis showed similar microbiologic and clinical response between the two antibiotics. Efficacy data extracted from reviews and meta-analyses for other indications (including acute bacterial rhinosinusitis and group A streptococcal tonsillopharyngitis) also show similar cure rates; however these results are limited to indirect comparisons only without adjusting for inter-study variabilities, and thus should be interpreted with caution.

  

PubMed: cefdinir AND cefpodoxime [filter: Clinical Trial]= 6 results; cefdinir AND cefuroxime [filter: Clinical Trial]: 2 results (one relevant)

Background

According to the 2004 guidelines for acute bacterial rhinosinusitis (ABRS) guidelines, originally developed by the Sinus and Allergy Health Partnership in 2000, common bacterial isolates covered from infected individuals comprised of Streptococcus pneumoniae, Haemophilus influenzae, other streptococcal species, and Moraxella catarrhalis, and antimicrobial activities against these pathogens were discussed separately. Based on available pharmacokinetic and pharmacodynamic (PK/PD) data, oral cefdinir exhibited similar activity against S pneumoniae to second-generation cephalosporins (e.g., cefuroxime axetil, cefpodoxime proxetil). While its activity against H influenzae was comparable to cefuroxime axetil, the activity was lower compared to cefpodoxime proxetil. For adult and pediatric patients with mild disease and no recent antimicrobial use (past 4-6 weeks), cefpodoxime proxetil, cefuroxime axetil, and cefdinir are recommended as initial agents, along with high-dose amoxicillin/clavulanate and amoxicillin. While both cefpodoxime proxetil and cefuroxime axetil outperformed cefdinir for adults and children with ABRS on calculated clinical efficacy and bacteriologic efficacy based on therapeutic outcome model using two surveillance data sets, the presented values do not guarantee clinical success or failure. The suspension formulation of cefdinir had been historically preferred among the pediatric population, given high patient acceptance. The guidelines provide no further head-to-head comparisons between cefdinir and cefpodoxime or cefuroxime in terms of their clinical efficacy. [1]

Though specific subgroup analyses based on individual cephalosporins were not performed, a 2007 meta-analysis involving five randomized controlled trials (N= 1,030) compared the bacterial eradication rates achievable with shortened courses of 2nd- and 3rd-generation cephalosporins compared with 10-day penicillin therapy for Group A streptococcal (GAS) tonsillopharyngitis treatment of adults. One of the evaluated trials compared cefuroxime with penicillin, one compared cefdinir with penicillin, and two compared cefpodoxime with penicillin. Overall, five days of select cephalosporins (cefpodoxime, cefuroxime, cefotiam, and cefdinir) was noninferior to ten days of penicillin (odds ratio [OR] 1.46; 95% confidence interval [CI] 0.96 to 2.22; p= 0.08) with respect to bacterial eradication rate. Individual ORs (95% CIs) vs. penicillin for cefpodoxime, cefuroxime, and cefdinir were 1.81 (0.29 to 11.25) and 1.65 (0.36 to 7.62) from two studies, 1.11 (0.22 to 5.70), and 1.67 (0.97 to 2.87), respectively. Of note, the ORs reported from each study do not account for inter-study variabilities and thus do not represent comparative efficacy among different cephalosporins. [2]

A 2004 meta-analysis included 35 randomized controlled trials (N= 7,125) comparing cephalosporins to penicillin treatment for group A beta-hemolytic streptococcal tonsillopharyngitis in children. Overall, results of the analysis showed that bacterial cure significantly favored cephalosporins (OR 3.02; 95% CI 2.49 to 3.67); individual cephalosporin showed superior bacteriologic cure rates. Compared to penicillin, individual ORs were 3.29 (95% CI 2.01 to 5.4), 3.31 (95% CI 1.47 to 7.45), and 7.06 (95% CI 4.34 to 11.49) for cefpodoxime (n= 396), cefuroxime (n= 510), and cefdinir (n= 455), respectively. Although individual cephalosporins were not compared directly, the overall bacterial cure rates were 93% for cefpodoxime, 92% for cefuroxime, and 94% for cefdinir. Although the individual cephalosporins showed high cure rates compared to penicillin, comparisons between these agents were not made directly, and indirect comparisons of reported cure efficacy rates should be interpreted with caution. [3]

References:

[1] Anon JB, Jacobs MR, Poole MD, et al. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis [published correction appears in Otolaryngol Head Neck Surg. 2004 Jun;130(6):794-6]. Otolaryngol Head Neck Surg. 2004;130(1 Suppl):1-45. doi:10.1016/j.otohns.2003.12.003
[2] Pichichero ME, Casey JR. Bacterial eradication rates with shortened courses of 2nd- and 3rd-generation cephalosporins versus 10 days of penicillin for treatment of group A streptococcal tonsillopharyngitis in adults. Diagn Microbiol Infect Dis. 2007;59(2):127-130. doi:10.1016/j.diagmicrobio.2007.04.010
[3] Casey JR, Pichichero ME. Meta-analysis of cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis in children. Pediatrics. 2004;113(4):866-882. doi:10.1542/peds.113.4.866

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Are there comparison data/studies on the efficacy of Cefdinir versus Cefpodoxime or Cefuroxime?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→



Please see Table 1 for your response.


 

International Study Comparing Cefdinir and Cefuroxime Axetil in the Treatment of Patients with Acute Exacerbation of Chronic Bronchitis

Design

Double-blind, randomized, multicentered, parallel-group study

N= 1,045

Objective

To evaluate the efficacy and safety of two dosages of cefdinir (600 mg once daily [o.d.] and 300 mg twice daily [b.i.d.]) with cefuroxime axetil (250 mg b.i.d.) administered for 10 days in patients with acute exacerbation of chronic bronchitis (AECB)

Study Groups

Cefdinir once a day (n= 349)

Cefdinir twice a day (n= 347)

Ceftuoxime twice a day (n= 349)

Inclusion Criteria

At least 13 years old (at least 18 y in Germany and two centers in the United Kingdom, and at least 21 y in one center in the United Kingdom) and had a history of chronic bronchitis and a current diagnosis of acute exacerbation of chronic bronchitis of presumptive bacterial origin (the diagnosis had to be accompanied by cough productive of mucopurulent or purulent sputum and a pretreatment sputum culture positive for a lower respiratory tract pathogen)

Exclusion Criteria

Evidence of pneumonia on a pre-screen roentgenogram; any disease or condition (e.g., cystic fibrosis, bronchiectasis, bronchial carcinoma, or pulmonary structure defects) likely to affect evaluation of the study medication; evidence of significant systemic disease (e.g., cardiovascular, gastrointestinal, psychiatric disease); hepatic or renal impairment; hypersensitivity to B-lactams; baseline pathogen known to be resistant to either study drug; concomitant infection requiring a systemic antibiotic; and use of a systemic antibiotic in the 48 hours (or 5 plasma half-lives) prior to starting treatment

Methods

Each patient was randomized 1:1:1 to receive cefdinir 600 mg once a day, 300 mg twice a day, or cefuroxime axetil 250 mg twice a day, for 10 days, the latter being used as an active control in preference to a placebo.

At baseline, each patient’s medical history was taken, and he or she underwent a physical examination, chest roentgenogram, clinical assessment, Gram stain, sputum culture and susceptibility testing, and clinical laboratory evaluations (hematology, blood chemistry, and urinalysis).

Duration

Treatment: 10 days

Trial: November 1992 to January 1995

Outcome Measures

Microbiologic eradication rate, by pathogen and by patient, and clinical response rate, by patient

Baseline Characteristics

 

Intent-to-Treat Group (n = 1,045)

Evaluable Test-of-Cure Group (n= 589) 

 

Cefdinir o.d. Cefdinir b.i.d. Cefuroxime b.i.d. Cefdinir o.d. Cefdinir b.i.d. Cefuroxime b.i.d.
Number of patients 349 347 349 201 195 193

Female

36% 42% 40% 38% 39% 42%
Age 59 59 61 59 59 59
≥ 1 episode of lower respiratory tract infection within the last 12 months 63% 70% 72% -- -- --

Over 95% of enrolled patients had a moderate or severe cough at baseline, and over 90% had moderate or severe sputum production. Most patients also had rhonchi (71%) and wheezing (52%), and almost half had moderate or severe dyspnea (49%). Approximately one-third of patients presented with rales, 20% with fever, and less than 10% with fremitus or pleural rub. In each treatment group, 34% of patients were past smokers, and between 28% and 32% were current smokers.

Results

Pathogen Susceptibility to Treatment at Baseline

Pathogen (n = 882)

Cefdinir

Cefuroxime

S (n= 798)

I (n= 33)

R (n= 36)

U (n= 15)

S (n= 752)

I (n= 83)

R (n= 28)

U (n= 19)

Gram-positive 

Streptococcus pneumoniae (n= 137)

Staphylococcus aureus (n= 74)

Streptococcus pyogenes (n= 17)

Other (n= 8)

132

69

17

0

0

0

4

3

0

1

2

0

0

132

68

15

6

2

2

2

2

1

1

0

2

3

0

0

Gram-negative

Haemophilus influenzae

β-lactamase + (n= 29)

β-lactamase - (n= 243)

β-lactamase unknown (n= 5)

29

218

5

0

19

0

0

3

0

0

3

0

28

233

5

1

3

0

0

4

0

3

0

Haemophilus parainfluenzae

β-lactamase + (n= 10)

β-lactamase - (n= 63)

β-lactamase unknown (n= 12)

8

56

10

1

4

0

1

1

2

0

2

0

10

61

12

0

2

0

0

0

0

0

0

0

Moraxella catarrhalis

β-lactamase + (n= 37)

β-lactamase - (n= 37)

β-lactamase unknown (n= 2)

37

35

0

0

2

0

0

0

0

0

0

2

34

33

0

3

3

0

0

0

0

0

1

2

Escherichia coli (n= 52)

49  2 1 32 18 0

Klebsiella pneumoniae (n= 30)

30 0 0 0 22 8 0 0

Other (n= 126)

95 7 20 4 61 37 22 6

Microbiologic Eradication Rate by Pathogen at Test-of-Cure and Long-Term Follow-up Examinations

  At Test-of-Cure Visit (n= 666) At Long-Term Follow-up Visit (n= 430)
Pathogen 

Cefdinir o.d.

199/221

Cefdinir b.i.d

192/225

Cefuroxime b.i.d

193/220

Cefdinir o.d.

144/152

Cefdinir b.i.d

134/136

Cefuroxime b.i.d

140/142

S. aureus

S. pneumoniae

S. pyogenes

Other

16/16

34/38

4/4

0/0 

19/20

35/40

4/5

3/3 

23/23

30/30

4/4

2/2 

10/10

23/27

3/3

0/0 

10/11

27/27

3/3

0/0 

18/18

21/21

1/1

2/2 

H. influenza

β-lactamase +

β-lactamase -

β-lactamase unknown

 

4/4

51/65

1/1

 

4/7

53/66

1/1

 

8/10

43/60

1/1

 

--

--

38/42

 

--

--

40/40

 

--

--

38/39

H. parainfluenzae

β-lactamase +

β-lactamase -

β-lactamase unknown

 

2/2

13/13

4/4 

 

3/3

21/24

3/3 

 

3/3

15/16

2/2

 

--

--

13/13 

 

--

--

19/19 

 

--

--

13/13

M. catarrhali

β-lactamase +

β-lactamase -

β-lactamase unknown

 

14/14

5/5

--

 

4/6

13/14

--

 

8/9

12/12

-- 

 

--

--

15/15 

 

--

--

11/11 

 

--

--

14/14 

E. coli

10/12

7/9

13/16

8/8

5/6

13/13

K. pneumoniae

12/12

6/8

3/3

8/8

3/3

3/3

Other

29/31

16/16

26/29

26/26

16/16

17/18

Summary of Drug-Related Adverse Events
  Cefdinir o.d. Cefdinir b.i.d. Cefuroxime b.i.d
Number of patients 349 345 349
Diarrhea 29 27 19
Nausea 7 3 8
Skin and appendages  9 6 1
Urogenital system 3 1 1
Special senses 1 1 2
Nervous system 1 0 1
Metabolic or nutritional 0 1 0

Intensity of drug-related events

Mild

Moderate

Severe

 

8.9%

6.0%

1.1%

 

7.2%

5.2%

0.3%

 

8.0%

2.3%

1.1%

Treatment discontinuation owing to drug-related adverse events 

4.3%

2.9%

2.6%

The microbiologic eradication rates by pathogen were 90% with once-daily cefdinir, 85% with twice-daily cefdinir, and 88% with twice-daily cefuroxime. The corresponding values for microbiologic eradication rate by patient were 90% (once-daily cefdinir), 85% (twice-daily cefdinir), and 86% (twice-daily cefuroxime). The respective clinical response rates by patient were 81%, 74%, and 80%. 

Clinical cure rates in patients 65 years of age and older were similar to those in younger adults in all treatment groups. Smoking history did not appear to affect successful clinical outcomes, except among cefuroxime-treated patients, in whom clinical cure rates were slightly higher among patients who had never smoked.

Abbreviations: S= susceptible (MIC < 0.06 mg/L); I= intermediate susceptibility (MIC 0.1-l.0 mg/L); R= resistance (MIC > 2.0 mg/L); U= unknown; += positive; -= negative

Adverse Events

See result

Study Author Conclusions

Cefdinir 600 mg once a day was as effective as cefuroxime 250 mg twice a day in terms of microbiologic response by pathogen and clinical response in patients with AECB of presumptive bacterial origin. Cefdinir 300 mg twice a day was as effective as cefuroxime twice a day in terms of microbiologic response by patient. All three treatments were well tolerated, with no significant differences among regimens in terms of frequency of adverse events or numbers of patients discontinuing treatment because of adverse events.

InpharmD Researcher Critique

The study lacked clear criteria for patient selection, potentially leading to the overuse of antibiotics. The study did not stratify patients by exacerbation type and had limited long-term follow-up, preventing a comprehensive understanding of treatment durability. Resistance data were not extensively evaluated, and the study population may not fully represent the broader patient population. Adverse event reporting could be more detailed.



References:

Van Herwaarden CL, Langan CE, Siemon G, et al. International study comparing cefdinir and cefuroxime axetil in the treatment of patients with acute exacerbation of chronic bronchitis. Int J Infect Dis. 2000;4(1):26-33. doi:10.1016/s1201-9712(00)90062-6