What are the differences between cefdinir and cefpodoxime? Which one is better?

Comment by InpharmD Researcher

Cefdinir and cefpodoxime are oral third-generation cephalosporins commonly used for mild-to-moderate community-acquired infections, including respiratory tract infections and uncomplicated pediatric illnesses. Both have strong activity against Streptococcus pneumoniae and retain partial activity against penicillin-intermediate strains, while cefdinir is more potent against methicillin-susceptible Staphylococcus aureus and cefpodoxime shows greater activity against Haemophilus influenzae; both are active against Moraxella catarrhalis, including β-lactamase-producing strains. Pooled data indicate high bacterial cure rates for both drugs in tonsillopharyngitis, approximately 94% for cefdinir and 93% for cefpodoxime, though indirect comparisons should be interpreted cautiously. Overall, both agents provide a balanced antimicrobial spectrum and are considered effective first-line options, with selection guided by the likely pathogen, patient population, and practical considerations rather than an inherent superiority of one over the other.

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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 in terms of their clinical efficacy. [1]

A 2007 review of the spectrum and potency of orally administered cephalosporins and amoxicillin/clavulanate provides a cohesive framework for comparing cefdinir and cefpodoxime within the broader context of outpatient antimicrobial therapy. The review describes cefpodoxime proxetil as an orally administered prodrug that is rapidly absorbed and de-esterified in vivo to its active form, cefpodoxime, a third-generation cephalosporin with high stability against commonly encountered plasmid-mediated β-lactamases. Cefdinir, approved by the US Food and Drug Administration in 1997, is characterized as an oral third-generation expanded-spectrum cephalosporin with improved β-lactamase stability compared with first- and second-generation agents, and is indicated for several mild-to-moderate community-acquired infections, including community-acquired pneumonia, acute bacterial exacerbations of chronic bronchitis, acute maxillary rhinosinusitis, streptococcal pharyngitis/tonsillitis, and uncomplicated skin and skin structure infections in pediatric patients. [2]

The authors emphasize that these oral β-lactam agents are widely used in the outpatient setting for community-acquired respiratory tract and other mild-to-moderate infections, and that the comparative data were drawn from critical reviews of each compound. Earlier-generation oral cephalosporins such as cephalexin and cefaclor were among the least potent agents and exhibited the narrowest antimicrobial spectra. In contrast, cefdinir and cefpodoxime, along with cefprozil and cefuroxime, demonstrated high activity against penicillin-susceptible Streptococcus pneumoniae and retained partial activity against penicillin-intermediate strains, although amoxicillin/clavulanate showed the greatest activity against S. pneumoniae, including most penicillin-nonsusceptible isolates. [2]

Pathogen-specific differences were also highlighted. Amoxicillin/clavulanate and cefdinir were the most potent agents against methicillin-susceptible Staphylococcus aureus, whereas cefpodoxime showed the greatest potency against Haemophilus influenzae. All three agents (amoxicillin/clavulanate, cefdinir, and cefpodoxime) maintained activity against Moraxella catarrhalis, including β-lactamase-producing strains. Overall, the review concluded that oral third-generation or extended-spectrum cephalosporins, including cefdinir and cefpodoxime, offer a more balanced antimicrobial spectrum against key outpatient respiratory pathogens than earlier-generation oral cephalosporins or amoxicillin alone, with selection between agents best guided by the target pathogen and clinical context rather than a single superior option. [2]

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 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 and cefdinir were 1.81 (0.29 to 11.25) and 1.65 (0.36 to 7.62) from two studies, and 1.67 (0.97 to 2.87) from one study, 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. [3]

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) and 7.06 (95% CI 4.34 to 11.49) for cefpodoxime (n= 396) and cefdinir (n= 455), respectively. Although individual cephalosporins were not compared directly, the overall bacterial cure rates were 93% for cefpodoxime and 94% for cefdinir. Furthermore, while 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. [4]

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] Sader HS, Jacobs MR, Fritsche TR. Review of the spectrum and potency of orally administered cephalosporins and amoxicillin/clavulanate. Diagn Microbiol Infect Dis. 2007;57(3 Suppl):5S-12S. doi:10.1016/j.diagmicrobio.2006.12.014
[3] 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
[4] 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:

What are the differences between cefdinir and cefpodoxime? Which one is better?

Level of evidence

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



Please see Table 1 for your response.


 

Overview of Cefdinir and Cefpodoxime (Derived from Prescribing Information)  
Parameter Cefdinir Cefpodoxime
Formulation  Capsule.  Tablet (film-coated).
Mechanism of Action Bactericidal; inhibits bacterial cell wall synthesis; stable against some β-lactamases Bactericidal; inhibits bacterial cell wall synthesis; active against some β-lactamases (penicillinases and cephalosporinases)
Mechanism of Resistance Hydrolysis by some β-lactamases, altered PBPs, decreased permeability; inactive vs Enterobacter spp., Pseudomonas spp., Enterococcus spp., penicillin-resistant streptococci, MRSA, BLNAR H. influenzae Hydrolysis by β-lactamases, altered PBPs, decreased permeability
Gram-Positive Activity S. aureus (methicillin-susceptible), S. pneumoniae (penicillin-susceptible), S. pyogenes; in vitro: S. epidermidis (MSSA), S. agalactiae, Viridans group streptococci S. aureus (MSSA, penicillinase-producing), S. saprophyticus, S. pneumoniae (excluding penicillin-resistant), S. pyogenes; in vitro: S. agalactiae, Groups C/F/G streptococci
Gram-Negative Activity H. influenzae, H. parainfluenzae, M. catarrhalis; in vitro: Citrobacter koseri, E. coli, K. pneumoniae, P. mirabilis E. coli, K. pneumoniae, P. mirabilis, H. influenzae (including β-lactamase-producing), M. catarrhalis, H. parainfluenzae, N. gonorrhoeae (penicillinase-producing)
Anaerobic Activity - Peptostreptococcus magnus (in vitro)
Indications  Adults CAP, acute bacterial exacerbation of chronic bronchitis, acute maxillary sinusitis, pharyngitis/tonsillitis, uncomplicated skin and skin structure infections CAP, acute bacterial exacerbation of chronic bronchitis, acute maxillary sinusitis, pharyngitis/tonsillitis, uncomplicated skin and skin structure infections, uncomplicated UTIs, gonorrhea
Indications  Pediatrics Acute otitis media, pharyngitis/tonsillitis, uncomplicated skin and skin structure infections Acute otitis media, pharyngitis/tonsillitis, uncomplicated skin and skin structure infections, uncomplicated UTIs
Special Notes Suspension formulation historically preferred in pediatrics; effective for β-lactamase–producing H. influenzae and M. catarrhalis Dose-dependent efficacy for skin infections; N. gonorrhoeae efficacy differs by site; some indications have limited clinical data
 
References:
[1] Cefdinir capsule. Prescribing information. Lupin Pharmaceuticals, Inc.; 2025
[2] Cefpodoxime proxetil tablet (film coated). Prescribing information. Amici Pharmaceuticals, LLC.; 2023.