Efficacy of cefditoren pivoxil and amoxicillin/clavulanate in the treatment of pediatric patients with acute bacterial rhinosinusitis in Thailand: A randomized, investigator-blinded, controlled trial

doi:10.1016/j.clinthera.2008.10.001

Clinical Therapeutics

Volume 30, Issue 10, October 2008, Pages 1870-1879

https://doi.org/10.1016/j.clinthera.2008.10.001 Get rights and content

Abstract

Background: The recommended treatment for acute bacterial rhinosinusitis in adults and children is 10 to 14 days of high doses of oral cephalosporins or amoxicillin/clavulanate.

Objective: This study compared the clinical efficacy and tolerability of cefditoren pivoxil and amoxicillin/ clavulanate in children with uncomplicated acute bacterial rhinosinusitis.

Methods: This was a randomized, investigator-blinded, controlled study in pediatric patients (age 1–15 years) with clinical and radiographic signs and symptoms of acute rhinosinusitis. Patients were allocated to receive either cefditoren (8–12 mg/kg daily) or amoxicillin/clavulanate (80–90 mg/kg amoxicillin daily) for 14 days. Changes in sinus symptoms were assessed daily by patients or their parents using a quantitative symptom score (the S5 score). Rates of improvement, the primary efficacy measure, were also evaluated by the study investigators 7 and 14 days after the initial visit. Secondary outcome measures included time to improvement, adverse effects, and rates of relapse (assessed at days 21 and 28) and recurrence (assessed at day 60) of sinus symptoms. Relapse was defined as a subjective rating of lack of improvement at day 21 or 28 in a patient rated as improved on day 14, and recurrence was defined as sinus symptoms lasting for ≥10 days during the second month of follow-up in a patient rated as improved on day 28. Time to improvement was defined as the number of days between the initial visit and the time at which caregivers noted an improvement in patients' symptoms. Adverse events were monitored by parents/caregivers using a self-administered questionnaire and were also elicited by telephone contact.

Results: The study enrolled 142 pediatric patients: 70 in the cefditoren group (42 males, 28 females; median age, 7.15 years) and 72 in the amoxicillin/clavulanate group (37 males, 35 females; median age, 6.60 years). Four patients in the cefditoren group were excluded from the study analyses (2 who were noncompliant [used <80% of the assigned medication] and 2 who developed infection at other sites). There were no significant differences in baseline medical history or signs and symptoms between the 2 groups. Rates of improvement at day 14 in the cefditoren and amoxicillin/clavulanate groups were 78.8% (52/66) and 84.7% (61/72), respectively (P = NS). There was no significant difference in the change in S5 scores between groups at day 14. The median time to improvement was 3.0 days in both groups. There were no significant differences between groups in rates of relapse (9.1% and 11.1%) or recurrence (3.0% and 5.6%) of sinus symptoms. The most common adverse event in both groups was diarrhea, occurring in 4.5% of the cefditoren group and 18.1 % of the amoxicillin/clavulanate group (P = 0.02).

Conclusion: In these children with acute bacterial rhinosinusitis, there were no significant differences between cefditoren and amoxicillin/clavulanate, the currently recommended treatment, in terms of rates of response, relapse, or recurrence.

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Similar to other studies, there were more side effects in the antibiotic-treated group compared with placebo treatment (44% vs 14% of children, P = .014). In another RCT in patients 1 to 15 years of age with clinical and radiographic signs and symptoms of ABRS, patients received a cephalosporin (8–12 mg/kg of cefditoren daily) or amoxicillin-clavulanate (80–90 mg/kg of amoxicillin daily) for 14 days.402 The results showed comparable rates of improvement at 14 days: 78.8% for cefditoren and 84.7% for amoxicillin-clavulanate.
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A pediatric trial was performed on patients with pharyngotonsillitis caused by S. pyogenes; this study concluded that the shorter treatment period for cefditoren (5 days) was favorable to the 10-day course of amoxicillin therapy with similar efficacy (Ozaki et al., 2008). Another pediatric trial compared cefditoren and amoxicillin/clavulanate in the treatment of acute bacterial rhinosinusitis, with results showing similar response, relapse, and recurrence rates (Poachanukoon and Kitcharoensakkul, 2008). An overall assessment of 7 clinical trials was published in the latter part of 2006 to review the efficacy of cefditoren in the treatment of lower RTIs, which included CAP and AECB trials mentioned earlier (Jose Granizo et al., 2006).
Antimicrobial resistance rates have noticeably increased among commonly isolated species associated with respiratory tract infections and skin and skin structure infections, particularly Streptococcus pneumoniae and Staphylococcus aureus. Cefditoren, an oral 3rd-generation–like cephalosporin, has been shown to be very active against many Gram-positive and Gram-negative species with favorable attributes including bactericidal activity and stability against many β-lactamase enzymes. Clinical trial data worldwide support the use of cefditoren for infections and species that have been approved by the US Food and Drug Administration (US-FDA). This review and a contemporary study report provide an update of clinical trial and in vitro data for cefditoren especially against pathogens within the spectrum of activity since 2002. A large collection of 7279 clinical isolates collected during 2002 and 2003 from medical centers in North and Latin America and Europe were tested to confirm cefditoren potency and spectrum compared with other oral cephalosporins and other class agents. Isolates were tested at a reference laboratory using reference broth microdilution methods. Cefditoren was shown to be active against nearly all (>99%) isolates of penicillin-susceptible S. pneumoniae isolates (MIC₉₀, ≤0.03 μg/mL) and was the most potent orally administered cephalosporin against this organism. Cefditoren was the most active oral cephem tested against Haemophilus influenzae (MIC₉₀, ≤0.03 μg/mL) and had >99% activity versus both β-lactamase–positive and β-lactamase–negative isolates. The potency of cefditoren (MIC₉₀, 0.5 μg/mL) was similar to that of amoxicillin/clavulanate and cefdinir (MIC₉₀, 0.25 μg/mL) when tested against Moraxella catarrhalis. Cefditoren was the most potent cephalosporin tested against oxacillin-susceptible S. aureus with an MIC₉₀ value of only 1 μg/mL, and it was 100% active against the tested β-hemolytic streptococci. Using the data generated from the large collection of isolates tested in this global surveillance collection, as well as other summarized supporting studies and clinical trial information, we show that cefditoren has sustained in vitro activity and documented clinical efficacy for indications that have been approved by regulators (US-FDA).
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Systemic antibiotic therapy of patients with acute bacterial sinusitis taking into account resistance
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Efficacy of cefditoren pivoxil and amoxicillin/clavulanate in the treatment of pediatric patients with acute bacterial rhinosinusitis in Thailand: A randomized, investigator-blinded, controlled trial

Abstract

J Allergy Clin Immunol

J Allergy Clin Immunol

Diagn Microbiol Infect Dis

Int J Antimicrob Agents

J Allergy Clin Immunol

J Allergy Clin Immunol

Controlled Clin Trials

Clin Ther.

Antimicrobial treatment guidelines for acute bacterial rhinosinusitis [published correction appears in Otolaryngol Head Neck Surg. 2004;130: 794-796]

Otolaryngol Head Neck Surg

Susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae to 10 oral antimicrobial agents based on pharmacodynamic parameters: 1997 US Surveillance study

Antimicrob Agents Chemother

Acute otitis media caused by Streptococcus pneumoniae in children's hospitals between 1994 and 1997

Pediatr Infect Dis J

The Alexander Project 1998-2000: Susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents

J Antimicrob Chemother

Systemic Haemophilus influenzae disease in Thai children

Southeast Asian J Trop Med Public Health

Clinical practice guideline: Management of sinusitis [published correction appears in Pediatrics. 2002;109:40]

Pediatrics

Clinical practice guidelines on the management of rhinosinusitis [in Thai]

Siriraj Hosp Gaz