This report was reviewed for medical and scientific accuracy by Frank P. Murphy, MD, Chief, Division of Dermatology, University of Medicine & Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Introduction

Oral antibiotics are commonly prescribed for the treatment of uncomplicated skin and skin-structure infections; however, the development of drug-resistant organisms has made the choice of antibiotic therapy more complicated. Ideally, agents used for the treatment of these infections should demonstrate good skin penetration and a broad spectrum of antibacterial activity, including activity against the most common skin pathogens, Staphylococcus aureus (S. aureus) and Streptococcus pyogenes (S. pyogenes).

Cefdinir (Omnicef) is an extended-spectrum cephalosporin with good skin penetration (92-108%) as gauged by skin blister fluid model¹ and wide range of antimicrobial activity.² Two well-designed randomized, controlled trials have demonstrated that cefdinir is a safe and effective treatment option for patients of all ages with uncomplicated skin and skin-structure infections.^3,4 These studies support findings from earlier laboratory studies demonstrating the excellent in vitro activity of cefdinir against common skin and skin-structure pathogens, including S. pyogenes (MIC₉₀, 0.015 µg/mL) and beta-lactamase producing isolates of S. aureus (MIC₉₀, 0.5 µg/mL).²

Pediatric Patients Experience Clinical Cure and Microbiologic Eradication

Tack and colleagues evaluated the comparative safety and efficacy of cefdinir and cephalexin (Keflex) oral suspensions in a multicenter, randomized, investigator-blind study conducted in 394 pediatric patients (median age 5.3 years; range, 0.5 to 13.1 years) with acute skin and skin-structure infections (57% impetigo, 9% infected dermatitis, 8% wound infection, 7% cellulitis).³ Patients were randomized to receive either cefdinir suspension 7 mg/kg twice daily for 10 days or cephalexin suspension 10 mg/kg four times daily for 10 days. Efficacy was evaluated at 2 follow-up visits, one visit 7 to 14 days post-therapy (test-of-cure) and the second visit 21 to 35 days post-therapy (long-term follow-up). Safety was evaluated for all patients through questioning (of the parent or guardian) about the occurrence of adverse events, by looking for changes on physical examination, and by routine laboratory screening (complete blood count with differential, blood urea nitrogen, creatinine, hepatic enzymes, and urinalysis) performed at study admission and repeated after completion of therapy at the test-of-cure visit.

Baseline cultures identified a total of 517 pathogens. Gram-positive pathogens predominated; S. aureus (284 isolates) and S. pyogenes (111 isolates) were the most frequently occurring pathogens. Enterobacter agglomerans (E. agglomerans) was the most frequently identified gram-negative pathogen (12 isolates). Susceptibility testing at baseline demonstrated that fewer pathogens were resistant to cefdinir than to cephalexin (40 vs 56, respectively; P<.001). None of the most commonly encountered pathogens (S. aureus, S. pyogenes, E. agglomerans) were resistant to cefdinir, though occasional isolates of S. aureus demonstrated only intermediate susceptibility.

Data from 118 patients in the cefdinir treatment group and 113 patients in the cephalexin treatment group were considered evaluable for efficacy (patients had cultures positive for cefdinir- and cephalexin-susceptible organisms at baseline, did not take concurrent systemic or topical antibacterial therapy, and took study medication as prescribed). Both cefdinir and cephalexin had eradicated the majority of pathogens by the first post-therapy visit (99.4% vs 97.4%, respectively) (Figure 1A). Cefdinir led to microbiologic cure (eradication) in 99% (96/97) of infections caused by S. aureus and 100% (42/42) of infections caused by S. pyogenes. Both agents were associated with excellent clinical response (98.3% vs 93.8% of patients in the cefdinir and cephalexin treatment groups experienced clinical cure, respectively) (Figure 1B). Statistical analyses (Cochran-Mantel-Haenzel testing) confirmed that the microbiologic and clinical response rates of the 2 antibiotics were not statistically different (P = .135 and P = .056 for microbiologic and clinical response rates, respectively). Recurrence was observed at the second post-therapy visit in only 1.9% and 4.1% of patients in cefdinir and cephalexin treatment groups, respectively.

Both treatments were well tolerated. Adverse event rates in the 2 treatment groups were similar (16% vs 11% of patients in the cefdinir and cephalexin treatment groups experienced one or more adverse events, respectively; P = .11).

Highly Effective Treatment of Skin and Skin-structure Infections in Adults and Adolescents

Tack and colleagues also evaluated the comparative safety and efficacy of cefdinir and cephalexin in adults and adolescents with skin and skin-structure infections.⁴ This multicenter, randomized, double-blind study was conducted in 952 adults and adolescents (ages 13 to 88 years) with acute skin and skin-structure infections (abscess, infected traumatic/surgical wound, paronychia, infected dermatitis, impetigo, cellulitis, furuncle, folliculitis, carbuncle, acutely infected cutaneous ulcer, or infected burn). Patients were randomized to treatment with either cefdinir (capsules) 300 mg twice daily for 10 days or cephalexin (capsules) 500 mg four times daily for 10 days. Safety and efficacy were assessed at 2 follow-up visits, one of which occurred 7 to 16 days after completion of therapy (test-of-cure).

Baseline cultures identified a total of 821 pathogens, of which S. aureus was the most common (present in 35% of cefdinir-treated patients and 32% of cephalexin-treated patients). Approximately one-fifth of patients (18% and 19% of patients in the cefdinir and cephalexin treatment groups, respectively) had polymicrobial infections, the most common of which involved S. aureus plus Streptococcus agalactiae (S. agalactiae) and S. aureus plus S. pyogenes. Susceptibility testing at baseline demonstrated that significantly fewer pathogens were resistant to cefdinir than to cephalexin (88 vs 150, respectively; P<.001).

Data from 178 patients in the cefdinir treatment group and 204 patients in the cephalexin treatment group were considered microbiologically assessable (cultures positive for cefdinir- and cephalexin-susceptible organisms at baseline, presented for follow-up visit 7 to 16 days post-therapy or at the time of withdrawal, did not take concurrent systemic or topical antibacterial therapy, and took study medication as prescribed) and were included in the efficacy analysis. Both cefdinir and cephalexin eradicated the majority of pathogens (93% vs 89%, respectively) (Figure 2A). Cefdinir led to microbiologic cure (eradication) in 92% (131/143) of infections caused by S. aureus and 100% (17/17) of infections caused by S. pyogenes. Both agents demonstrated good clinical response (88% vs 87% were cured or improved in the cefdinir and cephalexin treatment groups, respectively) (Figure 2B). Statistical analyses (Cochran-Mantel-Haenzel test) confirmed that the microbiologic and clinical response rates were similar (P = .105 and P = .617 for microbiologic and clinical response rates, respectively).

Study treatments were well-tolerated by most patients. Diarrhea was more common in the cefdinir treatment group than the cephalexin treatment group (16% vs 7%, P<.001); however, most cases were mild and self-limiting, and did not require discontinuation of therapy. The investigators concluded that cefdinir is as effective as cephalexin for the treatment of mild-to-moderate skin and skin-structure infections in adults and adolescents and is generally well-tolerated. They noted that the higher rate of diarrhea with cefdinir should be viewed in light of its increased antibacterial activity.

Conclusion

Cefdinir is a safe and effective treatment option for adults and children presenting with skin and skin-structure infections. It has good penetration into the skin and demonstrates excellent in vitro activity against the most common skin infection pathogens (S. pyogenes and S. aureus). The favorable palatability of cefdinir suspension^5,6 may enhance compliance in pediatric patients for whom taste and palatability are significant issues.

References

1. Richer M, Allard S, Manseau L, Vallee F, Pak R, LeBel M. Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses. Antimicrob Agents Chemother. 1995;39:1082-1086.
2. Omnicef prescribing information [package insert]. Abbott Laboratories. Available at http://www.omnicef.com. Accessed June 25, 2003.
3. Tack KJ, Keyserling CH, McCarty J, Hedrick JA, for the Cefdinir Pediatric Skin Infection Study Group. Study of use of cefdinir versus cephalexin for treatment of skin infections in pediatric patients. Antimicrob Agents Chemother. 1997;41:739-742.
4. Tack KJ, Littlejohn TW, Mailloux G, Wolf MM, Keyserling CH, for the Cefdinir Adult Skin Infection Study Group. Cefdinir versus cephalexin for the treatment of skin and skin-structure infections. Clinical Therapeutics. 1998;20:244-256.
5. Steele RW, Thomas MP, Begue RE. Compliance issues related to the selection of antibiotic suspensions for children. Pediatr Infect Dis J. 2001;20:1-5.
6. Powers JL, Gooch WM, Oddo LP. Comparison of the palatability of the oral suspension of cefdinir vs amoxicillin/ clavulanate potassium, cefprozil and azithromycin in pediatric patients. Pediatr Infect Dis J. 2000;19:S174-S180.

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Disclosure

Frank P. Murphy, MD
No significant relationships to disclose.

This report contains no information on commercial products that are unlabeled for use or investigational uses of products not yet approved.

This report is supported by an educational grant from Abbott Laboratories.

The opinions expressed in this publication are those of the participating faculty and do not necessarily reflect the opinions or the recommendations of their affiliated institutions: University of Medicine & Dentistry of New Jersey; MMC, Inc.; or any other persons. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this publication should not be used by clinicians without evaluation of their patients' conditions, assessment of possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with the recommendation of other authorities. This Skin Infections Newsletter does not include discussion of treatment and indications outside of current approved labeling. This Skin Infections Newsletter was made possible through an educational grant from Abbott Laboratories.

© 2003 Millennium Medical Communications, Inc. and UMDNJ-Center for Continuing and Outreach Education