Drugs

, Volume 64, Issue 22, pp 2597–2618 | Cite as

Cefditoren Pivoxil

A Review of its Use in the Treatment of Bacterial Infections
Adis Drug Evaluation

Summary

Abstract

Cefditoren pivoxil (Spectracef®, Meiact®) is a third-generation oral cephalosporin with a broad spectrum of activity against pathogens, including both Gram-positive and -negative bacteria, and is stable to hydrolysis by many common β-lactamases. Cefditoren pivoxil is approved for use in the treatment of acute exacerbations of chronic bronchitis (AECB), mild-to-moderate community-acquired pneumonia (CAP), acute maxillary sinusitis, acute pharyngitis/tonsillitis and uncomplicated skin and skin structure infections (indications may differ between countries).

In clinical trials in adults and adolescents, cefditoren pivoxil demonstrated good clinical and bacteriological efficacy in AECB, CAP, acute maxillary sinusitis, acute pharyngitis/tonsillitis and uncomplicated skin and skin structure infections and was generally well tolerated. Thus, cefditoren pivoxil is a good option for the treatment of adult and adolescent patients with specific respiratory tract or skin infections, particularly if there is concern about Streptococcus pneumoniae with decreased susceptibility to penicillin, or β-lactamase-mediated resistance among the common community-acquired pathogens.

Antibacterial Activity

Cefditoren has a broad spectrum of antibacterial activity against a number of the common Gram-positive and -negative pathogens. In vitro studies conducted since 1998 have shown that cefditoren has good activity against meticillin-susceptible Staphylococcus aureus, Streptococcus pyogenes and penicillin-susceptible and -intermediate S. pneumoniae. Minimum inhibitory concentrations of cefditoren required to inhibit 90% of bacterial strains (MIC90) of penicillin-resistant S. pneumoniae were considerably lower than those of cefuroxime and cefdinir. In the ARISE (Antibiotic Resistance Isolates in Southern Europe) project, the MIC90 of cefditoren (0.5 mg/L) against 877 clinical isolates of S. pneumoniae, 16.5% of which were resistant to penicillin, was lower than those of all other antibacterials tested, including cefpodoxime, cefotaxime, amoxicillin/ clavulanic acid and levofloxacin.

Cefditoren was highly active against the Gram-negative organisms Haemophilus influenzae, H. parainfluenzae and Moraxella catarrhalis, including β-lacta-mase-producing strains. Indeed, cefditoren is stable to hydrolysis by many of the common 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, CARB-4, LCR-1, TLE-1 and OHIO-1. However, cefditoren is susceptible to hydrolysis by a number of plasmid-mediated extended-spectrum β-lactamases (e.g. TEM-3, TEM-4, TEM-5, TOHO-1, SHV-2, SHV-7, SHV-9, SHV-12 and PER-1).

By binding to penicillin-binding proteins, cefditoren inhibits bacterial cell wall synthesis, leading to cell lysis and death of susceptible bacteria. Cefditoren is bactericidal against S. pneumoniae (including penicillin-resistant strains), S. pyogenes, H. influenzae, M. catarrhalis and S. aureus at concentrations of one to four times the MIC.

Pharmacokinetic Properties

Cefditoren is formulated as a pivoxil ester in order to increase bioavailability. After oral administration, cefditoren pivoxil is hydrolysed by intestinal esterases to form cefditoren (the active metabolite) and pivalate. A single 400mg oral dose administered with food afforded a mean maximum plasma concentration (Cmax) of 3.8–4.6 mg/L after 2.4–3.1 hours. Mean area under the plasma concentration-time curve (AUC) values were 11.4–17.4 mg · h/L. After a 7-day course of twice-daily cefditoren pivoxil 400mg, Cmax and AUC values for cefditoren were similar to those after a single dose. Binding of cefditoren to plasma proteins averages 88%, and the mean volume of distribution of cefditoren at steady state is 9.3L.

Cefditoren has been shown to penetrate into bronchial mucosa, epithelial lining fluid, skin blister fluid and tonsillar tissue and, although data are limited, clinically relevant concentrations against common pathogens are achieved in these tissues for at least 4 hours.

Cefditoren is predominantly eliminated by the kidneys as unchanged drug and has a renal clearance of 4.1–5.6 L/h after multiple doses; its elimination half-life is 1.5 hours. Dosage adjustments may be required in patients with renal dysfunction.

Coadministration of cefditoren pivoxil with histamine H2-receptor antagonists or aluminium/magnesium-containing antacids is not recommended because of the resulting decrease in plasma cefditoren concentrations.

Therapeutic Efficacy

The clinical and bacteriological efficacy of oral cefditoren pivoxil in the treatment of adult and adolescent patients with community-acquired respiratory tract infections or skin and skin structure infections has been established in numerous trials conducted in Europe, the US and South Africa.

The clinical and microbiological efficacy of cefditoren pivoxil 200mg twice daily for 5 days was shown to be equivalent to that of cefuroxime axetil 250mg twice daily for 10 days in the treatment of patients with AECB (Anthonisen I and II). Cefditoren pivoxil 200 or 400mg twice daily for 10 days also demonstrated good clinical and bacteriological efficacy in the treatment of AECB.

Clinical cure rates with twice-daily cefditoren pivoxil 200 or 400mg for 14 days (86.5–88.4%) were similar to those with 14-day regimens of amoxicillin/ clavulanic acid or cefpodoxime proxetil in patients with mild-to-moderate CAP. Bacteriological eradication rates of 77.3–85.7%, 79.8% and 91.7% were seen with cefditoren, amoxicillin/clavulanic acid and cefpodoxime proxetil.

In patients with acute maxillary sinusitis, cefditoren pivoxil 200 or 400mg twice daily for 10 days produced clinical cure rates (63.6–94.9%) similar to standard regimens of amoxicillin/clavulanic acid or cefuroxime axetil. Bacterial eradication rates were reported in one study: 72.3% with twice-daily cefditoren pivoxil 200mg and 86.4% with cefuroxime axetil.

Cefditoren pivoxil 200mg twice daily for 5 or 10 days produced clinical cure rates of >92% in patients with acute pharyngitis/tonsillitis, which were similar to those achieved with standard 10-day courses of penicillin V. Microbiological cure rates with cefditoren pivoxil 200mg twice daily for 10 days were 90.4%, compared with 82.7% with penicillin V 250mg four times daily for 10 days in patients with streptococcal pharyngitis/tonsillitis.

Clinical cure rates with cefditoren pivoxil 200 or 400mg twice daily for 10 days (81.5–85.3%) in patients with skin and skin structure infections were similar to those seen with cefuroxime axetil or cefadroxil; corresponding bacteriological eradication rates (54% of isolated pathogens were S. aureus) were 80.9–87.4%, 88.6% and 76.6%.

Tolerability

Cefditoren pivoxil is generally well tolerated, with most adverse events being of mild-to-moderate severity and self-limiting. Gastrointestinal adverse events (e.g. diarrhoea, nausea and abdominal pain) were the most commonly reported adverse events, although they seldom led to treatment discontinuation. Diarrhoea was the most common adverse event with cefditoren pivoxil (incidence of >10% in most trials) and often occurred with a significantly higher incidence than with comparator drugs.

As with other pivalate-producing agents, cefditoren pivoxil can cause transient decreases in plasma carnitine levels and is, thus, contraindicated in patients with primary carnitine deficiency.

Keywords

Eradication Rate Cefpodoxime Cefadroxil Clinical Cure Rate Cefprozil 

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© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, AucklandNew Zealand

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