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Cefixime

Cefixime: A Broad-Spectrum Oral Cephalosporin for Community-Acquired Infections

Introduction

In the landscape of antibiotic therapy, oral third-generation cephalosporins represent a vital bridge between outpatient treatment convenience and robust antimicrobial coverage. Among these, Cefixime has emerged as a cornerstone in the treatment of various community-acquired infections. Marketed under multiple brand names such as Suprax, Cefixime is particularly valuable for its efficacy against a wide range of Gram-negative bacteria and ease of oral administration. Cefixime is a broad-spectrum, beta-lactam antibiotic that has proven efficacy in conditions like respiratory tract infections, urinary tract infections, and certain sexually transmitted infections.

Pharmacological Overview

  • Class: Third-generation cephalosporin

  • Type: Oral beta-lactam antibiotic

  • Chemical Formula: C16H15N5O7S2

  • Molecular Weight: 453.45 g/mol

  • Brand Names: Suprax, Zifi, Cefspan, others

Cefixime is a semi-synthetic derivative of cephalosporin C and is primarily used for treating infections caused by Gram-negative organisms, although it retains some Gram-positive coverage.

Mechanism of Action

Like other beta-lactam antibiotics, Cefixime works by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) on the bacterial cell wall, disrupting the final transpeptidation step of peptidoglycan synthesis. This leads to a weakened cell wall, bacterial lysis, and ultimately cell death.

Cefixime is bactericidal and is more stable to beta-lactamase enzymes than earlier cephalosporins, although it is still susceptible to certain resistance mechanisms.

Antibacterial Spectrum

Gram-Negative Bacteria

  • Haemophilus influenzae

  • Escherichia coli

  • Klebsiella pneumoniae

  • Proteus mirabilis

  • Salmonella spp.

  • Shigella spp.

  • Neisseria gonorrhoeae

  • Moraxella catarrhalis

Gram-Positive Bacteria (limited)

  • Streptococcus pneumoniae

  • Streptococcus pyogenes

Anaerobes

  • Generally ineffective against anaerobes

Cefixime is especially effective against beta-lactamase-producing strains of H. influenzae and M. catarrhalis, making it a key choice for respiratory infections.

Pharmacokinetics

  • Bioavailability: 40–50% (oral)

  • Peak Plasma Concentration: 2–6 hours after administration

  • Half-Life: 3–4 hours

  • Protein Binding: ~65%

  • Elimination: Renal (primarily) and biliary routes

Food may slightly delay absorption but does not significantly reduce the extent of absorption. Therefore, Cefixime can be taken with or without food.

Formulations and Dosage

Cefixime is available in several oral forms:

  • Tablets (200 mg, 400 mg)

  • Oral Suspension (100 mg/5 mL)

  • Dispersible tablets (for pediatric use)

Adult Dosage

  • 200–400 mg once daily or divided into two doses

  • Duration: 5–14 days depending on infection

Pediatric Dosage

  • 8 mg/kg/day once daily or divided into two doses

  • Max: 400 mg/day

Dosage adjustments are recommended in patients with renal impairment.

Clinical Indications

Cefixime is widely used in both adults and children for various infections, especially when outpatient oral treatment is preferred.

1. Upper Respiratory Tract Infections

  • Pharyngitis and tonsillitis: Effective against Streptococcus pyogenes

  • Otitis media: Especially when caused by H. influenzae or M. catarrhalis

2. Lower Respiratory Tract Infections

  • Bronchitis: Cefixime may be used in acute exacerbations of chronic bronchitis

  • Mild pneumonia: As an outpatient option in selected cases

3. Urinary Tract Infections (UTIs)

  • Both uncomplicated and complicated UTIs

  • Particularly useful in E. coli and Proteus infections

4. Sexually Transmitted Infections

  • Uncomplicated gonorrhea: Single 400 mg dose is effective against N. gonorrhoeae

  • Often co-administered with azithromycin to cover Chlamydia trachomatis

5. Gastrointestinal Infections

  • Typhoid fever (enteric fever): Effective against Salmonella typhi, including multidrug-resistant strains

6. Other Indications

  • Skin and soft tissue infections (limited use)

  • Sinusitis

  • Traveler’s diarrhea due to E. coli

Efficacy and Clinical Studies

Numerous clinical trials have established the efficacy of Cefixime:

  • Pharyngitis/Tonsillitis: Comparable to penicillin in eradicating S. pyogenes

  • Gonorrhea: 96%–98% cure rates in uncomplicated cases

  • Typhoid Fever: Studies show success rates over 90%, particularly in endemic areas

Its oral availability, good tissue penetration, and convenient dosing schedule contribute to strong patient compliance and clinical success.

Adverse Effects

Cefixime is generally well tolerated. However, like all antibiotics, it may cause side effects.

Common Side Effects

  • Diarrhea

  • Nausea

  • Abdominal pain

  • Headache

Less Common Effects

  • Rash or urticaria

  • Vaginal candidiasis

  • Dizziness

Serious (Rare) Effects

  • Hypersensitivity or anaphylaxis

  • Stevens-Johnson syndrome (very rare)

  • Hepatotoxicity

  • Clostridioides difficile-associated diarrhea (CDAD)

As with other cephalosporins, caution is warranted in patients with a history of penicillin allergy due to potential cross-reactivity.

Drug Interactions

  • Probenecid: May decrease renal excretion of Cefixime

  • Warfarin: May increase anticoagulant effect—monitor INR

  • Live vaccines (e.g., typhoid): Antibiotic therapy may affect efficacy

No significant interactions with oral contraceptives or most common medications have been reported.

Resistance Patterns

While Cefixime retains activity against many beta-lactamase-producing strains, resistance is rising in certain areas due to:

  • Overuse and self-medication

  • Plasmid-mediated beta-lactamases

  • Mutations in penicillin-binding proteins (PBPs)

Organisms Showing Resistance

  • ESBL-producing E. coli and Klebsiella

  • N. gonorrhoeae (emerging resistance; CDC recommends dual therapy)

Periodic susceptibility testing and local antibiogram consultation are crucial for effective prescribing.

Special Populations

Pregnancy

  • FDA Pregnancy Category B

  • No known teratogenicity; safe when indicated

Lactation

  • Small amounts secreted in breast milk; generally considered safe

Pediatrics

  • Commonly used; dosing available in suspension and dispersible tablets

Elderly

  • No special dosage changes unless renal impairment is present

Renal Impairment

  • Dose adjustment necessary for creatinine clearance <60 mL/min

Advantages of Cefixime

  • Broad-spectrum activity with oral administration

  • Once-daily dosing option improves compliance

  • Effective in pediatric and adult populations

  • Useful against beta-lactamase-producing organisms

  • Well-tolerated with a good safety record

Limitations

  • Ineffective against anaerobes

  • Limited Gram-positive coverage (e.g., MRSA and Enterococcus)

  • Emerging resistance, especially in gonorrhea and E. coli

  • Not suitable for severe infections requiring IV therapy

Cefixime in Antimicrobial Stewardship

Due to its broad activity and outpatient use, Cefixime should be prescribed judiciously. Key stewardship strategies include:

  • Avoid use in viral infections (e.g., colds)

  • Prescribe only when culture sensitivity or guidelines support it

  • Monitor local resistance patterns

  • Educate patients on completing the full course

Global Usage and Accessibility

Cefixime is listed on the WHO Model List of Essential Medicines, highlighting its importance in treating common infections globally, especially in low- and middle-income countries. Its generic availability ensures affordability and accessibility.

In many countries, it is a first-line treatment for typhoid fever and UTIs. However, concerns remain regarding over-the-counter misuse, which contributes to resistance.

Future Perspectives and Research

Research continues to assess:

  • Cefixime combinations with beta-lactamase inhibitors

  • Pharmacokinetic optimization in special populations

  • Utility in MDR-Typhoid and Salmonella paratyphi

Scientists are also exploring nanoformulations and fixed-dose combinations to enhance bioavailability and reduce dosing frequency.

Conclusion

Cefixime is a versatile, well-tolerated, and clinically effective oral antibiotic with a key role in the outpatient management of respiratory, urinary, gastrointestinal, and sexually transmitted infections. Its oral convenience, relatively broad spectrum, and favorable safety profile have cemented its place in both adult and pediatric care.