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Cefadroxil

Cefadroxil: A First-Generation Cephalosporin Antibiotic

Introduction

Cefadroxil is a widely used first-generation cephalosporin antibiotic, known for its broad-spectrum antibacterial activity, favorable pharmacokinetic properties, and excellent oral bioavailability. It serves as a potent alternative to penicillin in patients with minor allergic sensitivities and is particularly valuable for managing infections of the skin, throat, and urinary tract. Approved by the FDA in the early 1980s, Cefadroxil remains a mainstay in outpatient antimicrobial therapy. It bridges the gap between efficacy and convenience, making it a go-to option in primary care and pediatrics.

Basic Overview

  • Class: First-generation cephalosporin

  • Chemical Formula: C16H17N3O5S

  • Molecular Weight: 363.39 g/mol

  • Route of Administration: Oral

  • Common Brand Names: Duricef®, Ultracef®, Biodroxil®

Mechanism of Action

Cefadroxil acts by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs)—enzymes involved in the final stages of assembling the bacterial cell wall. Disruption of this process leads to:

  • Compromised cell wall integrity

  • Osmotic imbalance

  • Cell lysis and death (bactericidal effect)

Cefadroxil’s mechanism is similar to that of penicillin, but with enhanced resistance to some beta-lactamases and greater stability in acidic environments, which improves its oral absorption.

Antibacterial Spectrum

Effective Against:

Gram-positive bacteria:

  • Staphylococcus aureus (methicillin-sensitive)

  • Streptococcus pyogenes

  • Streptococcus pneumoniae

Gram-negative bacteria:

  • Escherichia coli

  • Klebsiella pneumoniae

  • Proteus mirabilis

Ineffective Against:

  • MRSA (methicillin-resistant Staphylococcus aureus)

  • Pseudomonas aeruginosa

  • Anaerobes

  • ESBL-producing organisms

Cefadroxil is best suited for uncomplicated infections caused by common community-acquired pathogens.

Pharmacokinetics

Parameter Detail
Absorption Well absorbed orally (~90–95%)
Time to Peak Plasma 1.5–2 hours after oral dose
Half-life 1.2–2 hours
Protein Binding ~20%
Excretion Renal (unchanged in urine)
Tissue Distribution Skin, tonsils, urine, soft tissues

Cefadroxil’s long half-life allows once or twice daily dosing, a significant advantage for improving patient adherence, especially in pediatric and elderly populations.

Formulations

Cefadroxil is available in the following oral dosage forms:

  • Capsules: 500 mg

  • Tablets: 1 g

  • Oral Suspension: 250 mg/5 mL, 500 mg/5 mL

The suspension must be refrigerated after reconstitution and used within 14 days.

Clinical Indications

1. Pharyngitis and Tonsillitis

Cefadroxil is an excellent alternative to penicillin for treating Group A streptococcal infections, especially in patients with non-anaphylactic penicillin allergies. A single daily dose is typically effective.

2. Skin and Soft Tissue Infections (SSTIs)

Effective against Staphylococcus aureus and Streptococcus pyogenes, Cefadroxil is widely used to treat:

  • Impetigo

  • Cellulitis

  • Erysipelas

  • Infected wounds

3. Urinary Tract Infections (UTIs)

Although resistance is rising, Cefadroxil remains useful for uncomplicated UTIs, particularly cystitis in women, due to its high urinary concentrations.

4. Bone Infections

Cefadroxil has been used off-label in osteomyelitis cases, particularly when long-term oral therapy is needed, and the causative organism is sensitive.

5. Dental Infections

Prophylaxis in dental procedures, especially for patients at risk of infective endocarditis, is another application where Cefadroxil has proven useful.

Dosage Recommendations

Condition Adults Children
Pharyngitis/Tonsillitis 1 g/day (single or divided dose) 30 mg/kg/day (divided once or twice daily)
Skin infections 500 mg–1 g every 12–24 hours 30 mg/kg/day
UTIs 1 g/day in single or divided dose 30–50 mg/kg/day

Patients with renal impairment require dose adjustments based on creatinine clearance.

Adverse Effects

Cefadroxil is generally well tolerated. The most common adverse effects include:

Gastrointestinal

  • Diarrhea

  • Nausea

  • Abdominal discomfort

Dermatologic

  • Rash

  • Urticaria

Allergic

  • Cross-reactivity with penicillin (~10%)

  • Anaphylaxis (rare)

Others

  • Eosinophilia

  • Vaginal candidiasis

  • Positive Coombs test (without hemolysis)

As with other antibiotics, Clostridioides difficile-associated diarrhea is a rare but serious complication.

Contraindications and Precautions

  • Known allergy to cephalosporins

  • Use cautiously in patients with penicillin allergy

  • Renal impairment: reduce dosage

  • Monitor for signs of superinfection with prolonged use

Drug Interactions

Cefadroxil has a low potential for drug interactions, making it a safer option in polypharmacy. However:

  • Probenecid: Increases serum concentration by reducing renal clearance.

  • Antacids: May delay absorption slightly, though not clinically significant.

  • Oral contraceptives: Theoretical interaction; additional contraception is advised during antibiotic use.

Resistance Patterns

The emergence of antibiotic-resistant bacteria is a global concern. Cefadroxil resistance is primarily due to:

1. Beta-lactamase Production

Some E. coli and Klebsiella strains can hydrolyze Cefadroxil, rendering it ineffective.

2. Altered Penicillin-Binding Proteins

Especially in Streptococcus pneumoniae and other Gram-positives, these changes reduce binding affinity.

3. Efflux Pumps and Permeability Barriers

In Gram-negative bacilli, efflux mechanisms reduce intracellular drug concentration.

Current data indicate rising resistance in UTIs caused by E. coli, leading clinicians to prefer nitrofurantoin or fosfomycin in some areas.

Comparison with Other First-Generation Cephalosporins

Feature Cefadroxil Cephalexin Cefazolin
Route Oral Oral Parenteral (IV/IM)
Half-life 1.5 hours 0.5–1 hour 1.8 hours
Dosing Q12–24H Q6–12H Q8H
Use SSTIs, UTIs, pharyngitis SSTIs, bone infections Surgical prophylaxis

Cefadroxil is often preferred over cephalexin when less frequent dosing is desired.

Advantages of Cefadroxil

  • Once-daily dosing improves adherence

  • Good safety profile

  • Well-tolerated in children

  • Cost-effective

  • Proven efficacy in common infections

Limitations

  • Limited Gram-negative coverage

  • Not effective against MRSA or resistant Enterobacteriaceae

  • Potential for resistance with overuse

  • No activity against anaerobes or atypical pathogens

Cefadroxil and Antimicrobial Stewardship

Prescribers must use Cefadroxil judiciously to prevent unnecessary resistance. It should not be used for viral infections or when a narrower spectrum agent (like penicillin) would suffice.

Best practices include:

  • Targeting use to confirmed/suspected susceptible pathogens

  • Avoiding for empiric therapy in areas with high resistance

  • Using proper duration and dose

  • Educating patients on adherence

Use in Special Populations

Pediatrics

  • Commonly used and well tolerated

  • Palatable oral suspension aids compliance

Pregnancy

  • Category B: No evidence of fetal harm

  • Safe alternative when penicillin is contraindicated

Lactation

  • Minimal excretion in breast milk

  • Generally considered safe

Elderly

  • Adjust dose in renal impairment

  • Monitor for side effects due to polypharmacy

Future of Cefadroxil

With increasing antibiotic resistance, Cefadroxil’s role is evolving. It remains a cornerstone for uncomplicated outpatient infections, especially where local resistance data supports its use. Continued surveillance, diagnostic stewardship, and appropriate use will determine its long-term utility.

Conclusion

Cefadroxil is a reliable, effective, and convenient first-generation cephalosporin. Its role in treating common bacterial infections—especially skin, throat, and urinary tract infections—makes it invaluable in both pediatric and adult medicine. Its once-daily dosing, affordability, and safety profile give it a unique advantage, particularly in settings where adherence is a concern.