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Cefaclor

Cefaclor: A Second-Generation Cephalosporin Antibiotic

Introduction

Cefaclor, a second-generation cephalosporin antibiotic, represents a key advancement in the beta-lactam class of antimicrobials. It provides broader activity than first-generation agents, particularly against Gram-negative bacteria, while maintaining good Gram-positive coverage. Since its introduction in the late 1970s, Cefaclor has been widely used for treating respiratory tract infections, otitis media, urinary tract infections, and skin infections. With the growing concern over antimicrobial resistance, understanding the pharmacology, mechanisms, and clinical applications of Cefaclor remains crucial for healthcare professionals.

Basic Overview

  • Drug Class: Second-generation cephalosporin

  • Type: β-lactam antibiotic

  • Chemical Formula: C15H14ClN3O4S

  • Molecular Weight: 367.81 g/mol

  • Administration: Oral

  • Common Brand Names: Ceclor®, Raniclor®, Keflor®

Mechanism of Action

Cefaclor exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. It does this by binding to penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. These proteins are crucial for peptidoglycan cross-linking, which provides strength and rigidity to the cell wall.

When PBPs are inhibited:

  • Cell wall synthesis is disrupted

  • Osmotic pressure increases

  • Bacteria undergo lysis and die

Cefaclor, like other beta-lactams, exhibits time-dependent killing, meaning its efficacy relies on maintaining drug concentrations above the minimum inhibitory concentration (MIC) for a sufficient duration.

Spectrum of Activity

Gram-positive Bacteria

  • Streptococcus pneumoniae

  • Streptococcus pyogenes

  • Staphylococcus aureus (non-MRSA strains)

Gram-negative Bacteria

  • Haemophilus influenzae

  • Escherichia coli

  • Klebsiella pneumoniae

  • Proteus mirabilis

  • Moraxella catarrhalis

Not Active Against:

  • MRSA

  • Pseudomonas aeruginosa

  • Enterococci

  • Bacteroides species (limited anaerobic activity)

Compared to first-generation cephalosporins like cephalexin, Cefaclor has improved efficacy against H. influenzae and M. catarrhalis, making it particularly useful in treating respiratory infections.

Pharmacokinetics

Parameter Details
Absorption Rapidly absorbed orally (bioavailability ~90%)
Peak Plasma Level Reached within 30–60 minutes
Protein Binding ~25%
Half-Life 0.6–0.9 hours
Excretion Renally excreted unchanged (~60–85%)
Dosage Forms Capsules, tablets, oral suspension

Food may slightly delay the absorption but does not significantly affect the extent of absorption.

Dosage and Administration

Indication Typical Adult Dose
Respiratory tract infections 250–500 mg every 8 hours
Otitis media or sinusitis 500 mg every 8 hours
Skin and soft tissue infections 250–500 mg every 8 hours
Urinary tract infections 250 mg every 8 hours
Pediatric dosing 20–40 mg/kg/day in divided doses

Dosing adjustments are generally not required in patients with mild to moderate renal impairment, though caution is advised in severe renal dysfunction.

Clinical Uses

1. Acute Otitis Media

Cefaclor is effective against S. pneumoniae, H. influenzae, and M. catarrhalis, the major pathogens in pediatric otitis media.

2. Pharyngitis and Tonsillitis

Primarily caused by Streptococcus pyogenes, which is highly susceptible to Cefaclor.

3. Sinusitis

Offers good penetration into the sinuses and activity against typical causative bacteria.

4. Community-Acquired Pneumonia (CAP)

Useful in mild to moderate CAP where S. pneumoniae or H. influenzae are likely pathogens.

5. Urinary Tract Infections

Particularly in uncomplicated lower UTIs caused by E. coli and Proteus spp.

6. Skin and Soft Tissue Infections

Active against staphylococcal and streptococcal infections, excluding MRSA.

Adverse Effects

Cefaclor is generally well tolerated. Most side effects are mild and self-limiting.

Common Reactions

  • Gastrointestinal: nausea, vomiting, diarrhea

  • Skin: rash, urticaria

  • CNS: headache, dizziness

Rare but Serious Reactions

  • Serum-sickness–like reactions: Especially in children, characterized by rash, arthralgia, and fever.

  • Hypersensitivity: Cross-reactivity in penicillin-allergic individuals (~5–10%)

  • Hematologic: Eosinophilia, transient leukopenia

  • Renal: Rare interstitial nephritis

Contraindications and Cautions

  • Allergy to cephalosporins or penicillins

  • History of serum sickness with cephalosporins

  • Use with caution in patients with:

    • Renal impairment

    • Gastrointestinal disease (e.g., colitis)

    • History of allergic diathesis

Drug Interactions

  • Probenecid: Inhibits renal excretion, increasing Cefaclor levels.

  • Warfarin: Cephalosporins can enhance anticoagulant effect—monitor INR.

  • Oral contraceptives: Potential to reduce efficacy, although this remains controversial.

Resistance Mechanisms

Antibiotic resistance has emerged as a major public health challenge. Cefaclor’s activity can be compromised through several mechanisms:

1. β-lactamase production

Many Gram-negative organisms, especially H. influenzae and E. coli, produce β-lactamases that can hydrolyze Cefaclor.

2. Altered PBPs

Some bacteria modify their PBPs, reducing Cefaclor’s binding efficacy.

3. Efflux pumps and reduced permeability

Particularly in Gram-negative bacilli, these can decrease intracellular concentrations of the drug.

Cefaclor is not resistant to extended-spectrum beta-lactamases (ESBLs), and it is ineffective against organisms producing these enzymes.

Comparison with Other Cephalosporins

Drug Generation Route Spectrum Indications
Cephalexin 1st Oral Gram-positive mainly Skin infections, pharyngitis
Cefaclor 2nd Oral Extended Gram-negative RTIs, AOM, UTI
Cefuroxime axetil 2nd Oral Stronger Gram-negative, some anaerobes RTIs, Lyme disease, sinusitis
Cefixime 3rd Oral Strong Gram-negative UTIs, gonorrhea, respiratory infections

Advantages of Cefaclor

  • Broad spectrum for outpatient respiratory infections

  • Effective oral bioavailability

  • Pediatric-friendly formulations (suspensions)

  • Relatively low cost

  • Mild side effect profile

Limitations

  • Not effective against MRSA or Pseudomonas

  • Not stable against many β-lactamases

  • Resistance is increasing in E. coli and H. influenzae

  • Requires multiple daily dosing (three times daily)

Role in Antimicrobial Stewardship

Cefaclor should be used judiciously to limit the development of resistance. Its role in outpatient therapy is valuable when used appropriately, especially when pathogen susceptibility is known or highly likely.

Key stewardship strategies include:

  • Avoid use in confirmed ESBL infections

  • Prefer narrow-spectrum agents (e.g., penicillin) when effective

  • Confirm diagnosis before starting therapy

  • De-escalate based on culture results

Formulations and Storage

Cefaclor is available in multiple oral dosage forms:

  • 250 mg and 500 mg capsules

  • 500 mg extended-release tablets

  • Oral suspension (125 mg/5 mL, 250 mg/5 mL)

The oral suspension should be refrigerated and discarded after 14 days of reconstitution.

Cefaclor in Special Populations

  • Pediatrics: Commonly used and generally safe

  • Pregnancy: Category B – no proven harm in humans

  • Breastfeeding: Low concentrations in breast milk; generally considered safe

  • Elderly: Use with caution in renal impairment; monitor renal function

Conclusion

Cefaclor continues to be an important option in the treatment of common bacterial infections, particularly in outpatient settings. Its excellent oral bioavailability, favorable safety profile, and broad-spectrum coverage make it a versatile choice. However, its utility is challenged by rising antimicrobial resistance, emphasizing the need for targeted use.