Keflex (Cephalexin): A Comprehensive Review

Keflex, the brand name for cephalexin, is a widely used antibiotic belonging to the cephalosporin class of medications. It is commonly prescribed to treat a variety of bacterial infections, ranging from respiratory tract infections to skin infections. Understanding Keflex’s pharmacology, mechanism of action, clinical uses, side effects, and precautions is essential for healthcare professionals and patients alike. This article provides an in-depth exploration of Keflex, aiming to serve as a comprehensive educational resource.

1. Introduction to Keflex

Cephalexin, marketed as Keflex, is an oral cephalosporin antibiotic first introduced in the 1960s. It remains one of the most prescribed antibiotics globally due to its broad-spectrum activity against gram-positive and some gram-negative bacteria. Cephalexin is a first-generation cephalosporin, primarily effective against streptococci, staphylococci, and some strains of Escherichia coli, among others. The drug is available in various forms including capsules, tablets, and oral suspensions, enabling flexible dosing for different patient populations, including children.

Its popularity stems from effectiveness, safety profile, and ease of administration. However, as with any antibiotic, appropriate use is critical to avoid resistance development and adverse effects. This guide will systematically cover its mechanism, clinical indications, dosage regimens, pharmacokinetics, side effect profile, interactions, contraindications, and monitoring essentials.

2. Chemical and Pharmacological Profile

2.1 Chemical Structure and Classification

Cephalexin is classified as a beta-lactam antibiotic within the cephalosporin family. Structurally, it contains a beta-lactam ring that is vital for its bactericidal activity. This ring enables cephalexin to interfere with bacterial cell wall synthesis, leading to cell death. Its molecular formula is C₁₆H₁₇N₃O₄S, and it is chemically defined as (6R,7R)-7-{[(R)-2-amino-2-phenylacetyl]amino}-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.

Being a first-generation cephalosporin, cephalexin displays high activity against gram-positive organisms, particularly Staphylococcus aureus and Streptococcus pyogenes. However, its activity against gram-negative organisms is generally lower than more advanced generations.

2.2 Mechanism of Action

Keflex exerts its antibacterial effects by inhibiting bacterial cell wall synthesis. It achieves this by binding to penicillin-binding proteins (PBPs), enzymes involved in the final stage of peptidoglycan cross-linking. This binding inhibits their activity, leading to defective cell wall formation, cell lysis, and ultimately bacterial death—an example of a bactericidal mechanism. Cephalexin’s beta-lactam ring is essential for this binding; bacterial enzymes called beta-lactamases can hydrolyze this ring, resulting in resistance. However, some bacteria produce beta-lactamases insensitive to cephalexin, reducing its effectiveness in such cases.

2.3 Spectrum of Activity

Cephalexin demonstrates excellent efficacy against many gram-positive cocci and a limited range of gram-negative bacteria.
Gram-positive organisms: Highly effective against Streptococcus species and methicillin-sensitive Staphylococcus aureus (MSSA). It is not effective against methicillin-resistant Staphylococcus aureus (MRSA).
Gram-negative organisms: Moderate activity against Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae.
Other bacteria such as Pseudomonas spp., Enterobacter, and anaerobes are generally resistant to cephalexin.

3. Clinical Applications of Keflex

3.1 Approved Indications

Keflex is approved for the treatment of various bacterial infections susceptible to cephalexin. Some key clinical indications include:

• Respiratory tract infections: Including pharyngitis, tonsillitis, and bronchitis caused by susceptible organisms.
• Skin and soft tissue infections: Such as cellulitis, impetigo, and wound infections.
• Urinary tract infections (UTIs): Upper and lower UTI caused by sensitive bacterial strains.
• Bone infections: Osteomyelitis caused by susceptible bacteria, in some cases as adjunctive therapy.
• Otitis media: Middle ear infections in children.

These indications highlight Keflex’s role as a versatile oral antibiotic for community-acquired infections.

3.2 Off-label and Special Uses

In certain cases, Keflex may be used off-label:

• Prophylaxis of surgical infections: To reduce postoperative infection risk in susceptible patients.
• Dental infections: For odontogenic infections caused by streptococci and staphylococci.
• Lyme disease: While doxycycline is preferred, cephalexin has occasional use in early treatment.

Although cephalexin is effective against many organisms, treatment decisions should be tailored based on culture sensitivities and clinical severity.

4. Pharmacokinetics of Keflex

4.1 Absorption

Cephalexin exhibits high oral bioavailability, approximately 90%, making oral administration effective without the need for intravenous routes in most uncomplicated infections. Peak plasma concentrations occur within 1 hour after ingestion. Food intake slows absorption but does not significantly reduce the overall extent of absorption, allowing Keflex to be taken with or without food.

4.2 Distribution

After absorption, cephalexin is widely distributed in body tissues and fluids, including skin, soft tissues, bone, and urine. It penetrates well into the respiratory tract, making it suitable for respiratory infections. However, it has poor penetration into cerebrospinal fluid and is thus not effective for central nervous system infections.

4.3 Metabolism and Excretion

Cephalexin undergoes minimal metabolism and is primarily excreted unchanged by the kidneys through glomerular filtration and tubular secretion. The elimination half-life is approximately 0.5 to 1.2 hours in individuals with normal renal function. Renal impairment necessitates dose adjustments to prevent accumulation and toxicity.

4.4 Dose Adjustments in Special Populations

In patients with renal impairment, dosing frequency of cephalexin should be reduced based on creatinine clearance levels. Children require weight-based dosing, adjusted according to the severity and type of infection. Elderly patients may also require monitoring due to potential renal function decline.

5. Dosage and Administration

5.1 Adult Dosage

The typical adult dose of Keflex varies depending on the infection severity and site. Common dosage regimens include:

• 250 mg to 500 mg every 6 hours (up to 4 grams daily) for most infections.
• Higher doses may be used in severe infections such as osteomyelitis.

Treatment duration usually spans 7 to 14 days but may be extended based on clinical response.

5.2 Pediatric Dosage

In pediatric patients, cephalexin dosing is weight-based:

• 25 to 50 mg/kg/day divided every 6 to 12 hours for mild to moderate infections.
• Higher doses (up to 100 mg/kg/day) may be required for severe infections.

Pediatric suspensions allow precise dosing in this population. Adherence to regimen is essential to ensure treatment success.

5.3 Administration Considerations

Keflex can be administered with or without food, though taking with food may help reduce gastrointestinal discomfort. Patients should be counseled on completing the full course to prevent bacterial resistance, even if symptoms improve early. Missed doses should be taken as soon as possible but not doubled to compensate.

6. Adverse Effects and Safety Profile

6.1 Common Side Effects

Keflex is generally well tolerated. Common adverse effects include:

• Gastrointestinal disturbances such as nausea, vomiting, diarrhea, and abdominal pain.
• Hypersensitivity reactions, including rash, urticaria, and pruritus.
• Occasional headache or dizziness.

These effects are usually mild and tend to resolve upon discontinuation.

6.2 Serious and Rare Adverse Reactions

Though rare, Keflex can cause serious adverse reactions:

• Allergic reactions: Anaphylaxis, Stevens-Johnson syndrome, or toxic epidermal necrolysis in susceptible individuals.
• Clostridioides difficile-associated diarrhea: Antibiotic-associated colitis presenting as severe diarrhea.
• Neutropenia or thrombocytopenia: Hematologic changes requiring monitoring in prolonged therapy.
• Renal toxicity: Particularly in patients with preexisting kidney disease if overdosed.

Healthcare providers should monitor for signs of these conditions, especially in high-risk groups.

6.3 Allergic Cross-Reactivity

Due to the beta-lactam structure, cross-reactivity with penicillin allergies is a concern. Studies suggest that cross-allergy rates between penicillins and cephalosporins like Keflex are relatively low (<10%), but caution is advised. Patients with a history of severe penicillin allergy should be evaluated carefully before cephalexin administration.

7. Drug Interactions

Cephalexin exhibits minimal clinically significant drug interactions compared to other antibiotics. However, certain interactions are noteworthy:

• Probenecid: Can decrease renal excretion of cephalexin, increasing plasma levels and half-life.
• Oral contraceptives: Antibiotic therapy may reduce efficacy; patients should consider alternative contraceptive measures.
• Metformin: Caution advised, as cephalexin is renally cleared and may affect metformin elimination.

No significant interactions have been reported with common medications such as anticoagulants or antacids.

8. Contraindications and Precautions

Keflex is contraindicated in patients with known hypersensitivity to cephalexin or other cephalosporins. Caution is necessary in patients with penicillin allergy, renal impairment, or a history of gastrointestinal disease, especially colitis. Special attention is required when prescribing to neonates and the elderly due to altered pharmacokinetics and susceptibility to adverse effects.

9. Monitoring and Patient Counseling

Routine laboratory monitoring is generally not necessary for short courses of Keflex. However, patients on prolonged therapy or with comorbidities should have renal function and complete blood counts monitored. Patients should be educated about the importance of adherence, recognizing allergic symptoms, and reporting severe diarrhea to healthcare providers immediately.

10. Resistance and Stewardship

Misuse and overuse of antibiotics like Keflex have contributed to the emergence of resistant bacterial strains. Extended-spectrum beta-lactamases (ESBLs) and methicillin-resistant organisms limit cephalexin’s effectiveness. Antimicrobial stewardship programs advocate for culture-guided therapy, appropriate dosing, and limiting unnecessary prescriptions to preserve Keflex’s clinical utility.

11. Summary and Conclusion

Keflex (cephalexin) is a cornerstone oral antibiotic in the cephalosporin class with a broad spectrum against gram-positive and some gram-negative bacteria. Its mechanism of action involves inhibition of bacterial cell wall synthesis through targeting penicillin-binding proteins. Clinically, Keflex is effective for respiratory, skin and soft tissue, urinary tract, and bone infections. It has favorable pharmacokinetic properties with high oral bioavailability and renal elimination, making dosing straightforward. While generally safe and well tolerated, clinicians should be vigilant about allergic reactions and antibiotic resistance. Proper patient education and antimicrobial stewardship are vital to maintaining Keflex’s effectiveness for current and future patients.

References

• Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 9th Edition, Elsevier, 2020.
• Sweetman, S.C. Martindale: The Complete Drug Reference, 39th Edition, Pharmaceutical Press, 2017.
• Brunton, L., et al. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 13th Edition, McGraw-Hill, 2018.
• Lexicomp Online, Cephalexin Monograph, Accessed June 2024.
• Centers for Disease Control and Prevention (CDC). Antibiotic Resistance Threats in the United States, 2019.
• Katzung BG. Basic and Clinical Pharmacology, 15th Edition, McGraw-Hill, 2021.