Introduction
Cephalexin is a first-generation cephalosporin antibiotic that has been widely used in clinical practice since its introduction in the 1970s. As a beta-lactam antibiotic, it belongs to the same class as penicillins but offers a broader spectrum of activity against gram-positive bacteria while maintaining some gram-negative coverage. Cephalexin remains a cornerstone of outpatient antimicrobial therapy due to its favorable safety profile, oral bioavailability, and effectiveness against common community-acquired pathogens.
Mechanism of Action
Cephalexin exerts its bactericidal effects by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall, which disrupts the final transpeptidation step of peptidoglycan synthesis. This action causes defective cell wall formation and ultimately leads to osmotic instability and bacterial cell lysis. As a beta-lactam antibiotic, cephalexin is particularly effective against actively dividing bacteria.
Indications
Cephalexin is FDA-approved for the treatment of:
- Respiratory tract infections caused by Streptococcus pneumoniae and group A beta-hemolytic streptococci
- Skin and skin structure infections caused by Staphylococcus aureus and/or Streptococcus pyogenes
- Bone infections caused by S. aureus and/or Proteus mirabilis
- Genitourinary tract infections, including acute prostatitis, caused by Escherichia coli, P. mirabilis, and Klebsiella species
- Otitis media caused by S. pneumoniae, Haemophilus influenzae, S. aureus, and Streptococcus pyogenes
Dosage and Administration
Standard adult dosing: 250-500 mg every 6 hours or 500 mg every 12 hours (depending on infection severity) Pediatric dosing: 25-100 mg/kg/day divided into 2-4 doses Renal impairment adjustments:- CrCl 10-50 mL/min: 250-500 mg every 8-12 hours
- CrCl <10 mL/min: 250-500 mg every 12-24 hours
- Hemodialysis: 250-500 mg after each session
Pharmacokinetics
Absorption: Well-absorbed from the gastrointestinal tract (90% bioavailability), with peak serum concentrations occurring within 1 hour of administration Distribution: Widely distributed to most tissues and body fluids, including bone, but achieves poor concentrations in cerebrospinal fluid. Protein binding is approximately 10-15% Metabolism: Primarily excreted unchanged in urine; minimal hepatic metabolism Elimination: Renal excretion is the primary route of elimination, with 80-100% excreted unchanged in urine within 8 hours. Elimination half-life is approximately 0.5-1.2 hours in patients with normal renal functionContraindications
- Known hypersensitivity to cephalexin or any cephalosporin antibiotic
- Patients with a history of severe hypersensitivity reactions (anaphylaxis) to penicillins or other beta-lactam antibiotics due to potential cross-reactivity
Warnings and Precautions
- Clostridium difficile-associated diarrhea: May range from mild diarrhea to fatal colitis
- Cross-sensitivity: Approximately 5-10% of penicillin-allergic patients may experience cross-reactivity
- Renal impairment: Dosage adjustment required in patients with significant renal dysfunction
- Superinfection: Prolonged use may result in fungal or bacterial superinfection
- Positive direct Coombs test: May occur during therapy
- False-positive urinary glucose tests: May occur with Benedict's solution, Fehling's solution, or Clinitest tablets
Drug Interactions
- Probenecid: Decreases renal tubular secretion of cephalexin, increasing serum concentrations
- Metformin: Cephalexin may increase metformin concentrations by reducing renal excretion
- Oral contraceptives: May reduce efficacy of estrogen-containing contraceptives
- Warfarin: May potentiate anticoagulant effects and increase INR
- BCG vaccine: Antibiotics may reduce vaccine efficacy
Adverse Effects
Common (≥1%):- Diarrhea (may indicate pseudomembranous colitis)
- Nausea/vomiting
- Abdominal pain
- Dyspepsia
- Fatigue
- Headache
- Dizziness
- Vaginal candidiasis or vaginitis
- Anaphylaxis
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Hemolytic anemia
- Acute interstitial nephritis
- Seizures (in renal impairment)
- Hepatitis
- Blood dyscrasias (neutropenia, thrombocytopenia)
Monitoring Parameters
- Clinical response to therapy (fever, symptoms improvement)
- Signs of superinfection (oral thrush, vaginal discharge, diarrhea)
- Renal function (serum creatinine, BUN) at baseline and during prolonged therapy
- Complete blood count with prolonged therapy
- Bowel patterns for development of C. difficile-associated diarrhea
- Signs of hypersensitivity reactions
Patient Education
- Complete the entire prescribed course even if symptoms improve
- Take with food to minimize stomach upset
- Report any signs of allergic reaction (rash, itching, swelling)
- Contact healthcare provider immediately if severe diarrhea or abdominal pain develops
- Shake oral suspension well before each dose
- Store suspension at room temperature and discard after 14 days
- Use alternative contraception methods if taking oral contraceptives
- Inform all healthcare providers of cephalexin use, especially before surgical procedures
References
1. Lexicomp Online®. Cephalexin: Drug Information. Wolters Kluwer Clinical Drug Information, Inc.; 2023. 2. Gilbert DN, Chambers HF, Eliopoulos GM, et al. The Sanford Guide to Antimicrobial Therapy. 53rd ed. Antimicrobial Therapy, Inc.; 2023. 3. Cephalexin [package insert]. Rockford, IL: Mylan Pharmaceuticals Inc.; 2022. 4. Powell MF, Nguyen MV. Cephalexin. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2023. 5. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 33rd ed. CLSI supplement M100. Wayne, PA: CLSI; 2023. 6. FDA Approved Drug Products: Keflex (cephalexin) capsules. Accessed October 2023. 7. Pichichero ME. A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics. 2005;115(4):1048-1057.