Cephalexin Recommendations
Cephalexin is a first-generation oral cephalosporin effective for treating skin and soft tissue infections, streptococcal pharyngitis, and uncomplicated urinary tract infections caused by susceptible organisms, but it is completely inactive against Lyme disease, MRSA, and many respiratory pathogens. 1, 2
Indications
Approved Uses
- Skin and soft tissue infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) and beta-hemolytic streptococci 2, 3
- Streptococcal pharyngitis in patients over 1 year of age 3
- Uncomplicated cystitis in patients over 15 years of age 3
- Otitis media in pediatric patients 3
- Bone infections (osteomyelitis) and respiratory tract infections caused by susceptible organisms 3
When Cephalexin Is NOT Appropriate
- Lyme disease: First-generation cephalosporins are inactive in vitro against Borrelia burgdorferi and ineffective clinically 1
- MRSA infections: Cephalexin has no activity against methicillin-resistant Staphylococcus aureus 2
- Acute bacterial sinusitis: Poor coverage of Haemophilus influenzae and Moraxella catarrhalis makes cephalexin inappropriate 2
- Infective endocarditis prophylaxis: High resistance rates among viridans group streptococci (96% resistance) preclude its use 2
- Purulent cellulitis with MRSA risk factors: Requires MRSA-active agents instead 2, 4
Adult Dosing
Standard Regimens
- Most infections: 500 mg orally every 6 hours (four times daily) 2, 3
- Mild to moderate infections: 250–500 mg every 6 hours 2, 3
- Streptococcal pharyngitis, skin infections, uncomplicated cystitis: 500 mg every 12 hours (twice daily) 3
- Severe infections: If daily doses exceeding 4 grams are required, switch to parenteral cephalosporins (e.g., cefazolin 1 g IV every 8 hours) 2, 3
Infection-Specific Dosing
- Skin and soft tissue infections (MSSA): 500 mg four times daily for 5 days if clinical improvement occurs; extend only if symptoms persist 2, 4
- Mastitis: 500 mg every 6 hours (four times daily) for lactating women 2
- Uncomplicated cystitis: 500 mg every 12 hours for 7–14 days 3
- Streptococcal pharyngitis: 500 mg every 12 hours for at least 10 days to prevent rheumatic fever 2, 3
Pediatric Dosing
Standard Regimens
- Mild to moderate infections: 25–50 mg/kg/day divided into 4 doses (every 6 hours) 2, 3
- MSSA skin and soft tissue infections: 75–100 mg/kg/day divided into 3–4 doses 2
- Otitis media: 75–100 mg/kg/day in 4 divided doses 3
- Streptococcal pharyngitis and skin infections: Total daily dose may be divided every 12 hours in patients over 1 year of age 3
- Severe infections: Dosage may be doubled 3
Weight-Based Dosing Table (from FDA label)
For 125 mg/5 mL suspension (four times daily):
- 10 kg (22 lb): ½–1 teaspoon
- 20 kg (44 lb): 1–2 teaspoons
- 40 kg (88 lb): 2–4 teaspoons
For 250 mg/5 mL suspension (four times daily):
- 10 kg (22 lb): ¼–½ teaspoon
- 20 kg (44 lb): ½–1 teaspoon
- 40 kg (88 lb): 1–2 teaspoons 3
Renal Dose Adjustments
Dosing in Renal Impairment
- Creatinine clearance < 30 mL/min: Reduce dosage proportional to reduced renal function 5
- Creatinine clearance 30–70 mL/min: Standard dosing (500 mg every 6 hours) typically requires no adjustment for most infections 2
- End-stage renal disease on hemodialysis: Therapeutic drug monitoring of serum cephalexin concentrations is recommended; measure levels approximately 2 and 6 hours post-dose to guide adjustments 2
- Elderly patients: Because cephalexin is substantially excreted by the kidney, dose selection should be cautious and renal function monitoring may be useful 3
Contraindications
Absolute Contraindications
- History of anaphylaxis, angioedema, or urticaria to penicillins or cephalosporins: Cross-reactivity risk, particularly with cephalosporins sharing identical R1 side chains (e.g., amoxicillin and cephalexin) 1, 2
Relative Contraindications and Precautions
- Non-severe penicillin allergy (e.g., delayed rash): Cephalexin may be used cautiously, as cross-reactivity is only 2–4% 1, 2
- Patients with confirmed immediate-type amoxicillin allergy: Avoid cephalexin due to identical R1 side chains 2
- Patients requiring MRSA coverage: Cephalexin is ineffective; use clindamycin, trimethoprim-sulfamethoxazole, or doxycycline instead 2, 4
Pregnancy and Lactation
Pregnancy
- Pregnancy Category B: Reproduction studies in mice and rats at doses 0.6–1.5 times the maximum human dose showed no fetal harm 3
- Use during pregnancy: Cephalexin should be used only if clearly needed, as animal studies are not always predictive of human response 3
- Pregnant patients with Lyme disease: Doxycycline should be avoided; use amoxicillin or cefuroxime axetil instead (cephalexin is ineffective for Lyme disease) 1
Lactation
- Excretion in breast milk: Cephalexin levels in milk peak at 4 mcg/mL within 4 hours of a 500 mg dose and disappear by 8 hours 3
- Safety for nursing infants: Cephalexin is considered safe for breastfeeding, with minimal disruption to nursing 2, 3
- Caution advised: Exercise caution when administering cephalexin to nursing women 3
Drug Interactions
Metformin
- Interaction: Cephalexin increases metformin plasma Cmax by 34% and AUC by 24%, while decreasing renal clearance by 14% 3
- Recommendation: Careful patient monitoring and dose adjustment of metformin are recommended when co-administered with cephalexin 3
Probenecid
- Interaction: Probenecid inhibits renal excretion of cephalexin, increasing serum levels 3
- Clinical significance: AUC increases from 68.1 µg·h/mL to 117 µg·h/mL when co-administered 6
Laboratory Test Interference
- False-positive urine glucose: Cephalexin may cause false-positive reactions with Benedict's and Fehling's solutions and Clinitest® tablets 3
Common Pitfalls and Caveats
Avoid These Errors
- Do not use cephalexin for Lyme disease: It is completely ineffective against Borrelia burgdorferi 1
- Do not use cephalexin for purulent cellulitis or MRSA infections: It lacks MRSA activity 2, 4
- Do not use cephalexin for acute sinusitis: Poor H. influenzae coverage makes it inappropriate 2
- Do not extend prophylactic antibiotics beyond 24 hours post-operatively: This increases resistance without improving outcomes 2
- Do not use cephalexin for endocarditis prophylaxis: High resistance rates among target organisms preclude its use 2
Critical Clinical Considerations
- Incision and drainage is primary treatment for abscesses: Antibiotics play only a subsidiary role 2, 4
- Treatment duration for uncomplicated cellulitis is 5 days: Extend only if warmth, tenderness, or erythema persist 2, 4
- Streptococcal pharyngitis requires 10 days of therapy: Shorter courses risk rheumatic fever 2, 3
- Reassess patients within 24–48 hours: Treatment failure rates of 21% have been reported with oral regimens 2, 4
Administration and Storage
Oral Suspension Preparation
- 125 mg/5 mL (100 mL bottle): Add 71 mL water in 2 portions, shaking well after each 3
- 250 mg/5 mL (100 mL bottle): Add 71 mL water in 2 portions, shaking well after each 3
- Storage: Refrigerate after mixing; stable for 14 days without significant potency loss 3
Capsule Administration
- Capsules should only be used in children and adolescents capable of swallowing them 3
- Take exactly as directed: Skipping doses or not completing the full course decreases effectiveness and promotes resistance 3
Pharmacokinetics
Absorption and Distribution
- Absorption: Rapidly and completely absorbed in the upper intestine (not from the stomach) 5
- Peak serum levels: Achieved within 1 hour of oral administration 5, 6
- Protein binding: Low binding to human serum proteins 5
- Tissue penetration: Rapid distribution to most tissues except CSF and aqueous humor; does not penetrate host cells 5
Elimination
- Renal excretion: 70–100% of the dose appears unchanged in urine within 6–8 hours 5
- Urinary concentrations: 500–1000 µg/mL following 250–500 mg oral doses, far exceeding MICs for urinary pathogens 5
- Half-life: Approximately 1 hour in patients with normal renal function 6
Spectrum of Activity
Effective Against
- Gram-positive cocci: Beta-hemolytic streptococci (Streptococcus pyogenes), methicillin-susceptible Staphylococcus aureus 2, 3
- Gram-negative organisms: Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae (non-ESBL) 7