What are the uses of cephalexin?

How Cephalexin Can Be Used

Primary Clinical Indications

Cephalexin is a first-line oral antibiotic for skin and soft tissue infections (particularly cellulitis without purulence), urinary tract infections, and serves as an alternative to penicillin for streptococcal pharyngitis and endocarditis prophylaxis in penicillin-allergic patients without severe hypersensitivity reactions. 1, 2, 3

Skin and Soft Tissue Infections

• Cephalexin is recommended as first-choice therapy for mild skin and soft tissue infections where methicillin-sensitive Staphylococcus aureus (MSSA) and streptococci are the predominant pathogens 1, 2
• The WHO upgraded cephalexin from second-choice to first-choice status for these infections in 2021 1
• Standard adult dosing is 500 mg four times daily (every 6 hours) for MSSA infections 4
• Pediatric dosing is 75-100 mg/kg/day divided into 3-4 doses for MSSA infections 1, 4

Urinary Tract Infections

• Cephalexin achieves urinary concentrations of 500-1000 mcg/mL following 250-500 mg oral doses, far exceeding the minimum inhibitory concentration for common uropathogens 5, 6
• For febrile UTIs in infants and children (2-24 months), cephalexin is an appropriate oral option at 50-100 mg/kg per day in 4 doses for a total duration of 7-14 days 1
• Recent evidence suggests twice daily dosing (500 mg BID) may be as effective as four times daily dosing for UTIs, potentially improving adherence 7
• Do not use cephalexin for catheter-associated asymptomatic bacteriuria, as treatment promotes antimicrobial resistance 2

Respiratory Tract Infections

• FDA-approved for respiratory infections caused by Streptococcus pneumoniae and Streptococcus pyogenes 3
• Critical limitation: Cephalexin has poor activity against Haemophilus influenzae, with 50% failure rates in H. influenzae otitis media 8, 9
• Should not be used for acute bacterial sinusitis due to inadequate H. influenzae coverage 4
• Effective for streptococcal pharyngitis as an alternative to penicillin in non-severely allergic patients 10, 8

Endocarditis Prophylaxis

• The American Heart Association recommends cephalexin 2g orally as an alternative to amoxicillin for dental procedures in penicillin-allergic patients without history of anaphylaxis, angioedema, or urticaria 2, 10
• However, high resistance rates (96%) among viridans group streptococci to cephalexin limit its reliability for this indication 4

Other FDA-Approved Indications

• Otitis media due to S. pneumoniae, H. influenzae, S. aureus, S. pyogenes, and Moraxella catarrhalis (though H. influenzae coverage is problematic) 3
• Bone infections caused by S. aureus and Proteus mirabilis 3
• Genitourinary tract infections including acute prostatitis caused by E. coli, P. mirabilis, and Klebsiella pneumoniae 3

Critical Situations to Avoid Cephalexin

Absolute Contraindications

• MRSA infections: Cephalexin has zero activity against methicillin-resistant S. aureus 2
• Animal bite wounds: Poor activity against Pasteurella multocida makes it inappropriate 2
• Patients with history of anaphylaxis, angioedema, or urticaria to penicillins: Risk of cross-reactivity is significant 2, 10, 4

Clinical Scenarios Where Cephalexin is Inadequate

• Pseudomonas aeruginosa infections: Completely ineffective 4
• Beta-lactamase-producing Moraxella catarrhalis: Inadequate activity 4
• Severe infections requiring broad gram-negative coverage: Use ceftriaxone or cefotaxime instead 10
• Meningitis: Cephalexin produces little to no cerebrospinal fluid levels 9

Dosing Algorithms

Adults with Normal Renal Function

• Standard dose: 500 mg every 6 hours (four times daily) for most infections 4
• Mild to moderate infections: 250-500 mg every 6 hours 4
• Duration: 7-10 days depending on clinical response 4

Pediatric Patients

• MSSA infections: 75-100 mg/kg/day divided into 3-4 doses 1, 4
• Mild to moderate infections: 25-50 mg/kg/day in 4 divided doses 4
• Children may require higher doses per kilogram than adults due to greater body water turnover 5

Renal Impairment

• Patients with creatinine clearance <30 mL/min require dose reduction proportional to reduced renal function 5
• 70-100% of the dose is excreted unchanged in urine within 6-8 hours 5

Pharmacological Advantages

• Completely and rapidly absorbed in the upper intestine, not from the stomach 5
• Does not disturb lower bowel flora because absorption occurs high in the intestinal tract 5
• Low protein binding and no metabolism during circulation 5
• Does not penetrate host tissue cells, likely accounting for low incidence of side effects 5
• Minimal adverse effects: Mostly gastrointestinal upset, rash, and urticaria, rarely requiring discontinuation 8

Antimicrobial Stewardship Considerations

• For non-severe infections caused by third-generation cephalosporin-resistant Enterobacterales (3GCephRE), cephalexin may be considered as step-down therapy following initial carbapenem treatment once patients are stabilized 1
• Avoid using new beta-lactam/beta-lactamase inhibitors for infections treatable with cephalexin to preserve these agents for extensively resistant bacteria 1
• Culture and susceptibility testing should be initiated prior to and during therapy, with local resistance patterns guiding empiric selection 3