Is cephalexin in the same drug class as cefazolin, and should a 6‑year‑old girl with a urinary tract infection on oral cephalexin be switched to cefazolin?

Is Cephalexin in the Same Category as Cefazolin?

Yes, cephalexin and cefazolin are both first-generation cephalosporins in the same drug class, but they differ critically in route of administration—cephalexin is oral while cefazolin is parenteral—and switching from oral cephalexin to IV cefazolin for a 6-year-old with uncomplicated UTI is unnecessary and represents overtreatment. 1, 2, 3

Drug Classification and Structural Relationship

Both agents belong to the first-generation cephalosporin class and share the core cephalosporin bicyclic ring structure, which differs from penicillins in the structure of this ring system. 2, 3 However, cefazolin has a unique R1 side chain that results in very low cross-reactivity with penicillins despite being a first-generation cephalosporin, with reaction rates of only 0.7% (95% CrI: 0.1%-1.7%) among patients with unverified penicillin allergy. 1

In contrast, cephalexin shares identical R1 side chains with amoxicillin and other aminopenicillins, placing it in the aminocephalosporin category with a much higher cross-reactivity risk of 16.45% (95% CI: 11.07-23.75) in patients with proven penicillin allergy. 1, 4

Antimicrobial Spectrum and Clinical Use

Both agents provide excellent coverage against:

• Beta-hemolytic streptococci (especially Streptococcus pyogenes)
• Methicillin-susceptible Staphylococcus aureus (MSSA)
• Common gram-negative uropathogens including E. coli 1, 5, 6

For uncomplicated UTI in a 6-year-old, oral cephalexin 50-100 mg/kg/day divided into 3-4 doses for 7-14 days is the appropriate first-line therapy. 1 Cephalexin achieves high urinary concentrations routinely exceeding 1000 mg/L and retains full activity against common uropathogens. 6, 7

When Switching from Cephalexin to Cefazolin Is NOT Indicated

Do not switch to parenteral cefazolin for uncomplicated UTI unless:

• The child is "toxic" appearing with systemic signs
• The child cannot retain oral intake or medications
• There is concern for pyelonephritis with urosepsis requiring bloodstream antimicrobial concentrations 1

Cephalexin is specifically recommended for febrile UTI in children 2-24 months when oral therapy is appropriate, with the caveat that agents excreted only in urine (like nitrofurantoin) should be avoided because parenchymal concentrations may be insufficient for pyelonephritis. 1 Cephalexin does not fall into this category—it achieves adequate serum levels in addition to high urinary concentrations. 6

Critical Allergy Considerations

If the patient has a documented penicillin allergy:

• Avoid cephalexin if there is history of anaphylaxis, angioedema, or urticaria to amoxicillin/ampicillin due to shared R1 side chains 1, 4
• Cefazolin remains safe in most penicillin-allergic patients due to its unique side chain, with only 0.8% (95% CI: 0.13%-4.1%) reaction rate among confirmed penicillin-allergic patients 1
• Cephalosporins should never be used in patients with history of severe immediate hypersensitivity reactions to any beta-lactam 1

Practical Algorithm for This Clinical Scenario

For a 6-year-old with uncomplicated UTI currently on oral cephalexin:

1. Continue cephalexin if the child is tolerating oral intake, afebrile or improving, and has no systemic toxicity 1
2. Switch to parenteral cefazolin only if:
   • Child develops inability to retain oral medications
   • Clinical deterioration with systemic inflammatory response
   • Concern for bacteremia or urosepsis requiring IV therapy 1
3. Total treatment duration remains 7-14 days regardless of route 1

Common Pitfall to Avoid

Do not reflexively switch to IV antibiotics based solely on the diagnosis of UTI. The 2011 AAP guideline specifically states that most children with febrile UTI can be treated orally, and only 1% of 309 febrile infants in their referenced study were too ill for oral therapy. 1 Switching from effective oral cephalexin to IV cefazolin without clinical indication increases cost, requires vascular access, and provides no additional benefit for uncomplicated infection.