Which organisms are reliably covered by cephalexin, particularly for an uncomplicated cystitis presentation?

Organisms Targeted by Cephalexin

Cephalexin reliably covers common gram-positive cocci and select gram-negative bacilli, making it particularly effective for Staphylococcus aureus (including penicillinase-producing strains), Streptococcus species, Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae—the primary pathogens in uncomplicated urinary tract infections. 1

FDA-Approved Spectrum of Activity

Gram-Positive Organisms:

• Staphylococcus aureus (including penicillinase-producing strains but not methicillin-resistant strains) 1
• Streptococcus pneumoniae (penicillin-susceptible strains only) 1
• Streptococcus pyogenes (Group A Streptococcus) 1

Gram-Negative Organisms:

• Escherichia coli 1
• Proteus mirabilis 1
• Klebsiella pneumoniae 1
• Haemophilus influenzae 1
• Moraxella catarrhalis 1

Critical Coverage Gaps

Cephalexin does NOT cover:

• Methicillin-resistant Staphylococcus aureus (MRSA) 1
• Most Enterococcus species (including Enterococcus faecalis) 1
• Most Enterobacter species 1
• Morganella morganii 1
• Proteus vulgaris 1
• Pseudomonas aeruginosa 1
• Acinetobacter calcoaceticus 1
• Penicillin-resistant Streptococcus pneumoniae (usually cross-resistant to all β-lactams) 1

Clinical Context for Uncomplicated Cystitis

For uncomplicated urinary tract infections, cephalexin targets the most common uropathogens:

• E. coli causes 75–95% of uncomplicated cystitis cases and remains susceptible to cephalexin in most regions 2
• Proteus mirabilis and Klebsiella pneumoniae account for most remaining cases and are reliably covered 1

However, cephalexin is NOT a first-line agent for uncomplicated cystitis because β-lactams achieve only approximately 89% clinical cure and 82% microbiological eradication—significantly inferior to nitrofurantoin (93% clinical cure, 88% microbiological eradication), trimethoprim-sulfamethoxazole (93% clinical cure, 94% microbiological eradication when susceptible), or fosfomycin (91% clinical cure) 2

When Cephalexin Is Appropriate

Reserve cephalexin for uncomplicated UTIs only when:

• First-line agents (nitrofurantoin, fosfomycin, trimethoprim-sulfamethoxazole) are contraindicated due to allergy, intolerance, or documented resistance 2
• Culture confirms susceptibility to cephalexin and resistance to preferred agents 1
• The patient is pregnant and requires treatment for Proteus mirabilis (which is intrinsically resistant to nitrofurantoin) 3

For pregnancy-related UTIs:

• Cephalexin (typically 500 mg four times daily for 7–14 days) is safe throughout all trimesters and provides reliable coverage for E. coli, Proteus mirabilis, and Klebsiella pneumoniae 3
• It serves as an appropriate alternative when nitrofurantoin or fosfomycin cannot be used 3

Practical Dosing for UTI Treatment

Standard regimen for uncomplicated cystitis:

• Cephalexin 500 mg orally twice daily for 5–7 days 4
• A recent 2023 study demonstrated 81.1% clinical success with short courses of twice-daily cephalexin for empiric treatment of uncomplicated UTIs 4

For pregnancy:

• Cephalexin 500 mg orally four times daily for 7–14 days 3

Common Pitfalls to Avoid

• Do not use cephalexin empirically for uncomplicated cystitis when first-line agents are available; β-lactams have inferior efficacy and promote more rapid UTI recurrence due to disruption of protective peri-urethral and vaginal microbiota 2
• Do not use cephalexin for pyelonephritis without an initial parenteral dose of ceftriaxone or another long-acting agent, as oral β-lactams alone are inadequate for upper-tract infections 5
• Do not assume cephalexin covers enterococci; most strains are resistant and require alternative therapy 1
• Obtain culture and susceptibility testing before using cephalexin for UTI to confirm the pathogen is susceptible, especially given rising resistance rates to β-lactams 1