Bacterial Coverage of Cephalexin in UTIs
Cephalexin is active against methicillin-sensitive Staphylococcus aureus (MSSA), Streptococcus species, and common gram-negative uropathogens including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Haemophilus influenzae, and Moraxella catarrhalis. 1
Gram-Positive Coverage
- Staphylococcus aureus (including penicillinase-producing strains, but NOT methicillin-resistant strains) 1
- Streptococcus pneumoniae (penicillin-susceptible strains only) 1
- Streptococcus pyogenes 1
Critical Limitation for Gram-Positives
- Methicillin-resistant staphylococci (MRSA) are resistant to cephalexin and require alternative agents such as trimethoprim-sulfamethoxazole, doxycycline, or clindamycin 2, 1
- Most enterococci (Enterococcus faecalis) are resistant to cephalexin 1
- Penicillin-resistant Streptococcus pneumoniae is usually cross-resistant to cephalexin 1
Gram-Negative Coverage
- Escherichia coli - the most commonly isolated uropathogen (85.4% in recent studies) 1, 3
- Klebsiella pneumoniae 1
- Proteus mirabilis 1
- Haemophilus influenzae 1
- Moraxella (Branhamella) catarrhalis 1
Critical Limitations for Gram-Negatives
- NOT active against most strains of Enterobacter species - first and second-generation cephalosporins are generally not effective against Enterobacter infections 4, 1
- NOT active against Morganella morganii 1
- NOT active against Proteus vulgaris 1
- NO activity against Pseudomonas species 1
- NO activity against Acinetobacter calcoaceticus 1
Resistance Considerations
- Avoid cephalexin if local E. coli resistance to first-generation cephalosporins exceeds 20% 5
- Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are resistant to cephalexin and require alternative agents 4, 6
- Newer cefazolin-cephalexin surrogate testing has recategorized some previously resistant organisms to susceptible, improving the utility of cephalexin 6
Clinical Efficacy Data
- Recent studies demonstrate 81-85% clinical success rates for uncomplicated UTIs when organisms are susceptible 7, 3, 8
- Twice-daily dosing (500 mg BID) is as effective as four-times-daily dosing for UTIs, improving adherence 3, 8, 6
- Cephalexin achieves peak urine concentrations of approximately 1000-5000 mcg/mL depending on dose, with over 90% excreted unchanged in urine 1
Key Pitfalls to Avoid
- Do not use cephalexin for MRSA UTIs - it will be ineffective 2
- Always obtain urine culture before initiating therapy to guide definitive treatment and detect resistance 2, 5
- Do not use for complicated UTIs without culture data, particularly in catheter-associated UTIs where resistant organisms and polymicrobial infections are more common 5
- Avoid treating asymptomatic bacteriuria with cephalexin, as this promotes resistance (47% of reinfecting organisms become highly resistant) 5
- Not appropriate for febrile infants with suspected pyelonephritis due to inadequate serum concentrations 2