cephalexin
Brand: Keflex
Prototype Drug
Drug Class: antibiotic
Drug Family: antibiotic
Subclass: first-generation cephalosporin / beta-lactam
Organ Systems: infectious-disease
Mechanism of Action
Beta-lactam antibiotic inhibiting bacterial PBPs and cell wall synthesis; first-generation cephalosporins have excellent gram-positive coverage (MSSA, streptococci) with modest gram-negative activity (E. coli, Klebsiella, Proteus mirabilis); not active against MRSA.
penicillin-binding proteins (PBPs)
Indications
- uncomplicated skin and soft tissue infections (MSSA)
- streptococcal pharyngitis (penicillin alternative)
- uncomplicated UTI (susceptible E. coli)
- surgical prophylaxis (alternative)
- bone/joint infections (step-down therapy)
Contraindications
- severe cephalosporin or penicillin allergy (anaphylaxis — <1% cross-reactivity with penicillins)
Adverse Effects
Common
- diarrhea
- nausea
- rash
Serious
- anaphylaxis
- C. difficile colitis
- neutropenia (prolonged high-dose)
- elevated LFTs
Pharmacokinetics (ADME)
| Absorption | Well absorbed orally (~90%); not significantly affected by food |
| Distribution | Protein binding ~15% |
| Metabolism | Not significantly metabolized |
| Excretion | Renal; dose adjustment for CrCl <30 mL/min |
| Half-life | 0.9–1.2 hours |
| Onset | 1 hour |
| Peak | 1 hour |
| Duration | 6 hours |
| Protein Binding | 15% |
| Vd | ~0.26 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| probenecid | reduces renal tubular secretion; increases cephalexin levels | minor |
| warfarin | possible INR elevation; monitor | minor |
Nursing Considerations
- Administer with food if GI side effects occur; suspension must be refrigerated and discarded after 14 days
- For mild-moderate SSTI: cephalexin is first-line per IDSA skin/soft tissue infection guidelines — covering MSSA and streptococci; if MRSA suspected (risk factors: prior MRSA, failed cephalexin), use TMP-SMX or doxycycline
- Dose adjustments are required in renal impairment (CrCl <30 mL/min); monitor renal function in elderly patients
- Complete full course of therapy even if symptoms resolve; incomplete courses promote antimicrobial resistance
Clinical Pearls
- Cross-reactivity between cephalosporins and penicillins is determined by the R1 side chain, not the beta-lactam ring — modern estimates of true cross-allergy are 1–2% (not the historically quoted 10%), and the risk is concentrated in patients with documented anaphylaxis to penicillin
- Cephalexin does NOT cover MRSA — for skin infections where MRSA is suspected (abscesses, failure of cephalexin), TMP-SMX or doxycycline should be used
Safety Profile
Pregnancy generally-safe
Lactation safe
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
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