Generic Name

Keflex

Mechanism

Keflex exerts its antibacterial effect by targeting the bacterial cell wall synthesis process:
• Binds to Penicillin‑Binding Proteins (PBPs)—particularly PBP2x and PBP2a in susceptible organisms.
• Inhibits transpeptidase (cross‑linking) activity, preventing the cross‑linking of the peptidoglycan layer.
• This weakens the cell wall, leading to osmotic lysis.
• The drug is inactivated by most β‑lactamases but retains activity against β‑lactamase–producing streptococci and methicillin‑sensitive Staphylococcus aureus (MSSA).

Pharmacokinetics

• Route & Absorption: Oral; high oral bioavailability (≈60‑80%).
• Peak Plasma Concentration (Tmax): 0.5‑1 h after dosing.
• Protein Binding: ~25% (mostly to albumin).
• Half‑Life: 1‑2 h in healthy adults; prolonged in renal impairment.
• Distribution: Well distributed in skin, soft tissues, and the urinary tract.
• Metabolism: Minimal hepatic metabolism.
• Elimination: Excreted unchanged via the kidneys (≈70‑80% of dose).

Renal Dosing: Adjust dose in patients with creatinine clearance <30 mL/min (reduce frequency or dose).

Indications

• Dermatology: Impetigo, cellulitis, abscesses, folliculitis, and other superficial skin infections.
• Otology: Acute otitis media.
• Pharyngology: Streptococcal pharyngitis.
• Urology: Lower urinary tract infections (cystitis).
• Infectious Diseases: Prophylaxis of infective endocarditis in susceptible patients undergoing dental procedures.
• Others: Zoonotic infections, streptococcal pharyngitis, and surgical prophylaxis in clean‑contaminated wounds (rare).

Contraindications

• Drug Hypersensitivity: Severe allergy to cephalosporins or penicillin (history of anaphylaxis).
• Cross‑reactivity: High risk if a severe penicillin allergy (≥3 years data suggest ~1–2% cross‑reactivity).
• Drug Interaction: Probenecid (increases plasma concentrations); concomitant use should be avoided or dose adjusted.
• Pregnancy/Lactation: Category B; safe in pregnancy but avoid routine use in lactation if the infant is at higher risk for allergic reactions.
• Renal Impairment: Requires dose adjustment.
• C. difficile‑associated colitis: Monitor for watery diarrhea; discontinue if severe colitis develops.

Dosing

_All dosages assume normal renal function._

• Route: Oral capsules, tablets, or liquid suspension; can be taken with or without food.
• Special Considerations: Ensure adequate hydration; if using IV formulation (2 % solution), use 2 % cefazolin instead because cefazolin is a stable IV preparation.

Adverse Effects

Common
• Gastrointestinal upset (nausea, vomiting, diarrhea, abdominal pain)
• Skin rash or pruritus
• Headache
• Mild changes in liver enzymes

Serious
• Anaphylaxis or severe allergic reactions (esp. with β‑lactam cross‑reactivity)
• *Clostridioides difficile* colitis (watery diarrhea, abdominal pain)
• Hematologic abnormalities (anemia, thrombocytopenia, neutropenia)
• Hepatotoxicity (elevated transaminases)
• Superinfection with gram‑negative rods or fungi (≥3 rd day of therapy)

Monitoring

• Renal function: serum creatinine, eGFR (baseline, every 48–72 h if >7 days therapy).
• CBC & Differential: at baseline and if signs of cytopenia appear.
• Liver enzymes: AST/ALT if signs of hepatotoxicity.
• Clinical response: resolution of infection signs, afebrile status.
• Signs of anaphylaxis: monitor if patient has history of β‑lactam allergy.

Clinical Pearls

• Food Interaction: Cephalexin is well absorbed whether taken on an empty stomach or with food; no timing restrictions needed.
• Probenecid: Avoid or co‑administer with a 12‑h interval; probenecid inhibits renal excretion, raising cephalexin levels and risk of toxicity.
• Dialysis: Cephalexin can be effectively cleared by peritoneal dialysis; adjust dose according to drug clearance.
• Prophylaxis for Dental Extraction: A single 500 mg dose 1 h before procedure is effective; repeated dosing not required.
• Renal Impairment: The 30 % dose reduction (q12 h rather than q6 h) yields comparable trough levels in CrCl <30 mL/min.
• Red‐flag Symptoms: Severe GI distress, persistent rash, new onset fever post‑treatment are red flags for ∗C. difficile*; consider stool toxin test.
• Drug Mislabeling: Keflex mis‑prescribed as sofene (a generic of cefpirome) can lead to over‑aggressive dosing in pediatric patients.
• Terminology: _Cephalexin_ is ‘letter 1’ on the cephalosporin ladder; it is active against MSSA and β‑lactamase–producing streptococci but does not cover MRSA, gram‑negative rods, or anaerobes—clarify therapy needs in empirical settings.
• Oral Bioavailability: 60‑80 % makes it very dosing‑flexible; vaccinations rarely affected.

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• Key terms: *cephalexin*, *Keflex*, *first‑generation cephalosporin*, *β‑lactam*, *PBP inhibition*, *cell wall lysis*, *renal dosing*, *C. difficile colitis*.