Cephalexin
Cephalexin
Generic Name
Cephalexin
Mechanism
- Inhibits bacterial cell‑wall synthesis by binding to penicillin‑binding proteins (PBPs) on the cell membrane.
- Binding blocks transpeptidation, preventing peptidoglycan cross‑linking → bacterial lysis.
- Primarily active against gram‑positive cocci (e.g., *Staphylococcus aureus*, *Streptococcus pyogenes*, *S. pneumoniae*) and selective gram‑negative rods (*E. coli*, *Proteus vulgaris*).
Pharmacokinetics
- Absorption: 65‑90 % oral bioavailability; peak plasma 1–2 h post‑dose.
- Distribution: 35‑41 % plasma protein binding; distributes into skin, soft tissue, urine, bronchial alveolar fluid.
- Metabolism: Largely unchanged; minimal hepatic metabolism.
- Elimination: Renally excreted (≈ 90 % unchanged). Half‑life ≈ 0.7–1 h (normal renal function).
- Adjustments: In renal impairment, dosing interval or amount is reduced based on GFR.
Indications
- Skin and soft‑tissue infections: cellulitis, abscesses, impetigo
- Respiratory tract infections: strep tonsillitis, pharyngitis, sinusitis (suspected gram‑positive organisms)
- Urinary tract infections: cystitis, urethritis, pyelonephritis when susceptible
- Bone and joint infections: osteomyelitis, septic arthritis
- Other: dental abscesses, postoperative prophylaxis for certain procedures
Contraindications
- IgE‑mediated hypersensitivity to cephalosporins or first‑generation cephalosporins in patients with a history of penicillin allergy (cross‑reactivity ≈ 10 %).
- Severe renal dysfunction: avoid or use extreme caution.
- Pregnancy: Category B – use only if benefits outweigh risks.
- Lactation: excreted in breast milk; caution advised.
- Concurrent use with tetracyclines: risk of altered absorption – avoid unless no alternative.
- Concurrent NSAIDs: may increase renal toxicity.
Dosing
| Population | Dose | Schedule | Notes |
| Adults | 250 mg – 1 g | q6h or q8h (divide total daily dose) | Use 500 mg q6h for severe infections; 500 mg q8h for mild‑to‑moderate. |
| Pediatric | 20–45 mg/kg/day | q8h (divide total daily dose) | Must weigh for dosing; max 500 mg q6h in children > 5 kg. |
| Renal impairment | Reduce dose/interval per CrCl: < 10 mL/min → 500 mg q48h; 10–30 mL/min → 500 mg q24h; 31–60 mL/min → 500 mg q12h |
• Route: Oral tablets or liquid suspension.
• Food interaction: Food does not significantly affect absorption; may be taken with or without food to improve tolerability.
Adverse Effects
- GI: nausea, vomiting, diarrhea, abdominal pain (most frequent).
- Allergic reactions: rash, pruritus, urticaria; severe: anaphylaxis, Stevens‑Johnson syndrome.
- Metabolic: hypokalemia (rare), hyperuricaemia.
- Hematologic: neutropenia, thrombocytopenia (often reversible).
- Superinfections: *Clostridioides difficile* colitis (rare).
- Renal: acute interstitial nephritis (very rare).
Monitoring
- Renal function: serum creatinine, eGFR at baseline; repeat if dosing > 3 weeks or at dose changes.
- CBC: for prolonged therapy (> 14 days) due to neutropenia risk.
- Signs of severe infection: worsening fever, chills, hypotension → switch to broader coverage if no response.
- Allergic history: monitor for rash or hypersensitivity reactions, especially during the first 24 h.
Clinical Pearls
- Use the lowest effective dose for the shortest duration to curb resistance; discontinue after 7–10 days for uncomplicated infections.
- Renal dosing calculators are essential—especially in elderly or dialysis patients—to avoid toxicity.
- Cephalexin retains potency against penicillin‑susceptible MRSA (PSSA) but not MRSA‑resistant strains; use synergy with clindamycin or linezolid for MRSA coverage.
- Concurrent NSAIDs (e.g., ibuprofen) should be avoided in renal impairment due to additive nephrotoxicity.
- Rapid transition from IV to oral is supported by pharmacokinetics: achieve comparable serum levels 1 h after oral dose.
- Always ensure your photonicity: some rural areas have started to demonstrate resistance in *E. coli*—culture/susceptibility testing is prudent for UTIs with unclear etiology.
- Pregnancy & lactation: although Category B, minimize use unless benefit outweighs minimal risk; consider alternative beta‑lactams if maternal allergy is suspected.
Key Takeaway: Cephalexin’s efficacy, safety, and oral bioavailability make it a first‑line agent for many community‑acquired infections, provided dosing is adjusted for renal function and patient allergy status.