Antimicrobials · First-Generation Cephalosporins
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Cephalexin is a first-generation cephalosporin that acts by inhibiting bacterial cell wall synthesis via binding to penicillin-binding proteins (PBPs).
The primary clinical indication for cephalexin is the treatment of skin and soft tissue infections (SSTIs), specifically those caused by methicillin-sensitive Staphylococcus aureus (MSSA) and Streptococcus pyogenes.
Cephalexin provides excellent coverage against Gram-positive cocci but lacks significant activity against Gram-negative anaerobes or methicillin-resistant Staphylococcus aureus (MRSA).
Cephalexin is the preferred first-line antibiotic for the treatment of uncomplicated cellulitis or impetigo in patients without a history of severe penicillin allergy.
Patients with a history of anaphylaxis, angioedema, or urticaria following penicillin exposure should avoid cephalexin due to the risk of cross-reactivity.
Cephalexin is considered a safe antibiotic for use during pregnancy and is frequently utilized for the treatment of urinary tract infections (UTIs) in pregnant patients.
The mechanism of resistance to cephalexin is primarily mediated by the alteration of penicillin-binding proteins or the production of beta-lactamases.
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A 32-year-old female at 24 weeks gestation presents to the clinic with a 3-day history of a spreading, erythematous, warm, and tender rash on her right lower leg. She denies fever, chills, or systemic symptoms. Physical examination reveals a poorly demarcated area of erythema with associated lymphangitic streaking. She has no known drug allergies. Her vital signs are stable.
What is the most appropriate empiric antibiotic treatment for this patient?
Cephalexin
The patient presents with uncomplicated cellulitis, for which cephalexin is the first-line treatment due to its coverage of MSSA and Streptococcus, and its established safety profile during pregnancy.
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Classification
First-generation cephalosporin; beta-lactam antibiotic.
Indications
Skin and soft tissue infections (SSTI), cellulitis, and impetigo.
Mechanism of Action
Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs).
Side Effects
Diarrhea, nausea; anaphylaxis, Clostridioides difficile colitis.
Contraindications / Monitoring
History of severe penicillin allergy; monitor renal function in elderly.
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Mechanism of Action
Cephalexin binds to penicillin-binding proteins (PBPs) located on the inner bacterial cell membrane. This binding inhibits the final transpeptidation step of peptidoglycan synthesis, leading to cell wall instability. The resulting osmotic imbalance causes bacteriolysis. It is primarily active against Gram-positive cocci.
Unique Properties
It is the oral agent of choice for MSSA (methicillin-susceptible *Staphylococcus aureus*) and *Streptococcus* species. Unlike later generations, it has minimal Gram-negative coverage and does not cross the blood-brain barrier effectively.
Indications
It is the first-line treatment for non-purulent cellulitis and impetigo. It is also used for urinary tract infections in pregnancy and as a prophylactic agent for minor surgical procedures. It is ineffective against MRSA.
Pharmacokinetics
Cephalexin is well-absorbed orally and is primarily excreted unchanged by the kidneys. Dosage adjustments are required in patients with significant renal impairment to prevent accumulation. It does not undergo significant hepatic metabolism.
Side Effects & Adverse Events
Common side effects include gastrointestinal distress and diarrhea. Clostridioides difficile-associated diarrhea is a serious risk with any cephalosporin. Hypersensitivity reactions ranging from urticaria to anaphylaxis can occur, particularly in patients with cross-reactivity to penicillins.
Contraindications
Absolute contraindication is a history of IgE-mediated hypersensitivity (e.g., anaphylaxis, angioedema) to any beta-lactam antibiotic. Use with extreme caution in patients with a history of seizures, as high doses can lower the seizure threshold.
Monitoring
Monitor for signs of superinfection (e.g., oral thrush, vaginal candidiasis) during prolonged therapy. In patients with chronic kidney disease, monitor serum creatinine and BUN to guide dose titration. Assess for resolution of erythema and warmth in SSTI cases.
Clinical Pearls
On boards, Cephalexin is the answer for MSSA skin infections. Remember the rule of thumb: if a patient has a mild penicillin rash, cephalosporins are generally safe, but if they have a history of anaphylaxis to penicillin, avoid all cephalosporins.