First and Second Generation Cephalosporins

Bounded Spectrum Wall Inhibitors

First generation cephalosporins stand out for their excellent antibacterial potency against Gram-positive cocci, while the second generation expands their range of activity towards enteric Gram-negative bacilli and specific anaerobic microorganisms.

Mechanism

💊 Generic and Commercial Names

Primera Gen: Cefazolina (Kefol), Cefadroxilo (Duracef), Cefalexina (Kefloridina). Segunda Gen: Cefuroxima (Zinnat, Curoxima), Cefoxitina (Mefoxin).

🔬 Pharmacological Group

Beta-lactámicos. Cefalosporinas de espectro Gram-positivo predominante (1.ª gen) y espectro intermedio (2.ª gen).

Mechanism of Action

Inhiben de forma covalente las PBPs implicadas en la polimerización del peptidoglicano:

Afinidad PBP Selectiva de Primera Generación: Cefazolina presenta una elevadísima afinidad por la PBP1 y PBP3 de cocos Gram-positivos, induciendo una bactericidia rápida. Es estable frente a las penicilinasas estafilocócicas pero completamente vulnerable a cefalosporinasas AmpC, BLEE y carbapenemasas.
Modificaciones de Segunda Generación y Cefamicinas: Cefuroxima posee un grupo metoximino en su cadena lateral que incrementa su estabilidad frente a las beta-lactamasas de Clase A producidas por enterobacterias. Las cefamicinas (como Cefoxitina) poseen un grupo metoxilo en la posición 7 del núcleo cefem, lo que les confiere una estabilidad única frente a la hidrólisis por betalactamasas de espectro extendido y una notable potencia contra anaerobios al inhibir selectivamente PBPs específicas de estos gérmenes.

Pharmacokinetics

Key Pharmacokinetics

Parameter	Cefazolin	Cefuroxime Axetil (Oral) / Cefuroxime Sodium (IV)
Routes of Administration	Exclusively IV or IM. Not available orally.	Oral (axetil - prodrug) and IV (sodium).
Dural absorption	No oral absorption. IM reaches C_max in 1-1.5 hours.	Low to moderate oral bioavailability (~30-50%), increases if ingested with fatty foods.
Volume of Distribution	Low (0.12 - 0.16 L/kg). Excellent tissue penetration in bone and synovial tissue.	Low (0.15 - 0.22 L/kg). Does not reliably penetrate CSF, even with meningitis.
Protein Binding	Very high (~80-85%). Requires high doses in severe hypoalbuminemia to avoid accelerated clearance.	Moderate (~33-50%).
Excretion and Half-Life	Renal glomerular excretion unchanged by 90%. Half-life of 1.8 to 2.2 hours.	Renal glomerular excretion and tubular secretion. Half-life of 1.2 to 1.7 hours.

Antimicrobial Spectrum

First Generation: Excellent against Staphylococcus aureus sensitive to methicillin (MSSA), Streptococcus pyogenes and Streptococcus pneumoniae. Gram-negative coverage limited to non-betal-lactamase-producing community Enterobacteriaceae (E. coli, K. pneumoniae, P. mirabilis).
Second Generation: Extended spectrum. Covers Haemophilus influenzae, Moraxella catarrhalis and additional Enterobacteriaceae. Cephamycins (Cefoxitin) cover anaerobes such as Bacteroides fragilis, which makes them useful in abdominal surgical prophylaxis.

Indicators and dose

Dosage and Adjustment

Cefazolin (IV): 1 to 2 g every 8 hours. Surgical prophylaxis: 2 g IV as a single dose (3 g if patient's body weight ≥ 120 kg) administered 30 to 60 minutes before the initial skin incision.
Cefuroxime Sodium (IV): 750 mg to 1.5 g every 8 hours.
Adjustment in Renal Failure of Cefazolin:
- Cl_cr 35-54 mL/min: Administer standard doses every 8 hours.
- Cl_cr 11-34 mL/min: Administer 50% of the standard dose every 12 hours.
- Cl_cr < 10 mL/min: Administer 50% of the standard dose every 24 hours.

Security

Contraindications and ADRs

Contraindications: Documented IgE-mediated allergy to cephalosporins.
Adverse Effects (ADR): Excellent tolerance in general. Mild maculopapular rash in 1-3% of treatments. Serious skin reactions (exanthematous pustulosis) of very rare course. Lower risk of nephrotoxicity if coadministered with high doses of loop diuretics.

Cefazolin as the Gold Choice in Surgical Prophylaxis and SASM

Cefazolin is the world standard of choice for perioperative surgical prophylaxis of almost all clean surgeries (cardiovascular, trauma, plastic), thanks to its excellent tissue penetration and long plasma half-life that ensures local bactericidal concentrations during the surgical procedure. In addition, it constitutes the treatment of choice for bacteremia and endocarditis caused by MSSA, showing significantly higher tolerance and lower risk of interstitial nephritis compared to isoxazole penicillins (Cloxacillin).

Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.

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System: Antimicrobial and Infectious
Cluster: Bounded Spectrum Wall Inhibitors

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