Which cephalosporin is good for skin infection? A Guide to Selection

October 10, 2025 •

3 min read

According to research published by the National Institutes of Health, cephalexin remains a highly effective antibiotic for streptococcal and staphylococcal skin infections, achieving high cure rates even after many years of use. The best choice for which cephalosporin is good for skin infection? depends on the type, severity, and causative bacteria of the particular condition.

Quick Summary

Different cephalosporin antibiotics are effective for bacterial skin infections, with the best option depending on the specific bacteria, infection severity, and administration route. First-generation cephalosporins like cephalexin are commonly used for mild cases, while others like ceftriaxone or ceftobiprole may be needed for severe or resistant infections.

Key Points

First-Gen for Common Infections: Oral first-generation cephalosporins like cephalexin or cefadroxil are effective for most uncomplicated skin infections caused by common Gram-positive bacteria.
IV for Severe Cases: Intravenous cephalosporins, such as cefazolin or ceftriaxone, are typically used for more serious or deep skin infections requiring hospitalization.
Specialized for MRSA: While most older cephalosporins do not cover MRSA, the advanced-generation cephalosporin ceftobiprole is effective against this resistant bacteria.
Dosing Flexibility: Cefadroxil offers less frequent dosing compared to cephalexin, potentially improving patient adherence.
Allergy Awareness: Penicillin allergy history is important, though cross-reactivity with cephalosporins is relatively low.
Pathogen Determines Choice: Identifying the specific bacteria causing the infection is crucial for selecting the most appropriate cephalosporin.

Cephalosporins are a broad class of beta-lactam antibiotics used to treat various bacterial infections, including skin and soft tissue infections. They are categorized into generations based on their spectrum of activity. The optimal cephalosporin selection is guided by the specific type of bacteria causing the infection.

Understanding Common Skin Pathogens

Common uncomplicated bacterial skin infections are typically caused by Gram-positive bacteria such as Staphylococcus aureus (MSSA) and Streptococcus pyogenes. More severe or complicated infections, especially in hospital settings, may involve MRSA or Gram-negative bacteria like Pseudomonas aeruginosa.

First-Generation Cephalosporins: For Uncomplicated Cases

First-generation cephalosporins are frequently preferred for mild to moderate skin and soft-tissue infections caused by susceptible organisms. They effectively target common Gram-positive skin bacteria and are available orally.

Cephalexin (Keflex): A widely used oral cephalosporin effective against MSSA and S. pyogenes for conditions like impetigo and cellulitis. It has high bioavailability and is generally well-tolerated.
Cefadroxil (Duricef): Similar to cephalexin but with a longer half-life, allowing for less frequent dosing (once or twice daily).
Cefazolin (Ancef): An IV option typically used for moderate to severe infections or surgical prophylaxis.

Third- and Advanced-Generation Cephalosporins: For More Serious Needs

Later-generation cephalosporins are considered for more serious or complex skin infections, particularly those involving multi-drug resistant organisms or requiring IV administration.

Ceftriaxone (Rocephin): A third-generation IV/IM cephalosporin with a broader spectrum, suitable for severe skin infections, including those caused by a mix of bacteria. It offers convenient once-daily dosing. However, it may be less effective against some MSSA strains compared to first-gen options.
Ceftobiprole (Zevtera): An advanced-generation cephalosporin approved in 2024 with activity against MRSA, useful for treating certain acute bacterial skin and skin structure infections (ABSSSI).

Comparing Common Cephalosporins for Skin Infections


Feature	Cephalexin (Keflex)	Cefadroxil (Duricef)	Cefazolin (Ancef)	Ceftriaxone (Rocephin)	Ceftobiprole (Zevtera)
Generation	First	First	First	Third	Advanced
Administration	Oral	Oral	IV/IM	IV/IM	IV
Spectrum	Good for Gram-positive (MSSA, S. pyogenes)	Good for Gram-positive (MSSA, S. pyogenes)	Excellent for Gram-positive (MSSA, S. pyogenes)	Broad, including Gram-negative and some Gram-positive	Broad, including MRSA and Gram-negatives
Best For	Uncomplicated skin infections (cellulitis, impetigo)	Uncomplicated skin infections (alternative to cephalexin)	Serious infections, surgical prophylaxis	Severe or multi-organism skin infections	ABSSSI, including MRSA infections
Dosing Frequency	2-4 times daily	1-2 times daily	Multiple times daily (IV)	Once daily	Multiple times daily (IV)
MRSA Coverage	No	No	No	No (some studies show limited efficacy)	Yes

Other Factors Influencing Choice

Antibiotic selection also considers factors like penicillin allergies (cross-reactivity with cephalosporins is lower than previously believed but still a factor), renal function, age, and infection severity. Cost and availability are also practical considerations.

Conclusion

First-generation oral cephalosporins like cephalexin or cefadroxil are often the preferred treatment for most uncomplicated skin infections caused by common bacteria. For more severe or complex cases, intravenous options like cefazolin or ceftriaxone are used. Newer agents such as ceftobiprole are available for MRSA infections. A healthcare provider should always determine which cephalosporin is good for skin infection based on the individual clinical situation to ensure effective and safe treatment.

Important Note: This information is for educational purposes only and not a substitute for professional medical advice. Consult a healthcare provider for diagnosis and treatment. For detailed drug information, refer to official labels or resources like MedlinePlus.

Frequently Asked Questions

Yes, cephalexin is a very common and effective oral first-generation cephalosporin used to treat mild to moderate skin infections caused by susceptible Staphylococcus aureus (MSSA) and Streptococcus pyogenes.

For mild cellulitis, an oral first-generation cephalosporin like cephalexin or cefadroxil is often prescribed. For moderate to severe cellulitis requiring hospitalization, intravenous cephalosporins like cefazolin or ceftriaxone may be used.

Yes, standard first- and third-generation cephalosporins do not cover MRSA. However, the advanced-generation cephalosporin ceftobiprole (Zevtera) was approved in 2024 specifically for acute bacterial skin and skin structure infections (ABSSSI) caused by MRSA.

Both cephalexin and cefadroxil are first-generation oral cephalosporins with a similar spectrum of activity. The main difference is dosing frequency, as cefadroxil has a longer half-life, allowing for less frequent dosing (once or twice daily) compared to cephalexin (typically two to four times daily).

It is crucial to inform your doctor about a penicillin allergy. While the risk of cross-reactivity with cephalosporins is lower than previously thought (around 2-5%), a detailed allergy history is necessary to determine the risk. In some cases, a different class of antibiotic may be prescribed to be safe.

Oral cephalosporins like cephalexin and cefadroxil are taken by mouth and used for less severe infections managed outside of a hospital. Intravenous (IV) cephalosporins, such as cefazolin and ceftriaxone, are administered directly into a vein and are used for more serious, hospital-managed infections.

While the antibiotic starts killing bacteria quickly, it may take 2 to 3 days to notice significant improvement in a skin infection. It is important to complete the entire prescribed course of treatment, even if symptoms begin to clear up earlier.