Does Keflex (cephalexin) cover gram-negative bacilli?

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Cephalexin's Coverage of Gram-Negative Bacilli

Cephalexin has limited activity against gram-negative bacilli, covering only select species such as Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae, but lacks coverage against Pseudomonas, Acinetobacter, Enterobacter, and many other gram-negative bacilli.

Spectrum of Activity

  • Cephalexin is a first-generation cephalosporin with FDA approval for treating genitourinary tract infections caused by specific gram-negative bacilli including Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae 1
  • Cephalexin has no activity against Pseudomonas species or Acinetobacter calcoaceticus, and is not active against most strains of Enterobacter species, Morganella morganii, and Proteus vulgaris 1
  • When compared to other cephalosporins, cephalexin demonstrates inferior activity against gram-negative bacilli, with studies showing it to be less effective than cefazolin against common gram-negative pathogens 2

Clinical Applications

  • For mild infections where gram-negative coverage is needed, cephalexin is listed as an option primarily for uncomplicated urinary tract infections caused by susceptible strains of E. coli, P. mirabilis, and K. pneumoniae 1
  • For moderate to severe infections involving gram-negative bacilli, cephalexin is inadequate and other agents such as third-generation cephalosporins, carbapenems, or combination therapy are recommended instead 3
  • In diabetic foot infections, cephalexin is only recommended for mild infections primarily targeting gram-positive organisms, not for moderate or severe infections where gram-negative coverage is essential 3

Comparative Efficacy

  • Studies have demonstrated that cephalexin has significantly less activity against gram-negative bacilli compared to other cephalosporins, with one study showing 57.5% of gram-negative isolates were resistant to cephalexin 4
  • When gram-negative coverage is required, particularly for Enterobacteriaceae, other agents such as cefazolin, cefoxitin, ceftriaxone, or fluoroquinolones are preferred over cephalexin 3
  • For serious infections involving gram-negative bacilli, particularly in critically ill patients, combination therapy with two antimicrobial agents of different classes with gram-negative activity is recommended initially 3

Common Pitfalls and Caveats

  • A major pitfall is assuming cephalexin provides adequate coverage against all gram-negative bacilli, which could lead to treatment failure in infections caused by Pseudomonas, Acinetobacter, or Enterobacter species 1
  • For infections potentially involving ESBL-producing Enterobacteriaceae, cephalexin and other cephalosporins should be avoided due to high rates of resistance 3
  • When treating infections with potential gram-negative involvement, culture and susceptibility testing is essential before relying on cephalexin, as resistance patterns vary significantly 1
  • In settings with high prevalence of multidrug-resistant gram-negative organisms, cephalexin is not an appropriate empiric choice 3

Summary of Coverage

  • Cephalexin does cover: E. coli, P. mirabilis, K. pneumoniae, and Moraxella catarrhalis 1
  • Cephalexin does not cover: Pseudomonas species, Acinetobacter species, most Enterobacter species, Morganella morganii, Proteus vulgaris, and other non-fermenting gram-negative bacilli 1
  • For serious infections involving gram-negative bacilli, broader-spectrum agents or combination therapy should be selected 3

References

Research

Evaluation of antibacterial activities of cephalosporin antibiotics: cefazolin, cephaloridine, cephalothin, and cephalexin.

Zhonghua Minguo wei sheng wu xue za zhi = Chinese journal of microbiology, 1975

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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