What is the antimicrobial spectrum of ceftriaxone?

Antimicrobial Spectrum of Ceftriaxone

Ceftriaxone is a third-generation cephalosporin with broad-spectrum activity against most gram-negative bacteria and moderate activity against gram-positive organisms, but it lacks coverage against MRSA, atypical pathogens, and has limited anaerobic activity. 1, 2

Gram-Negative Coverage

Ceftriaxone demonstrates excellent activity against the following gram-negative organisms:

• Enterobacteriaceae: Highly active against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, and Citrobacter species 2, 3

• Respiratory pathogens: Excellent activity against Haemophilus influenzae (including beta-lactamase-producing strains) and Moraxella catarrhalis (including beta-lactamase-producing strains), with 95-100% susceptibility based on pharmacokinetic/pharmacodynamic breakpoints 4, 2

• Neisseria species: Outstanding bactericidal activity against Neisseria gonorrhoeae (both penicillinase and non-penicillinase-producing strains) with 98.9% cure rates, and Neisseria meningitidis 1, 2, 5

• Pseudomonas aeruginosa: Has some activity but cannot be recommended as sole therapy for pseudomonal infections—agents like piperacillin-tazobactam, ceftazidime, cefepime, or carbapenems should be used instead 1, 3

Gram-Positive Coverage

Ceftriaxone has moderate to good activity against select gram-positive organisms, but with important limitations:

• Streptococcus pneumoniae: Moderate activity with 95-97% susceptibility based on pharmacokinetic/pharmacodynamic breakpoints, achieving 91-99% calculated bacteriologic efficacy in pediatric acute bacterial rhinosinusitis 4, 1, 2

• Drug-resistant S. pneumoniae (DRSP): Limited activity similar to other third-generation oral cephalosporins; in areas with high prevalence of penicillin- and cephalosporin-resistant pneumococci, vancomycin should be added empirically until susceptibilities are known 1

• Viridans group streptococci: Excellent activity against most strains; for relatively penicillin-resistant strains causing endocarditis, combination therapy with ceftriaxone plus gentamicin for the first 2 weeks is recommended 1, 2

• Group B streptococci and Streptococcus pyogenes: Outstanding bactericidal activity 2, 5

• Methicillin-susceptible Staphylococcus aureus (MSSA): Good activity, but cefazolin is preferred for MSSA infections to provide narrower-spectrum, more potent anti-staphylococcal coverage 1, 6

• Methicillin-resistant Staphylococcus aureus (MRSA): No activity—vancomycin, linezolid, or daptomycin are required 1

• Staphylococcus epidermidis: Some activity documented in limited cases of meningitis and shunt infections 2

Anaerobic Coverage

Ceftriaxone has limited anaerobic activity:

• Bacteroides fragilis: Some activity documented in skin/soft tissue and intra-abdominal infections 2

• Peptostreptococcus species: Active 2

• Clostridium species: Some activity, but most strains of Clostridium difficile are resistant 2

• Clinical implication: For intra-abdominal infections, ceftriaxone must be combined with metronidazole for adequate anaerobic coverage 1, 6

Critical Coverage Gaps

Atypical Pathogens

Ceftriaxone lacks coverage against all atypical organisms and requires addition of a macrolide or fluoroquinolone when these pathogens are suspected 1:

• No activity against Mycoplasma, Ureaplasma, Chlamydophila, and Legionella species 1

• For severe community-acquired pneumonia requiring hospitalization, combining ceftriaxone with a macrolide (azithromycin or clarithromycin) or using a respiratory fluoroquinolone as monotherapy is recommended 1

• For pelvic inflammatory disease, when Chlamydia trachomatis is a suspected pathogen, appropriate antichlamydial coverage must be added 2

Enterococcus

• No clinically significant activity against Enterococcus species 1

FDA-Approved Indications

The FDA label specifies ceftriaxone is indicated for infections caused by susceptible organisms in the following sites 2:

• Lower respiratory tract infections
• Acute bacterial otitis media
• Skin and skin structure infections
• Urinary tract infections (complicated and uncomplicated)
• Uncomplicated gonorrhea (cervical/urethral, rectal, and pharyngeal)
• Pelvic inflammatory disease
• Bacterial septicemia
• Bone and joint infections
• Intra-abdominal infections
• Meningitis
• Surgical prophylaxis

Common Pitfalls and Clinical Caveats

• Avoid using ceftriaxone as monotherapy when narrower-spectrum agents are appropriate (such as cefazolin for MSSA) to minimize resistance development and collateral damage to normal flora 1, 6

• Never use ceftriaxone alone for intra-abdominal infections—always combine with metronidazole for anaerobic coverage 1, 6

• Do not rely on ceftriaxone for MRSA infections—alternative agents are required 1

• Cannot be used as sole therapy for pseudomonal infections despite having some in vitro activity 1, 3

• For severe community-acquired pneumonia, always add atypical coverage with a macrolide or use a respiratory fluoroquinolone instead 1

• The broader spectrum of ceftriaxone compared to first-generation cephalosporins comes with increased risk of promoting antimicrobial resistance 6