What is the spectrum of activity of Ceftriaxone (a third-generation cephalosporin antibiotic) against Gram-positive and Gram-negative bacteria?

Ceftriaxone Spectrum of Activity

Ceftriaxone is a third-generation cephalosporin with excellent activity against most Gram-negative bacteria (including Enterobacteriaceae, H. influenzae, N. gonorrhoeae, N. meningitidis) and good activity against methicillin-susceptible Gram-positive cocci (S. pneumoniae, MSSA, Streptococcus species), but it lacks coverage against MRSA, Enterococcus, atypical organisms, and has limited anaerobic activity. 1, 2

Gram-Negative Coverage

Ceftriaxone demonstrates robust activity against the following Gram-negative organisms:

Enterobacteriaceae

• Excellent activity against E. coli, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, P. vulgaris, Morganella morganii, and Serratia marcescens with resistance rates consistently <5% 2, 3
• Effective against Enterobacter aerogenes, E. cloacae, Citrobacter species, Providencia species, and Salmonella/Shigella species 2
• Resistance among E. cloacae is notably higher (21.7-23.9%) compared to other Enterobacteriaceae 3

Respiratory Pathogens

• Outstanding activity against Haemophilus influenzae (including beta-lactamase producing strains) with 100% susceptibility 2, 3
• Excellent coverage of Moraxella catarrhalis (including beta-lactamase producing strains) 2
• Highly effective against Neisseria meningitidis for meningitis treatment 2

Sexually Transmitted Infections

• 98.9% cure rates for uncomplicated urogenital and anorectal Neisseria gonorrhoeae infections, including penicillinase-producing strains 1, 2
• 100% susceptibility documented among tested N. gonorrhoeae isolates 3

Limited Pseudomonal Activity

• Ceftriaxone has some activity against Pseudomonas aeruginosa but cannot be recommended as sole therapy for pseudomonal infections 2, 4
• For infections requiring anti-pseudomonal coverage, agents like piperacillin-tazobactam, ceftazidime, cefepime, or carbapenems should be used instead 5

Gram-Positive Coverage

Streptococcal Species

• Excellent activity against Streptococcus pneumoniae with 5.0-6.6% resistance rates, achieving 91-99% bacteriologic efficacy in respiratory infections 1, 3
• Limited activity against drug-resistant S. pneumoniae (DRSP), similar to other third-generation oral cephalosporins 1
• Outstanding activity against S. pyogenes (group A streptococci) and group B streptococci with 0% resistance 2, 3
• Good coverage of viridans group streptococci with 5.1-6.9% resistance 2, 3

Staphylococcal Species

• Good activity against methicillin-susceptible Staphylococcus aureus (MSSA) with 0.1-0.3% resistance, though cefazolin is preferred for MSSA infections 1, 6, 3
• Covers S. epidermidis in skin/soft tissue infections and has been used successfully in limited cases of shunt infections 2
• No activity against methicillin-resistant S. aureus (MRSA) 1

Critical Coverage Gaps

• No coverage of Enterococcus species—when treating pelvic inflammatory disease or intra-abdominal infections where enterococci may be present, alternative agents or combination therapy should be considered 2, 5

Anaerobic Coverage

• Limited anaerobic activity—covers Bacteroides fragilis, Clostridium species (most C. difficile strains are resistant), and Peptostreptococcus species 2, 5
• Requires metronidazole addition for adequate anaerobic coverage in intra-abdominal infections 5, 1
• Third-generation cephalosporins including ceftriaxone plus metronidazole are recommended options for mild-to-moderate intra-abdominal infections 5

Atypical Organism Coverage

• No coverage of atypical organisms including Mycoplasma, Ureaplasma, Chlamydophila, and Legionella species 1
• Requires addition of a macrolide (azithromycin, clarithromycin) or respiratory fluoroquinolone when atypical pathogens are suspected in community-acquired pneumonia 1
• For pelvic inflammatory disease, when Chlamydia trachomatis is suspected, appropriate antichlamydial coverage must be added 2

Clinical Context and Comparative Spectrum

• Ceftriaxone has broader spectrum than first- and second-generation cephalosporins against Gram-negative bacteria, but less activity than earlier cephalosporins against many Gram-positive bacteria 4
• Compared to cefazolin, ceftriaxone has broader overall spectrum but cefazolin should be preferred for MSSA infections to minimize antimicrobial resistance 6
• The extended half-life (5.8-8.7 hours) allows once-daily dosing, offering convenience advantages over other parenteral antibiotics 7, 8

Common Pitfalls and Caveats

• Do not use ceftriaxone as monotherapy when narrower-spectrum agents like cefazolin are appropriate for MSSA, as this contributes to antimicrobial resistance 1, 6
• Do not rely on ceftriaxone alone for intra-abdominal infections—always combine with metronidazole for anaerobic coverage 5, 1
• Do not use for MRSA infections—vancomycin, linezolid, or daptomycin are required 5
• Do not use as sole therapy for severe community-acquired pneumonia without adding macrolide or fluoroquinolone coverage for atypicals 1
• Avoid as monotherapy for Pseudomonas infections—use anti-pseudomonal beta-lactams or carbapenems instead 4
• For diabetic foot infections, ceftriaxone is listed as an option for moderate-to-severe infections but has suboptimal activity against S. aureus compared to other agents 5