What are the recommended first‑line antibiotic regimens for infections caused by the gram‑negative diplococci Neisseria gonorrhoeae, Neisseria meningitidis, and Moraxella catarrhalis?

Antibiotic Treatment for Gram-Negative Diplococci Infections

For Neisseria gonorrhoeae, use ceftriaxone 500 mg IM as a single dose (or 1 g IM if weight ≥150 kg); for Neisseria meningitidis, use penicillin G or ceftriaxone; and for Moraxella catarrhalis, use amoxicillin-clavulanate or a respiratory fluoroquinolone, as these organisms have distinct resistance patterns and clinical presentations requiring pathogen-specific therapy.

Neisseria gonorrhoeae (Gonococcal Infections)

First-Line Treatment for Uncomplicated Infections

• Ceftriaxone monotherapy is now the recommended first-line treatment, with azithromycin no longer routinely added due to rising macrolide resistance 1.
• The standard dose is ceftriaxone 500 mg IM as a single dose (or 1 g IM if patient weight ≥150 kg) 1.
• Cefixime 400 mg orally as a single dose is an alternative when ceftriaxone is unavailable, though it is less effective for pharyngeal infections 2, 3.

Critical Resistance Considerations

• Ceftriaxone resistance is emerging globally, particularly with the FC428 strain harboring the penA-60.001 allele, with resistance rates approaching 9% in some regions of China 1.
• Pharyngeal infections are particularly problematic because they are harder to treat due to unfavorable cephalosporin pharmacokinetics in pharyngeal tissue and play a pivotal role in resistance emergence 1.
• Historical regimens using penicillin are obsolete for empiric therapy due to widespread penicillinase-producing strains 1, 4.

Treatment Failure Management

• For ceftriaxone treatment failures, consider higher doses (1-2 g IM daily) for 3 days or extended duration therapy 1.
• Ertapenem 1 g IM daily for 3 days is recommended by European guidelines as an alternative for ceftriaxone-resistant strains 5.
• Gentamicin 240 mg IM plus azithromycin 2 g orally is another alternative regimen when susceptibility testing is available 1.
• Ciprofloxacin can be used only when molecular testing confirms susceptibility (MIC <0.125 mg/L), as it treats 92-100% of pharyngeal infections in susceptible strains 1.

Site-Specific Treatment Nuances

• Pharyngeal infections require particular attention: combination regimens (ceftriaxone plus azithromycin or doxycycline) may be more effective than monotherapy, with persistent infection rates of 1.8% versus 5.8% respectively 1.
• For neonatal gonococcal ophthalmia: use ceftriaxone 25-50 mg/kg IV or IM (not to exceed 125 mg) as a single dose, and hospitalize for evaluation of disseminated infection 1, 6.

Neisseria meningitidis (Meningococcal Infections)

Treatment Approach

• Penicillin G remains effective for meningococcal infections when strains are susceptible, using the same regimen as for pneumococcal endocarditis 1, 4.
• Ceftriaxone is an equally effective alternative and is often preferred empirically given its broader coverage 1.
• Meningococcal infections causing endocarditis or meningitis require immediate treatment and infectious disease consultation 1.

Clinical Context

• Meningococcal respiratory infections are rare but serious, requiring prompt recognition and treatment 7.
• Late complement component deficiencies are associated with increased risk of meningococcal and gonococcal endocarditis 1.

Moraxella catarrhalis

First-Line Treatment

• Most M. catarrhalis strains produce beta-lactamase (>90%), making amoxicillin ineffective 8.
• Amoxicillin-clavulanate, respiratory fluoroquinolones, or second/third-generation cephalosporins are appropriate choices 7, 8.
• Cefixime is FDA-approved for otitis media caused by M. catarrhalis at 8 mg/kg/day in pediatric patients 2.

Clinical Presentations

• M. catarrhalis commonly causes acute exacerbations of chronic bronchitis, pneumonia, sinusitis, and otitis media 2, 7, 8.
• It rarely causes endocarditis but when it does, typically involves abnormal or prosthetic valves 1.

Critical Pitfalls to Avoid

• Never use azithromycin monotherapy for gonorrhea due to high resistance rates and concerns about further resistance development in other pathogens 1.
• Do not substitute cefixime tablets for suspension in treating otitis media, as the suspension achieves higher peak blood levels 2.
• Always obtain cultures before treatment when possible for gonorrhea, as susceptibility testing is increasingly important given evolving resistance 1.
• Gram-positive diplococci on urethral smear do not indicate gonococcal infection—only gram-NEGATIVE intracellular diplococci are diagnostic 9.
• Treat mothers and sexual partners of infants with gonococcal or chlamydial ophthalmia according to adult STD guidelines to prevent reinfection 6.