gram-negative cocci

**Gram-negative cocci (GNC) – the "Big 3":** 1. **Neisseria meningitidis** (meningococcus) 2. **Neisseria gonorrhoeae** (gonococcus) 3. **Moraxella catarrhalis**

All are aerobic, **oxidase-positive**, non-spore-forming **diplococci** (kidney bean or coffee-bean shaped, with adjacent sides flattened). Veillonella (anaerobic GN cocci, oral/GI flora) is a rare, low-yield exception.

**Gram-negative structure:** The cell wall has a thin peptidoglycan layer and an outer membrane with **lipooligosaccharide (LOS)**. Neisseria has LOS rather than the O-antigen-bearing LPS of enteric rods. LOS is an endotoxin that activates TLR4, triggering cytokine release (IL-1, IL-6, TNF-α). This causes fever, DIC, and shock.

**Neisseria meningitidis** - Features: Polysaccharide capsule (virulence factor). Maltose fermenter. Grows on Thayer-Martin (chocolate agar with VPN: vancomycin, polymyxin/colistin, nystatin) in a CO₂-enriched environment. Transmitted by respiratory droplets. Humans are the only reservoir (nasopharyngeal carriers). - Disease: Meningitis (most common cause in adolescents and young adults), meningococcemia with a petechial or purpuric rash, and **Waterhouse-Friderichsen syndrome** (adrenal hemorrhage with DIC and shock). - Risk factors: Crowded living (dorms, military), asplenia, and **terminal complement deficiency (C5–C9)**, which causes recurrent Neisseria infections. - Treatment: Ceftriaxone or penicillin G. - Prophylaxis for close contacts: Rifampin, ciprofloxacin, or ceftriaxone. - Vaccines: Conjugate (MenACWY), and serogroup B (MenB) vaccines. Serogroup B is not in the MenACWY vaccine.

**Neisseria gonorrhoeae** - Features: **No capsule**. Does not ferment maltose (it ferments glucose only). Pili mediate attachment, and **antigenic variation** of pilus proteins (Opa and pilin) prevents lasting immunity and prevents effective vaccine development. IgA protease is also produced. Typically found **intracellularly in neutrophils** on Gram stain. - Disease: Urethritis and cervicitis, PID (with risk of infertility and ectopic pregnancy), epididymitis, **Fitz-Hugh–Curtis syndrome** (perihepatitis with "violin-string" adhesions), septic arthritis (the most common cause in sexually active young adults, which can be a **disseminated gonococcal infection** with the triad of migratory polyarthralgia, tenosynovitis, and dermatitis), and **neonatal conjunctivitis** (ophthalmia neonatorum, which presents 2–5 days after birth). Prophylaxis is erythromycin ointment. - Treatment: Ceftriaxone, **plus** doxycycline for presumptive chlamydial coinfection if chlamydia is not excluded. Always test for and treat coinfection with Chlamydia trachomatis.

**Moraxella catarrhalis** - Features: Often a **β-lactamase producer**, so it is resistant to penicillin and ampicillin. - Disease: Otitis media, sinusitis, and pneumonia or COPD exacerbations (a common cause in elderly or COPD patients). Along with Streptococcus pneumoniae and nontypeable H. influenzae, it is one of the most common causes of otitis media. - Treatment: Amoxicillin-clavulanate, a second- or third-generation cephalosporin, or a macrolide or TMP-SMX.

**Distinguishing Neisseria species** - Both ferment glucose. Only N. meningitidis ferments **maltose** (MeninGOCOCCUS = Maltose and Glucose; GONOCOCCUS = Glucose only). - Capsule: N. meningitidis has one. N. gonorrhoeae does not. - Vaccine: Available for N. meningitidis. None for N. gonorrhoeae (antigenic variation). - Neisseria species are the only bacteria in this group that grow on Thayer-Martin (selective for pathogenic Neisseria).

**Test pearls** - A gram-negative diplococcus in CSF suggests meningococcal meningitis. In synovial fluid or urethral discharge (intracellular in neutrophils), it suggests gonorrhea. - A teenager in a dorm with fever, headache, neck stiffness, and a petechial rash points to meningococcus. - A COPD patient with an exacerbation and gram-negative diplococci in sputum suggests Moraxella catarrhalis. - Recurrent Neisseria infections should raise suspicion for a terminal complement deficiency (check CH50). - Gonococcal and chlamydial infections often coexist, so treat for both.