Gram Negative Cocci: Neisseria and Moraxella

Neisseria species are Gram negative diplococci, classically described as kidney bean or coffee bean shaped, with adjacent flattened surfaces.

They are oxidase positive, a key genus-level identifying test, aerobic, fastidious, requiring enriched media for growth, and capnophilic, growing better with added CO2.

Two species are of major medical importance, both human-restricted pathogens with no significant animal or environmental reservoir: Neisseria meningitidis and Neisseria gonorrhoeae.

Morphology. Gram negative diplococci, encapsulated.

Important laboratory features. Oxidase positive, ferments both glucose and maltose, distinguishing it from N. gonorrhoeae, which ferments glucose only, a classic differentiating biochemical test.

Reservoir. Human nasopharynx. Asymptomatic carriage is common, up to 10 to 25 percent of the population at any time, with invasive disease representing an uncommon consequence of an otherwise typically benign colonisation state.

Transmission. Respiratory droplets, close and prolonged contact, household, university dormitory, military barracks settings are classically associated with outbreaks given close-quarters living.

Virulence factors. Polysaccharide capsule, antiphagocytic, serogroup-defining, lipooligosaccharide, LOS, the meningococcal equivalent of LPS, directly responsible for the severe endotoxin-mediated shock seen in fulminant meningococcaemia, IgA protease, pili, adhesion and colonisation.

Major diseases. Meningitis presents with fever, headache, neck stiffness, photophobia, potentially rapidly progressive. Meningococcaemia is bloodstream invasion, with a classic non-blanching petechial or purpuric rash, and in fulminant cases, disseminated intravascular coagulation, shock, and Waterhouse-Friderichsen syndrome, bilateral adrenal haemorrhage causing acute adrenal insufficiency, a specific complication of fulminant meningococcal sepsis.

Diagnosis. CSF Gram stain and culture, blood culture, PCR, increasingly the preferred rapid method given the organism's fragility and susceptibility to killing during transport, which reduces culture sensitivity, CSF and serum antigen testing in some settings.

Resistance patterns. Remains generally penicillin susceptible in most regions, though resistance is emerging and monitored. Empirical therapy for suspected meningitis is broader, typically a third-generation cephalosporin, pending organism identification, given the range of possible causative organisms at presentation.

Prevention. Conjugate vaccines targeting the major serogroups, A, C, W, Y commonly combined, a separate vaccine for serogroup B given its distinct, poorly immunogenic capsular polysaccharide, requiring a different, protein-based vaccine approach. Close contacts of a confirmed case require prompt antibiotic chemoprophylaxis regardless of their own vaccination status, since prophylaxis specifically targets eradication of nasopharyngeal carriage to interrupt onward transmission.

Morphology. Gram negative diplococci, nonencapsulated.

Important laboratory features. Oxidase positive, ferments glucose only, not maltose, distinguishing it from N. meningitidis.

Reservoir. Human genital, rectal, and oropharyngeal mucosa. No significant asymptomatic reservoir outside actively or recently infected individuals in the way meningococcal nasopharyngeal carriage exists.

Transmission. Sexual contact, genital, anal, oral. Vertical transmission from an infected mother to the neonate during vaginal delivery causes ophthalmia neonatorum, a sight-threatening neonatal conjunctivitis, historically a leading cause of infectious blindness, now largely prevented by routine neonatal ocular prophylaxis in most settings.

Virulence factors. Pili, adhesion, and a classic example of antigenic and phase variation, allowing repeated reinfection and immune evasion since antibody generated against one pilin variant does not protect against reinfection with an antigenically distinct variant. Opacity, Opa, proteins provide further adhesion and phase variation. IgA protease and lipooligosaccharide are also present.

Major diseases. In men, predominantly symptomatic urethritis, purulent discharge, dysuria.

In women, infection is frequently asymptomatic or mildly symptomatic cervicitis. This is an important epidemiological point, since asymptomatic infection facilitates ongoing transmission and delays presentation, increasing the risk of ascending complications.

The complications include:

• pelvic inflammatory disease, itself a risk factor for tubal infertility and ectopic pregnancy
• epididymo-orchitis in men
• disseminated gonococcal infection, bacteraemic spread causing a triad of migratory polyarthralgia, tenosynovitis, and a sparse pustular or vesiculopustular skin rash, sometimes with frank septic arthritis
• ophthalmia neonatorum

Diagnosis. Nucleic acid amplification testing, NAAT, PCR, is now the standard diagnostic approach given superior sensitivity to culture. Culture remains important where available specifically because it allows antimicrobial susceptibility testing, given the organism's evolving and clinically significant resistance profile. Gram stain of urethral discharge showing intracellular Gram negative diplococci within neutrophils is considered diagnostic in symptomatic men, but has lower sensitivity in women and is not relied upon alone in that context.

Resistance patterns. N. gonorrhoeae has progressively developed resistance to multiple antibiotic classes over recent decades, penicillins, tetracyclines, fluoroquinolones, and increasingly reduced susceptibility to some cephalosporins, a major and actively monitored global antimicrobial resistance concern, directly relevant to evolving treatment guideline recommendations.

Prevention. No vaccine currently available, a direct consequence of the organism's extensive antigenic variation capacity, which has historically frustrated vaccine development. Barrier contraception, partner notification and treatment, and routine screening in at-risk populations are the principal prevention strategies.

Morphology. Gram negative diplococci, resembling Neisseria morphologically.

Important laboratory features. Oxidase positive, distinguished from Neisseria species by the characteristic hockey puck sign, the colony can be pushed intact across the agar surface without disruption, and by specific biochemical testing, DNase positive, unlike Neisseria.

Reservoir. Human upper respiratory tract. Colonisation is common, particularly in children.

Transmission. Respiratory droplets. Disease typically arises from an endogenously colonising strain, often in the setting of a preceding viral upper respiratory infection or underlying chronic lung disease.

Virulence factors. Relatively low intrinsic virulence overall. Adhesins facilitate colonisation of the respiratory mucosa.

Major diseases. A common cause of otitis media and sinusitis in children, alongside S. pneumoniae and nontypeable H. influenzae, the three classic bacterial causes of these syndromes, and a cause of exacerbations of chronic obstructive pulmonary disease and, less commonly, pneumonia in adults with underlying chronic respiratory disease.

Diagnosis. Culture from the relevant respiratory specimen. Identification relies on the biochemical and morphological features above given its resemblance to Neisseria.

Resistance patterns. The great majority of isolates produce beta-lactamase, conferring resistance to amoxicillin unless combined with a beta-lactamase inhibitor, a clinically relevant point when selecting empirical therapy for suspected otitis media or sinusitis.