15.4 Gram-Negative Cocci/Coccobacilli & Fermentative/Nonfermenting Rods

Gram-Negative Cocci: Neisseria

The genus Neisseria contains Gram-negative diplococci (coffee-bean–shaped pairs). Two species are major pathogens:

N. meningitidis colonizes the nasopharynx and is transmitted by respiratory droplets; adolescents, military recruits, and asplenic/complement-deficient patients are at highest risk. Meningococcemia produces petechial/purpuric rash, septic shock, and Waterhouse-Friderichsen syndrome — bilateral adrenal hemorrhage with adrenal insufficiency. Endotoxin (lipooligosaccharide, LOS) drives the vasculitis and shock. Treatment is ceftriaxone (or penicillin); chemoprophylaxis of close contacts uses rifampin, ciprofloxacin, or ceftriaxone.

N. gonorrhoeae causes mucopurulent urethritis (dysuria and discharge), cervicitis, pelvic inflammatory disease (PID), and disseminated gonococcal infection (DGI) — migratory polyarthritis, tenosynovitis, and pustular rash on distal extremities. Neonatal ophthalmia neonatorum is prevented by silver nitrate or erythromycin eye prophylaxis. Drug resistance (penicillin, fluoroquinolones) is widespread; ceftriaxone (plus azithromycin or doxycycline for chlamydial co-infection) is first-line.

Gram-Negative Coccobacilli

Haemophilus influenzae

Small Gram-negative coccobacillus that requires both factor V (NAD) and factor X (hemin) for growth on chocolate agar (which provides both). It does not grow on blood agar unless a 'satellite' streak of S. aureus supplies factor V.

• Encapsulated type b (Hib): epiglottitis ('cherry-red' epiglottis, drooling, tripod posture), meningitis, cellulitis, septic arthritis in unvaccinated children. Hib conjugate vaccine transformed pediatric epidemiology.
• Nontypeable strains: otitis media, sinusitis, exacerbations of COPD.
• Treatment: ceftriaxone for serious disease; amoxicillin-clavulanate for otitis.

Bordetella pertussis

Strictly aerobic, small Gram-negative coccobacillus that causes whooping cough (pertussis). Virulence factors include pertussis toxin (PT) — an AB toxin that ADP-ribosylates Gi, locking adenylyl cyclase 'on' → increased cAMP, lymphocytosis, and sensitivity to histamine — filamentous hemagglutinin (FHA), adenylate cyclase toxin, and tracheal cytotoxin (ciliostasis).

Clinically, pertussis has three stages:

1. Catarrhal (1–2 wk): rhinorrhea, low fever, malaise — most contagious.
2. Paroxysmal (2–6 wk): paroxysms of coughing followed by inspiratory whoop and post-tussive vomiting.
3. Convalescent (weeks–months): lingering cough.

Diagnosis: nasopharyngeal PCR (most sensitive early) and culture on Bordet-Gengou (potato) agar (charcoal-containing Regan-Lowe transport). Treatment and post-exposure prophylaxis use macrolides (azithromycin); the acellular pertussis vaccine (Tdap) contains pertussis toxoid and filamentous hemagglutinin.

Enterobacteriaceae: Fermentative Gram-Negative Rods

The family Enterobacteriaceae comprises oxidase-negative, glucose-fermenting, nitrate-reducing Gram-negative rods. Most grow on MacConkey agar as lactose-fermenters (pink) or non-lactose-fermenters (colorless). They are the most common cause of urinary tract infections, intra-abdominal sepsis, and gram-negative bacteremia.

Lactose-Fermenters

Non-Lactose-Fermenters

Distinctions That Appear on Exams

• Salmonella vs. Shigella: Salmonella is motile, invades enterocytes and multiplies within macrophages, and bacteremia is common; Shigella is nonmotile, spreads cell-to-cell via actin rockets, and causes a more local colitis. Salmonella Typhi causes typhoid fever — step-ladder fever, rose spots, splenomegaly, ileal Peyer patch hypertrophy; treat with ceftriaxone (resistance to fluoroquinolones and chloramphenicol is common).
• E. coli diarrheagenic variants:
  • ETEC (enterotoxigenic): traveler's diarrhea (LT and ST toxins, no invasion).
  • EPEC (enteropathogenic): infantile diarrhea, attaching-and-effacing lesions.
  • EHEC (enterohemorrhagic, e.g., O157:H7): Shiga-like toxin; bloody diarrhea without fever; hemolytic-uremic syndrome (HUS). Avoid antibiotics — they increase Shiga toxin release.
  • EIEC (enteroinvasive): dysentery-like.
  • EAEC (enteroaggregative): persistent pediatric diarrhea.
• Klebsiella pneumonia classically presents with currant-jelly sputum in an alcoholic or diabetic patient.
• Proteus produces urease, raising urine pH and forming struvite (magnesium ammonium phosphate) stones.

Nonfermenting Gram-Negative Rods: Pseudomonas

Pseudomonas aeruginosa is a strict aerobe, oxidase-positive (distinguishes it from Enterobacteriaceae), and produces pyocyanin (blue) and pyoverdin (fluorescent green) pigments. It thrives in water and moist environments and is a major nosocomial and opportunistic pathogen.

Clinical Syndromes

• Ecthyma gangrenosum: hemorrhagic, necrotic skin lesions in bacteremic neutropenic patients.
• Malignant otitis externa: invasive Pseudomonas otitis in diabetics, spreading to skull base (osteomyelitis).
• Hot-tub folliculitis: self-limited pustular rash from contaminated water.
• Cystic fibrosis lung disease: chronic infection driven by mucoid (alginate) exopolysaccharide biofilm; multi-drug resistant over time.
• Burn-wound sepsis: green-blue exudate, high mortality.
• Contact-lens keratitis: rapid corneal ulceration.

Antibiotics

Pseudomonas is intrinsically resistant to many antibiotics. Active agents include piperacillin-tazobactam, ceftazidime or cefepime, meropenem/imipenem (imipenem requires cilastatin to block renal dehydropeptidase), aztreonam (safe in penicillin-allergic patients), aminoglycosides (amikacin, tobramycin), ciprofloxacin/levofloxacin, and colistin (last-line for carbapenem-resistant strains). Severe infections warrant combination therapy and source control.

Fermenter vs. Nonfermenter Summary