Gram-negative bacteria
Gram-negative bacteria for FCPS: Salmonella, Neisseria, Pseudomonas, Vibrio, H. pylori
Gram-negative bacteria for FCPS Part 1: Neisseria, E. coli, Salmonella, Shigella, Pseudomonas, Haemophilus, Vibrio, Campylobacter and H. pylori. Covers culture clues, endotoxin, diseases and drugs, with typhoid, cholera and meningococcal disease in detail.
The Gram-negative envelope and endotoxin
- Gram-negative bacteria have a thin peptidoglycan layer and an outer membrane. Endotoxin (lipopolysaccharide) sits in that outer membrane: O antigen outside, core polysaccharide, and lipid A, the toxic part.
- Lipid A binds CD14 and TLR4 on macrophages, which release IL-1, TNF and nitric oxide: fever, vasodilatation, septic shock and DIC. This is why a Gram-negative UTI (*E. coli*, *Klebsiella*, *Proteus*) can cause a shock-like state even in a well-controlled diabetic. Endotoxin is heat-stable and cannot be made into a toxoid.
Gram-negative cocci: *Neisseria*
| Feature | *N. meningitidis* | *N. gonorrhoeae* |
|---|---|---|
| Capsule | Yes (vaccines ACWY, B) | No |
| Sugars | Glucose and maltose | Glucose only |
| Disease | Meningitis, septicaemia with non-blanching rash, Waterhouse–Friderichsen adrenal haemorrhage | Urethritis, cervicitis, PID, septic arthritis, ophthalmia neonatorum (days 2–5), disseminated infection |
| Treatment | IV ceftriaxone (pre-hospital IM benzylpenicillin); contacts get single-dose ciprofloxacin or rifampicin | IM ceftriaxone, plus treat chlamydia |
- Both are oxidase-positive, kidney-bean Gram-negative diplococci grown on chocolate or Thayer–Martin agar in CO₂. Terminal complement deficiency (C5–C9) predisposes to recurrent neisserial infection.
- *Moraxella catarrhalis*: otitis media, sinusitis, COPD exacerbations; makes beta-lactamase.
Enterobacteriaceae
- Oxidase-negative facultative rods. Lactose fermenters (pink on MacConkey): *E. coli*, *Klebsiella*, *Enterobacter*, *Citrobacter*. Non-lactose fermenters: *Salmonella*, *Shigella*, *Proteus*, *Yersinia*. H₂S producers: *Salmonella*, *Proteus*.
- *Proteus mirabilis*: swarming in waves over the whole plate, produced by abundant peritrichous flagella; urease splits urea to ammonia, alkalinising urine and precipitating struvite (magnesium ammonium phosphate) staghorn stones, typically with long-term catheters. Pseudomonas is also a non-lactose fermenter in catheters, but it is oxidase positive and does not swarm. Stones must be cleared completely or infection persists.
*Escherichia coli*
| Type | Mechanism | Disease |
|---|---|---|
| Uropathogenic | P fimbriae | Commonest cause of UTI, pyelonephritis, urosepsis |
| ETEC | LT (cAMP) and ST (cGMP) toxins | Commonest cause of traveller's diarrhoea (watery) |
| EHEC O157:H7 | Shiga-like toxin; does not ferment sorbitol | Bloody diarrhoea, haemolytic uraemic syndrome; antibiotics may worsen toxin release |
| EIEC | Invasion | Dysentery |
| EPEC | Attaching and effacing | Infant diarrhoea |
| K1 capsule | Neonatal meningitis (with group B streptococcus) |
- Also biliary sepsis, spontaneous bacterial peritonitis, peritonitis after perforation, wound and hospital infections; ESBL producers need carbapenems.
*Klebsiella pneumoniae*
- Thick mucoid capsule, non-motile. Pneumonia in alcoholics and diabetics: upper lobe, cavitation, "red currant jelly" sputum, bulging fissure; also UTI, liver abscess (hypervirulent strains, which can seed the eye) and hospital infection, often with carbapenemases (KPC, NDM). It is a typical opportunistic and hospital pathogen.
- *K. granulomatis*: donovanosis (Donovan bodies).
*Salmonella*
- Typhoid: *S.* Typhi and Paratyphi; humans are the only reservoir. Organisms cross the gut through Peyer's patches, multiply in macrophages, and after bacteraemia settle in the liver, spleen, bone marrow and gallbladder.
- Step-ladder fever, relative bradycardia, rose spots, splenomegaly, coated tongue, leucopenia. Ulcers over Peyer's patches lie along the long axis of the ileum and perforate in the third week, usually in the terminal ileum.
- Diagnosis: blood culture in week one; bone marrow culture most sensitive; stool and urine later; Widal unreliable.
- Chronic carriers harbour it in the gallbladder (with gallstones); they should be identified, treated and kept from food handling; cholecystectomy if treatment fails.
- XDR typhoid (Sindh, 2016 onwards): resistant to first-line drugs, fluoroquinolones and third-generation cephalosporins; azithromycin for uncomplicated, meropenem for complicated disease. The typhoid conjugate vaccine (Vi antigen) is in Pakistan's EPI.
- Non-typhoidal Salmonella (poultry, eggs): gastroenteritis after 12–48 hours; osteomyelitis in sickle cell disease; bacteraemia in HIV.
*Shigella* and *Yersinia*
- *Shigella*: tiny infectious dose (10–200 organisms), non-motile, invades colonic M cells; Shiga toxin (*S. dysenteriae* type 1). Bloody mucoid dysentery with tenesmus; HUS, reactive arthritis, febrile seizures. Azithromycin or ceftriaxone.
- *Y. enterocolitica*: mesenteric adenitis and terminal ileitis that mimic appendicitis; grows at 4 °C (transfused blood).
- *Y. pestis* (plague): rats are the reservoir and the rat flea the vector; painful buboes, septicaemic and pneumonic forms; bipolar "safety-pin" staining; streptomycin, gentamicin or doxycycline.
*Pseudomonas aeruginosa*
- Oxidase positive, non-fermenter, strict aerobe; blue-green pigment (pyocyanin, fluorescein), grape-like smell; biofilm; exotoxin A (EF-2). Infections are worse with neutropenia, burns, diabetes, ventilation and catheters.
- Infections: burns, cystic fibrosis (mucoid strains; main cause of decline and death), ventilator-associated pneumonia, malignant otitis externa in elderly diabetics, hot-tub folliculitis, contact lens corneal ulcers, osteomyelitis of the foot after a nail through a trainer, catheter UTI, ecthyma gangrenosum.
- Antipseudomonal drugs: piperacillin–tazobactam, ceftazidime, cefepime, meropenem (not ertapenem), aminoglycosides, ciprofloxacin (the only oral option), aztreonam, colistin.
Other Gram-negative rods
| Organism | Key points |
|---|---|
| *Haemophilus influenzae* | Needs factors X (haemin) and V (NAD): chocolate agar, satellitism around *S. aureus*; type b capsule causes epiglottitis (thumb sign), meningitis, septic arthritis in unvaccinated children; non-typeable strains: otitis media, COPD; ceftriaxone; rifampicin for contacts |
| *H. ducreyi* | Chancroid: painful ulcer, suppurating buboes |
| *Bordetella pertussis* | Catarrhal, paroxysmal (whoop, post-tussive vomiting), convalescent stages; marked lymphocytosis; azithromycin; maternal vaccination |
| *Legionella* | Air-conditioning cooling towers, hotel water; pneumonia with hyponatraemia, diarrhoea, confusion; urinary antigen is the quickest test; BCYE agar; macrolide or quinolone; no person-to-person spread |
| *Brucella* | Unpasteurised milk, livestock; undulant fever, sweats, sacroiliitis, orchitis; doxycycline plus rifampicin |
| *Vibrio cholerae* | Curved, comma-shaped, darting motility; spread by contaminated water and food; humans the only reservoir; TCBS agar (yellow colonies), alkaline peptone water; toxin raises cAMP: painless rice-water stools; ORS or Ringer's lactate; doxycycline or azithromycin |
| *V. vulnificus* | Seafood, wound infection; septicaemia in liver disease |
| *Campylobacter jejuni* | Curved or "seagull" rods, microaerophilic, 42 °C; undercooked poultry; bloody diarrhoea; Guillain–Barré syndrome, reactive arthritis |
| *Helicobacter pylori* | Spiral, flagellated, urease makes ammonia that buffers acid and injures mucosa; antral gastritis, duodenal ulcer (about 90%), gastric ulcer, gastric adenocarcinoma, MALT lymphoma |
| *Bacteroides fragilis* | Main anaerobe of intra-abdominal abscess; metronidazole |
| *Fusobacterium necrophorum* | Lemierre syndrome: sore throat, then internal jugular thrombophlebitis and septic lung emboli |
| *Gardnerella vaginalis* | Bacterial vaginosis: clue cells, fishy whiff test, pH over 4.5 |
| *Pasteurella multocida* | Cat and dog bites; rapid cellulitis; co-amoxiclav |
| *Bartonella henselae* | Cat-scratch disease; bacillary angiomatosis in AIDS |
| *Burkholderia pseudomallei* | Melioidosis in diabetic rice farmers; safety-pin staining |
- *H. pylori* tests: the urea breath test and stool antigen are the most convenient non-invasive tests and confirm eradication (stop PPIs 2 weeks before); rapid urease (CLO) test and histology need endoscopy; serology stays positive after cure.
- Whipple disease (*Tropheryma whipplei*, a Gram-positive actinomycete, included here as a cause of malabsorption): arthritis years before steatorrhoea and weight loss, pigmentation; PAS-positive foamy macrophages in the lamina propria.
Remember Lactose fermentation on MacConkey and oxidase are the two first questions for any Gram-negative rod.
Exam trap Typhoid perforation happens in the third week, in the terminal ileum; XDR typhoid needs azithromycin or meropenem.
Exam trap Meningococcus ferments maltose; gonococcus does not. Swarming plus urease means *Proteus*, not *Pseudomonas*.
How FCPS asks about this
- Endotoxin: lipid A in the outer membrane causes fever and septic shock; no toxoid.
- Typhoid: organisms reside in the reticuloendothelial system and gallbladder; blood culture in week one; carriers must be treated.
- Traveller's diarrhoea: ETEC; O157:H7 causes HUS.
- Proteus: swarming from peritrichous flagella, urease and struvite stones in catheterised patients.
- Cholera: curved Gram-negative rod spread by water and food; rice-water stools; ORS.
- H. pylori: urea breath test or stool antigen; urease and ammonia injure mucosa.
- Plague, Legionella, Lemierre: rat reservoir and flea vector; cooling towers and urinary antigen; *Fusobacterium* with jugular thrombosis.
Test yourself on this topic
5 of the 59 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A healthy 19-year-old had a sore throat a week ago. He now has high fever, tender swelling along the side of the neck and pleuritic chest pain. CT shows thrombosis of the internal jugular vein and multiple cavitating lung nodules. Which organism is most likely?
Answer: Fusobacterium necrophorum
Lemierre syndrome is septic thrombophlebitis of the internal jugular vein after a pharyngeal infection (sometimes peritonsillar abscess or dental infection), typically in previously healthy adolescents and young adults. The usual cause is Fusobacterium necrophorum, an anaerobic Gram-negative rod that is part of the oral flora. Infection spreads into the parapharyngeal space and the neighbouring internal jugular vein, the infected thrombus sheds septic emboli, especially to the lungs (cavitating nodules, empyema), and occasionally to joints and liver. Treatment is prolonged antibiotics with anaerobic cover (a penicillin with a β-lactamase inhibitor, or metronidazole with a cephalosporin), plus drainage of collections.
Lemierre syndrome
- After pharyngitis in a young adult
- Internal jugular vein septic thrombophlebitis
- Septic lung emboli: cavitating nodules
- Organism: Fusobacterium necrophorum (anaerobe)
- Long antibiotics with anaerobic cover
Remember Sore throat, swollen neck vein, spots in the lungs.
Exam trap Remember the anaerobe: standard throat-infection antibiotics may not cover it adequately.
Why the other options are wrong
- Streptococcus pyogenes Group A streptococcus causes pharyngitis and quinsy, but internal jugular septic thrombophlebitis with lung emboli is classically fusobacterial.
- Epstein–Barr virus EBV causes glandular fever, not septic thrombophlebitis.
- Staphylococcus aureus S. aureus causes septic emboli, mostly from right-sided endocarditis.
- Corynebacterium diphtheriae Diphtheria causes a pseudomembrane and myocarditis.
Endoscopy shows a low-grade lymphoma of the gastric mucosa in a patient with chronic Helicobacter pylori gastritis. What is the first-line treatment for early disease?
Answer: H. pylori eradication
Gastric MALT lymphoma (extranodal marginal zone B-cell lymphoma) arises from lymphoid tissue acquired in response to chronic H. pylori gastritis; the B-cell proliferation is initially driven by H. pylori-specific T cells. Localised, early-stage disease often regresses completely after eradication therapy (e.g. PPI plus clarithromycin and amoxicillin or metronidazole). Tumours with t(11;18) are less likely to respond and may need radiotherapy or rituximab. Other H. pylori outcomes: peptic ulcer, chronic gastritis, gastric adenocarcinoma.
Gastric MALT lymphoma
- Driven by H. pylori gastritis
- Early: eradication therapy → regression
- t(11;18): poor response
- H. pylori also: ulcers, gastric adenocarcinoma
Remember Kill the bug, shrink the lymphoma.
Why the other options are wrong
- Total gastrectomy Rarely needed.
- Immediate high-dose chemotherapy Not first-line for early MALT lymphoma.
- Whole-abdomen radiotherapy Not first-line.
- Observation without treatment Treatment is needed.
In the third week of typhoid fever, a patient develops sudden peritonitis from intestinal perforation. Where does perforation usually occur and why?
Answer: Terminal ileum (Peyer's patches)
Salmonella Typhi invades through M cells over Peyer's patches (aggregated lymphoid follicles, most abundant in the terminal ileum on the antimesenteric border). Hyperplasia and necrosis of these patches produce longitudinal ulcers in the second to third week, which may bleed or perforate (typhoid perforation is common in South Asia). Tuberculous ulcers, by contrast, are transverse (following lymphatics). Perforation needs resuscitation, antibiotics and surgery.
Typhoid perforation
- Peyer's patches: terminal ileum, antimesenteric
- Ulcers are longitudinal (TB ulcers: transverse)
- Perforation: 3rd week
- Commonly seen in South Asia
Remember Typhoid ulcers run along the gut; TB ulcers run around it.
Why the other options are wrong
- Duodenum at the papilla Not the usual site.
- Jejunum at the plicae Peyer's patches are mainly ileal.
- Sigmoid colon at diverticula Diverticulitis, not typhoid.
- Appendix at its base Appendicitis, not typhoid.
A child has a tender enlarged axillary lymph node two weeks after being scratched by a kitten. Node biopsy shows stellate necrotising granulomas with central neutrophils. What is the organism?
Answer: Bartonella henselae
Cat-scratch disease is caused by Bartonella henselae, a small Gram-negative bacillus (seen with Warthin-Starry silver stain). After a cat scratch or bite, a papule forms and regional lymphadenopathy follows 1–3 weeks later. Nodes show necrotising granulomas with stellate (star-shaped) microabscesses containing neutrophils. It is usually self-limiting; azithromycin may help. In HIV, Bartonella causes bacillary angiomatosis. Pasteurella causes rapid cellulitis within a day of a bite.
Cat-scratch disease
- Bartonella henselae
- Node: stellate necrotising granulomas
- Silver stain (Warthin-Starry)
- HIV: bacillary angiomatosis
Remember Kitten scratch, star-shaped abscess.
Why the other options are wrong
- Mycobacterium tuberculosis Caseating granulomas, no stellate abscesses.
- Toxoplasma gondii Lymphadenopathy with reactive follicles; cat faeces.
- Pasteurella multocida Cellulitis within 24 hours of a bite.
- Sporothrix schenckii Rose-thorn injury, nodules along lymphatics.
What is the most common cause of acute haematogenous osteomyelitis in all age groups, and which organism is particularly linked to sickle cell disease?
Answer: S. aureus; Salmonella in sickle
S. aureus is the commonest cause overall. Salmonella is classically associated with sickle cell disease (infarcted bone, gut organisms), though S. aureus still occurs. Pseudomonas: puncture through trainers, IV drug users. TB: spine (Pott's disease). Children: metaphysis of long bones. Neonates: group B strep, E. coli.
Osteomyelitis organisms
- Commonest: S. aureus
- Sickle cell: Salmonella
- Foot puncture: Pseudomonas; spine: TB (Pott's)
Remember Staph everywhere; Salmonella in sickle cell.
Why the other options are wrong
- S. pyogenes; E. coli Not the commonest.
- M. tuberculosis; Pseudomonas TB affects the spine; Pseudomonas after foot punctures.
- Haemophilus; S. epidermidis Not the commonest.
- Pseudomonas; Salmonella Pseudomonas is not commonest.
Where this sits in the CPSP syllabus
- Paper 1: Microbiology, Gram-negative bacteria: enterics, Neisseria, Haemophilus, Pseudomonas, Vibrio, H. pylori
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