Key Facts

Microbiology is fundamental to understanding infectious disease, antimicrobial selection, and infection control. Correct identification of causative organisms guides targeted therapy and improves outcomes.

Epidemiology

Healthcare-associated infections (HCAIs) affect approximately 6.4% of hospital inpatients in the UK. Sepsis affects ~48,000 people per year, causing ~11,000 deaths. C. difficile causes ~13,000 cases per year in England. Antimicrobial resistance is a growing global threat.

Aetiology

Bacterial classification:

• Gram-positive cocci: S. aureus (clusters), S. pneumoniae (diplococci, lancet-shaped), S. pyogenes (chains)
• Gram-positive bacilli: Clostridium (anaerobic, spore-forming), Listeria, Bacillus
• Gram-negative cocci: Neisseria meningitidis, N. gonorrhoeae
• Gram-negative bacilli: E. coli, Klebsiella, Pseudomonas, Salmonella, Campylobacter
• Atypicals: Mycoplasma (no cell wall), Legionella, Chlamydia
• Acid-fast bacilli: Mycobacterium tuberculosis (Ziehl-Neelsen stain)

Pathophysiology

Virulence factors:

• Endotoxin (LPS): Gram-negative cell wall component — triggers TNF-α, IL-1, IL-6 release → sepsis cascade
• Exotoxins: Secreted proteins — e.g., Clostridium tetani (tetanospasmin), C. botulinum (botulinum toxin), S. aureus (TSST-1, PVL)
• Biofilm formation: Prosthetic device infections — protects bacteria from antibiotics and host immunity
• Immune evasion: Capsule (S. pneumoniae), protein A (S. aureus), antigenic variation (N. gonorrhoeae)

Antimicrobial mechanisms:

• Cell wall synthesis inhibitors: Beta-lactams, glycopeptides
• Protein synthesis inhibitors: Aminoglycosides (30S), macrolides, tetracyclines (30S), chloramphenicol (50S)
• Nucleic acid inhibitors: Fluoroquinolones (DNA gyrase), metronidazole, rifampicin (RNA polymerase)
• Folate synthesis inhibitors: Trimethoprim, sulphonamides

Community-Acquired Infections

• Pneumonia: Cough, fever, pleuritic pain, consolidation on CXR
• UTI: Dysuria, frequency, suprapubic pain; pyelonephritis adds flank pain, fever, rigors
• Skin/soft tissue: Cellulitis (S. aureus, S. pyogenes), abscess formation
• Meningitis: Headache, neck stiffness, photophobia, non-blanching rash (meningococcal)

Hospital-Acquired Infections

• MRSA: Wound infection, line-related bacteraemia
• C. difficile: Watery diarrhoea, abdominal pain after antibiotic exposure
• Pseudomonas: Ventilator-associated pneumonia, burns, immunocompromised
• Candidaemia: Central line infection, immunosuppressed patients

Red Flags

• Sepsis: qSOFA ≥2 (RR ≥22, altered mentation, systolic BP ≤100) — NICE Sepsis pathway
• Non-blanching petechial rash with fever — meningococcal septicaemia (give IM benzylpenicillin)
• Necrotising fasciitis: Rapidly progressive cellulitis with systemic toxicity, disproportionate pain

Bedside

• Observations: Temperature, HR, RR, BP, SpO2, GCS — NEWS2 score
• Urine dipstick: Leucocytes, nitrites, blood

Bloods

• Blood cultures: Two sets from different sites BEFORE antibiotics
• FBC: WCC (neutrophilia = bacterial, lymphocytosis = viral)
• CRP, procalcitonin: Inflammatory markers
• Lactate: >2 mmol/L raises concern for sepsis; >4 mmol/L = severe

Imaging

• CXR: Pneumonia, empyema, TB
• USS/CT: Abscess collections, source identification

Special Tests

• Gram stain and culture: Identify organism and sensitivities
• Sensitivity testing: MIC (minimum inhibitory concentration)
• PCR: Rapid detection — meningococcal PCR, TB PCR (GeneXpert), viral PCR
• Serology: HIV, hepatitis, EBV, CMV
• Lumbar puncture: CSF analysis — cell count, protein, glucose, Gram stain, culture, PCR

Non-pharmacological

• Infection control: Hand hygiene, isolation precautions (contact, droplet, airborne)
• Antimicrobial stewardship: Review antibiotics at 48-72 hours, narrow spectrum when cultures available
• Source control: Drain abscesses, remove infected lines/prostheses

Pharmacological

Common empirical regimens (local guidelines vary):

• CAP: Amoxicillin 500mg TDS ± clarithromycin 500mg BD (moderate severity)
• HAP: Co-amoxiclav 1.2g TDS IV or piperacillin-tazobactam 4.5g TDS IV
• UTI: Nitrofurantoin 100mg MR BD (lower) or co-amoxiclav (upper)
• Meningitis: Ceftriaxone 2g BD IV + dexamethasone 0.15mg/kg QDS IV (before or with first antibiotic dose)
• Sepsis: Piperacillin-tazobactam 4.5g TDS IV (+ gentamicin 5mg/kg if severe)
• C. difficile: Oral vancomycin 125mg QDS for 10 days; fidaxomicin 200mg BD for recurrence
• MRSA: Vancomycin IV (target trough 15-20 mg/L) or linezolid 600mg BD

Referral Criteria

• MDR organisms — microbiology/infectious diseases
• Suspected TB — respiratory/infectious diseases
• Sepsis with organ dysfunction — critical care
• Prosthetic joint infection — orthopaedics + microbiology

• Sepsis: Overall mortality 15-20%; septic shock mortality 40-50%
• Community-acquired pneumonia: CURB-65 score 0-1 = <3% mortality; score 4-5 = >25%
• Bacterial meningitis: Mortality 10-30% depending on organism; ~20% have significant sequelae
• C. difficile: Mortality 1-5%; recurrence rate 20-30%; fulminant colitis mortality >50%
• MRSA bacteraemia: 30-day mortality approximately 20-30%

Antimicrobial Spectrum Summary

CSF Findings in Meningitis