Distinguishing Colonization from Infection
Colonization is the presence of microorganisms on body surfaces without tissue invasion or inflammatory response, while infection involves microbial invasion into viable tissue with an inflammatory host response and clinical symptoms. 1, 2
Core Definitions
Colonization is characterized by:
- Microorganisms present on body tissue surfaces (skin, respiratory tract, wounds) without causing disease 2, 3
- Growth and multiplication of bacteria without clinical symptoms or immune response 3
- Significant bacterial growth (>15 CFU in semi-quantitative culture or >100 CFU in quantitative culture) without accompanying clinical manifestations 2
Infection is characterized by:
- Tissue invasion beyond surface colonization 2
- Inflammatory host response with clinical symptoms 1
- Presence of fever, increased white blood cell count, or organ dysfunction 1
Clinical Approach to Differentiation
Assess Clinical Symptoms
Look for specific signs of infection rather than just positive cultures:
- Fever, leukocytosis, or organ dysfunction indicate infection rather than colonization 1
- In C. difficile cases, positive PCR tests without typical clinical symptoms suggest colonization rather than active infection 4
- Symptom correlation with testing results and response to previous therapies helps distinguish colonization from infection 4
Evaluate Sample Source
The anatomical site determines interpretation:
- Growth from sterile sites (blood, CSF) always indicates infection, never colonization 1
- Surface samples (endotracheal aspirates, wound swabs) require quantitative interpretation 1
- Candiduria in non-catheterized patients strongly suggests infection, while in catheterized patients it may represent colonization 1
Use Quantitative Cultures
Specific thresholds distinguish colonization from infection in respiratory samples:
- Endotracheal aspirates: ≥10^6 CFU/ml indicates infection 1
- Bronchoalveolar lavage (BAL): ≥10^4 CFU/ml indicates infection 1
- Protected specimen brush (PSB): ≥10^3 CFU/ml indicates infection 1
Perform Gram Stain Evaluation
Microscopic findings provide rapid differentiation:
- Many leukocytes with few epithelial cells suggests infection 1
- Detection of intracellular organisms in ≥2-5% of recovered cells strongly suggests infection (sensitivity 69%, specificity 75%) 1
Risk Factors for Progression
Colonization increases subsequent infection risk, particularly in specific populations:
- Asymptomatic C. difficile colonization increases CDI risk 6-fold 4
- Previous colonization with ESBL-producing Enterobacteriaceae is the most important risk factor for ESBL bloodstream infections in hematological patients 4
- Immunosuppression, invasive devices, and antimicrobial therapy disrupt normal flora balance and promote progression to infection 3
- Candida colonization at two or more sites correlates with increased risk of invasive infection 1
Special Considerations by Pathogen
C. difficile
Molecular testing alone cannot distinguish colonization from infection:
- PCR confirms presence of toxigenic strain but not active toxin production 4
- The 2016 European guidelines recommend a 2-step approach: initial screening with glutamate dehydrogenase, enzyme immunoassay, or PCR, followed by confirmatory toxin testing 4
- Positive PCR without typical clinical picture suggests colonization rather than acute infection 4
Multidrug-Resistant Gram-Negative Bacteria
Colonization prevalence varies by setting:
- Hospital admission colonization rate is 8.1%, with previous hospitalization as the main risk factor 4
- Asymptomatic colonization prevalence is 3-26% in acute care hospitals versus <2% in community-dwelling adults 4
- Routine decolonization is not recommended for 3GCephRE and CRE carriers 4
Fungal Organisms
Multiple-site sampling is required:
- Obtain samples from urine, rectum, gastric aspirate, vascular access sites, sputum/throat, and wounds 1
- Surveillance cultures every 5 days in high-risk patients monitor for transition from colonization to infection 1
Critical Pitfalls to Avoid
Do not treat positive cultures without clinical correlation:
- Relying solely on culture positivity without clinical symptoms leads to overdiagnosis and unnecessary antibiotic use 1
- Cultures from existing drains may represent colonization; require new symptoms (fever, abdominal pain) and consistent imaging for infection diagnosis 4
- Single positive blood culture for coagulase-negative staphylococcus without symptoms is often contamination, not true bacteremia 4
Do not ignore recent antibiotic exposure:
- Recent antimicrobial therapy may yield false-negative culture results 1
- Antibiotic exposure alters normal flora and affects colonization patterns 3
Do not overlook molecular test limitations:
- Molecular diagnostics cannot distinguish infection from colonization 4
- Increased sensitivity may detect clinically insignificant bacteria, leading to overtreatment 4
- Molecular tests cannot determine bacterial viability or quantitation crucial for differentiating colonization from infection 4
Monitoring Strategy
Implement systematic surveillance in high-risk patients: