How do I differentiate between sensitive and resistant antibiotics and choose the appropriate therapy based on susceptibility testing?

Differentiating Sensitive vs Resistant Antibiotics and Choosing Appropriate Therapy

Choose antibiotics based on susceptibility testing results where susceptible bacteria are treated with standard doses, intermediate bacteria require higher doses or site-specific concentration, and resistant bacteria necessitate alternative antibiotic selection. 1

Understanding Susceptibility Categories

The classification system uses three distinct categories based on clinical response predictions:

• Susceptible bacteria lack resistance mechanisms or have only low-level resistance that doesn't affect clinical outcomes, and standard antibiotic doses are expected to be effective 1
• Intermediate bacteria fall between susceptible and resistant, showing variable responses to standard therapy but may be eliminated if the antibiotic concentrates at the infection site or if dosage is increased 2
• Resistant bacteria are unlikely to respond even to maximum antibiotic doses due to specific resistance mechanisms demonstrated phenotypically or genotypically 2, 1

Technical Basis for Classification

Susceptibility categories are determined using standardized laboratory methods:

• Minimum Inhibitory Concentration (MIC) is the lowest antibiotic concentration (mg/L) that prevents bacterial growth under defined conditions 2
• Breakpoints are specific MIC values or inhibition zone diameters that assign bacteria to susceptible, intermediate, or resistant categories 2
• These breakpoints directly guide antibiotic selection in clinical practice according to CLSI guidelines 1
• The intermediate category also serves as a technical buffer to minimize confusion for organisms with MICs close to breakpoints 2

Clinical Decision Algorithm

Step 1: Obtain Cultures Before Treatment

• Collect appropriate specimens for culture before initiating antimicrobials 3
• Intra-operative cultures should always be performed in hospital-acquired infections, community-acquired infections at risk for resistant pathogens, or critically ill patients 2

Step 2: Interpret Susceptibility Results

When culture results return with susceptibility data:

• If susceptible: Use standard doses of the reported antibiotic 1
• If intermediate: Consider higher doses (if safely achievable) or alternative antibiotics, particularly if the infection site allows drug concentration (e.g., urinary tract, biliary tract) 1, 2
• If resistant: Select an alternative antibiotic to which the organism is susceptible 1

Step 3: Apply Clinical Context

• If clinical improvement occurs on empirical therapy, continuation may be appropriate even if some isolated organisms show resistance to the prescribed agent 3
• If inadequate clinical response, adjust antimicrobial choice based on susceptibility results 3
• Perform de-escalation if the empirical regimen was too broad based on culture results 2

Critical Considerations for Specific Pathogens

Nontuberculous Mycobacteria

The correlation between in vitro susceptibility and clinical response varies significantly by species:

• M. kansasii, M. marinum, M. fortuitum: Clinical response closely parallels in vitro susceptibility patterns 2
• MAC (Mycobacterium avium complex): Clinical response correlates only with macrolides; test initial isolates to clarithromycin to establish baseline values 2
• M. abscessus: Limited correlation between in vitro susceptibility and clinical response for pulmonary disease, though correlation exists for skin/soft tissue infections 2

Treatment Failure Scenarios

When patients fail initial therapy:

• Enhanced resistance levels (MIC at least 2-fold higher than pretreatment) occur in approximately 49% of treatment failures 2
• Antibiotic exposure increases likelihood of β-lactam and doxycycline-resistant S. pneumoniae and β-lactamase producing H. influenzae and M. catarrhalis 2
• For treatment failure, use high-dose amoxicillin-clavulanate (4 g/d amoxicillin equivalent) or respiratory fluoroquinolones (levofloxacin, moxifloxacin) to cover multi-drug-resistant organisms 2

Common Pitfalls to Avoid

• Don't treat asymptomatic bacteriuria: This fosters antimicrobial resistance and increases recurrence episodes 3
• Don't ignore cross-resistance patterns: Resistance mechanisms like impermeability or efflux may affect multiple antibiotic classes (associated resistance) 2, 4
• Don't rely solely on susceptibility for all organisms: Unlike tuberculosis, some NTM disease may not be eradicated despite in vitro susceptibility results 2
• Don't use oral cephalosporins or macrolides for treatment failure: These offer inadequate coverage for multi-drug-resistant S. pneumoniae or H. influenzae 2

Resistance Mechanisms Recognition

Understanding resistance types guides therapy selection:

• Microbiological resistance: Organisms possess any resistance mechanism (phenotypic or genotypic), qualified as low-level, moderate, or high-level 2
• Clinical resistance: Infection highly unlikely to respond even to maximum antibiotic doses 2
• High-level resistance: Associated with lack of synergy between β-lactam antibiotics and aminoglycosides for enterococci 2