When should antibiotic susceptibility testing be performed and how should I select the most appropriate narrow‑spectrum antimicrobial based on the results and patient factors?

When to Perform Antibiotic Susceptibility Testing

Antimicrobial susceptibility testing (AST) should be performed on all initial bacterial isolates from sterile sites (blood, CSF, peritoneal fluid) and when treating serious infections, healthcare-associated infections, or when resistance cannot be reliably predicted based on organism identity alone. 1

Mandatory Indications for AST

Critical Clinical Scenarios Requiring Testing

• All initial isolates from normally sterile body sites including blood, cerebrospinal fluid, peritoneal fluid, pleural fluid, and deep tissue specimens 1, 2, 3

• Healthcare-associated intra-abdominal infections or community-acquired infections in patients at risk for resistant pathogens 1

• Critically ill patients with severe sepsis or septic shock where empiric therapy failure carries high mortality risk 1

• All tuberculosis cases - susceptibility testing for isoniazid, rifampin, and ethambutol should be performed on initial isolates from all patients, with repeat testing if cultures remain positive after 3 months of therapy 1

• Carbapenem-resistant Gram-negative bacilli (CRGNB) - MIC determination should be performed for all available antimicrobials including carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, polymyxins, and fosfomycin 1

When AST is NOT Required

• Predictably susceptible organisms such as Streptococcus pyogenes to penicillin, where empirical therapy is reliable 2, 3

• Mixed growth or normal flora from non-sterile sites where isolates bear little relationship to actual infection - results may be dangerously misleading 2

• Simple community-acquired appendicitis in low-risk patients, though this remains controversial 1

Selecting Narrow-Spectrum Antimicrobials Based on AST Results

Interpreting MIC Results

When microorganisms are identified in clinical cultures, AST must always be performed and reported as minimum inhibitory concentration (MIC) values, categorized as susceptible (S), intermediate (I), or resistant (R) according to CLSI or EUCAST breakpoints. 1

Preferred Testing Methods

• Broth microdilution (BMD) is the reference standard for most antimicrobials 1
• Agar dilution method is the reference for tuberculosis susceptibility testing 1
• E-test (gradient diffusion) shows 96% categorical agreement with BMD for newer agents like ceftazidime-avibactam 1
• Automated systems (VITEK 2, Phoenix) are acceptable but may overestimate MICs for carbapenems, leading to false resistance 1

Critical Pitfall: Fosfomycin Testing

For fosfomycin MIC testing, only agar dilution supplemented with glucose-6-phosphate is recommended by CLSI and EUCAST - broth dilution methods are NOT appropriate. 1

Algorithm for Antimicrobial Selection Based on AST

Step 1: Initiate Empiric Therapy While Awaiting Results

• Start empiric broad-spectrum therapy immediately in parallel with specimen collection and AST, particularly in severe infections 1
• Base empiric selection on local antibiograms, patient risk factors (healthcare exposure, prior antibiotics, ICU stay >1 week), and infection severity 1

Step 2: De-escalate Based on Susceptibility Results

Once AST results are available, transition to the narrowest-spectrum agent with documented susceptibility (reported as "S") that adequately covers the identified pathogen and achieves appropriate concentrations at the infection site. 1

Specific De-escalation Principles:

• For Gram-negative infections: If susceptible to first-generation cephalosporins, avoid third-generation agents 3
• For intra-abdominal infections: Expand coverage if initial choice was too narrow, or narrow if empiric regimen was unnecessarily broad 1
• For ESBL-producing organisms: Carbapenems remain treatment of choice even if in vitro susceptibility to cephalosporins is reported 4

Step 3: Consider Patient-Specific Factors

Selection must account for:

• Site of infection penetration - particularly important for biliary tract infections where obstructed ducts prevent adequate antibiotic concentrations 1
• Renal function for dose optimization of aminoglycosides and glycopeptides to avoid toxicity 3
• Pharmacokinetic/pharmacodynamic principles - prolonged beta-lactam infusions for time-dependent killing, higher fluoroquinolone doses for S. pneumoniae 1

Step 4: Avoid Common Extrapolation Errors

Never extrapolate susceptibility between structurally different agents within the same class - each cephalosporin requires independent testing (e.g., cefepime susceptibility does NOT predict cefoperazone susceptibility, with 8-fold MIC differences for E. coli) 5

Special Considerations for Resistant Organisms

Carbapenem-Resistant Organisms

• MIC testing is essential rather than categorical reporting alone, as MIC values near breakpoints significantly impact outcomes 1
• Combination therapy may be guided by synergy testing when available 1

Repeat Testing Indications

• Treatment failure - positive cultures after 3 months of appropriate therapy 1
• Relapse after initial microbiologic cure 1
• Each reoperation for persistent peritonitis, as flora progressively shifts toward multidrug-resistant organisms (41% at index surgery to 76% at third reoperation) 1

Implementation in Clinical Practice

Establish systems for automatic AST performance on all blood culture isolates and sterile site specimens, with pharmacist-triggered alerts for de-escalation opportunities based on susceptibility results. 1

• Develop ED-specific and unit-specific antibiograms updated at least yearly to guide empiric therapy 1
• Ensure 28-day turnaround time from specimen collection to susceptibility results for first-line agents 1
• Report results selectively to encourage use of narrowest effective agents 3