Antibiotic Selection for This Susceptibility Profile
Based on the susceptibility results showing sensitivity to carbapenems (imipenem and meropenem MIC ≤0.25), piperacillin-tazobactam (MIC ≤4), gentamicin (MIC ≤1), trimethoprim-sulfamethoxazole (MIC ≤20), and nitrofurantoin (MIC ≤16), with resistance to third-generation cephalosporins, the optimal treatment depends on infection severity and site.
Organism Classification
This susceptibility pattern indicates an extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E), likely producing extended-spectrum β-lactamases (ESBL), given:
- Resistance to ceftriaxone (MIC ≥64) and ceftazidime (MIC 16) 1
- Resistance to cefazolin (MIC ≥32) 1
- Intermediate susceptibility to cefepime (MIC 4) 1
- Preserved carbapenem susceptibility 1
Treatment Recommendations by Clinical Syndrome
For Severe Infections or Bloodstream Infections
Use a carbapenem (imipenem or meropenem) as definitive therapy 1:
- Meropenem 1 g IV every 8 hours (preferred for most severe infections) 1, 2
- Imipenem 500 mg to 1 g IV every 6-8 hours (alternative) 3, 4
- This is a strong recommendation with moderate certainty of evidence for BSI and severe infections due to ESCR-E 1
For BSI without septic shock, ertapenem may be used instead to preserve broader-spectrum carbapenems 1:
- Ertapenem 1 g IV every 24 hours 1
- This conditional recommendation balances efficacy with antimicrobial stewardship 1
For Non-Severe, Low-Risk Infections
Consider carbapenem-sparing alternatives based on infection site 1:
Piperacillin-tazobactam (susceptible, MIC ≤4):
- Dose: 3.375-4.5 g IV every 6 hours 1
- Conditional recommendation for low-risk, non-severe ESCR-E infections 1
- Caution: The MERINO trial showed increased 30-day mortality with piperacillin-tazobactam versus meropenem for ESBL E. coli BSI, so avoid in severe infections or BSI 1
For Complicated Urinary Tract Infections (cUTI) without septic shock:
- Gentamicin 5-7 mg/kg/day IV once daily for short-duration therapy (5-7 days) 1
- Trimethoprim-sulfamethoxazole for non-severe cUTI (good practice statement) 1
- Nitrofurantoin 100 mg PO four times daily for uncomplicated lower UTI only (3-7 days) 1
- Strong recommendation for IV fosfomycin in cUTI (if available) 1
For Complicated Intra-Abdominal Infections
If severe or high-risk:
- Meropenem 1 g IV every 8 hours by extended infusion 1
- Alternative: Imipenem-cilastatin 500 mg to 1 g IV every 6-8 hours 1, 3
If non-severe:
- Piperacillin-tazobactam 3.375-4.5 g IV every 6 hours (conditional recommendation) 1
- Duration: 5-7 days with adequate source control 1
Stepdown Therapy Strategy
Once clinically stabilized, de-escalate from carbapenems (good practice statement) 1:
- Trimethoprim-sulfamethoxazole (if susceptible and appropriate infection site) 1
- Oral fluoroquinolones (levofloxacin or ciprofloxacin) only if MIC confirms susceptibility despite "intermediate" reporting, and local resistance rates <10% 1
- This antimicrobial stewardship approach preserves carbapenems for resistant organisms 1
Critical Caveats
Avoid these agents despite in vitro activity:
- Do NOT use tigecycline for ESCR-E infections (strong recommendation against) 1
- Do NOT use cefepime despite intermediate MIC (conditional recommendation against for ESCR-E) 1
- Avoid fluoroquinolones if local E. coli resistance >10% or for empiric severe infections 1
Aminoglycoside considerations:
- Gentamicin monotherapy only for urinary tract infections, never for BSI or pneumonia 1
- Avoid in renal dysfunction or with other nephrotoxic agents 1
- Short-duration therapy only (5-7 days maximum) 1
Carbapenem stewardship:
- Reserve meropenem/imipenem for severe infections or when alternatives fail 1
- Use ertapenem for non-severe infections when carbapenem necessary 1
- Extended infusion (over 3 hours) recommended for high MIC organisms 1
Duration of Therapy
Tailor to infection site 1: