Carbapenem MIC and Colistin Susceptibility: No Direct Correlation
An imipenem or meropenem MIC <16 µg/mL does NOT predict colistin susceptibility. These are independent resistance mechanisms, and carbapenem MIC values cannot be used to infer colistin activity.
Why Carbapenem and Colistin Resistance Are Unrelated
Different Resistance Mechanisms
Carbapenem resistance in Gram-negative bacteria typically results from carbapenemase production, porin loss (e.g., OmpC disruption), or efflux pump overexpression 1, 2.
Colistin resistance arises from modifications to lipopolysaccharide (LPS) in the bacterial outer membrane, mediated by mutations in two-component regulatory systems (pmrAB, phoPQ) or plasmid-mediated mcr genes 2, 3.
These mechanisms operate independently—an isolate can be carbapenem-resistant yet colistin-susceptible, or vice versa 4, 2, 3.
Clinical Evidence of Discordance
Among 18 carbapenem-resistant Acinetobacter baumannii isolates (imipenem MIC 8–128 µg/mL, meropenem MIC 64–256 µg/mL), all remained colistin-susceptible (MIC 0.5–2 µg/mL) 5.
In 21 carbapenem-resistant Pseudomonas aeruginosa isolates, 100% were colistin-susceptible despite only 23.8% being imipenem-susceptible 4.
Conversely, colistin-resistant Enterobacter cloacae with imipenem/meropenem MIC of 32 µg/mL demonstrates that colistin resistance can emerge independently of carbapenem resistance 2.
Among 75 carbapenem-resistant Enterobacteriaceae (CRE) isolates, 18.7% were colistin-resistant, proving that carbapenem resistance does not guarantee colistin susceptibility 3.
Guideline-Based Approach to Testing
Mandatory Independent Testing
Always perform separate colistin susceptibility testing for carbapenem-resistant isolates using broth microdilution (BMD), the gold standard method 1, 3.
Disk diffusion and E-test are unreliable for colistin; BMD is required to detect heteroresistance and accurately determine MIC 2, 3.
When to Suspect Colistin Resistance
High-risk populations include patients with prolonged colistin exposure, ICU admission, or prior isolation of colistin-resistant organisms 1, 3.
Carbapenem-resistant Acinetobacter baumannii (CRAB) with colistin MIC ≥2 µg/mL by BMD should prompt consideration of alternative agents, as clinical outcomes worsen at higher MICs even within the "susceptible" range 1.
Interpreting Carbapenem MIC Values
For Acinetobacter baumannii, carbapenem MIC >16 µg/mL indicates high-level resistance, but isolates with MIC <16 µg/mL may still benefit from high-dose extended-infusion carbapenem therapy in combination regimens 1.
Sulbactam-containing regimens (ampicillin-sulbactam 9–12 g/day or cefoperazone-sulbactam 6–9 g/day) are preferred over colistin for CRAB when sulbactam MIC ≤4 mg/L, due to lower nephrotoxicity 1, 6.
Critical Clinical Pitfalls
Never assume colistin susceptibility based on carbapenem MIC—this can lead to treatment failure with colistin monotherapy in resistant isolates 1, 2, 3.
Avoid colistin monotherapy for CRAB infections; combination therapy with at least two active agents (e.g., colistin + high-dose sulbactam or colistin + tigecycline) improves outcomes, though colistin-carbapenem combinations show no mortality benefit in randomized trials 1.
Do not delay susceptibility testing—empiric therapy should cover both carbapenem-resistant and potentially colistin-resistant organisms in high-risk patients, then de-escalate based on culture results 1, 3.
Monitor for colistin heteroresistance, where subpopulations resistant to colistin exist within a susceptible isolate, detectable only by BMD or population analysis profiling 2.