Carbapenem-Intermediate Klebsiella pneumoniae in Blood
At 09:20, a 72-year-old man in the ICU has a blood culture flagged positive after 16 hours; Gram stain shows gram-negative rods. Subculture on MacConkey grows a mucoid lactose-fermenting colony identified by MALDI-TOF as Klebsiella pneumoniae. The AST panel reports ceftriaxone MIC >32 µg/mL, cefepime >16, ertapenem 4, meropenem 2, imipenem 2, amikacin 8, colistin 0.5, and ceftazidime-avibactam 1. The patient is on meropenem 1 g every 8 hours and has no travel history. The laboratory performs disk diffusion and MIC panels but does not routinely perform carbapenemase testing; no molecular platform is on site. The infectious disease consult asks whether the isolate is carbapenem-resistant and whether therapy should change.
1. Interpret the carbapenem MICs. Is this isolate carbapenem-resistant by CLSI criteria, and what confirmatory test should be added? Describe how the result would change reporting.
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Interpretation: For Enterobacterales, meropenem MIC 2 µg/mL is intermediate, imipenem MIC 2 is intermediate, and ertapenem MIC 4 is resistant. The isolate is therefore not categorically carbapenem-resistant on meropenem alone, but it is carbapenem-intermediate and ertapenem-resistant. That pattern is abnormal and raises concern for a carbapenemase, especially in a patient with prolonged ICU stay and meropenem exposure.
Confirmatory testing: Perform a carbapenemase inactivation method, such as the modified carbapenem inactivation method (mCIM), following the current CLSI procedure. If the mCIM is positive, add the EDTA-modified carbapenem inactivation method (eCIM) to distinguish serine carbapenemases (for example, KPC) from metallo-β-lactamases (for example, NDM). Do not infer the enzyme type from the MIC pattern alone.
Reporting effect: If the mCIM is negative, report the actual MICs and interpret them by CLSI breakpoints; do not call it a carbapenemase producer. If the mCIM is positive, report "carbapenemase-producing Enterobacterales" or the specific enzyme category when confirmed, in addition to the organism and susceptibility profile. A positive result is a communicable-disease and infection-prevention issue, not merely a susceptibility footnote.
2. What preliminary and final reports should be issued, and what infection-prevention action is indicated?
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Preliminary report: Report the Gram stain and organism identification as soon as the MALDI-TOF result is available: "Gram-negative rods, Klebsiella pneumoniae, identification pending confirmation." Include the critical antimicrobial results that are already actionable-ceftriaxone and cefepime resistance and ertapenem resistance-so the clinician does not continue an inactive β-lactam. State that carbapenemase testing is in progress.
Final report: Report the full MIC panel with CLSI interpretations. If carbapenemase testing is positive, add the mechanism and a comment that the result has infection-prevention implications. Avoid vague terms such as "resistant organism" without the drug-level data.
Infection prevention: Notify infection prevention and the patient's unit promptly. Place the patient on contact precautions according to facility policy for carbapenem-resistant or carbapenemase-producing Enterobacterales. Review whether the patient has a history of prior colonization, and determine whether screening of contacts or environmental sampling is indicated by local policy. Ensure that the ward knows the result is preliminary until confirmation.
Clinical communication: The laboratory should call the result rather than rely on the chart alone, because the patient is on meropenem and the isolate is not clearly susceptible. Document who was notified and when.
3. What susceptibility results would you verify or add to support therapy, and how does the carbapenemase type influence the choice?
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Verify the existing panel: Confirm that ceftazidime-avibactam MIC 1 is reproducible and that the inoculum was correct. Verify amikacin and colistin because both can be method-dependent; colistin in particular requires broth microdilution or a validated method, not disk diffusion. Check that the meropenem and imipenem MICs are not one-dilution errors before finalizing.
Add or consider: Depending on the formulary and the carbapenemase result, test meropenem-vaborbactam, cefiderocol, and possibly imipenem-relebactam if available. For a serine carbapenemase such as KPC, ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam are reasonable options. For a metallo-β-lactamase such as NDM, ceftazidime-avibactam alone is not active; cefiderocol or a combination regimen may be needed. For OXA-48-like enzymes, ceftazidime-avibactam is usually active.
The laboratory's job is to provide the mechanism and reliable MICs; the infectious disease clinician chooses therapy. If the mCIM is negative but the patient is failing meropenem, do not assume the isolate is fully susceptible-repeat testing and consider an alternative agent based on the actual MICs.