Carbapenemase-producing Klebsiella pneumoniae: description of outcomes at lower Imipenem MICs

Background: Vitek 2 data from our institution has shown that Klebsiella pneumoniae isolates with imipenem MICs ≥ 2 are likely to be carbapenemase producers (KPCs), as confirmed by modified Hodge test (MHT). Reports suggest that invasive KPC infection results in poor patient outcomes, such as higher crude mortality. Little is known about treatment outcomes in patients with KPC isolates that are MHT+ but whose Vitek 2 imipenem MICs are less than 1.

Objective: To compare risk factors and outcomes of patients with Klebsiella pneumoniae isolates that were resistant to ertapenem but sensitive to imipenem by disc diffusion, with an imipenem MIC ≤ 1 by Vitek 2. To compare clinical and treatment outcomes in MHT + vs MHT - isolates.

Methods: During Oct 2008 to Oct 2009, K. pneumoniae isolates resistant to ertapenem but sensitive to imipenem by disc diffusion with a Vitek 2 MIC ≤ 1 were subjected to MHT. Patient charts were reviewed for location of infection, risk factors for KPC (prior admissions, ICU stay, antibiotic use, comorbidities), type and duration of rx, and outcomes. Chart reviewers were blinded to MHT status. Student t, chi square, and Fischer exact tests were used where appropriate to compare MHT positive to MHT negative isolates.

Results: 24 K. pneumoniae isolates were collected.  The majority in both MHT+ and - groups were urine isolates (63%). The MHT + group had more sputum isolates (38% vs 12% in the MHT- group). MHT+ patients were significantly older, but the two groups did not differ in terms of KPC risk factors (including recent hospital admit, nursing home residence, or mean Charlson score). The two groups did not differ with respect to length of stay, ICU admission, total treatment days, or death. However there was a trend towards increased need for a second treatment course in the MHT+ group (71 vs 43%, p=0.36).

Four patients received imipenem as initial treatment; 2 were MHT+ and 2 were MHT-.  The MHT- infections were from an infected sacral decubitus and a urinary tract infection. Both infections were successfully treated with imipenem. The two patients with MHT+ K. pneumoniae were from a urine and pulmonary source. The urine source was treated for 1 day since it was found to be colonization; K. pneumoniae persisted in later urine samples. The second patient had a ventilator-associated pneumonia; microbiologic cure was achieved in 10 days with imipenem. Both patients later expired due to other multi-drug resistant gram negative infections.  

Conclusions: A modified Hodge test should be performed to detect the presence of possible KPC even with Vitek 2 imipenem MICs of ≤1. In our study, patient outcomes by MHT status did not differ with respect to mortality, length of stay, or ICU admission, though our sample size was very limited. Successful treatment of an MHT+ VAP with imipenem suggests that high tissue imipenem concentrations may overcome carbapenemase production at lower MICs.  However more research is required.