Risk Factors for Multidrug Resistance in Nosocomial Bacteremia Caused by Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae

Increasing multidrug resistance (MDR) among extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) is of a great concern, because the therapeutic options are severely limited. Thus, we performed a case-control study to evaluate risk factors for MDR among nosocomial bacteremia caused by ESBL-EK. All adult patients with ESBL-EK bacteremia from January 2009 through December 2010 were identified at our institution. MDR was defined as ESBL-EK that demonstrated in vitro resistance to trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolone (FQ), and gentamicin. Case patients were those with an MDR ESBL-EK isolate, and control patients were those with a non-MDR ESBL-EK isolate. Among a total of 123 ESBL-EK isolates (74 [60.2%] E. coli and 49 [39.8%] K. pneumoniae) causing nosocomial bacteremia, 33 (26.8%) cases were due to MDR ESBL-EK. In a univariate analysis, the factors significantly associated with acquisition of MDR ESBL-EK were neutropenia, immunosuppressant use, urinary tract infection, and prior use of antibiotics, especially FQ (all p<0.05). A multivariable analysis showed that a prior receipt of FQ (odds ratio [OR]=2.93; 95% confidence interval [CI]=1.07-8.01; p=0.036), percutaneous tube insertion (OR=4.04; 95% CI=1.56-10.75; p=0.005), and neutropenia (OR=4.22; 95% CI=1.56-11.45; p=0.005) were independent risk factors for MDR among ESBL-EK bacteremia in hospitalized patients. The CTX-M-15 enzyme was predominant in both the MDR ESBL-EK and non-MDR ESBL-EK groups (55% [11/20] vs. 55.6% [15/27]). Our data suggest that strategies designed to reduce MDR in ESBL-EK bacteremia should focus on limiting the use of FQ and minimizing invasive procedures such as tube insertion.