Incidence of Extended-Spectrum-β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolates That Test Susceptible to Cephalosporins and Aztreonam by the Revised CLSI Breakpoints

Abstract

The incidence of aztreonam and cephalosporin susceptibility, determined using the revised CLSI breakpoints, for extendedspectrum-␤-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates was evaluated. Our analysis showed that results for aztreonam and/or >1 cephalosporin were reported as susceptible or intermediate for 89.2% of ESBLproducing E coli isolates (569/638 isolates) and 67.7% of ESBL-producing K. pneumoniae isolates (155/229 isolates). Extended-spectrum-␤-lactamase (ESBL)-producing Enterobacteriaceae strains represent a challenging problem for health care providers, particularly in acute-care and long-term-care facilities and more recently in community-acquired infections (1-5). ESBL enzymes are capable of inactivating penicillins, aztreonam, cephalosporins, and ␤-lactamase inhibitors, which limits the number of effective antibiotics for treatment (1,2,4,5).The presence of an ESBL is suspected in Escherichia coli and Klebsiella pneumoniae infections when resistance to one or more of the extended-spectrum cephalosporins (ESCs) (cefotaxime, ceftazidime, ceftriaxone, or cefepime) is detected (1, 2, 4). Based on pre-2010 guidelines from the Clinical and Laboratory Standards Institute (CLSI) (Wayne, PA), laboratories then confirmed the presence of an ESBL using labor-intensive manual methods. This supplemental testing often delayed ESBL identification by 24 to 48 h. Confirmatory testing for ESBLs has also been incorporated into automated susceptibility test systems. Since resistance to some ESCs and aztreonam may not always be detected by in vitro methods, strains were reported as resistant to all penicillins, cephalosporins (excluding the cephamycins), and aztreonam based on positive confirmatory test results, independent of the initial susceptibility test results. These guidelines were followed to prevent strains being reported inadvertently as being susceptible to ESCs and aztreonam, leading to potentially inappropriate treatment.In 2010, the CLSI Antibiotic Subcommittee lowered the MIC breakpoints and increased the disk diffusion size criteria for reporting of aztreonam, cefazolin, cefotaxime, ceftizoxime, ceftriaxone, and ceftazidime results. Interpretive criteria for cefuroxime and cefepime were not changed, because the committee determined that the available data did not support any changes in the breakpoints for these two drugs (6). In 2014, the CLSI recommended changing the MIC breakpoints for cefepime to Ͻ2 g/ml for sensitive, 4 to 8 g/ml for sensitive dose dependent (SDD), and Ͼ16 g/ml for resistant (7). The CLSI advises that treatment of ESBL-producing strains can be predicted solely on the basis of MIC values, regardless of the underlying resistance mechanisms. More-stringent interpretive criteria would eliminate the need for confirmatory testing for ESBL, and results could be reported as tested. In theory, this would decrease the time needed to identify ESBL-producing Enterobacteriaceae and the costs associated with additional laboratory work.There were significant conc...

Rapid Detection of ESBL-ProducingEnterobacteriaceaein Blood Cultures

“…A strong correlation between intermediate susceptibility or resistance to cefotaxime and positivity of the ESBL NDP test was observed ( Table 3 ). Similar correlation between resistance to cefotaxime and ESBL production in Enterobacteriaceae was obtained in the United States ( 12 ). A concomitant use of the Carba NP test ( 13 ) directly from blood culture will also identify carbapenemase producers (such as K. pneumoniae carbapenemase producers) that also confer clavulanic-acid–inhibited resistance to cephalosporins.…”

The Role of Cefepime in the Treatment of Extended-Spectrum Beta-Lactamase Infections

“…They are just one type of several beta-lactamases that mediate resistance to betalactam antibiotics, specifically penicillins, monobactams, and most third-generation cephalosporins with the exception of cephamycins. [1][2][3][4] Although the exact prevalence of ESBLs is not known, it is increasing in many parts of the world, with at least 10% to 40% of strains of E coli and K pneumoniaproducing ESBL enzymes globally. 5 Delineation between community and hospital-acquired ESBL infections can be challenging; however, it is necessary to distinguish them for treatment purposes as hospital-acquired infections tend to be more severe (Table 1).…”

“…They found that up to 20% of ESBL-producing E coli and 30% of ESBL-producing K pneumoniae isolates could be reported as susceptible to cefepime. 3 Therefore, even with lower break points, cefepime may be considered more often for the treatment of ESBL infections than it was in the past.…”

Commentary: Impact of CLSI Breakpoint Changes on Microbiology Laboratories and Antimicrobial Stewardship Programs

“…Organisms harboring extended-spectrum beta-lactamases (ESBLs) can have drug MICs that fall below the susceptibility threshold in the new CLSI guidelines (4). McWilliams and colleagues analyzed 638 ESBL-producing Escherichia coli isolates and 229 ESBL-producing Klebsiella pneumoniae isolates using the re-duced breakpoints for cephalosporins and aztreonam from the 2010 guidelines (5). A large proportion (89.2%) of ESBL-producing E. coli isolates and 67.7% of ESBL-producing K. pneumoniae isolates would be reported to be susceptible or intermediate to at least one extended-spectrum cephalosporin or aztreonam.…”