Case Exercises
By simulating real world antibiograms and clinical cases, Case Exercises help reinforce scientific principles explained and demonstrated in Modules and translate antibiogram data into clinical decision-making. Please select the case to review.
Case 2. Carbapenem Susceptibilities and New CLSI Breakpoints
A University Medical Center has heard that at a sister hospital located 25 miles away there is increasing resistance to both imipenem and meropenem for both E. coli and K. pneumoniae isolates. The Medical Center would like to evaluate its most recent antibiogram (see below) for any major issues with susceptibilities to its preferred carbapenem (imipenem/cilastatin). The Medical Center finds that its clinical microbiology laboratory is using the new CLSI cephalosporin breakpoints but has not yet adopted the new CLSI carbapenem breakpoints and it has never performed a Modified Hodge Test (MHT).
University Medical Center: Most recent antibiogram data
| Bacteria1 |
n |
% Susceptible |
| Ampicillin |
Cefazolin |
Ceftazidime |
Piperacillin/Tazobactam |
Tobramycin |
Ciprofloxacin |
Imipenem |
| E. cloacae |
412 |
12 |
12 |
82 |
76 |
68 |
89 |
100 |
| E. coli |
105 |
23 |
91 |
98 |
97 |
87 |
84 |
99 |
| K. pneumoniae |
482 |
16 |
89 |
93 |
89 |
77 |
86 |
98 |
| P. aeruginosa |
698 |
6 |
74 |
85 |
81 |
62 |
52 |
90 |
| A. baumannii |
135 |
4 |
58 |
67 |
73 |
56 |
44 |
94 |
1Non-UTI isolates only
CLINICAL CONSIDERATIONS
Which of the following is/are correct interpretation based on the antibiogram?
- ESBL rates appear to be 5% for E. coli and 20% for K. pneumoniae.
- CRE rates appear to be 1% for E. coli and 2% for K. pneumoniae.
- ESBL rates for E. coli may be as high as 2% and for K. pneumoniae 7%.
- CRE rates for E. coli are at least 1% and for K. pneumoniae at least 2%.
Answer & Rationale
Which of the following is true?
- KPCs and ESBLs are both Class A beta-lactamases and will therefore test resistant to most third-generation cephalosporins using the new CLSI cephalosporin breakpoints.
- KPCs and ESBLs are both Class C beta-lactamases and therefore separate phenotypic tests have to be performed to determine ESBLs and KPCs.
- Institutions using the new CLSI cephalosporin breakpoints are still recommended to perform ESBL testing to guide therapy.
- When using the new CLSI cephalosporin breakpoints, if an isolate tests positive for ESBL, it should be reported as resistant to all cephalosporins regardless of MIC.
Answer & Rationale
In the sample antibiogram, the susceptibility rate of E. cloacae to ceftazidime is 82%. E. cloacae is one of the most potent ESBL-producers based on the published literature when molecular-based tests are performed by research laboratories. However, in the hospital microbiology laboratory, why are ESBL screening and confirmation not routinely performed on isolates of E. cloacae?
- E. cloacae produces a unique ESBL that is not detected by routine microbiology laboratory tests.
- E. cloacae frequently has the ampC inducible gene in the chromosome that produces the AmpC beta-lactamase. This interferes with the phenotypic test for ESBLs done in most hospital laboratories.
- E. cloacae rarely causes life-threatening infections and remains highly susceptible to other first-line antimicrobial agents (thus, ESBL screening is unnecessary).
- None of the above is true.
Answer & Rationale
The correct answers are: ESBL rates for E. coli may be as high as 2% and for K. pneumoniae 7% and CRE rates for E. coli are at least 1% and for K. pneumoniae 2%.
ESBL rates for E. coli and K. pneumoniae can be estimated based on susceptibility to third-generation cephalosporins, such as ceftazidime in this example. Therefore, in this example, the ESBL rate for E. coli is approximately 2%, while the rate is approximately 7% for K. pneumoniae. However, it is important to note that this may be an underestimation if there are CTX-M type ESBLs present in the hospital. CTX-M is a predominant ESBL in E. coli in the United States. CTX-M ESBLs are more susceptible to ceftazidime and therefore these isolates would not be identified as ESBL-producers. A confirmatory test with cefotaxime or ceftriaxone is needed to get a better estimate of ESBL-producers.
CRE (carbapenem-resistant Enterobacteriaceae) can be due to the production of carbapenemases (such as KPC or MBL) or via production of a cephalosporinase combined with porin loss. This hospital is using the older CLSI breakpoints to determine carbapenem resistance. In this situation, many KPC-producers can test susceptible to imipenem. CLSI recommends a Modified Hodge Test (MHT) for isolates with elevated MICs to the carbapenems (i.e., 2 to 4 µg/mL) to get a more accurate assessment of KPC at an institution. However, this hospital does not perform MHT, and therefore the KPC rate can be estimated to be at least 1% for E. coli and 2% for K. pneumoniae.
The correct answer is KPCs and ESBLs are both Class A beta-lactamases and will therefore test resistant to most third-generation cephalosporins using the new CLSI cephalosporin breakpoints.
KPCs and ESBLs belong to the Class A beta-lactamases and are likely to test resistant to third-generation cephalosporins when using the new CLSI breakpoints. For institutions using the new breakpoints, CLSI recommends that ESBL testing is not required to guide therapeutic decisions, though confirmatory testing can be useful for epidemiological purposes. If ESBL testing is performed, ESBL-producing isolates should be reported as “susceptible” or “resistant” to cephalosporins based on the MIC. This is contrary to the previous recommendations that stated all identified ESBL-producers should be reported resistant to cephalosporins regardless of MIC.
The correct answer is E. cloacae frequently has the ampC inducible gene in the chromosome that produces the AmpC beta-lactamase. This interferes with the phenotypic test for ESBLs done in most hospital laboratories.
E. cloacae is part of the SPACE bacteria that commonly produce a chromosomal-inducible AmpC beta-lactamase. Stable derepression of the ampC gene results in hyperproduction of the beta-lactamase that allows resistance to third-generation cephalosporins. Hyperproduction of the AmpC beta-lactamase can interfere with the phenotypic test for ESBL-production performed by clinical microbiology laboratories, and therefore ESBL screening is not routinely performed for these isolates.