Infectious Diseases II
ii.
Maintains sensitivity with cephamycins (e.g., cefotetan, cefoxitin) and cloxacillin
iii.
Confirmatory test with E-test containing cephamycin alone or a combination of cephamycin
and cloxacillin. If the MIC is decreased by more than three 2-fold dilutions, the presence of
AmpC Ξ²-lactamase is confirmed.
| d. | Carbapenemase |
|---|
Metallo-Ξ²-lactamase (e.g., New Delhi metallo-Ξ²-lactamase [NDM]; Verona integrin-encoded
metallo-Ξ²-lactamase [VIM]); imipenimase-type carbapenemase)
| (a) | Hydrolyzes both Ξ²-lactam and carbapenem antibiotics, but aztreonam maintains |
|---|
susceptibility. Clinically, about 80% of metallo-Ξ²-lactamaseβcontaining pathogens are
resistant to aztreonam because of other resistance mechanisms.
| (b) | Zinc-mediated metallo-Ξ²-lactamase can be repressed by ethylene-diamine tetraacetic acid |
|---|
(EDTA). Reduction in imipenem MIC by more than three 2-fold dilutions in the presence
of EDTA confirms presence of zinc-mediated metallo-Ξ²-lactamase.
ii.
KPC
| (a) | KPC enzyme can produce a slightly higher MIC that may still be in the range considered |
|---|
sensitive. This is in contrast to other carbapenem-resistant mechanisms in Pseudomonas
and Acinetobacter, which generally produce a fully resistant MIC. Hence, a carbapenem
MIC of 1 mcg/mL or greater in an Enterobacterales should be evaluated through further
confirmatory testing.
| (b) | Modified Hodge test should be performed for pathogens with an elevated carbapenem |
|---|
MIC.
| (1) | Place standard sensitive E. coli strain on entire plate. |
|---|---|
| (2) | Place meropenem or carbapenem disk in center of test area. |
| (3) | Streak test organism in a straight line from edge of carbapenem disk to edge of plate |
(up to four different organisms can be tested).
| (4) | Positive carbapenemase results from modified Hodge test have a clover leafβlike |
|---|
indentation of the E. coli growing along the test organismβs streak.
| (c) | Starting in 2010, CLSI lowered the susceptibility breakpoints for carbapenem (0.5 mcg/ |
|---|
mL and 1.0 mcg/mL or less for ertapenem and other carbapenems, respectively), with the
intent of eliminating the need for confirmatory tests.
| (1) | Clinicians should inquire about the practices of their local microbiology laboratory |
|---|
regarding carbapenem susceptibility.
| (2) | Particularly when confirmatory tests are not being performed, and a laboratory |
|---|
continues to use the older MIC breakpoints, a higher clinical suspicion for
carbapenemase is warranted.
| (3) | Ertapenem resistance seen on AST is a sensitive marker for the presence of |
|---|
carbapenemase. Before the 2010 reclassification of carbapenem susceptibility
breakpoints, there were reports of up to 46% of clinical isolates with genotypic
evidence of KPC-producing enzymes being inadvertently labeled as imipenem
sensitive.
| (4) | Deleterious outcomes associated with the use of carbapenems in carbapenemase- |
|---|
producing organisms have been reported.
process. CLSI promotes the development of voluntary consensus standards within the medical community.
Determining CLSI breakpoints could be based on several conflicting interests, which may include some of
the following:
Microbiological: MIC that distinguishes wild-type bacteria from those that have acquired additional
resistance mechanisms