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InfectIon control

OXA-mediated Carbapenem resistant Acinetobacter spp. have occurred in many parts of the world, including the UAE. Despite the relatively common occurrence of OXA Carbapenemase in Acinetobacter spp., these enzymes are uncommon in other genera of bacteria. Although this situation appears to be

dire, several possibilities exist in an attempt to mitigate the damage caused by these resistant pathogens. A straightforward means, that can be implemented almost immediately, involves infection control approaches to minimize the spread of these organisms within a healthcare facility.

STRATEGY FOR CARBAPENEMASE DETECTION The detection strategy includes a screening step followed by phenotypic and genotypic confirmation. Screening is based on detection of reduced susceptibility to Carbapenem by Carbapenemase- producing isolates compared with isolates of the wild-type population. For each class of Carbapenemase, and for each species and isolate, the MIC may vary from MICs of the wild-type population to >256 mg/L, dependent on the presence of other resistance mechanisms. Setting of the screening breakpoints should therefore be guided by the following principles:  The breakpoint MIC should be higher than the highest MIC of the wild-type population, as the specificity of the screening test may otherwise become too low  The MIC breakpoint should be lower than the lowest Carbapenem MICs described in the literature for strains shown to have a Carbapenemase gene.

MEROPENEM Based on these criteria, the MIC screening breakpoint for Meropenem could be set at ≥0.5 mg/L for all Enterobacteriaceae, enabling detection of the vast majority of Carbapenemase-producers. Only sporadic Carbapenemase producers with Meropenem MICs < 0.5 mg/L will not be detected using this breakpoint. The zone diameter screening breakpoint for Meropenem has been set at ≤23mm. The Meropenem zone diameter breakpoint is slightly less sensitive than the MIC screening breakpoint of 0.5 mg/L (84% vs. 100%, respectively), but it was shown to

detect all VIM- and KPC-producing isolates. Although a Meropenem zone diameter screening breakpoint of ≤27mm was reported to have a sensitivity of 100% for Carbapenemase production; this would result in an unacceptably high level of false- positive isolates based on the published Meropenem zone diameter distributions.

IMIPENEM For Imipenem it is not possible to set a breakpoint for all Enterobacteriaceae as some species (Proteus spp., Serratia spp., Providencia spp. and Morganella morganii) have a high Imipenem MIC owing to mechanisms other than Carbapenemase production.

ERTAPENEM Ertapenem is not advised as an indicator Carbapenem in this guideline since it has lower specificity than Imipenem and Meropenem. Ertapenem is less specific because isolates with AmpC/ESBL and decreased permeability having higher MICs for Ertapenem than for Imipenem or Meropenem.

Phenotypic confirmation of

Carbapenemase production is based on detection of a diffusible Carbapenemase and in vitro inhibition of Carbapenemase activity upon addition of an inhibitor. The genotypic confirmation consists of polymerase chain reaction (PCR) detection and sequencing of Carbapenemase Bla genes. Carbapenemase screening should be a

standard component of the susceptibility testing on all Enterobacteriaceae isolated in routine diagnostics. This can take

Surveillance All acute care facilities should review microbiology records for the preceding six to 12 months to ensure that previously unrecognized CRE cases have not occurred. If previously unrecognized cases are

identified, facilities should conduct a point prevalence survey (a single round of active surveillance cultures) in units with patients at high risk (e.g., intensive care units, units where previous cases have been identified, and units where many 

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place by assessing the Carbapenem MICs or by an alert from the expert system. When using automatic systems for susceptibility testing (e.g. Phoenix, Vitek or MicroScan), panels containing Meropenem are preferred. The preferred lowest concentration in the panels should be 0.25 mg/L for Meropenem. Use of a correct inoculum is important both for broth microdilution methodology and the automatic systems since a moderate decrease in the inoculum may lead to inaccurate susceptibility results.

PHENOTYPIC CONFIRMATION OF CARBAPENEMASE PRODUCTION On the first isolate from a patient with a positive Carbapenemase screen test, a PCR-based test should be performed to confirm the presence of Carbapenemase genes. However, if genotypic confirmation is not immediately available, phenotypic confirmation tests can be performed in order to avoid delayed reporting of potential Carbapenemase-producers to the clinic. Phenotypic confirmation may be performed using one or two methods, the modified Hodge test and the Carbapenemase inhibition tests. The modified Hodge test is used for detection of diffusible Carbapenemase, and the inhibition tests are used to distinguish between the different classes of Carbapenemase.

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