Expanded-Spectrum Cephalosporin Resistance and Carbapenemase Resistance
المؤلف:
Patricia M. Tille, PhD, MLS(ASCP)
المصدر:
Bailey & Scotts Diagnostic Microbiology
الجزء والصفحة:
13th Edition , p324-327
2025-07-12
398
The explosion of molecular biology in the past two decades has provided alternatives to phenotypic strategies for the identification of organisms and the genotyping of drug resistance. The bacterial chromosome represents the majority of the genetic make-up or genome within a single organism. However, many genes may be located on extra-chromosomal elements, including transposons and plasmids that are capable of independent replication and movement between organisms. Plasmids exist as double-stranded, closed, circular miniature chromosomes. A single bacterial cell may contain several plasmids. Transposable elements are pieces of DNA that move from one genetic element to another, such as from the plasmid to the chromosome or vice versa. Multi-drug resistant organisms are increasing in frequency on a worldwide basis due to the presence of these mobile genetic elements. In addition, these elements may have a complex structure, including the presence of integrans, which are genetic elements specifically designed to take up and incorporate or integrate genes such as those that encode antibiotic resistance.
In the last decade, a very serious emerging mechanism of resistance referred to as carbapenemase resistance has developed in the Enterobacteriaceae family in both hospital and community-acquired infections. Carbapene mase is currently the last treatment option for infections caused by multi-drug resistant bacteria. The various classes of carbapenemases include KPC (Class A) VIM, IMP, NDM (Class B), and OXA-48 (Class D). Class A, C, and D β-lactamases are the enzymes that contain serine at the active site. The metallo-β-lactamases (Class B) require a zinc ion for hydrolysis. Genes encoding the β-lactamase enzymes mutate continuously in response to the heavy pressure exerted by antibiotic use. Amp-C class (Class C) genes that were originally carried on chromosomes are now found on plasmids. The last class of β-lactamases is referred to as oxacillanses (Class D) and contains a higher hydrolysis rate for oxacillin than penicillin.
The resistant mechanism is typically plasmid-borne, and the gene product is capable of hydrolyzing almost all known β-lactam antibiotics. The plasmids that harbor these mobile genetic elements include the various classes of non-typeable plasmids (using current PCR-based replicon typing) and the IncHI family of plasmids. These plasmids demonstrate conjugative transfer (movement between individual bacterial cells) at a higher frequency at 30 °C than at 37 °C. The carbapenemase resistance gene within these plasmids may also be included in a cassette of genes that are flanked by insertion sequences or small transposons that facilitate the movement of the gene between genetic elements. In addition, many of these genes in particular the NDM (Class B) are neither species- nor plasmid-specific, therefore indicating a limit less boundary for spread of this resistance. OXA-48 is carried on a composite transposon known as TN1999 or variants of the transposon known as TN1999.2 and TN1999.3. The metallo-β lactamases are also transferable via a plasmid, and in addition to β-lactamase resistance, the strains are frequently resistant to aminoglycosides and fluorquinolones while remaining susceptible to polymixins.
It appears that these resistant determinants are capable of existing in a very diverse genetic background and able to move from one genetic element to another, one organ ism to another, and across genus and species lines in an unlimited capacity. It is therefore important for practitioners and laboratorians to not overlook or ignore any new emerging antibiotic patterns of resistance where they least expect them to occur. On February 14, 2013 the Center for Disease Control distributed an official CDC Health Alert through their Health Alert Network indicating that new carbapenem-resistant Enterobacteriaceae warrant additional action by healthcare providers. This alert was based on four key points:
1. While carbapenemase resistance may still be uncommon in some areas, at least 15 unusual biochemical resistance forms have been reported in the United States since July, 2012.
2. This increases the need for healthcare providers to work to aggressively prevent the emergence of CRE.
3. Guidelines are currently available from CDS to prevent CRE (e.g., contact precautions). Guidelines are avail able at http://www.cdc.gov/hai/organisms/cre/cre toolkit/index.html.
4. Many of these organisms have been identified in patients within the United States following previous treatment and/or medication outside of the United States. These isolates should be referred to a reference laboratory for confirmatory susceptibility testing that should minimally include an evaluation for KPC and NDM carbapenemases.
الاكثر قراءة في البكتيريا
اخر الاخبار
اخبار العتبة العباسية المقدسة
