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Impact of the New Delhi metallo-beta-lactamase on beta-lactam antibiotics.

Zmarlicka MT, Nailor MD, Nicolau DP - Infect Drug Resist (2015)

Bottom Line: It is thus surprising that the literature examining clinical experiences with NDM does not report corresponding poor clinical outcomes.However, animal studies do begin to shed more light on this phenomenon.They imply that the in vivo expression of NDM may not confer clinical resistance to all cephalosporin and carbapenem antibiotics as predicted by in vitro testing but other resistance mechanisms need to be present to generate a resistant phenotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Hartford Hospital, Hartford, CT, USA.

ABSTRACT
Since the first New Delhi metallo-beta-lactamase (NDM) report in 2009, NDM has spread globally causing various types of infections. NDM-positive organisms produce in vitro resistance phenotypes to carbapenems and many other antimicrobials. It is thus surprising that the literature examining clinical experiences with NDM does not report corresponding poor clinical outcomes. There are many instances where good clinical outcomes are described, despite a mismatch between administered antimicrobials and resistant in vitro susceptibilities. Available in vitro data for either monotherapy or combination therapy does not provide an explanation for these observations. However, animal studies do begin to shed more light on this phenomenon. They imply that the in vivo expression of NDM may not confer clinical resistance to all cephalosporin and carbapenem antibiotics as predicted by in vitro testing but other resistance mechanisms need to be present to generate a resistant phenotype. As such, previously abandoned therapies, particularly carbapenems and beta-lactamase inhibitor combinations, may retain utility against infections caused by NDM producers.

No MeSH data available.


Related in: MedlinePlus

Geographic distribution of NDM producers.Note: Reproduced with permission from the Hindawi Publishing Corporation. Copyright © 2014. Dortet L, Poirel L, Nordmann P. Worldwide dissemination of the NDM-type carbapenemases in gram-negative bacteria. Biomed Res Int. 2014;2014:249856.4Abbreviation: NDM, New Delhi metallo-beta-lactamase.
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f1-idr-8-297: Geographic distribution of NDM producers.Note: Reproduced with permission from the Hindawi Publishing Corporation. Copyright © 2014. Dortet L, Poirel L, Nordmann P. Worldwide dissemination of the NDM-type carbapenemases in gram-negative bacteria. Biomed Res Int. 2014;2014:249856.4Abbreviation: NDM, New Delhi metallo-beta-lactamase.

Mentions: NDM was named so after its place of origin: New Delhi, India.3 Organisms carrying genetic material for NDM have been found to be very capable of transferring genes encoding NDM, as well as any other resistance genes the pathogen may be carrying.8 The ease with which the genes are transferred is concerning, and the implications for dissemination of NDM are immense. Indeed, since its discovery, it has spread across the globe.9 The most recently published surveillance study reported a total of 135 NDM isolates from around the world.9 Despite the fact that about half of the isolates came from India, the study established the presence of NDM-producing organisms in other parts of the world, such as Vietnam, Serbia, the Philippines, the Middle East, Guatemala, and the USA. Reports of NDM-producing organisms have also surfaced from Pakistan,10 the UK,10 Japan,11 the Netherlands,12 and Australia.13Figure 1 depicts the geographical distribution of NDM; the areas where NDM producers are most commonly isolated are located on the Asian continent.4 Outbreaks have also been reported around the world in areas such as the UK and the Middle East. The clinical cases outlined in Table 1 also help demonstrate the wide spread of NDM producers. A variety of non-beta-lactam antimicrobials are sometimes utilized, including as a part of combination therapy. However, often these organisms producing NDM are resistant to many other antimicrobials, if not all antimicrobials, which may limit non-beta-lactam options. Additionally, the antibiotics that retain activity have high rates of side effects or have limitations in drug delivery, colistin, and fosfomycin, respectively. Given the worldwide spread and the broad resistance patterns detected, it is important to fully explore all our therapeutic options, including the clinical impact of these enzymes on beta-lactam antibiotics.


Impact of the New Delhi metallo-beta-lactamase on beta-lactam antibiotics.

Zmarlicka MT, Nailor MD, Nicolau DP - Infect Drug Resist (2015)

Geographic distribution of NDM producers.Note: Reproduced with permission from the Hindawi Publishing Corporation. Copyright © 2014. Dortet L, Poirel L, Nordmann P. Worldwide dissemination of the NDM-type carbapenemases in gram-negative bacteria. Biomed Res Int. 2014;2014:249856.4Abbreviation: NDM, New Delhi metallo-beta-lactamase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554481&req=5

f1-idr-8-297: Geographic distribution of NDM producers.Note: Reproduced with permission from the Hindawi Publishing Corporation. Copyright © 2014. Dortet L, Poirel L, Nordmann P. Worldwide dissemination of the NDM-type carbapenemases in gram-negative bacteria. Biomed Res Int. 2014;2014:249856.4Abbreviation: NDM, New Delhi metallo-beta-lactamase.
Mentions: NDM was named so after its place of origin: New Delhi, India.3 Organisms carrying genetic material for NDM have been found to be very capable of transferring genes encoding NDM, as well as any other resistance genes the pathogen may be carrying.8 The ease with which the genes are transferred is concerning, and the implications for dissemination of NDM are immense. Indeed, since its discovery, it has spread across the globe.9 The most recently published surveillance study reported a total of 135 NDM isolates from around the world.9 Despite the fact that about half of the isolates came from India, the study established the presence of NDM-producing organisms in other parts of the world, such as Vietnam, Serbia, the Philippines, the Middle East, Guatemala, and the USA. Reports of NDM-producing organisms have also surfaced from Pakistan,10 the UK,10 Japan,11 the Netherlands,12 and Australia.13Figure 1 depicts the geographical distribution of NDM; the areas where NDM producers are most commonly isolated are located on the Asian continent.4 Outbreaks have also been reported around the world in areas such as the UK and the Middle East. The clinical cases outlined in Table 1 also help demonstrate the wide spread of NDM producers. A variety of non-beta-lactam antimicrobials are sometimes utilized, including as a part of combination therapy. However, often these organisms producing NDM are resistant to many other antimicrobials, if not all antimicrobials, which may limit non-beta-lactam options. Additionally, the antibiotics that retain activity have high rates of side effects or have limitations in drug delivery, colistin, and fosfomycin, respectively. Given the worldwide spread and the broad resistance patterns detected, it is important to fully explore all our therapeutic options, including the clinical impact of these enzymes on beta-lactam antibiotics.

Bottom Line: It is thus surprising that the literature examining clinical experiences with NDM does not report corresponding poor clinical outcomes.However, animal studies do begin to shed more light on this phenomenon.They imply that the in vivo expression of NDM may not confer clinical resistance to all cephalosporin and carbapenem antibiotics as predicted by in vitro testing but other resistance mechanisms need to be present to generate a resistant phenotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Hartford Hospital, Hartford, CT, USA.

ABSTRACT
Since the first New Delhi metallo-beta-lactamase (NDM) report in 2009, NDM has spread globally causing various types of infections. NDM-positive organisms produce in vitro resistance phenotypes to carbapenems and many other antimicrobials. It is thus surprising that the literature examining clinical experiences with NDM does not report corresponding poor clinical outcomes. There are many instances where good clinical outcomes are described, despite a mismatch between administered antimicrobials and resistant in vitro susceptibilities. Available in vitro data for either monotherapy or combination therapy does not provide an explanation for these observations. However, animal studies do begin to shed more light on this phenomenon. They imply that the in vivo expression of NDM may not confer clinical resistance to all cephalosporin and carbapenem antibiotics as predicted by in vitro testing but other resistance mechanisms need to be present to generate a resistant phenotype. As such, previously abandoned therapies, particularly carbapenems and beta-lactamase inhibitor combinations, may retain utility against infections caused by NDM producers.

No MeSH data available.


Related in: MedlinePlus