The Complexities of Gram‑NegativeCarbapenem Resistance

The Complexities of Gram‑NegativeCarbapenem Resistance

Many Gram‑negative bacteria are resistant to multiple antibiotics and are becoming more resistant at an increasing rate from year to year.1

Carbapenem‑resistant (CR) infections are associated with significant complications and a high mortality rate.2

In order to stay ahead of the curve, it is important to follow local CR trends, prescribe antibiotics appropriately, and support new antimicrobial development.

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Mechanisms of Carbapenem
Resistance: Exploring the Complexities

Watch this educational video to learn more about coexisting mechanisms of resistance and their role in Gram‑negative pathogens.

The major mechanisms of Gram‑negative CR

These 3 mechanisms often coexist, which adds to the challenge of treating CR pathogens.3

β‑LACTAMASES break the critical β‑lactam bond, rendering the antibiotic inactive.4

PORIN CHANNEL changes reduce the amount of β‑lactam antibiotic reaching the periplasm through the following3:

  • Decrease or deficiency in porin protein
  • Mutation of the porin channel

EFFLUX PUMPS contribute to β‑lactam resistance by expelling antibiotic from the periplasm.3

Based on a US analysis,

Non‑fermenters (A. baumannii and P. aeruginosa) had the highest rate of CR and caused over 80% of CR infections.5


*Data from hospitalized patients with infections due to Gram‑negative (N=292,742) pathogens were gathered from the Premier Healthcare Database between 2009 and 2013. From these data, the total number of infections and proportion of CR infections by pathogen and infection site were calculated.5

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RESOURCES

Here are some helpful resources and scientific posters analyzing trends of Gram‑negative infections:

‡ Dr. Echols is a paid consultant of Shionogi Inc.

ORGANIZATIONS

The organizations listed below are following trends in Gram-negative CR infections.
Click on the links below to learn more.

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SHIONOGI: AN EXTENSIVE HISTORY OF INNOVATION AND ANTI‑INFECTIVES


For over 100 years, Shionogi has been dedicated to developing and commercializing groundbreaking medicines to address some of the most complex public health challenges, such as antibiotic resistance.


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S-649266 - A siderophore cephalosporin for carbapenem-resistant Gram-negative infections
S-033188 - Novel anti-influenza drug with new mechanism of action
2014 - A single tablet HIV regimen
2013 - An HIV integrase inhibitor was launched
2010 - An antiviral drug for the treatment of influenza
2005 - A fourth-generation synthetic fluoroquinolone antibacterial agent
2005 - A novel carbapenem
1997 - A third-generation oral cephalosporin antibiotic
1993 - A fourth-generation cephalosporin
1992 - A third-generation oral cephalosporin antibiotic
1990 - A fluoroquinolone antibiotic
1988 - Second of two oxacephems approved globally
1984 - A second-generation broad-spectrum cephalosporin
1982 - A second-generation cephalosporin
1982 - First of two oxacephems approved globally
1981 - A Gram-positive anti-MRSA antibiotic used for a number of bacterial infections
1976 - A sulfa antibiotic used to treat bacterial infections
1970 - A first-generation cephalosporin used to treat a number of bacterial infections
1959 - A sulfa antibiotic used to treat a number of bacterial infections
1953 - A macrolide antibiotic was licensed in Japan
1878 - Shionogi was founded by Gisaburo Shiono, Sr, as a drug wholesaler
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References:

  1. Centers for Disease Control and Prevention. Gram‑negative bacteria infections in healthcare settings. /www.cdc.gov/hai/organisms/gram-negative-bacteria.html. Updated January 17, 2011. Accessed September 23, 2016.
  2. Ogura E, Magee G, Arjona Ferreira JC, et al. Impact of carbapenem‑resistant pathogens on mortality among hospitalized adult patients. Poster presented at: ID Week 2015; October 7‑11, 2015; San Diego, CA. Poster 1801.
  3. Fernandez L, Hancock REW. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin Microbiol Rev. 2012;25(4):661‑681.
  4. Madigan MT, Martinko JM, Dunlap PV, Clark DP. Brock Biology of Microorganisms. 12th ed. San Francisco, CA: Pearson; 2009.
  5. Cai B, Echols R,§ Magee G, et al. Geographic distribution of carbapenem‑resistant Gram‑negative infections in adult patients in US hospitals. Poster presented at: ASM‑Microbe; June 16‑20, 2016; Boston, MA. Poster 268.
  6. Echols R,§ Cai B, Ogura E, et al. What is best available therapy (BAT) for the treatment of carbapenem‑resistant (CR) Gram‑negative infections in the US? Poster presented at: ID Week 2015; October 7‑11, 2015; San Diego, CA. Poster 1802.

§ Dr. Echols is a paid consultant of Shionogi Inc.

 

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