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

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, 7

*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, 7


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

Dr. Echols is a paid consultant of Shionogi Inc.


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

© 2020 SHIONOGI INC. Florham Park, NJ 07932 USFET‑0006 01/2020


  1. Centers for Disease Control and Prevention. Gram‑negative bacteria infections in healthcare settings. 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.
  7. Cai B, et al. Open Forum Infectious Diseases.2017; DOI:10.1093/ofid/ofx176.

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


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