diease

Carbapenem Resistant Infection


Carbapenem Resistant Infection overview and Definition

Carbapenem are strongest antibiotics but some bacterias tends to develop resistant to these drugs.

The main bacteria that is resistant to the carbapenem group of drug is Enterobacteriaceae.

The Enterobacteriaceae include E.coli and Kleibsella pnemoniae


Pathophysiology

The genetic study of Enterobacteriaceae are complex; many genera and strains possess genetic material that codes for resistance against many types of antibiotics. As a strain develops resistance to an antibiotic, not only does it become resistant to that antibiotic, the genes confor resistance to one antibiotic might be causing resistance to other bacterias. Consequently, as different antibiotic resistance occurs, the genetic material can become linked together thus conferring antibiotic resistance to several antibiotics in a single bacterial strain. Such bacteria that are resistant to several antibiotics are considerably more dangerous to humans they may infect than are bacteria susceptible to antibiotics.

As new antibiotics are introduced, they can pressure the bacteria to adapt to survive even the newest and most powerful ones; bacteria survive by allowing to replicate those few bacteria that develop stable resistance components that are genetically coded and then pass on genetic antibiotic resistance to other bacteria. This new genetic ability is then again linked to other antibiotic-resistant genetic material and it goes on like a chain , thus resulting in "dangerous" bacterial strains that are resistant to many, if not all, antibiotics. That is the current situation for CRE bacteria. Keep in mind that there are strains of CRE bacteria that can fairly easily transfer genetic information to other bacterial strains that do not have multiple drug resistance but may have the potential to be dangerous under certain circumstances (for example, enterotoxigenic E.Coli).

 

The beta lactam antibiotic, penicillin G is a simple beta lactam ring. It impairs the function of the bacterial cell wall at the penicillin binding protein leading to the destruction of the organisms. The production of the beta lactamases can induce bacterial resistance to this antibiotics. These betalactamase enzymes hydrolyses the penicillin at its beta lactam ring. The subtype of penicillin such as the cephalosporins and carbapenems shows the same effect at the Penicillin Binding Protein site. Carbepenemases are beta lactamases active against carbapenem antibiotics.

Because gram negative bacteria have a cell wall and cell membrane they are better able to control what molecules pass through their outer membrane. Hence large amount of carbapenem molecules are required to produce the desired effect and to breakdown the pencillin binding protein.

 


Clinical signs & symptoms

  • Shortness of breath (from pneumonia)
  • Cyanosis
  • Hypotension
  • Pain with urination (from urinary tract infection)
  • Pain and swelling of the skin (from skin infection)
  • Belly pain (from liver or splenic infection)
  • Stiff neck and reduced consciousness (from meningitis infection)
  • Fever, chills, and fatigue (from infection in any location)


Differential Diagnosis

The specific assays used to detect the presence of known carbapenemase genes is located on plasmids or efflux pump mutations are normally gene based and amplify the potential genes present by the use of oligomer primers and probes.

Screening for CRE colonization is usually based on microbiological evaluation of the rectal swabs. Nasal swabs, pharyngeal swab, bronchial aspirates , urine cultures in catherized patients should be carefully evaluated. The rectal swab helps in detection to view the presence of intestinal CRE. The following are the surveillance test used to detect CRE :

1. culture-based methods;

2. nucleic acid amplification technology (NAAT)-based assays.

Culture based method for CRE screening:

Culture based methods have been widely used for CRE screening, several different cultural approaches have been described

a) inoculation onto McConkey agar plate after broth enrichment

b) direct inoculation onto McConkey agar plate containing a meropenem disk

c) direct inoculation onto specific selective chromogenic media  

but the above protocol is time consuming and it might take atleast 48-72 hours.

The main advantage of direct inoculation onto the McConkey agar plate containing a meropenem disk include low cost, and evaluation of the suspected colonies and also the possibility of checking the quality of the samples.

NAAT for molecular screening:

Molecular based methods (NAAT) for CRE screening usually detect the presence of one or more carbapenemase genes. For these characteristics these assays are able to identify only previously known resistance determinants.

NAAT-based assays validated for carbapenemase genes detection from rectal swabs can also be used as a confirmatory test for suspected colonies identified by culture-based methods, although not all commercial assays have an on-label indication for this.

The three types of NAAT based assays for the Surveillance of  CRE  is as follows:

In house molecular methods

Commercial molecular assays

Rapid/easy to use commercial molecular assays:

In house molecular methods can reveal best level of sensitivity and specificity . Moreover, these assays are less expensive if compared to molecular commercial method. Also it has important disadvantages are low level of automation, standardization and validation, and suboptimal inter-laboratory reproducibility.

Commercial molecular assays:

they are highly sensitive, specific and standardized, with TAT of few hours; the level of automation of these methods can vary from poor (need of sample preparation step, including extraction or lysis, and/or multiple hands-on steps), to good, but for all these assays laboratory experience and equipment are required.

Rapid/easy to use commercial molecular assays (REU-CMA) :

They might provide the same high standard of quality of results with shorter hands-on time and TAT (less than 1 h) and no requirement for batching


Prognosis

The prognosis is good when the treatment are started earlire and appropriate antibiotics are given.


Prevention

Tell the healthcare provider if you have been hospitalized in another healthcare facility, including hospitals in other countries.

Clean your hands properly and also ask the opposite person to follow the hygiene protocols.

Clean the hands:

    • Before preparing or eating food
    • Before touching your eyes, nose, or mouth
    • Before and after changing wound dressings or bandages
    • Before handling medical devices or touching tubes going into your body
    • After using the bathroom
    • After blowing nose, coughing, or sneezing
  • Follow the prescribed antibiotics properly.
  • Talk to your healthcare provider about your care and any concerns you have. Ask them what they are doing to protect you from getting an infection while receiving care.
  • Avoid preventable infections by making sure you are up to date on all recommended vaccinations.