Tuesday, August 30, 2016

mBio: 1st Colistin & Carbapenem Resistant E. Coli Infection In A U.S. Patient


Just over six years ago, in NDM-1: A New Acronym To Memorize, we looked at a Lancet Study by Walsh & Livermore et al., that examined the recent rise and export of an emerging antibiotic resistance gene dubbed New Delhi metallo-ß-lactamase-1 from Southeast Asia.

NDM-1 conveyed resistance to Carbapenems - drugs often used to treat difficult bacterial infections - including Escherichia coli (E. coli) and Klebsiella pneumoniae.

Of even greater concern, this NDM enzyme was carried by a plasmid – a snippet of portable DNA  - that can be easily transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species).

Since then, we've seen scattered variants of NDM-1 emerge around the globe, including  NDM-2, NDM-4, NDM-5, NDM-7 and NDM-9.  While ominous developments, there still remained a handful of drugs - most notably Colistin - available to treat these infections.

But last November the bad news broke (see MCR-1: The Return Of The Plasmids) of the discovery of another resistance gene in China - dubbed mcr-1 - that conveys resistance to Colistin.

The saving grace - at least at that time - was the initial samples with the MCR-1 resistance gene were still susceptible to Carbapenems, meaning they could still be treated.

The concern was that should  E. Coli, or CRE, pick up both resistance genes, we could find ourselves dealing with a nearly pan-drug resistant organism.

And in March of this year, in The Lancet's Emergence of the mcr-1 colistin resistance gene in carbapenem-resistant Enterobacteriaceae, we saw exactly that out of China; a report on two K pneumoniae isolates that carried the MCR-1 gene and the gene for NDM-5, providing it near pandrug resistance.

In May, we saw the CDC Statement On 1st MCR-1 Colistin Resistant Infection in U.S., - which, while still treatable with Carbapenems - sparked increased testing on new (and archived) samples looking for other cases.

Although it has been telegraphed in the media for the past 24 hours, today the open-access journal mBio has published the account of the first detection of a Colistin-Carbapenem resistant organism in the United States.
  • The good news, is while resistant to Colistin and Carbapenums, this E. coli bacteria was still susceptible to a small handful of drugs. 
  • The bad news, this sample was collected in 2014 - meaning it has been in this country at least two years, and likely more widespread than we know. 

The full report is available online, but below you'll find the abstract and summary.

Colistin- and Carbapenem-Resistant Escherichia coli Harboring mcr-1 and blaNDM-5, Causing a Complicated Urinary Tract Infection in a Patient from the United States

José R. Mediavillaa, Amee Patrawallab, Liang Chena, Kalyan D. Chavdaa, Barun Mathemac, Christopher Vinnarda, Lisa L. Deverd, Barry N. Kreiswirtha


Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States.
Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States.
Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene blaNDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole.
The mcr-1- and blaNDM-5-harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized.


Colistin has become the last line of defense for the treatment of infections caused by Gram-negative bacteria resistant to multiple classes of antibiotics, in particular carbapenem-resistant Enterobacteriaceae (CRE). Resistance to colistin, encoded by the plasmid-borne gene mcr-1, was first identified in animal and clinical samples from China in November 2015 and has subsequently been reported from numerous other countries.
In April 2016, mcr-1 was identified in a carbapenem-susceptible Escherichia coli strain from a clinical sample in the United States, followed by a second report from a carbapenem-susceptible E. coli strain originally isolated in May 2015. We report the isolation and identification of an E. coli strain harboring both colistin (mcr-1) and carbapenem (blaNDM-5) resistance genes, originally isolated in August 2014 from urine of a patient with recurrent urinary tract infections.
To our knowledge, this is the first report in the United States of a clinical bacterial isolate with both colistin and carbapenem resistance, highlighting the importance of active surveillance efforts for colistin- and carbapenem-resistant organisms.
(Continue . . . )

While detections of these dual-resistant organisms are still  exceedingly rare, this is the kind of nightmare resistance combination that could someday propel us into a post-antibiotic era, one where even minor infections are no longer treatable.

Lest anyone think this hyperbole, that is the exact phrase used by WHO Director General Chan more than 4 years ago (see Chan: World Faces A `Post-Antibiotic Era’).

For more on this newest antimicrobial threat - MCR-1 - you may wish to revisit:

Eurosurveillance Editorial: Plasmid-Mediated Colistin Resistance (MCR-1 gene):The Story Unfolds

The Lancet: Dissemination Of The MCR-1 Colistin Resistance Gene 

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