Friday, January 13, 2017

MMWR: Fatal Pan-Drug Resistant CRE - Nevada 2016

Credit CDC - Vital Signs


While pandemics and outbreaks of novel diseases like avian flu, MERS, and Zika make the immediate headlines, in terms of long-to-medium term threats, there is little that can match the potential harm from the rise of antibiotic resistant bacteria around the globe.
It's a threat that has prompted both CDC Director Thomas Frieden and WHO Director General Margaret Chan to warn that the world faces a `post-antibiotic' era One where even simple infections could one day become untreatable.
 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 a year ago 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 is that eventually one or more of these resistant bacteria could eventually develop pan-resistance -  where no effective treatment option remains.
Completely resistant infections have been - thankfully - extrodinarily rare, although last March, in The Lancet's Emergence of the mcr-1 colistin resistance gene in carbapenem-resistant Enterobacteriaceae, we saw a report from China on two K pneumoniae isolates that carried the MCR-1 gene and the gene for NDM-5, providing it near pandrug resistance. 

Yesterday, however, the MMWR published a report on a fatal infection - of a patient who had previously been hospitalized in India, and then later in Nevada - which proved resistant to all 26 types of antibiotics approved for use in the United States.

The organism in question was identified as a pan-resistant CRE (Carbapenem-resistant Enterobacteriaceae), specifically Klebsiella pneumoniae. K. Pneumoniae’s opportunistic qualities – attacking those with weakened immune systems - makes it an important, and difficult to control, hospital acquired infection.

While no other cases were found in the hospital where this patient was treated, this first salvo of pan-resistant CRE won't be the last. 

Notes from the Field: Pan-Resistant New Delhi Metallo-Beta-Lactamase-Producing Klebsiella pneumoniae — Washoe County, Nevada, 2016

Weekly / January 13, 2017 / 66(1);33

Lei Chen, PhD1; Randall Todd, DrPH1; Julia Kiehlbauch, PhD2,3; Maroya Walters, PhD4; Alexander Kallen, MD4 (View author affiliations)
View suggested citation

On August 25, 2016, the Washoe County Health District in Reno, Nevada, was notified of a patient at an acute care hospital with carbapenem-resistant Enterobacteriaceae (CRE) that was resistant to all available antimicrobial drugs. The specific CRE, Klebsiella pneumoniae, was isolated from a wound specimen collected on August 19, 2016. After CRE was identified, the patient was placed in a single room under contact precautions. The patient had a history of recent hospitalization outside the United States. Therefore, based on CDC guidance (1), the isolate was sent to CDC for testing to determine the mechanism of antimicrobial resistance, which confirmed the presence of New Delhi metallo-beta-lactamase (NDM).

The patient was a female Washoe County resident in her 70s who arrived in the United States in early August 2016 after an extended visit to India. She was admitted to the acute care hospital on August 18 with a primary diagnosis of systemic inflammatory response syndrome, likely resulting from an infected right hip seroma. The patient developed septic shock and died in early September. During the 2 years preceding this U.S. hospitalization, the patient had multiple hospitalizations in India related to a right femur fracture and subsequent osteomyelitis of the right femur and hip; the most recent hospitalization in India had been in June 2016.

Antimicrobial susceptibility testing in the United States indicated that the isolate was resistant to 26 antibiotics, including all aminoglycosides and polymyxins tested, and intermediately resistant to tigecycline (a tetracycline derivative developed in response to emerging antibiotic resistance). Because of a high minimum inhibitory concentration (MIC) to colistin, the isolate was tested at CDC for the mcr-1 gene, which confers plasma-mediated resistance to colistin; the results were negative. The isolate had a relatively low fosfomycin MIC of 16 μg/mL by ETEST.* However, fosfomycin is approved in the United States only as an oral treatment of uncomplicated cystitis; an intravenous formulation is available in other countries.

A point prevalence survey, using rectal swab specimens and conducted among patients currently admitted to the same unit as the patient, did not identify additional CRE. Active surveillance for multidrug-resistant bacilli including CRE has been conducted in Washoe County since 2010 and is ongoing; no additional NDM CRE have been identified.

This report highlights three important issues in the control of CRE. First, although CRE are commonly sent to CDC as part of surveillance programs or for reference testing, isolates that are resistant to all antimicrobials are very uncommon. Among >250 CRE isolate reports collected as part of the Emerging Infections Program, approximately 80% remained susceptible to at least one aminoglycoside and nearly 90% were susceptible to tigecycline (2). Second, to slow the spread of bacteria with resistance mechanisms of greatest concern (e.g., gene encoding NDM or mcr-1) or with pan-resistance to all drug classes, CDC recommends that when these bacteria are identified, facilities ensure that appropriate infection control contact precautions are instituted to prevent transmission and that health care contacts are evaluated for evidence of transmission (3). Third, the patient in this report had inpatient health care exposure in India before receiving care in the United States. Health care facilities should obtain a history of health care exposures outside their region upon admission and consider screening for CRE when patients report recent exposure outside the United States or in regions of the United States known to have a higher incidence of CRE (1).