Wednesday, June 05, 2019

ECDC Rapid Risk Assessment: Large Outbreak of NDM-producing CRE in Tuscany Region, Italy

Credit CDC - Vital Signs


It’s been nearly 9 years since The Lancet published a study (see NDM-1: A New Acronym To Memorize)  by Walsh, Toleman, Livermore, et al. that awakened the world to the emergence and growing prevalence of the NDM-1 (New Delhi metallo-β-lactamase) enzyme that can make many types of bacteria resistant to a wide spectrum of antibiotics - including Carbapenems.
Carbapenems are newer generation beta-lactam antibiotics (a class that includes penicillins, cephalosporins, cephamycins, and carbapenems) that are usually reserved as an antibiotic of last resort.
Complicating matters, this enzyme is carried by a plasmid – a snippet of portable DNA  - that can be transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species) in a shared environment.

Since then, we've watched the spread - not only of NDM-1 - but of other NDM variants (see First Imported Case Of NDM-4 Reported In Hong Kong) around the globe, often in travelers recently returned from the Indian Subcontinent (see VOA News report  Concerns Mount Over India's Role In Incubating Drug-Resistant Bacteria). 
Completely resistant infections have been - thankfully - extraordinarily rare, with other - often last resort drugs - still being effective.
In 2017, 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 pneumoniaeK. Pneumoniae’s opportunistic qualities – attacking those with weakened immune systems - makes it an important, and difficult to control, hospital acquired infection.
All of which brings us to a new ECDC RRA (Rapid Risk Assessment) on a very large, multi-hospital, outbreak of Carbapenum resistant CRE in the Tuscany region of Italy. While difficult to treat, these infections are not - as in the case of the fatal case in Nevada - pan resistant. 
The ECDC puts the risk of further spread within Italy as `high', while the risk of cross border spread is currently `moderate'.
This is a long, and detailed report.  I've only included the summary, so follow the link to read it in its entirety.   When you return, I'll have a postscript:

Rapid risk assessment: Regional outbreak of New Delhi metallo-betalactamase-producing carbapenem-resistant Enterobacteriaceae, Italy, 2018–2019 Risk assessment
4 Jun 2019
A large outbreak of New Delhi metallo-beta-lactamase (NDM)-producing carbapenem-resistant Enterobacteriaceae (CRE) has been reported from the Tuscany region in Italy. Between November 2018 and May 2019, seven Tuscan hospitals notified a total of 350 cases.
Due to its size and the resulting change in the epidemiology of CRE, the reported outbreak is a significant event, despite previous endemicity of Klebsiella pneumoniae carbapenamase (KPC)-producing CRE in this geographic area. The change in the type of carbapenemase further reduces treatment options because NDM-producing CRE are not susceptible to some of the new beta-lactam/beta-lactamase inhibitor combinations such as ceftazidime-avibactam and meropenem-
Numerous reported outbreaks and examples of cross-border transmission of NDM-producing CRE in the European Union/European Economic Area (EU/EEA) demonstrate the transmission potential of NDM-producing CRE in European healthcare systems. Outbreaks such as the one in Tuscany present a risk for cross-border transmission and further spread to other EU/EEA countries, especially since the affected area is a major tourist destination.
Given the previous rapid establishment of KPC-producing CRE in Italy (which resulted in an endemic situation), the risk for further spread of NDM-producing CRE from the current outbreak is considered to be high for Italy and moderate for cross-border spread to other EU/EEA countries.
Sporadic cases of community acquisition of NDM-producing CRE have also been described for other European countries. However, the introduction and dissemination of these bacteria have mainly been associated with healthcare settings. Therefore, the risk of acquisition of NDM-producing CRE related to this outbreak is likely restricted to persons with recent healthcare contact.
        (Continue . . . .)

In addition to death and taxes, two more inevitabilities of life are:
1) the world will someday face another pandemic and   
2) evolutionary pressures due to overuse and misuse of antibiotics will continue to erode our limited armamentarium of these lifesaving drugs.
Pandemics tend to produce a sharper, more dramatic impact, but over time antimicrobial resistance (AMR) could prove far deadlier.

Each year we draw a little closer to a long-predicted, but highly plausible `post-antibiotic era', where even common infections become resistant to most antibiotics, and something as simple as a scraped knee, or elective surgery, could be deadly. 
Considerable efforts are underway to try and stave off that day (see CIDRAP's Antimicrobial Stewardship Project), but inappropriate prescribing or use of antibiotics, rampant (and unnecessary) use in farm animals, and the plethora of fake or adulterated antibiotics sold around the world threaten to undermine their success.
 Some of my more recent blogs on the threat of antibiotic resistance include:

WHO Report: Wide Differences In Antibiotic Use Between Countries

The Lancet: Attributable Deaths & Disability Due To Infections With Antibiotic-Resistant Bacteria - EU 2015

Pakistan Media Reports: Scores Of `Counterfeit' Drugs Removed From Punjab Hospitals

mBio: The Gathering Storm: Is Untreatable Typhoid Fever on the Way?
Global AMR Threat: Centrally Approved & Unapproved Antibiotic Formulations Sold In India
WHO: First Global Antimicrobial Surveillance System (GLASS) Report

You'll also want to check out the CIDRAP-ASP Youtube Channel, which has more than 24 hours of lectures and webinars on Antimicrobial stewardship.