Physicians at Massachusetts General Hospital today reported the first documented healthcare transmission of bacteria harboring the MCR-1 gene in the United States.
In a case study published in Clinical Infectious Diseases, the physicians report that two patients at the hospital had highly related MCR-1–positive Klebsiella pneumoniae samples isolated from clinical cultures, and that the transmission of the multidrug-resistant bacteria between the two patients is linked to shared exposure to a duodenoscope—a medical device used to diagnose and treat digestive tract issues. An epidemiologic investigation identified no other avenues of transmission.
The case highlights continuing problems with duodenoscopes, which have been implicated in superbug outbreaks in the United States and Europe in recent years. Because of complex designs, the devices have been found to harbor dangerous bacteria that can be transmitted to other patients, even after being properly cleaned. While device manufacturers and the Food and Drug Administration (FDA) have made efforts improve duodenoscope safety, the issues have persisted.
The authors of the report say the case also shows why routine testing for colistin resistance is needed. The mobile MCR-1 gene confers resistance to the last-resort antibiotic, which is being increasingly used to treat multidrug-resistant infections. The spread of MCR-1 into already multidrug-resistant pathogens like carbapenem-resistant Enterobacteriaceae (CRE) could make those pathogens impossible to treat.
Case identification and investigation
The investigation was initiated in April 2017, when physicians at the hospital identified colistin-resistant K pneumoniae in a patient who had undergone endoscopic retrograde cholangiopancreatography (ERCP) using a duodenoscope. In the procedure, physicians thread the long, flexible tube with a light and camera at the end through the throat and stomach and into the top of the small intestine to examine the inside of the digestive system and treat problems with fluid drainage. ERCP is typically performed when a patient’s bile or pancreatic ducts have become narrowed or blocked.
After antibiotic susceptibility testing found that the bacteria were resistant to colistin, polymerase chain reaction (PCR) testing performed by the Centers for Disease Control and Prevention (CDC) confirmed the presence of MCR-1 and other resistance genes. Prior to the investigation, MCR-1 had not been identified at the hospital.
A few weeks later, a second patient who had undergone ERCP was identified as carrying colistin-resistant K pneumoniae, and PCR testing of the bacteria also confirmed the presence of MCR-1 and additional resistance genes. Further molecular analysis of isolates from both patients showed that they were very closely related, suggesting transmission between the two patients.
Interviews with the index patient revealed that he had visited multiple Caribbean islands 4 months before admission. Because other previous MCR-1 patients in the United States have also reported Caribbean travel, that could explain how the patient acquired the gene. But the second patient had no documented travel outside of the United States, or any recent hospitalizations, and the two patients did not share healthcare providers. Furthermore, tests of rectal swab samples from household contacts of both patients and other patients at the hospital were all negative for colistin resistance and MCR-1.
That left the duodenoscope, which was used in both procedures and had been thoroughly cleaned according to the manufacturer’s instructions, as the likely culprit. Testing of the device at the CDC detected the presence of K pneumoniae and Escherichia coli bacteria, though none of the samples tested positive for MCR-1 or any of the other resistance genes found in the patients’ isolates. In addition, further investigation by the manufacturer, Pentax Medical, found that adhesive on a cap at the tip of the device had peeled off, allowing bodily fluids to get into a sealed area that can’t be cleaned.
Persistent issues with duodenoscopes
The authors of the report say the case illustrates that efforts to improve the safety of duodenoscopes, which are used in more than 500,000 ERCP procedures in the United States each year, have not solved the problem.
In the wake of a handful of outbreaks of drug-resistant bacteria that were linked to use of duodenoscopes, including a January 2015 CRE outbreak that resulted in two deaths at a Los Angeles hospital, the FDA in 2015 issued a safety communication warning that the design of the devices may impede effective cleaning. Duodenoscope manufacturers subsequently updated cleaning instructions, and the FDA provided details on supplementary cleaning measures.
Pentax Medical updated cleaning instructions for the particular device in this case—the ED-3940TK duodenoscope—in 2016. But problems remained.
“Although the manufacturer’s updated processing instructions and FDA-issued supplemental measures were used, the duodenoscope was persistently contaminated with enteric bacteria, most likely due to a distal cap defect that allowed material to penetrate a sealed area inaccessible to cleaning,” they write.
Furthermore, the authors argue, guidance issued by Pentax and the FDA in January 2017 to notify customers of potential problems with the distal end cap was of limited use. The guidance recommended that hospitals inspect the adhesive binding on the cap for damage and to stop using devices that showed any problems, but experts at the hospital and the CDC couldn’t find any damage on the device that was used on the two patients. This indicates that, in practice, “it is difficult for even experienced users to identify subtle defects in these complex devices.”
In February 2018—after these two cases were discovered—Pentax issued a recall for the ED-3940TK duodenoscope to replace the distal end cap and other parts of the device and to update the operational manual to recommend annual maintenance. The safety communication issued by the FDA notes that the design changes are intended to “reduce the potential for leakage of patient fluids into the closed elevator channel and under the distal cap.”
The authors of the new study say further changes in duodenoscope design, including disposable components and heat-stable components that allow for steam-cleaning, are urgently needed.
They also suggest that the two cases of MCR-1 carriage, which were identified through the vigilance of clinicians and lab technicians at the hospital, highlight the need for an FDA-approved colistin susceptibility test to prevent the silent spread of MCR-1 in healthcare facilities.
Sep 11 Clin Infect Dis abstract
Feb 7 FDA safety communication
February 2015 FDA safety communication