The March of Antibiotic Resistance Leads to Another CRE Outbreak

Today there was much attention devoted to the "superbug" outbreak involving a California hospital. The basic facts surrounding this event are that duodenoscopes, a telescopic medical device used during ERCP procedures, were found to be contaminated with carbapenem-resistant Enterobacteriaceae (CRE). An ERCP is a procedure employed to evaluate the pancreas and bile ducts and is an essential part of modern medical diagnosis treatment for myriad conditions. Thus far, 7 people were infected with 2 succumbing to their infections; 179 were exposed from October 2014 through January 2015.

A couple of important points regarding these events:

  • Expect more CRE outbreaks as the march of antibiotic resistance continues
  • This type of hospital-acquired (nosocomial) infection is exactly what is meant by antibiotic resistance threatening modern medicine (i.e. can procedures be performed safely when the risk of contracting an untreatable infection is considerable)
  • Anytime one has a breach of an immune defense, there is risk for infection. Sticking an intricate and flexible telescope through the mouth into the small intestine is most definitely a breach (albeit one that is necessary to treat and diagnose certain conditions)
  • Scope related infections are nothing new and this outbreak reinforces the need for device sterilization to be performed meticulously and without fail (at my institution gas sterilization using ethylene oxide has been employed with great success since an 18 person outbreak was uncovered)

CRE are labeled an urgent threat by the CDC because they are near impossible to treat and have a high attributable mortality.  As this outbreak remains in the headlines I believe it is an important opportunity to reiterate to the public that this is the end result of injudicious antibiotic use and there is a desperate need for new approaches to combat bacterial infections (monoclonal antibodies, vaccines, bacteriophages, lysins, antimicrobial peptides, virulence disruptors).

The often unwarranted demand for antibiotics--and physician acquiescence--must stop or else the antibiotic age, which dawned in the first half of the 20th Century, will become a mere memory.

Cerberus visits Pittsburgh: A CRE Like No Other

In most discussions of antimicrobial resistance, the menace of carbapenemase-producing Enterobacteriaceae (CRE) is mentioned. This family of bacteria,  which includes E.coli and Klebsiella species, often cause hospital-acquired infections and are extremely difficult--if not impossible to treat.

The carbapenem class of drugs are, in many ways, the last line of resort and include the drugs: imipenem-cilastatin, meropenem, ertapenem, and doripenem. CRE employ one of 3 enzymes to inactivate this class of drugs:

  1. KPC: the most common mechanism in the US
  2. NDM-1: reported multiple times in the US and also linked to medical tourism in India
  3. OXA-48: only reported twice in the US

A team from the University of Pittsburgh led by Yohei Doi--who I am honored to have been a co-fellow with--recently reported Klebsiella pneumoniae isolated from a patient in Pittsburgh that produces both OXA-48 and NDM-1. The isolate also possessed mutations that conferred high level aminoglycoside resistance.

The patient was a woman initially hospitalized in India for a neurologic condition who was subsequently transferred to Pittsburgh for further care. Once in Pittsburgh, she bounced between the hospital and long term acute care facilities-- a common theme amongst patients who harbor pathogens such as this one. Fortunately, this pathogen was merely colonizing the patient's urinary system and not causing an overt infection meriting treatment.

This case highlights the fact that bacteria, who have dominated the earth for billions of years, are genetically very plastic and can possess several modes of resistance due to selection pressure from antibiotics, uptake of plasmids from other bacteria, or other reasons. Also, the fact that this patient had been hospitalized in India should serve to remind clinicians of the high prevalence of these resistant isolates in other countries (see this excellent review on medical tourism for more information).