Another warning sign of a looming post-antibiotic era comes in the form of a fatal infection resistant to all available antibiotics in the United States, the CDC reports.1
The case occurred last August in a female patient in an acute care hospital in Reno, NV, who died of carbapenem-resistant Enterobacteriaceae (CRE) that was resistant to 26 antibiotics. The pathogen was Klebsiella pneumoniae that was isolated from a wound specimen. Of note, the patient had recently been hospitalized in India, and the specific enzyme conferring pan resistance was first discovered in that country: New Delhi metallo-beta-lactamase (NDM).
The patient in her 70s was admitted to the unnamed hospital on Aug. 18, 2016, with systemic inflammatory response syndrome likely triggered by a hip infection.
“The patient developed septic shock and died in early September,” the CDC reported. “During the two 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.”
What was remarkable about the infection was that it was resistant to whole classes of antibiotics and impervious to the last-line option colistin. The isolate appeared to have some susceptibility to fosfomycin, which is not available as an IV drug in the United States.
“It’s not approved by the FDA,” says Alex Kallen, MD, one of the CDC investigators in the case. “It’s approved for oral use to treat urinary tract infections, so that wouldn’t be an appropriate antibiotic to use in this case.”
Though there are other mechanisms of resistance in gram negative bacteria, the CDC is still hoping to surround and contain NDM as cases are identified.
“As of Jan 6, 2017, there have been 175 [NDM] cases in U.S. so far,” Kallen says. “The place where we see it most commonly is in Illinois, and interestingly that is related to a duodenoscope outbreak that they had a few years ago where there was transmission to some 30 patients. So, a big chunk of that comes from that outbreak.”
In terms of CRE overall, it is still very unusual to find isolates that are resistant to all antibiotics.
“We have a big surveillance system that looks for CRE around the country,” Kallen says. “We didn’t identify any pan-resistant isolates out of hundreds of isolates that we tested from that. We also do a lot of reference testing, particularly for gram negatives like Pseudomonas and Acinetobacter. You do see more resistance in those from time to time. If you look at all of those, we have seen less than 10 [that are pan-resistant].”
That said, it is almost certain that more are out there because the CDC surveillance system is passive and relies primarily on clinicians voluntarily reporting unusual isolates.
“There is no requirement for people to report to us,” he says. “They send them to us when they want specialized testing.”
One of the take-home messages of the Nevada case — as was found critical during the Ebola outbreak — is that the travel history of the patient may trigger isolation and containment measures before a culture is confirmed.
“That is a risk factor that is under-appreciated,” Kallen says. “I think, unfortunately, the history of exposures outside the United States is not [captured] as regularly as it should be. If you identified someone you could get them in appropriate precautions quicker, which decreases the risk of transmission. Time and again when we see these, it is usually the same story — a person who has had a hospitalization for a long period of time gets transferred, ends up in a U.S. hospital, and a week or so into their stay they end up with one of these organisms. That results in us having to screen lots of contacts and things like that [that could be avoided] if we took the history up front.”
No secondary transmission was found, suggesting that spread may be less likely to occur in short-stay acute care hospitals as opposed to long-term acute care facilities that can be reservoirs for CRE. In the latter setting, there are more opportunities for contact for longer periods, and isolation measures are much more difficult to maintain.
“We are taking a kind of containment approach, so when we identify these novel organisms we screen contacts and try to find evidence of transmission,” Kallen says. “The good news is, we don’t find a lot of transmission, especially in short-stay acute care hospitals. But where we are finding problems with transmission are in longer-stay facilities like long-term acute care hospitals.”
- CDC. Notes from the Field: Pan-Resistant New Delhi Metallo-Beta-Lactamase-Producing Klebsiella pneumoniae — Washoe County, Nevada, 2016. MMWR 2017;66(1):33