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An emerging strain of Pseudomonas aeruginosa with a novel mechanism of resistance to most antibiotics has been detected in healthcare outbreaks in Lubbock, TX, and Tijuana, Mexico, the Centers for Disease Control and Prevention (CDC) reports.
The outbreaks were described at the CDC’s recent Epidemic Intelligence Service (EIS) conference by two of the agency’s EIS officers, the vaunted “medical detectives” who traditionally have investigated the first cases of emerging pathogens. The etiologic agent in both outbreaks is Verona integron-encoded metallo-beta-lactamase carbapenem-resistant P. aeruginosa (VIM-CRPA).
Genetic analysis thus far shows no epidemiologic link between the ongoing regional outbreak in Lubbock and an outbreak among U.S. patients who traveled to Tijuana for weight loss surgery.
As carbapenems are typically last-line drugs, organisms like VIM-CRPA that develop resistance to these antibiotics are an immediate threat to proliferate. For example, in 2001, only one state reported Klebsiella pneumoniae that had acquired carbapenem resistance. In 2018, all 50 states had reported cases of this resistant strain.1
“Resistance like VIM is found in mobile genetic elements and can be transferred horizontally among different bacteria,” said Christopher Prestel, MD, a CDC EIS officer. “They are almost exclusively found in healthcare settings, and so we consider this an important healthcare threat. Internationally, similar antibiotic-resistance elements and detected rates of carbapenem-resistant isolates can skyrocket from 5% to close to 30% within two years.”
VIM-CRPA is spreading among hospitals, skilled nursing facilities, and other settings in Lubbock, with 33 clinical infections confirmed, and three deaths. With little more than 100 cases detected nationally, Lubbock has a disproportionate number of infections but no clear reservoir for the pathogen.
“Essentially, this town of 250,000 people makes of one of every three VIM-CRPA detections in the U.S.,” Prestel said.
The outbreak was discovered because two hospitals in Lubbock were routinely sending isolates to the CDC Antibiotic Resistance Laboratory Network. The network has participating labs in all states, as well as seven regional labs that can perform cutting-edge genetic analysis of pathogens.
“In June of 2017, an 84-year-old woman developed clinical infection in her abdomen following abdominal surgery for pancreatic cancer,” Prestel said of the index case. “The culture grew Pseudomonas aeruginosa, and it was resistant to all common antibiotics, including carbapenems. Over the next 13 months, 24 more people developed infections with VIM-CRPA. There were no clear epidemiologic links.”
The case count had increased to 33 when Prestel presented the findings2 at the EIS meeting. In the ongoing investigation, facilities with VIM-CRPA patients were offered infection control consultations and screenings of patients for colonization. Screening of a selected sample of 265 patients from seven hospitals showed no colonization with VIM-CRPA.
Whole genome sequencing showed the Lubbock cases form a distinct cluster when compared to isolates in other geographic cases.
“From the genome sequencing, it’s clear that the isolates kind of cluster among themselves but don’t really appear to be related to other parts of the country,” he said.
That said, the genetic analysis shows signs of nosocomial transmission from one patient to another. “Some of the snips [single nucleotide polymorphisms] are so close they suggest transmission within the same healthcare facility,” he said.
In the absence of a clear environment reservoir, is it possible the mobile plasmids in VIM-CRPA could be transferring resistance to susceptible strains of P. aeruginosa and potentially to other gram-negative bacteria?
“I think that is the million-dollar question,” he said. “One thing that we are looking into is the community cases that were cultured close to the time of admission. We are trying to find out if there are common risk factors or exposures that these individuals have.”
P. aeruginosa already is one of the most common hospital-associated infections, and mortality can approach 60% in bloodstream infections, he said.
The majority of the cases are wound infections, urine cultures, and respiratory infections. Although no environmental reservoir has been found, the connection to hospitalization and healthcare is clear. Overall, 48% of cases were hospitalized three months prior to positive culture, he said.
“Going a year out increases that to 80%,” he added.
In other risk factors in infected patients, 64% underwent surgery in the previous year and 33% lived in a nursing home.
“These exposures happened at multiple different facilities across Lubbock,” he said. “We identified 15 different locations for patients receiving care.”
These included acute care hospitals, long-term acute care facilities, and skilled nursing facilities that included one with patients on ventilator support.
Infection prevention assessments included hand hygiene observations, and environmental cleaning assessments using fluorescent markers on high-touch surfaces in random rooms. These assessments were performed at seven facilities in the city.
“All but two facilities had someone in charge of their infection prevention that had received accredited training,” he said. “All but one facility had written policies for things like hand hygiene and contact precautions for patients with multidrug-resistant organisms.”
The hand hygiene observation results seemed fairly typical of historical examinations in the absence of a major quality improvement push.
“About 50% of hand hygiene compliance was carried out at these seven facilities, and that ranged from zero to 77% of hand hygiene observations at different facilities,” Prestel said. “Similarly, we found about half of the rooms were appropriately cleaned with a range of 16% to 84%.”
The CDC and clinical partners provided on-site training at each facility to engage staff to improve hand hygiene and environmental cleaning. Communication between facilities transferring and receiving patients across the continuum also was called into question.
“We identified some gaps in communication,” he said. “All seven of the facilities indicate that they talk to the receiving facility when they are transferring a patient out. However, when asked if they were given the same information when receiving a patient, only three out of seven facilities reported receiving that information.”
The CDC worked with the local health department and clinicians to create a patient transfer form that calls for identification of the pathogen, personal protective equipment needed, and other key information for the receiving facility.3
Considering the assessment findings, Lubbock health officials and infection preventionists formed a collaboration to “BOOT VIM Out of Lubbock.” The “BOOT” acronym generally stands for these concepts:
“That was really a grassroots effort intended to engage the local people, and it was mostly attended by infection preventionists,” he said of the launch of the campaign.
Prestel and CDC colleagues were preparing to return to Lubbock after the EIS conference for a six-month follow-up visit. A 12-month follow-up also is planned, as well as ongoing consultations with facilities and educational webinars.
“We are continuing to do some investigations to see if there is an underlying reservoir, but I think it is clear that this is regional transmission,” he said. “Whether we find a reservoir or not, we want to ensure that the infection prevention practices that we know work are being carried out to prevent further transmission.”
Denise Cardo, MD, director of the CDC division of healthcare quality promotion, was the moderator of the EIS session. Infection prevention is being emphasized in hospitals but tends to diminish in other facilities across the healthcare continuum, she said. Handwashing is generally better in hospitals and worse in lower-resourced skilled nursing facilities, Cardo noted.
“It is a shock to us to see how care is being delivered in these places,” she said. “We don’t have a baseline, but know that everywhere we go — especially for skilled nursing facilities with ventilators — practice is very bad.”
Skilled nursing facilities for ventilated, high-acuity patients have been implicated in outbreaks of other pathogens, including multidrug-resistant Candida auris. (See Hospital Infection Control & Prevention, January 2019.)
The other outbreak of VIM-CRPA described at the EIS meeting was traced to a healthcare facility in Tijuana, where the CDC received reports of 31 cases of the emerging infection from September through November of last year. Six of these cases were in U.S. patients who had traveled to the facility for bariatric surgery.4
With the cooperation of a travel agency that set up the medical tourism program, the CDC was able to identify many more cases.
“In March , the travel agency voluntarily provided CDC with a list of 741 individuals that they had referred for surgery since August of 2018 to the identified facility,” said Ian Kracalik, PhD, MPH, a CDC EIS officer.
“In total, we identified 30 patients with highly resistant Pseudomonas aeruginosa infections in 17 states.”
Of those patients, 26 underwent surgery at the same facility. Almost half of all 30 patients were hospitalized upon returning to the U.S. No infections have been reported in patients who underwent surgery after Feb. 1, 2019.
“Mexican authorities visited Facility 1 and identified multiple infection control breaches, including failure to adhere to standard practices of reprocessing surgical equipment,” Kracalik and colleagues reported.4 “This investigation highlights the potential for persons to acquire highly antibiotic-resistant organisms not commonly found in the U.S. when receiving healthcare abroad.”
In addition to bacterial infections, the assessment identified infection control lapses that potentially put patients at risk for acquiring bloodborne pathogens, Kracalik said.
Mexican health authorities closed the surgical suite of the facility.
“Patients with subsequent U.S. hospitalizations present opportunities for VIM-CRPA transmission,” he said. “Providers evaluating patients with healthcare exposure abroad should be vigilant for infections and colonization with antibiotic-resistant bacteria.”
People considering elective medical care abroad should consult with a travel medicine clinician at least a month before leaving, and be aware of the risk of antibiotic-resistant bacteria, he added.
“There was one patient death, but this patient also had several underlying risk factors, and it was not clear whether [mortality] resulted from the infection,” Kracalik said.
Patients who become ill after returning to the U.S. following medical treatment abroad are advised to report any hospitalizations, he said.
“Providers should take a travel history and screen patients with recent hospitalization abroad for resistant organisms on admission to a U.S. hospital.”
In response to questions from HIC, Kracalik said he was not aware whether any of these travel patients went to Lubbock. “[The outbreaks] are not related,” he emphasized. “They are different strains. [VIM-CRPA] is emerging.”
Financial Disclosure: Peer Reviewer Patrick Joseph, MD, reports that he is a consultant for Genomic Health, Siemens, and CareDx. Senior Writer Gary Evans, Editor Jesse Saffron, Editor Jill Drachenberg, Nurse Planner Patti Grant, RN, BSN, MS, CIC, and Editorial Group Manager Leslie Coplin report no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study.