US surveillance finds low level of worrisome resistant bacterium

Scientist with bacteria cultures
Scientist with bacteria cultures

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A new multistate surveillance study by the Centers for Disease Control and Prevention (CDC) has found that the incidence of a multidrug-resistant bacterial pathogen capable of causing severe infections and spreading easily is low and mainly confined to healthcare facilities. And CDC officials would like to keep it that way.

In a paper today in Emerging Infectious Diseases, a team of researchers from the CDC and public health departments across the country report that the overall annual incidence of carbapenem-nonsusceptible Acinetobacter baumannii is 1.2 cases per 100,000 persons, and that nearly all the cases were healthcare-associated. The incidence rate is lower than those reported for other invasive, healthcare-associated bacterial pathogens, including carbapenem-resistant Enterobacteriaceae (CRE), methicillin-resistant Staphylococcus aureus (MRSA), and Clostridium difficile.

But the study also confirmed that carbapenem-nonsusceptible A baumannii is associated with substantial rates of illness and death. Nearly half of all A baumannii samples isolated from clinical cultures in the United States are resistant to carbapenems, which are important last-line antibiotics for treating severe bacterial infections. In addition, the organism is frequently resistant to other classes of antibiotics. That leaves clinicians with few options to treat patients, who tend to be older and have underlying conditions.

A baumannii is a recognized cause of healthcare-associated infections (HAIs) such as pneumonia, bacteremia, and urinary tract infection (UTI), and rising resistance to carbapenems has caused concern among global health officials. Carbapenem-resistant A baumannii was recently named as one of the top-three "priority pathogens" by the World Health Organization.

"Acinetobacter has a lot of intrinsic resistance, so once you start picking off other classes of antibiotics, like carbapenems, you really find yourself in a quandary," CDC epidemiologist and study co-author Alex Kallen, MD, MPH, told CIDRAP News. "It's probably one of the most challenging HAIs that we face."

Primarily healthcare-associated infections

The results are from laboratory- and population-based surveillance conducted among 15.2 million people in eight US metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee from 2012 through 2015. The surveillance is part of the CDC's Emerging Infections Program, a network of state and local health departments and academic institutions that work with the CDC to monitor incidence of infectious diseases. These surveillance efforts can help inform control and prevention programs.

To identify cases, the investigators actively collected reports of all carbapenem-nonsusceptible A baumannii isolates from clinical laboratories serving the catchment areas. They also collected data on antibiotic susceptibility, patient demographics, healthcare exposures, types of infection diagnosed, and patient outcomes. The aim was to estimate the crude population-based incidence of carbapenem-nonsusceptible A baumannii and describe the epidemiology over the surveillance period.

Overall, a total of 621 cases from 539 unique patients were reported during the study period, with most cases occurring in Georgia (300, 48.3%) and Maryland (236, 38%). Almost all of the cases were based on isolation of carbapenem-nonsusceptible A baumannii from urine (429, 71.7%) and blood (157, 26.3%), and the most common infections reported were UTI (328, 65.2%) and bacteremia (158, 31.4%). Complete data were available for 598 of the cases.

The overall crude incidence rate of 1.2 cases per 100,000 persons in the surveillance population is lower than found in surveillance of the same population for CRE infections (2.93 cases/100,000), and significantly lower than estimated incidence rates for MRSA (25.1/100,000) and C difficile (141.8/100,000).

The median age of the patients was 58.6 years, and only 3% of patients had no identified underlying conditions. Nearly all the cases (590, 98.7%) had healthcare exposure in the year before sample collection or an indwelling device, such as a urinary catheter, at the time of sample collection. Most of the patients had either been admitted to a short-stay acute-care hospital (469, 78.4%) or a long-term care facility (360, 60.2%).

"I think the fact that 99% of our patients had some sort of exposure to a healthcare facility…or had an indwelling device…reiterates the fact that these are healthcare-associated infections," said Sandra Bulens, MPH, lead study author and epidemiologist with the CDC.

Bulens and her co-authors argue that this finding not only supports the current focus on preventing A baumannii transmission in acute-care settings, but also highlights the need for hospitals to notify nursing homes when they are transferring patients with A baumannii or other multidrug-resistant infections, so that those facilities can take appropriate precautions.

Looking at outcomes, the investigators found that in 75% of the cases (449), patients were hospitalized at the time of sample collection or within 30 days. Of these cases, 168 (37.4%) were admitted to the intensive care unit. The overall death rate was 17.9% (106 of 594 cases), but was significantly higher when the pathogen was isolated from a sterile site, such as blood, than when it was isolated only from urine (41.3% vs. 8.3%).

Antimicrobial susceptibility testing showed that most of the isolates were also nonsusceptible to several classes of antibiotics—cephalosporins, fluoroquinolones, trimethoprim/sulfamethoxazole, ampicillin, and piperacillin/tazobactam. But 72.9% were susceptible to at least one aminoglycoside, and a subset were susceptible to tigecycline and colistin. Bulens said this underscores the dangers of the pathogen, since these drugs are either associated with high toxicity or are considered last-resort antibiotics. "But at least we had some that were still susceptible," she said.

Keeping A baumannii in check

Bulens and Kallen said it's unclear why the incidence of carbapenem-nonsusceptible A baumannii is lower than for other HAI pathogens, but they say it could be related to low virulence and the lack of dominant clones—strains that share a common ancestor—that are capable of spreading easily from person to person.

But Kallen noted that it could also be because cases of MRSA and C difficile are being increasingly reported in non-healthcare settings, a pattern he hopes won't be repeated.

"We really want to address these things when they are uncommon, because if you wait until they are common, like MRSA or C difficile, they're really challenging to get a handle on," he said. "I think what the data have shown us, as they did with CRE, is that these bugs are still in a place where, although they're problematic, they're relatively uncommon, and that affords us the opportunity to be aggressive about prevention and be much more successful," he said.

Kallen said identifying new and emerging drug-resistant pathogens and stopping them before they can spread in the healthcare setting will be the focus of a new containment strategy the CDC will soon be announcing. The three-part strategy will involve increasing laboratory capacity for quick detection of drug-resistant organisms, improving infection control infrastructure, and colonization screening to detect asymptomatic patients who can spread pathogens but would otherwise fly under the radar.

"This is like a whole new mindset change at the CDC and within the US for controlling emerging and novel resistance," said Kallen. "And Acinetobacter is right in that spot."

See also:

Mar 14 Emerg Infect Dis study

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