Carbapenem-resistant Acinetobacter baumannii (CRAB): An urgent public health threat in United States healthcare facilities

Main Points

• Carbapenem-resistant Acinetobacter baumannii (CRAB) are bacteria resistant to nearly all antibiotics and difficult to remove from the environment. As a result, CRAB can cause deadly infections and large outbreaks among hospitalized patients and nursing home residents.
• Although all CRAB pose a risk to patients, some CRAB can carry genes that enable the bacteria to make carbapenemase enzymes that destroy carbapenem antibiotics. These carbapenemase genes can move among bacteria, increasing the likelihood that multidrug resistance will spread. Resistance to carbapenems further reduces patient treatment options.
• Testing in the Antibiotic Resistance Laboratory Network (AR Lab Network) during 2019 found that carbapenemase genes were detected in 83% of CRAB isolates tested. These carbapenemase gene-positive CRAB (CP-CRAB) are divided into two categories based on the type of gene present:Most CP-CRAB possess genes for carbapenemases that have been specifically identified among Acinetobacter species. These more common genes make OXA-23-like, OXA-24/40-like and OXA-58-like oxacillinases. Because these genes were detected frequently, they are not targeted for routine molecular testing. A small proportion of CP-CRAB possessed mobile genes that encode carbapenemases (KPC, IMP, NDM, VIM, OXA-48-like) found often in other gram-negative bacteria, such as Enterobacterales. These genes are amplifying the problem of resistance and are targeted for further molecular testing.
• The AR Lab Network continues to prioritize testing for the mobile but less common genes in each CRAB isolate submitted for testing.
• Regardless of gene type, identification of any CRAB within a healthcare facility should prompt rapid implementation of interventions to contain transmission including: use of Transmission-Based Precautions (Contact Precautions in acute care settings and Enhanced Barrier Precautions in nursing homes), enhanced environmental cleaning, and consultation with the local or state health department for assistance with infection control interventions and colonization screening.

The Impact of Carbapenem-Resistant Acinetobacter baumannii (CRAB) on U.S. Healthcare

CRAB, which stands for carbapenem-resistant Acinetobacter baumannii(sometimes referred to as CRAB), is a gram-negative bacterium that is often resistant to nearly all antibiotics including the broad-spectrum carbapenem drugs: meropenem, imipenem, and doripenem. CRAB typically causes infections in the blood, urinary tract, lungs, and wounds in people who have been cared for in healthcare settings, are very sick, are immunocompromised, or require invasive medical devices, like urinary or bloodstream catheters or ventilators. It is unusual for healthy individuals to get infected with CRAB.

Patients can become colonized with CRAB, meaning that the organism can live on the skin or another part of the body, but is not causing signs or symptoms of disease. Both infected and colonized patients can shed CRAB into the environment, which contaminate surfaces and shared medical equipment. Implementation of infection prevention interventions in healthcare settings, such as use of Transmission-Based Precautions and thorough environmental cleaning and disinfection, are critical in preventing spread.

From 2012 to 2017, the incidence of CRAB from clinical cultures appeared to be decreasing in the U.S. hospital settings¹. However, CDC estimated there were still 8,500 cases among U.S. hospitalized patients in 2017, resulting in 700 deaths, and nearly 281 million dollars in excess healthcare costs.

The potential for further spread of certain CRAB strains threatens to reverse the decline in infections.

Mechanisms of Resistance in CRAB

Some of the most concerning CRAB, called carbapenemase gene-positive CRAB (CP-CRAB), carry antibiotic resistance genes that allow the bacteria to make carbapenemase enzymes. These enzymes can degrade most β-lactam antibiotics, including carbapenems. Additionally, carbapenemase genes are often encoded on mobile genetic elements (e.g., plasmids) that can carry additional resistance genes, making CRAB multidrug-resistant. These genes are easily shared with other bacteria, which can lead to transmission of multidrug resistance between different bacteria and, ultimately, different patients and different facilities. Given the difficulty of eradicating CRAB once present in healthcare settings and the emergence of strains that cause infections with transmissible carbapenemase genes and limited treatment options, the threat level of CRAB was raised to Urgent in the 2019 Antibiotic Resistance Threats Report. These organisms remain a focus of public health networks around the world.

The Antimicrobial Resistance Laboratory Network

In the United States, antibiotic-resistant bacteria are monitored through the Antimicrobial Resistance Laboratory Network (AR Lab Network). The AR Lab Network includes labs in 50 states, plus several cities and Puerto Rico. Seven state laboratories also serve as regional laboratories, providing sentinel surveillance testing through collaboration with a subset of clinical laboratories that have detected emerging AR threats, including CRAB. The AR Lab Network characterizes these isolates to better understand their prevalence, geographic location, resistance patterns and resistance mechanisms. In turn, this information helps public health authorities and healthcare facilities to slow or stop their spread.

In 2019, the AR Lab Network regional laboratories added testing for additional carbapenemase genes previously identified in and specific to Acinetobacter species. This testing was conducted to better understand and compare their prevalence to the carbapenemase genes that are less common in Acinetobacter species but more often found in other resistant organisms, like carbapenem-resistant Enterobacterales.

The Molecular Epidemiology of CRAB

In 2019, a total of 2,223 CRAB were tested for at least one carbapenemase gene.

• Among 1,208 CRAB isolates that were tested for carbapenemase genes commonly associated with Acinetobacter species, 78.9% (n=953) were positive for at least one gene. The prevalence of these carbapenemase genes varied by AR Lab Network region, ranging from 38% to 100% (median 74%) (Figure 1). These findings confirm that carbapenemase genes are common among CRAB and that the OXA-like genes are identified most commonly.
• Among 2,190 CRAB isolates that were tested for carbapenemase genes less common in Acinetobacter species, 1.2% (n=26) were positive for at least one. The frequency of positivity also varied by AR Lab Network region, ranging from 0% to 3.4% (median 0.6%) (Figure 2). These findings demonstrate that these less common carbapenemase genes, though potentially emerging, are still rare in the United States.

These maps display the frequency of CP-CRAB detected in 2019, by carbapenemase category and AR Lab Network Region. Note: In 2019, the AR Lab Network tested for OXA-23-like, OXA-24/40-like, and OXA-58-like oxacillinases in addition to KPC, NDM, VIM, IMP, and OXA-48-like carbapenemases.

Carbapenemase Genes and CRAB Carbapenem Susceptibility

The AR Lab Network continues to characterize all CRAB submitted for testing, including testing for carbapenemase genes and performing antimicrobial susceptibility testing (AST), which is a laboratory procedure that determines whether antibiotics, like carbapenems, might be effective in treating the bacteria being tested (Figure 3). CRAB isolates, both with and without carbapenemase genes, demonstrated a high frequency of resistance to all carbapenems, ranging from 50-100%. For isolates without a CP-CRAB gene detected, 81-89% of isolates were either intermediate or resistant (‘not susceptible’) to carbapenems; for isolates with a CP-CRAB gene detected, 100% of isolates were not susceptible to all carbapenems.

CRAB infections pose a significant risk to patient safety because they are highly resistant to all carbapenem drugs, regardless of whether a carbapenemase gene was present. Furthermore, the presence of mobile carbapenemase genes in CRAB poses an additional public health threat because of the facilitated spread of these resistance genes to other pathogens.

To view the full interactive version, please visit the AR Lab Network homepage.

This figure displays the results of CRAB antimicrobial susceptibility testing (AST) by carbapenemase gene-negative isolates, any carbapenemase gene-positive isolates, and specific carbapenemase gene-positive isolates. Carbapenemase genes tested include those for:KPC, NDM, VIM, IMP, OXA-48-like, OXA-23-like, OXA-24/40-like, and OXA-58-like.Isolates positive for more than one of these carbapenemases are excluded.

AST results were interpreted using the most current version of the CLSI M100 document for breakpoints where available. For doripenem, most evaluable drug concentration ranges tested prevented distinguishing intermediate versus resistant interpretations.

More information is needed to better understand the environmental reservoirs for these carbapenemase gene-positive isolates, how the presence of these genes could affect person to person transmission, or if they are associated with worse disease characteristics. Furthermore, testing to identify the presence of a targeted carbapenemase genes among CRAB isolates can help target public health efforts to control these emerging AR pathogens.

Infection Control and Response - Healthcare Facilities and Public Health Collaboration

CRAB can spread quickly in healthcare facilities and can be difficult to eradicate. Implementation of infection control interventions promptly, once CRAB is identified, is essential to protect hospitalized patients and nursing home residents.

Preventing CRAB spread requires a coordinated effort among healthcare facilities and public health departments. Healthcare facilities are encouraged to learn about CRAB epidemiology, including underlying mechanisms of resistance, and discuss the availability of CRAB carbapenemase and antimicrobial susceptibility testing with their state health departments and public health laboratories.

CDC recommends that infection preventionists, in collaboration with their clinical teams and facility laboratory team, work with their health department's Healthcare-Associated Infection (HAI) Prevention Program to perform a public health investigation when single cases of certain CP-CRAB are identified or in the event of a suspected CRAB outbreak. Detection of even a single case of CRAB carrying a less common carbapenemase gene requires an aggressive public health response to prevent spread. Public health response to CRAB carrying more commonly identified Acinetobacter carbapenemase genes will vary based on the local epidemiology, the overall antibiotic susceptibility profile of the CRAB isolates, and the number of patients who are affected. However, all CRAB are highly resistant and have the potential to spread rapidly in healthcare facilities and require meticulous adherence to recommended infection control precautions.

Facility CRAB Prevention Strategies

Refer to the Multidrug-resistant organisms (MDRO) Management Guidelines for more details.

• When available, house patients infected or colonized with CRAB in single patient rooms. If the number of single patient rooms is limited, reserve these rooms for patients with highest risk for transmission (e.g., incontinence).
• Use gown and gloves (e.g., Contact Precautions in Acute Care settings and Enhanced Barrier Precautions in long-term care settings for patients/residents who are infected or colonized with CRAB). Consider empiric use of these precautions for patients transferred from high-risk settings.
• Review facility infection prevention and control practices and provide staff with feedback, particularly for: Hand hygiene adherence Personal protective equipment donning and doffing and adherence Environmental cleaning and disinfection