Drug-resistant infections, including pneumonia, bloodstream infections, urinary tract infections, and wound infections, are surging according to a recent CDC report. We connected with Teresa Austin Karre, Member of the College of American Pathologists Microbiology Committee, Associate Professor and Medical Director of the Clinical Microbiology Laboratory at the University of Nebraska Medical Center, to discuss how pathologists are working to detect these infections.
The CDC’s latest findings highlight a sharp rise in dangerous drug-resistant bacteria. From your perspective, what are the most important diagnostic implications of this increase?
The marked increase in carbapenemase-producing organisms (CPOs) highlights the need for robust laboratory processes to recognize unusual resistance patterns and perform additional testing when they occur. Beyond diagnostic testing of clinical specimens, laboratories play a key role in supporting infection prevention and control teams through targeted screening programs. As case numbers rise, clinical laboratories may be called upon more frequently to screen patients – either as part of active surveillance initiatives or outbreak investigations.
Another critical diagnostic consideration is the need for mechanism-guided therapy. Some of the newer β-lactam/β-lactamase inhibitor combinations are effective against Klebsiella pneumoniae carbapenemase (KPC) but not against New Delhi metallo-β-lactamase (NDM) or OXA-48-like carbapenemases. The increasing prevalence of NDM and OXA-48-like CPOs makes it more important than ever for laboratories to identify the specific resistance mechanism – information that is essential to guide appropriate treatment decisions.
Were there particular pathogens or resistance patterns identified in the report that laboratories should prioritize monitoring?
According to the latest CDC report, carbapenemases once considered rare in the US are now increasingly common. NDM has recently surpassed KPC as the most prevalent carbapenemase in the country. Because NDM can occur in a broader and more diverse range of species than KPC, laboratories should remain alert to its presence in organisms beyond Enterobacterales.
In addition, OXA-48-like carbapenemases are also rising in prevalence. These can be particularly challenging to detect, as they often produce only low-level carbapenem resistance and may not hydrolyze cephalosporins – making them difficult to identify using standard susceptibility methods. To ensure accurate detection, laboratories may need to employ specific carbapenemase testing methods, such as molecular assays, the modified carbapenem inactivation method (mCIM), or rapid lateral flow assays.
What diagnostic technologies are proving most effective in detecting emerging resistance patterns?
It’s important to distinguish between technologies used for screening asymptomatic populations and those used to confirm carbapenemase production in clinical isolates from infection sites. These represent two distinct pathways to identifying CPOs.
Screening for colonization may involve testing some or all patients on admission, conducting periodic screening within high-risk units, or testing individuals with an epidemiologic link to a known positive case. This is considered an active detection approach, as laboratories are proactively looking for the organism. By contrast, detection through clinical samples represents passive detection, in which confirmatory testing follows the recognition of an unusual resistance pattern in a culture from an infection site. While there is some overlap in the technologies used, the starting point and purpose differ between these approaches.
Rapid phenotypic assays are increasingly favored for screening because of their affordability and speed; however, their sensitivity is lower than that of molecular methods. Molecular assays, which directly detect carbapenemase genes, remain the gold standard for confirmation due to their high sensitivity and specificity. These assays typically target the “big five” carbapenemase genes, meaning less common or novel enzymes may go undetected. Molecular tests also tend to be more costly, making them less practical as an initial screening tool in some settings.
Next-generation sequencing (NGS) offers a powerful way to identify novel or uncommon carbapenemase genes. While highly informative, it is resource-intensive and time-consuming, and is therefore primarily used for genotyping and epidemiologic surveillance, rather than routine diagnostic testing.
Ultimately, there is no one-size-fits-all approach to identifying emerging resistance mechanisms. Laboratories should review local and institutional resistance trends to tailor their testing strategies accordingly. Cost is another key consideration – while molecular methods are sensitive and rapid, they may be cost-prohibitive for smaller facilities. Open communication with infection prevention and antimicrobial stewardship teams is essential to ensure the laboratory’s diagnostic approach aligns with institutional priorities and patient care goals.
What are the biggest barriers laboratories face in implementing advanced resistance detection methods?
Many clinical laboratories – particularly those in smaller or resource-limited settings – do not routinely perform specific carbapenemase testing. This gap can lead to delayed or missed diagnoses, resulting in suboptimal antibiotic use and an increased risk of transmission.
Advanced antimicrobial resistance detection methods, especially molecular-based technologies, can be costly and may require specialized equipment and ongoing maintenance. Laboratories without sustainable funding often face barriers to implementing these tools effectively.
Successful adoption of robust resistance detection and facility-level surveillance also depends on strong collaboration among microbiologists, physicians, pharmacists, and antimicrobial stewardship teams. In settings where this coordination is limited or absent, efforts to identify and control resistance are often less effective.
What improvements are needed in laboratory reporting infrastructure to strengthen real-time surveillance and response?
Laboratories should consider integrating surveillance activities into their routine clinical workflows. Establishing processes to recognize unusual resistance patterns in clinical isolates and reflex to appropriate confirmatory testing is a critical first step. Incorporating colonization screening for high-risk patients may also help detect CPOs early.
Close coordination with infection prevention teams is essential to ensure that laboratory detection of a CPO triggers prompt isolation or containment measures. Finally, laboratories should share relevant data and isolates with local public health authorities and the CDC to support ongoing monitoring of resistance trends and tracking the spread of resistant organisms across regions and healthcare settings.
In your view, what role can pathology play in bridging the gap between diagnostic detection and antimicrobial stewardship?
The clinical microbiology laboratory is a critical partner to antimicrobial stewardship teams, playing a key role in curbing resistance, guiding appropriate therapy, and optimizing patient outcomes. In the context of carbapenemase detection, laboratories ensure the use of effective methods to rapidly identify and characterize CPOs.
Once a CPO is detected, laboratories can apply interpretive rules to suppress potentially misleading results – such as reporting cefepime susceptibility in KPC producers – to prevent inappropriate therapy. Additionally, selective reporting of agents most likely to be effective based on the carbapenemase type helps direct clinicians toward optimal treatment choices.
Are there lessons from this CDC report that can guide laboratories in preparing for future outbreaks or surges in resistant infections?
The rapid rise of carbapenemases – including a 460 percent increase in NDMs between 2019 and 2023 – offers several important lessons for clinical laboratories. First, this trend underscores that resistance patterns are constantly evolving, with mechanisms once considered rare now becoming dominant. Laboratory professionals must stay informed and ready to adapt to this shifting antimicrobial resistance landscape.
It is also essential to recognize that multiple resistance mechanisms can coexist within a single facility or even in a single patient. Developing testing protocols that account for such co-resistance scenarios can improve diagnostic accuracy and guide effective treatment decisions.
Finally, because standard susceptibility testing alone is insufficient to identify specific carbapenemase types – and optimal therapy often depends on knowing the exact mechanism – laboratories should consider prioritizing mechanism-based resistance testing to ensure precise and clinically meaningful results.
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