The acronym CRE is universally used in infectious disease and public health to denote Carbapenem-Resistant Enterobacteriaceae. These bacteria represent a serious global threat because they have developed defenses against some of the most potent antibiotics available to clinicians. This resistance makes infections caused by these organisms difficult to treat, often leading to prolonged hospital stays, increased medical costs, and higher rates of severe illness and death. Understanding the danger requires examining the components of this organism and the mechanisms it uses to evade treatment.
Decoding the Acronym and the Threat
The “E” in CRE stands for Enterobacteriaceae, a large family of bacteria that naturally inhabit the gut of humans and animals, including common organisms like Escherichia coli and Klebsiella pneumoniae. While many are harmless, they can cause serious infections, such as pneumonia, urinary tract infections, and bloodstream infections, when they spread outside the gut. The “C” refers to carbapenems, a class of broad-spectrum antibiotics, including drugs like meropenem and imipenem, that have historically been reserved as a last line of defense. These drugs work by interfering with the bacteria’s ability to build a cell wall.
The “R,” or resistant, component describes the bacteria’s ability to neutralize carbapenem antibiotics, primarily through the production of enzymes called carbapenemases. These enzymes are a type of beta-lactamase that chemically break down the carbapenem molecule, rendering it inactive. Well-known carbapenemases include Klebsiella pneumoniae carbapenemase (KPC) and New Delhi Metallo-beta-lactamase (NDM). These resistance genes are often carried on mobile genetic elements called plasmids, which can be easily transferred between different bacterial species, rapidly spreading resistance through horizontal gene transfer.
Alternative Resistance Mechanisms
Beyond carbapenemases, some CRE strains achieve resistance through other biological changes. They may reduce the number of porins, small channels in the outer membrane that antibiotics use to gain entry into the cell, limiting the amount of drug that reaches the target site. Furthermore, some bacteria employ efflux pumps, specialized proteins that actively pump the antibiotic out of the cell after it has entered, preventing the drug from accumulating to a lethal concentration.
How CRE Spreads and Who is at Risk
CRE primarily spreads through direct or indirect contact within healthcare environments, making them a significant source of hospital-acquired infections. Transmission occurs via the contaminated hands of healthcare personnel or through contact with contaminated environmental surfaces and medical equipment. Individuals who are “colonized” with CRE—meaning the bacteria are present without causing an active infection—can still transmit the organism to others.
The risk of developing a CRE infection is highest among patients who are medically fragile and receiving intensive care. A major risk factor is the presence of invasive medical devices, such as urinary catheters or central venous lines, which provide a direct pathway for the bacteria to enter the body. Patients with prolonged or repeated stays in healthcare facilities face an elevated risk of exposure and colonization. Additionally, receiving long courses of broad-spectrum antibiotics can disrupt the body’s natural microbial balance, allowing resistant organisms like CRE to flourish.
Clinical Management and Treatment Challenges
Diagnosing a CRE infection is challenging because initial symptoms often resemble those of common, less-resistant infections. Diagnosis requires isolating the bacteria from a patient sample and performing laboratory susceptibility testing to confirm resistance to carbapenems. Obtaining a definitive diagnosis can take several days, which may delay the start of effective, targeted therapy and increase the risk of poor patient outcomes.
The primary difficulty in managing CRE infections is the limited arsenal of effective antibiotics. Treatment often required resorting to older drugs largely abandoned due to high toxicity, such as polymyxins (like colistin) or tigecycline. These older agents are associated with concerning side effects, including kidney damage, which complicates patient care. Treatment regimens frequently involve using combinations of two or more antibiotics to achieve a synergistic effect and overcome resistance mechanisms.
Novel Antibiotic Agents
More recently, several new agents have been developed to specifically combat CRE, including combination drugs like ceftazidime-avibactam and meropenem-vaborbactam. These newer drugs incorporate a beta-lactamase inhibitor designed to block the carbapenemase enzymes, thus restoring the effectiveness of the antibiotic component. However, the effectiveness of these novel agents is often dependent on the specific type of carbapenemase produced by the bacteria; for instance, many new drugs are less effective against metallo-beta-lactamases like NDM. The need to tailor treatment based on the specific resistance mechanism underscores the ongoing therapeutic difficulty.
Strategies for Prevention and Control
Controlling the spread of CRE relies on coordinated infection prevention and control (IPC) measures implemented across all healthcare facilities. Rigorous adherence to hand hygiene protocols is the single most effective measure for preventing the transmission of CRE between patients. This is paired with enhanced environmental cleaning and disinfection of patient rooms and reusable medical equipment.
A central component of control is the use of transmission-based precautions, such as contact precautions, for patients known to be infected or colonized with CRE. This involves healthcare workers wearing gloves and gowns and isolating the patient in a single room or cohorting them with other CRE patients. Public health surveillance systems track the movement of CRE cases, especially when patients are transferred between different hospitals or long-term care settings.
The broader strategy involves the implementation of comprehensive Antibiotic Stewardship Programs (ASP). These programs focus on ensuring that antibiotics are prescribed only when necessary, at the correct dose, and for the appropriate duration. By reducing the overall and inappropriate use of antibiotics, stewardship programs lessen the selective pressure that drives bacteria to develop and spread resistance.