What is a drug in CRE? Understanding Treatment Options for Resistant Bacteria

October 7, 2025 •

3 min read

According to the Centers for Disease Control and Prevention (CDC), carbapenem-resistant Enterobacterales (CRE) caused approximately 13,100 infections in U.S. hospital patients in 2017 alone, with about 1,100 deaths. The critical public health threat lies in the fact that these bacteria are resistant to carbapenem antibiotics, making the question of what is a drug in CRE a complex challenge for infectious disease specialists.

Quick Summary

This article defines Carbapenem-resistant Enterobacterales (CRE), explains how these bacteria acquire resistance, and explores the limited but crucial antimicrobial options available for treating infections caused by these 'superbugs.'

Key Points

CRE is Resistant to Carbapenems: Carbapenem-resistant Enterobacterales (CRE) are bacteria that have developed resistance to carbapenems, a powerful class of antibiotics previously used for severe infections.
Resistance Due to Carbapenemase Enzymes: A primary mechanism of resistance in CRE is the production of carbapenemase enzymes, such as KPC, NDM, and OXA-48, which destroy carbapenem antibiotics.
Treatment Requires Alternative Antibiotics: Effective drugs for CRE are not carbapenems, but other agents like polymyxins, tigecycline, aminoglycosides, and newer beta-lactam/beta-lactamase inhibitor combinations.
Novel Drug Combinations Offer New Hope: Newer drug combinations like ceftazidime-avibactam and meropenem-vaborbactam are used as first-line therapy for susceptible CRE strains, particularly those producing KPC.
Combination Therapy is Common: Because CRE is multi-drug resistant, treatment often involves a combination of different antibiotics, sometimes including older drugs or novel agents like cefiderocol.
Treatment Selection Depends on Resistance Profile: The specific drug or combination chosen for a CRE infection is determined by laboratory testing that identifies the strain and its unique resistance mechanisms.
Prevention and Stewardship are Key: Responsible antibiotic use and strict infection control in healthcare settings are crucial to prevent the spread of CRE and preserve the effectiveness of current drugs.

What Is a Drug in CRE?: Understanding Carbapenem Resistance

Carbapenem-resistant Enterobacterales (CRE), also known as Carbapenem-resistant Enterobacteriaceae, are a group of bacteria resistant to carbapenem antibiotics, which are often used as a last resort for severe infections. Because CRE are often resistant to multiple antibiotics, treating these infections is challenging, and the appropriate drug is typically not a carbapenem but an alternative antimicrobial agent, frequently used in combination. The effectiveness of treatment depends on the specific CRE strain and its resistance profile.

The Role of Carbapenems

Carbapenems like meropenem, imipenem, and ertapenem are broad-spectrum antibiotics that work by inhibiting bacterial cell wall synthesis. While previously effective against many resistant bacteria, their overuse has contributed to the development of resistance in organisms like CRE.

Mechanisms of Drug Resistance in CRE

CRE employ various mechanisms to resist antibiotics, primarily through producing enzymes that inactivate carbapenems or by making structural changes.

Carbapenemase Enzymes

Carbapenemase enzymes are a significant resistance mechanism, breaking down carbapenem antibiotics. Genes for these enzymes, often on mobile plasmids, can spread resistance quickly. Key examples include KPC, NDM, OXA-48-like, VIM, and IMP.

Non-Enzymatic Mechanisms

Other resistance mechanisms include efflux pumps that expel antibiotics and the loss of porin channels in the bacterial outer membrane, preventing antibiotic entry.

Treatment Strategies for CRE Infections

Treating CRE infections requires a personalized approach based on susceptibility testing and identified resistance mechanisms, often involving combination therapy.

Older Antimicrobial Options

Older antibiotics like polymyxins (e.g., colistin), tigecycline, and aminoglycosides (e.g., amikacin, gentamicin) were used against CRE, but resistance is increasing, and some have significant toxicities.

Newer Beta-Lactam/Beta-Lactamase Inhibitor Combinations

Novel combinations of beta-lactam antibiotics and beta-lactamase inhibitors are now often first-line treatments for susceptible CRE strains, depending on the specific carbapenemase. These include ceftazidime-avibactam (effective against KPC and OXA-48), meropenem-vaborbactam (targets KPC), and imipenem-cilastatin-relebactam (targets KPC). However, these are often ineffective against metallo-beta-lactamases.

Other Novel Antibiotics

Cefiderocol is a newer siderophore cephalosporin with broad activity, including against metallo-beta-lactamase-producing CRE. Eravacycline, a tetracycline derivative, may be considered for complicated intra-abdominal infections.

Comparison of CRE Treatment Options


Drug/Class	Primary Mechanism	Target Carbapenemases (where applicable)	Typical Use Case	Key Considerations
Polymyxins	Disrupts cell membrane	N/A	Combination therapy, older drug option	High nephrotoxicity risk
Tigecycline	Inhibits protein synthesis	N/A	Complicated intra-abdominal infections	Less effective for bloodstream/urinary tract infections
Aminoglycosides	Inhibits protein synthesis	N/A	Urinary tract infections, combination therapy	Nephrotoxicity and ototoxicity risk
Ceftazidime-avibactam	Beta-lactam/Beta-lactamase Inhibitor	KPC, OXA-48	First-line for susceptible strains	Ineffective against metallo-beta-lactamases like NDM
Meropenem-vaborbactam	Beta-lactam/Beta-Lactamase Inhibitor	KPC	First-line for susceptible strains	Ineffective against metallo-beta-lactamases
Cefiderocol	Siderophore Cephalosporin	Broad activity, including MBLs	Treatment of multi-drug resistant infections, including MBLs	Potential resistance development

The Path Forward: Challenges and Hope

The emergence of metallo-beta-lactamases (MBLs) is a challenge for some newer drug combinations. Research into novel antibiotics, responsible antibiotic stewardship, and infection control are vital for managing CRE. The CDC provides comprehensive information on CRE.

Conclusion: The Evolving Answer to 'What is a Drug in CRE?'

The question "what is a drug in CRE?" highlights the difficulty in treating these resistant bacteria. Effective treatment relies on a limited selection of older and newer antibiotics, often used in combination, chosen based on laboratory determination of the specific CRE strain's resistance profile. Continuous research and antibiotic stewardship are essential to combat this evolving public health threat.

Frequently Asked Questions

CRE stands for Carbapenem-resistant Enterobacterales, a family of bacteria that has developed resistance to the potent carbapenem class of antibiotics.

Carbapenems are not effective against CRE infections because the bacteria have developed resistance, often by producing enzymes called carbapenemases that destroy the antibiotic.

A carbapenemase is a type of enzyme produced by some bacteria, including CRE, that breaks down and inactivates carbapenem antibiotics, rendering them ineffective.

Older antibiotics that have been used to treat CRE include polymyxins (like colistin), tigecycline, and aminoglycosides (like gentamicin or amikacin).

Yes, newer drug combinations have been developed, including ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol.

Combination therapy involves using two or more antibiotics simultaneously to treat a CRE infection. This strategy is often used to overcome resistance and increase the chance of treatment success.

Healthy people are generally not at high risk. CRE infections most commonly affect patients in healthcare settings, particularly those with invasive medical devices or weakened immune systems.

Yes, people can carry CRE bacteria on or in their body without experiencing an infection or symptoms. This is known as colonization and typically does not require antibiotic treatment.

Determining the best drug requires laboratory testing of the CRE bacteria to identify its specific resistance profile and any carbapenemase enzymes it produces. Treatment is then tailored based on these results.

Prevention involves strict infection control in healthcare facilities, including hand hygiene and environmental cleaning, as well as practicing antibiotic stewardship to reduce overuse.