Is the prevalence of carbapenem‑resistant Enterobacteriaceae rising worldwide, and what are the recommended infection‑control and antimicrobial therapy strategies?

Carbapenem-Resistant Enterobacteriaceae: Rising Global Threat

Yes, CRE prevalence is unequivocally increasing worldwide, with carbapenem resistance in Enterobacteriaceae rising from 1.2% in 2001 to 4.2% in 2011, representing a more than 3-fold increase over the past decade. 1

Epidemiological Trends

The global spread of CRE has accelerated at an alarming pace over the past two decades:

• In the United States, the proportion of Enterobacteriaceae resistant to carbapenems increased from 1.2% to 4.2% between 2001-2011, with Klebsiella species showing the most dramatic rise from 1.6% to 10.4%. 1

• In Asia, carbapenem resistance rates during 2000-2012 remained relatively low but showed a stably escalating trend, with average resistance rates of 0.6% to imipenem and 0.9% to meropenem. 2

• By 2012, 4.6% of acute-care hospitals in the U.S. reported at least one CRE healthcare-associated infection, with long-term acute-care hospitals showing particularly high rates at 17.8%. 1

• Recent data from 2016-2021 confirms the prevalence continues to rise rapidly worldwide, with mortality rates reaching 42.2% among ICU patients with CRE. 3

Predominant Organisms and Resistance Mechanisms

The microbiology of CRE shows consistent patterns globally:

• Klebsiella pneumoniae accounts for the largest proportion of CRE isolates (77.4% in recent studies), followed by Enterobacter cloacae (13.5%) and Escherichia coli (4.6%). 3

• Carbapenemase-producing Enterobacteriaceae (CPE) represent 76.1% of CRE cases, with Klebsiella pneumoniae carbapenemase (KPC) being the most common mechanism (65.9%), followed by Guiana extended-spectrum β-lactamase (GES) at 25.7%. 3

• Transmissible carbapenem resistance carried on mobile genetic elements is the key mechanism driving the rapid global dissemination of these pathogens. 4

Infection Control Strategies

Active surveillance and contact precautions are essential, as 92% of CRE episodes occur in patients with substantial healthcare exposures. 1

Surveillance Recommendations:

• Weekly rectal swabs should be performed for high-risk patients until discharge, as this approach successfully identified outbreaks and enabled control measures. 3, 5

• Active CRE surveillance can control person-to-person transmission outbreaks, as demonstrated with GES outbreak containment. 3

• Health departments should coordinate surveillance efforts, situational awareness, and prevention strategies across facilities. 1

High-Risk Populations Requiring Enhanced Monitoring:

• Patients with hematologic malignancies (OR 4.02 for carriage; HR 5.74 for acquisition) 5
• Those receiving carbapenem treatment (OR 2.54 for carriage; HR 2.68 for acquisition) 5
• Patients transferred from other institutions (OR 2.16) 5
• Those with multi-drug resistant infections within the previous 6 months (OR 2.81) 5
• Patients undergoing invasive procedures (OR 2.18) 5
• Those sharing a room with known CRE carriers (OR 3.0) 5
• Patients exposed to colonization pressure ≥10% (HR 5.03) 5

Infection Control Measures:

• Contact precautions for all CRE-colonized or infected patients 1, 3
• Cohorting of CRE-positive patients when possible 5
• Enhanced environmental cleaning in rooms housing CRE patients 4
• Hand hygiene compliance enforcement among healthcare workers 4

Antimicrobial Stewardship

Antibiotic stewardship programs must be improved to prevent nosocomial spread, with particular focus on restricting unnecessary carbapenem use. 5

• Carbapenem restriction is critical, as carbapenem treatment independently increases both CRE carriage (OR 2.54) and acquisition (HR 2.68). 5

• Regional surveillance networks need establishment worldwide to track resistance patterns and guide empiric therapy. 2

• Effective antibiotic stewardship combined with infection control measures are necessary to prevent further spread. 2

Critical Clinical Pitfalls

• Distinguishing colonization from infection is essential, as 74.3% of CRE cases represent colonization rather than active infection, yet both require infection control measures. 3

• Mortality risk is substantial, with CRE infection (not just colonization) independently associated with higher mortality in ICU patients. 3

• Bedridden state, longer ICU stay, chronic kidney disease, malignancy, connective tissue disease, and ICU admission for cardiac arrest are all associated with higher mortality in CRE patients. 3

• Failure to implement active surveillance allows silent transmission, as gastrointestinal colonization can occur without clinical signs. 5, 4