Update on the Management of Carbapenemase-Producing Enterobacteriaceae (CPE)

PATHCHAT Edition No. 35
Please contact your local Ampath pathologist for more information.

Author: Dr. Jennifer Coetzee

Introduction

🔹 What Are Carbapenemase-Producing Enterobacteriaceae (CPE)?

• CPE are a subset of carbapenem-resistant Enterobacteriaceae (CRE) that produce carbapenemase enzymes.
• Carbapenemases hydrolyze the β-lactam ring of carbapenems, rendering them ineffective.
• CPE infections are associated with high mortality and are a major healthcare challenge.

✅ Types of Carbapenemases Found in South Africa:

• New Delhi metallo-β-lactamase (NDM).
• Verona integron-mediated metallo-β-lactamase (VIM).
• Klebsiella pneumoniae carbapenemase (KPC).
• Oxacillinase-48 (OXA-48) and OXA-48-like enzymes.

📌 CPE was first detected in South Africa in 2011, and cases have since increased significantly.

Mechanisms of Carbapenem Resistance in Enterobacteriaceae

✅ CRE resistance mechanisms include:

1. Overproduction of extended-spectrum β-lactamases (ESBLs) or AmpC β-lactamases, combined with porin loss.
2. Carbapenemase production, leading to widespread β-lactam resistance.

🔹 Common CPE Enzymes & Their Characteristics:

• NDM, VIM, and IMP: Metallo-β-lactamases (require zinc for activity, inhibited by EDTA).
• KPC and GES: Serine carbapenemases (inhibited by β-lactamase inhibitors).
• OXA-48 and OXA-48-like enzymes: Weak hydrolysis of carbapenems, often with low minimum inhibitory concentrations (MICs).

📌 CPE spreads rapidly via plasmids, which carry resistance genes and transfer between bacterial species.

Laboratory Detection of CPE

✅ CPE Detection Requires:

1. Identification of Enterobacteriaceae with reduced carbapenem susceptibility.
2. Phenotypic or molecular confirmation of carbapenemase production.

🔹 Ampath’s CPE Detection Strategy:

• PCR testing for the most common carbapenemase genes (NDM, VIM, KPC, GES, OXA-48).
• Screening rectal swabs or stool samples for asymptomatic carriers.
• Phenotypic confirmatory tests, including modified Hodge test and carbapenem inactivation methods.

📌 Some OXA-48-like CPE may have MICs within the susceptible range but can become resistant upon antibiotic exposure.

Epidemiology of CPE in South Africa

🔹 CPE cases have increased dramatically since 2011.
✅ Current epidemiological trends show:

• OXA-48 and OXA-48-like enzymes are the dominant carbapenemases.
• CPE is more prevalent in hospitals, especially in ICU settings.
• Multiple outbreaks have been reported across South African healthcare facilities.

📌 CPE transmission is driven by healthcare worker contact, contaminated environments, and prolonged hospital stays.

Risk Factors for CPE Acquisition

✅ Patients at highest risk include those with:

• Prolonged hospitalization or ICU admission.
• Invasive medical devices (central venous catheters, urinary catheters, ventilators).
• Immunosuppression (e.g., cancer, organ transplantation).
• Prior exposure to multiple antibiotic agents (especially carbapenems, fluoroquinolones, and aminoglycosides).

📌 Community-acquired CPE cases are emerging as patients are discharged into step-down facilities and frail-care homes.

Clinical Spectrum of CPE Infections

✅ CPE Infections Can Present as:

1. Colonization (asymptomatic carrier state).
2. Non-invasive infections (e.g., urinary tract infections).
3. Invasive infections (e.g., bloodstream infections, pneumonia).

📌 Colonization precedes infection, and the gastrointestinal tract is the most common site of carriage.

Clinical Management of CPE Infections

✅ Key Principles of CPE Management:

1. Distinguish between colonization and infection.
   • Colonized patients do not require antibiotics.
2. Combination therapy is preferred over monotherapy for invasive infections.
3. Carbapenems may still be effective in combination if MIC ≤ 8 µg/mL.
4. Antibiotic selection should be guided by minimum inhibitory concentration (MIC) testing.

🔹 Combination Therapy Options:

• Carbapenem + colistin.
• Carbapenem + fosfomycin.
• Tigecycline-based regimens.
• Aminoglycosides (e.g., amikacin) if susceptible.

📌 CPE infections should be managed in consultation with infectious disease specialists or microbiologists.

Infection Control Measures for CPE

✅ Strict infection control is essential to prevent CPE outbreaks.

🔹 Recommended Infection Control Strategies:

• Early identification of CPE-colonized or infected patients.
• Strict isolation with contact precautions.
• Hand hygiene compliance before and after patient contact.
• Cohorting of CPE-positive patients and dedicated nursing staff.
• Environmental disinfection of patient areas.
• Screening of all close patient contacts with rectal swabs.
• Ongoing surveillance cultures until no new cases are detected.

📌 The financial and healthcare burden of CPE is rising, making infection prevention a top priority.

Conclusion

✅ CPE poses a significant threat to global and South African healthcare systems.
✅ Early detection, strict infection control, and antimicrobial stewardship are essential.
✅ Combination antibiotic therapy offers the best outcomes for CPE infections.
✅ Healthcare workers play a critical role in preventing the spread of CPE.

📌 The continued spread of CPE threatens the efficacy of last-resort antibiotics, highlighting the urgent need for containment strategies.

References

1. Lowman W, et al. (2014). Consensus guidelines for the screening and laboratory detection of carbapenemase-producing Enterobacteriaceae in South Africa. South African Journal of Infectious Diseases, 29(1): 5–11.
2. Wilson APR, et al. (2015). Prevention and control of multi-drug-resistant Gram-negative bacteria: Recommendations from a Joint Working Party. Journal of Hospital Infection. Available online: DOI: 10.1016/j.jhin.2015.08.007.