How should Carbapenem-Resistant Enterobacteriaceae (CRE) with New Delhi metallo-beta-lactamase (NDM) genes be treated, especially in regions like India where they are more common?

From the Guidelines

The most effective treatment for Carbapenem-Resistant Enterobacteriaceae (CRE) with New Delhi metallo-beta-lactamase (NDM) genes, especially in regions like India, is the combination of ceftazidime/avibactam plus aztreonam, as it has shown to significantly reduce 30-day mortality rates compared to other treatment options 1.

Key Considerations

• The combination of ceftazidime/avibactam plus aztreonam is recommended due to its in vitro synergy and clinical efficacy in reducing mortality rates in patients with NDM-producing CRE infections.
• Cefiderocol may also be considered as an alternative option, although the strength of recommendation is conditional due to limited evidence 1.
• Treatment duration typically ranges from 7-14 days, depending on the infection site and clinical response.
• Therapeutic drug monitoring is essential to optimize dosing and minimize toxicity, particularly for colistin, which can cause nephrotoxicity.
• Source control through drainage of abscesses or removal of infected devices is crucial for successful treatment.

Regional Considerations

• In regions like India where NDM-producing CRE are endemic, the use of newer agents such as ceftazidime-avibactam with aztreonam may be effective, although availability may be limited.
• Strict infection control measures are necessary to prevent the spread of NDM-producing CRE, including contact precautions, environmental cleaning, and education of healthcare staff.

Patient-Specific Factors

• Patient-specific factors, such as renal function, should be considered when selecting and dosing antibiotics to minimize toxicity and optimize treatment outcomes.
• A multidisciplinary approach with infectious disease consultation is recommended to ensure comprehensive care and management of CRE infections with NDM genes.

From the Research

Treatment of Carbapenem-Resistant Enterobacteriaceae (CRE) with New Delhi metallo-beta-lactamase (NDM) genes

• The treatment of infections caused by CRE with NDM genes is challenging due to limited treatment options 2.
• Studies have shown that NDM-producing Enterobacteriaceae are often resistant to multiple antibiotics, including carbapenems, making treatment difficult 3, 4, 5.
• Some antibiotics that have shown effectiveness against NDM-producing Enterobacteriaceae include:
  • Tigecycline, with susceptibility rates ranging from 36.8% to 86.5% 2, 4.
  • Eravacycline, with a susceptibility rate of 66.2% 2.
  • Omadacycline, with a susceptibility rate of 59.6% 2.
  • Aminoglycosides, such as gentamicin and amikacin, which have shown susceptibility rates ranging from 39.7% to 57.3% 4, 5.
• Combination therapy may also be effective in treating CRE with NDM genes, but more research is needed to determine the best treatment options 2.

Prevalence of NDM genes in CRE in India

• Studies have shown that NDM-producing Enterobacteriaceae are more common in India, with a high prevalence of blaNDM variants in clinical isolates 3.
• The spread of NDM-producing Enterobacteriaceae in India is a significant public health concern, highlighting the need for infection control measures and surveillance 3, 6.
• The presence of NDM genes in environmental reservoirs, such as waterways and wastewater, also poses a risk of transmission to humans 6.

Molecular Characteristics of NDM-producing Enterobacteriaceae

• Molecular analysis of NDM-producing Enterobacteriaceae has shown that the blaNDM gene is often associated with other resistance genes, such as ISAba125 and bleomycin 3.
• The genetic environment of the blaNDM gene can vary, with some studies showing that the gene is often located on conjugative plasmids 3.
• The spread of NDM-producing Enterobacteriaceae is often facilitated by horizontal gene transfer, highlighting the need for strict infection control measures to prevent the spread of these bacteria 3, 6.