From the Guidelines
For patients with infections caused by KPC-producing carbapenem-resistant Enterobacterales (CRE), novel β-lactam agents such as ceftazidime/avibactam and meropenem/vaborbactam should be the first-line treatment options. The use of these agents is supported by recent studies, including a systematic review and meta-analysis of 54 studies involving 3352 patients with carbapenem-resistant K. pneumoniae infections, which found that approximately one in three patients died and <70% achieved a clinical or microbiological response when treated with traditional antibiotics 1. In contrast, observational studies have shown that ceftazidime/avibactam and meropenem/vaborbactam are associated with improved clinical outcomes, including higher clinical cure rates and reduced mortality 1.
Some key points to consider when treating CRE infections include:
- The site of infection, as meropenem/vaborbactam may be preferred for pneumonia due to its improved penetration into epithelial lining fluid 1
- Local epidemiology and the emergence of resistance to ceftazidime/avibactam, which may affect treatment choices 1
- The importance of susceptibility testing to guide treatment decisions, as the effectiveness of different antibiotics can vary depending on the specific CRE strain 1
- The need for infection control measures, including contact precautions, dedicated equipment, hand hygiene, and environmental cleaning, to prevent transmission of CRE 1
Overall, the treatment of CRE infections requires a comprehensive approach that takes into account the latest evidence and guidelines, as well as individual patient factors and local epidemiology. The use of ceftazidime/avibactam and meropenem/vaborbactam as first-line treatment options is supported by the strongest and most recent evidence, and these agents should be considered the preferred choice for patients with CRE infections, pending susceptibility testing and other individual factors 1.
From the Research
Carbapenem Resistant Enterobacteriaceae (CRE) Infections
- CRE infections are a significant threat to human health due to the limited availability of effective antibiotic options 2, 3, 4.
- The current treatment options for CRE infections include polymyxins, tigecycline, fosfomycin, and aminoglycosides, but these options are often limited by resistance and toxicity concerns 2, 4.
- Newer antibiotics, such as ceftazidime/avibactam and meropenem/vaborbactam, have shown promise in treating CRE infections, but their use is not interchangeable and requires careful consideration of the mechanism of carbapenem resistance and clinical data 5.
Treatment Strategies for CRE Infections
- Combination therapy with two or more drugs has been reported to be superior to monotherapy in providing a survival benefit for CRE infections 3, 6.
- High-dose and combination strategies, including the use of new β-lactam/β-lactamase inhibitors, may be considered in severe CRE infections to maximize treatment success 2.
- The use of carbapenems in association with other active drugs is likely ineffective for CRE isolates with carbapenem Minimum Inhibitory Concentrations (MICs) >8 mg/l 3.
New and Emerging Therapies for CRE Infections
- Novel antimicrobials, such as plazomicin and eravacycline, have shown in vitro activity against CRE and may provide additional therapeutic options in the future 2.
- Other potential anti-CRE antibiotics in development include imipenem/relebactam and cefiderocol, but more research is needed to determine their efficacy and safety 2.
- The development of resistance to new antibiotics is a concern, and efforts should be made to perform adequately sized clinical trials to answer well-defined research questions and guide effective treatment for CRE infections 6.