From the Guidelines
The treatment approach for Carbapenem-Resistant Enterobacteriaceae (CRE) infections, particularly when genes such as IMP and OXA-23 are present, should prioritize the use of novel β-lactam agents like ceftazidime/avibactam and meropenem/vaborbactam as first-line treatment options. These agents have shown efficacy against CRE infections, including those with specific carbapenemase genes, in recent studies 1.
Key Considerations:
- The choice of treatment should be guided by antimicrobial susceptibility testing, as resistance patterns can vary significantly among CRE isolates.
- For severe infections, combination therapy may be considered, but the addition of a third agent should be based on the results of susceptibility testing.
- Newer agents like imipenem/relebactam and cefiderocol may also be considered as potential alternatives for the treatment of infections involving CRE, though clinical studies on their efficacy in these patients are limited 1.
- The site of infection, local epidemiology, and the emergence of resistance to specific agents should also be considered when selecting a treatment regimen.
Treatment Options:
- Ceftazidime/avibactam: Recommended for the treatment of CRE infections, including those with IMP and OXA-23 genes, due to its efficacy and safety profile 1.
- Meropenem/vaborbactam: Also recommended as a first-line treatment option for CRE infections, with studies showing its effectiveness in reducing mortality and improving clinical outcomes 1.
- Imipenem/relebactam and cefiderocol: May be considered as alternative treatment options, though more evidence is needed to guide their use in different patient categories and infection types 1.
Duration of Treatment:
- The duration of treatment should be individualized based on the infection site, severity, and response to therapy, typically ranging from 7 to 14 days.
Source Control:
- Source control through drainage of abscesses or removal of infected devices is crucial in the management of CRE infections.
By prioritizing the use of novel β-lactam agents and considering the specific characteristics of the infection and the patient, healthcare providers can optimize treatment outcomes for CRE infections, including those with IMP and OXA-23 genes.
From the FDA Drug Label
AVYCAZ demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPCs), AmpC, and certain oxacillinases (OXA). Imipenem/relebactam demonstrated in vitro activity against some Enterobacteriaceae isolates genotypically characterized for some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: KPC, TEM, SHV, CTX-M, CMY, DHA, and ACT/MIR
The treatment approach for Carbapenem-Resistant Enterobacteriaceae (CRE) infections, particularly when genes such as IMP (Imipenemase) and OXA-23 (Oxacillinase) are present, involves the use of combination antibiotics that can counteract these resistance mechanisms.
- AVYCAZ (ceftazidime-avibactam) and RECARBRIO (imipenem-cilastatin-relebactam) are two such combinations that have shown in vitro activity against certain beta-lactamases, including some ESBLs and carbapenemases.
- However, it is crucial to note that AVYCAZ is not active against bacteria that produce metallo-beta lactamases and RECARBRIO is not active against most isolates containing metallo-beta-lactamases (MBLs), which includes the IMP gene, and certain oxacillinases like OXA-23.
- The choice of treatment should be guided by antimicrobial susceptibility testing and clinical judgment, taking into account the specific resistance profile of the infecting organism and the patient's clinical condition 2 3.
From the Research
Treatment Approach for CRE Infections
The treatment of Carbapenem-Resistant Enterobacteriaceae (CRE) infections is challenging due to limited therapy options 4. When genes such as IMP (Imipenemase) and OXA-23 (Oxacillinase) are present, the treatment approach may involve:
- Combination antimicrobial therapy, which has been shown to yield the best outcomes 5
- Use of newer antibiotics such as ceftazidime-avibactam, which has been found to be effective against Klebsiella pneumoniae carbapenemase-producing CRE infections 6
- Consideration of alternative treatments such as imipenem/cilastatin/relebactam, which has been approved for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia in adults 7
Resistance Mechanisms and Detection
CRE resistance can be induced by various mechanisms, including carbapenemase production, porin modification, and efflux pump activity 4. The detection of CRE and exploration of its resistance mechanisms are crucial for developing effective treatment strategies. Clinical and laboratory methods for detecting CRE and understanding its resistance mechanisms are being developed 4.
Clinical Therapies and New Treatment Methods
Clinical therapies for CRE infections include single or combined use of antibiotics, and new antibiotics and treatment methods are being developed 4. For example, ceftazidime-avibactam and meropenem/vaborbactam have been found to be effective against CRE infections, with higher rates of clinical cure and decreased mortality compared to colistin-based regimens 8. Additionally, imipenem/cilastatin/relebactam has been found to be effective against imipenem-nonsusceptible infections, including those caused by carbapenem-resistant pathogens 7.
Genes such as IMP and OXA-23
While genes such as IMP and OXA-23 are often associated with carbapenem resistance, they may appear less frequently in CRE infections. However, the presence of these genes can impact the treatment approach, and alternative therapies such as those mentioned above may be considered 6, 7.