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 choice between these two agents may depend on the site of infection, with meropenem/vaborbactam potentially being preferred for infections such as pneumonia due to its favorable pharmacokinetic properties 1.
Key Considerations
- The introduction of new antibiotics like ceftazidime/avibactam and meropenem/vaborbactam has improved clinical outcomes in patients with CRE infections compared to traditional antibiotic regimens 1.
- Imipenem/relebactam and cefiderocol may also be considered as potential alternatives for the treatment of infections involving KPC-producing CRE, although clinical studies on their efficacy in these patients are limited 1.
- Infection control measures, including contact precautions, hand hygiene, environmental cleaning, and patient isolation, are crucial to prevent the spread of CRE 1.
- Consultation with infectious disease specialists is strongly recommended due to the complexity of treating these multidrug-resistant infections.
Treatment Options
- Ceftazidime/avibactam 2.5 g IV q8h or meropenem/vaborbactam 4 g IV q8h for bloodstream infections or complicated urinary tract infections 1.
- Combination therapy may be considered for severe infections, but the choice of combination should be based on susceptibility testing and clinical judgment 1.
- Treatment duration should be individualized based on the infection site, source control, underlying comorbidities, and initial response to therapy, typically ranging from 7-14 days 1.
Mortality and Morbidity
- CRE infections are associated with high mortality rates, making rapid identification and appropriate antimicrobial therapy critical components of management 1.
- The use of novel β-lactam agents like ceftazidime/avibactam and meropenem/vaborbactam has been associated with improved clinical outcomes and reduced mortality compared to traditional antibiotic regimens 1.
From the Research
Treatment Options for Carbapenem-Resistant Enterobacteriaceae (CRE) Infections
- Current treatment options for CRE infections are limited, with polymyxins, tigecycline, fosfomycin, and aminoglycosides as the mainstays of therapy 2, 3.
- Newer antibiotics, such as ceftazidime/avibactam, meropenem/vaborbactam, plazomicin, and eravacycline, have shown potential in treating CRE infections 2, 4, 5.
- Combination therapeutic strategies, including high-dose tigecycline, high-dose prolonged-infusion of carbapenem, and double carbapenem therapy, are being explored to improve treatment outcomes 2.
Antibiotic Resistance and Treatment Considerations
- Carbapenem resistance is often associated with resistance to all traditional β-lactams and other classes of antibiotics, making treatment challenging 6.
- The development of resistance to new antibiotics, such as ceftazidime/avibactam and meropenem/vaborbactam, is a concern and requires careful consideration in treatment decisions 4, 5.
- The choice of treatment should be based on molecular phenotypes of resistance, susceptibility profiles, disease severity, and patient characteristics 2, 6.
Clinical Evidence and Research Needs
- The available evidence on the current management of CRE mostly comes from observational, non-comparative, retrospective, small studies, with a high risk of selection bias 6.
- Randomized clinical trials (RCTs) are needed to guide effective treatment for infections caused by CRE and to determine the most appropriate treatment strategies 2, 6.
- Further research is needed to optimize treatment regimens, including the use of combination therapy and newer antibiotics, and to improve patient outcomes 3, 4, 5.