From the Guidelines
The treatment of MDR and XDR Enterobacterales requires a combination therapy approach, with the choice of antibiotics depending on the specific resistance pattern and the severity of the infection, as recommended by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines 1. The ESCMID guidelines provide a framework for the treatment of infections caused by multidrug-resistant Gram-negative bacilli, including Enterobacterales, and emphasize the importance of selecting the optimal treatment based on clinical evidence. Some key points to consider when treating MDR and XDR Enterobacterales include:
- The use of combination antibiotic therapy to prevent the emergence of resistance and improve treatment outcomes
- The selection of antibiotics with in vitro activity against the specific MDR-GNB, as outlined in Table 2 of the ESCMID guidelines 1
- The importance of individualizing treatment based on susceptibility testing, infection site, and patient factors
- The need for early infectious disease consultation to ensure optimal management and prevent the spread of resistant organisms The ESCMID guidelines recommend a systematic review of clinical evidence to select the optimal treatment, including both single and combination therapies, and provide a summary of the recommendations in Table 1 1. In terms of specific treatment options, the guidelines suggest that the choice of antibiotics will depend on the specific resistance pattern and the severity of the infection, and that newer agents such as cefiderocol, plazomicin, or combinations with polymyxins may be necessary for XDR infections. Overall, the treatment of MDR and XDR Enterobacterales requires a careful and individualized approach, with a focus on preventing the emergence of resistance and improving treatment outcomes.
From the FDA Drug Label
In the FETROJA treatment group, 45 (31%) patients had ESBL-producing bacterial isolates compared with 42 (28.6%) patients in the meropenem treatment group. All-cause mortality at Day 14 and Day 28 of patients with these ESBL-producing bacterial isolates was consistent with the overall results.
The drug label does not provide specific information regarding MDR and XDR Enterobacterales, but it does mention ESBL-producing bacterial isolates, which can be associated with multidrug resistance.
- Key points:
- 45 (31%) patients in the FETROJA treatment group had ESBL-producing bacterial isolates.
- 42 (28.6%) patients in the meropenem treatment group had ESBL-producing bacterial isolates.
- All-cause mortality at Day 14 and Day 28 of patients with these ESBL-producing bacterial isolates was consistent with the overall results 2.
From the Research
MDR and XDR Enterobacterales Findings
- The rate of susceptibility of MDR Enterobacterales strains to meropenem-vaborbactam was 99.1% 3.
- KPC was the most common carbapenemase (81.1%) in CRE isolates in the United States 3.
- The primary carbapenemase in the United States continues to be KPC, while MBL and OXA-48-like carbapenemases remain uncommon 3.
- Carbapenem-sparing strategies should be considered to avoid the selection of carbapenemase-producing Enterobacteriaceae 4.
- Combination therapy may be preferred over monotherapy for CRE, with the combination of a carbapenem-containing regimen with colistin or high-dose tigecycline or aminoglycoside 4.
Treatment Options
- Meropenem-vaborbactam is a valuable treatment option for Gram-negative infections caused by MDR organisms, including KPC-producing strains 3, 5.
- Ceftazidime-avibactam is a preferred treatment option for OXA-48-like-producing organisms 5.
- Ceftazidime-avibactam in combination with aztreonam is a viable option for MBL-producing Enterobacterales 5.
- Cefiderocol is an alternative for MBL-producing carbapenem-resistant Gram-negative bacteria 5.
Management of Infections
- Risk factors for harboring infections due to MDR-GN bacteria should be considered when choosing empirical treatment 6.
- An algorithm for the choice of empirical treatment when a MDR-GN pathogen is suspected should be established 6.
- Recommendations for first- and second-line treatment options for hospitalized patients with serious infections caused by MDR-GN pathogens should be based on the specific pathogen and infection type 6.