From the Guidelines
The treatment of choice for New Delhi metallo-beta-lactamase (NDM) producing Carbapenem-Resistant Enterobacteriaceae (CRE) infections is ceftazidime/avibactam plus aztreonam, as it has shown in vitro synergy and significantly lower 30-day mortality rates compared to other antibiotics active in vitro 1. When considering treatment options for NDM-producing CRE infections, it is essential to prioritize combination therapy due to the limited efficacy of single agents against these highly resistant organisms.
- The combination of ceftazidime/avibactam plus aztreonam is preferred due to its strong recommendation and moderate certainty of evidence, as stated in the guideline endorsed by the Italian Society of Infection and Tropical Diseases (SIMIT) and other reputable organizations 1.
- Cefiderocol may also be considered as an alternative option, although its recommendation is conditional and based on lower certainty of evidence 1.
- It is crucial to note that the treatment of NDM-producing CRE infections requires careful consideration of the patient's clinical condition, infection site, and antimicrobial susceptibility testing results to guide therapy selection.
- Regular monitoring of renal function is essential when using nephrotoxic agents, and infectious disease consultation is strongly recommended to guide therapy.
- Source control through drainage of abscesses or removal of infected devices is also crucial when applicable.
- The development of efficient MBL inhibitors is ongoing, and cefiderocol appears to be a promising therapeutic option, but its use against MBLs requires further investigation due to concerns about high MIC values, risk of treatment-emergent resistance, and the role of combination therapy 1.
From the FDA Drug Label
Among Gram-negative uropathogens from both arms of Trial 2, genotypic testing identified certain ESBL groups (e.g., TEM-1, SHV-12, CTX-M-15, CTX-M-27, KPC-2, KPC-3, OXA-48) and AmpC beta-lactamases expected to be inhibited by avibactam in isolates from 273/281 (97. 2%) patients in the mMITT population.
The treatment for New Delhi metallo-beta-lactamase (NDM) producing Carbapenem-Resistant Enterobacteriaceae (CRE) is not directly addressed in the provided drug label. However, avibactam in combination with ceftazidime has been shown to be effective against certain ESBL groups and AmpC beta-lactamases.
- The drug label does mention KPC-2 and KPC-3, which are carbapenemases, but it does not specifically mention NDM.
- Therefore, no conclusion can be drawn about the effectiveness of avibactam against NDM-producing CRE based on this label 2.
From the Research
Treatment Options for NDM-Producing CRE
The treatment of New Delhi metallo-beta-lactamase (NDM) producing Carbapenem-Resistant Enterobacteriaceae (CRE) is challenging due to limited treatment options.
- Available treatment options include:
- Tigecycline, with 86.5% of isolates found to be susceptible 3
- Eravacycline, with 66.2% of isolates found to be susceptible 3
- Omadacycline, with 59.6% of isolates found to be susceptible 3
- Aztreonam, with 18.2% of isolates found to be susceptible 3
- Plazomicin, which exhibited moderate activity (77.0% susceptible) against metallo-β-lactamase producers 4
- Ceftazidime-avibactam, which retained high susceptibility (98.7%) against OXA-48-like producers 4
- Combination therapy may be preferred over monotherapy for CRE, with options including:
Considerations for Treatment
- The choice of treatment should be based on the susceptibility of the isolate, as well as the severity of the infection and the patient's underlying health conditions 6, 5
- Carbapenem-sparing strategies should be considered to avoid the selection of carbapenemase-producing Enterobacteriaceae 5
- Optimization of dosing regimens and combination therapy are additional treatment strategies being explored 7