From the Research
For treating NDM and CTX-positive E. coli infections, combination therapy with meropenem-vaborbactam (2g/2g IV every 8 hours) is recommended as the optimal regimen, as it has been shown to be effective in treating carbapenem-resistant Enterobacteriaceae infections, including those with NDM and CTX-M resistance mechanisms, as demonstrated in the TANGO II randomized clinical trial 1. The choice of meropenem-vaborbactam is based on its ability to overcome the resistance mechanisms of NDM and CTX-M, which are carbapenemase and extended-spectrum beta-lactamase enzymes, respectively.
- The TANGO II trial showed that meropenem-vaborbactam monotherapy was associated with increased clinical cure, decreased mortality, and reduced nephrotoxicity compared to best available therapy (BAT) in patients with carbapenem-resistant Enterobacteriaceae infections 1.
- Alternative options, such as ceftazidime-avibactam (2.5g IV every 8 hours) plus aztreonam (2g IV every 6-8 hours), or combinations of polymyxins (colistin 9 million units loading dose followed by 4.5 million units every 12 hours) with tigecycline (100mg loading dose followed by 50mg every 12 hours) and/or high-dose carbapenems, may also be considered, but the evidence supporting their use is not as strong as that for meropenem-vaborbactam.
- Treatment duration is typically 7-14 days, depending on the infection site and clinical response, and should be guided by antimicrobial susceptibility testing whenever possible.
- Infectious disease consultation is strongly recommended due to the complexity of managing these multidrug-resistant infections.
- Recent studies have also explored the use of novel metallo-β-lactamase inhibitors, such as dexrazoxane, embelin, candesartan cilexetil, and nordihydroguaiaretic acid, which have shown promise in restoring the susceptibility of carbapenems to NDM-1-harbouring bacteria 2. However, more research is needed to fully evaluate their potential as therapeutic options.