From the Guidelines
NDM and OXA-48 are often co-located with other resistance genes, including ESBL genes (blaCTX-M, blaSHV, blaTEM), aminoglycoside resistance genes (rmtB, rmtC, armA), fluoroquinolone resistance genes (qnr variants), and plasmid-mediated colistin resistance genes (mcr), as reported in a recent study 1. These resistance mechanisms are frequently carried on mobile genetic elements that can harbor multiple resistance genes simultaneously, creating extensively drug-resistant or even pan-drug-resistant bacterial strains, severely limiting treatment options. The co-carriage of these resistance determinants occurs because resistance genes are often located on the same plasmids or mobile genetic elements, allowing for co-transfer between bacteria, as noted in a guideline endorsed by the Italian Society of Infection and Tropical Diseases 1. Some of the common genes of resistance that co-occur with NDM and OXA-48 include:
- ESBL genes (blaCTX-M, blaSHV, blaTEM)
- Aminoglycoside resistance genes (rmtB, rmtC, armA)
- Fluoroquinolone resistance genes (qnr variants)
- Plasmid-mediated colistin resistance genes (mcr) Understanding these co-resistance patterns is crucial for developing effective antimicrobial stewardship programs and designing appropriate combination therapies when treating infections caused by carbapenemase-producing organisms, as highlighted in a recent guideline for the diagnosis, treatment, prevention, and control of infections caused by carbapenem-resistant Gram-negative bacilli 1. The use of rapid testing strategies to identify specific carbapenemases, such as NDM and OXA-48, is strongly recommended to guide antibiotic therapy and improve patient outcomes 1. In addition, combination therapies, such as ceftazidime-avibactam plus aztreonam, have shown promising results in treating infections caused by NDM-producing and OXA-48-positive CRE isolates, with lower 30-day mortality rates and clinical treatment failure rates, as reported in a prospective study 1.
From the Research
Common Genes of Resistances NDM and OXA-48
- The genes responsible for NDM and OXA-48 resistances are blaNDM and blaOXA-48, respectively 2, 3, 4.
- These genes are often found in Klebsiella pneumoniae strains, which can exhibit pandrug resistance, making treatment challenging 2, 3.
- The co-occurrence of blaNDM and blaOXA-48 in K. pneumoniae strains has been reported, highlighting the need for effective treatment strategies 2, 4.
Treatment Strategies
- Ceftazidime-avibactam is considered a viable treatment option for OXA-48 producers, while colistin remains a second-line option 3.
- For NDM producers, ceftazidime-avibactam in combination with aztreonam or cefiderocol may be effective 3, 4.
- The synergistic combination of ceftazidime-avibactam and aztreonam has shown promise against OXA-48 + NDM K. pneumoniae strains 4.
- Other combination therapies, such as ceftazidime/avibactam plus colistin, tobramycin, or tigecycline, have also demonstrated effectiveness against OXA-48-producing Enterobacterales 5.
Resistance Mechanisms
- The resistance mechanisms of NDM and OXA-48 producers involve the production of carbapenemases, which can hydrolyze carbapenem antibiotics 6, 2.
- The spread of these resistance genes can occur through clonal expansion or horizontal gene transfer, highlighting the need for stringent infection control measures 2.