From the Guidelines

Ceftazidime/avibactam and meropenem/vaborbactam are the most effective antibiotics against KPC-2 producing Gram-negative rods.

Ceftazidime/avibactam: This combination is recommended as a first-line treatment option for infections caused by KPC-producing carbapenem-resistant Enterobacterales (CRE) due to its high clinical cure rate and low risk of nephrotoxicity compared to other drugs 1.
Meropenem/vaborbactam: This combination is also recommended as a first-line treatment option for CRE infections, with a higher clinical cure rate, decreased mortality, and reduced nephrotoxicity compared to the best available therapy (BAT) 1.

Imipenem/relebactam: This combination may be considered as a potential alternative for the treatment of infections involving KPC-producing CRE, although clinical studies of its efficacy in these patients are limited 1.
Cefiderocol: This antibiotic may also be considered as a potential alternative, but clinical studies of its efficacy in patients with KPC-producing CRE infections are not available 1.

The use of combination therapy, including two or more in vitro active antibiotics, may be beneficial in treating KPC-producing K. pneumoniae infections, especially in patients with severe disease or septic shock 1.
However, the evidence for specific antibiotic combinations is limited, and no firm conclusions can be drawn on which companion drug should be preferred when prescribing polymyxin and tigecycline 1.

The emergence of ceftazidime/avibactam resistance in carbapenemase-producing K. pneumoniae has been reported, and the combination of ceftazidime/avibactam with a carbapenem or colistin may be considered in these cases 1.
Ceftazidime/avibactam has a lower risk of nephrotoxicity compared to colistin, making it a safer option for patients with KPC-producing CRE infections 1.

From the Research

The combination of imipenem and clavulanic acid has been shown to be effective against KPC-2 producing Klebsiella pneumoniae, with synergies observed in 80% of strains 2.
Other combinations, such as meropenem and clavulanic acid, meropenem and ceftazidime, and meropenem and imipenem, have also demonstrated synergistic antibacterial activity, although to a lesser extent 2.
Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-cilastatin-relebactam are novel agents that have been approved and have shown favorable outcomes against KPC-producing K. pneumoniae infections 3.
Fosfomycin and colistin have also demonstrated good activity against multidrug-resistant K. pneumoniae complex strains, including those producing KPC-2 4.
Ceftazidime/avibactam has been shown to be effective against KPC-Kp, with a susceptibility rate of 97.14%, and combination therapy with amikacin, colistin, and tigecycline has been recommended 5.

The emergence of resistance to carbapenemase-producing Gram-negative rods is a significant concern, and the development of new therapeutic strategies is crucial 3.
The increased expression and amplification of blaKPC-2 has been shown to contribute to resistance to ceftazidime/avibactam in KPC-2 producing K. pneumoniae strains 6.
The use of combination therapy, such as ceftazidime/avibactam with amikacin, colistin, and tigecycline, may help to overcome resistance mechanisms and improve treatment outcomes 5.

Novel β-lactam/β-lactamase inhibitors, such as aztreonam-avibactam, cefepime-zidebactam, and meropenem-nacubactam, are in development and have shown promising activity against KPC-2 producing K. pneumoniae strains 3.
Cefiderocol, a novel siderophore cephalosporin, has also demonstrated activity against KPC-2 producing K. pneumoniae strains 3.
The development of new therapeutic strategies, including combination therapy and novel antimicrobial agents, is crucial to combat the increasing resistance to carbapenemase-producing Gram-negative rods 3, 4, 5.