What are the characteristics of carbapenemase-producing organisms, including Klebsiella pneumoniae carbapenemase (KPC), Oxacillinase-48 (OXA-48), New Delhi metallo-beta-lactamase (NDM), Verona integron-encoded metallo-beta-lactamase (VIM), and Imipenemase (IMP)?

From the Guidelines

For patients with infections caused by KPC-producing carbapenem-resistant Enterobacterales (CRE), the first-line treatment options should be novel β-lactam agents such as ceftazidime/avibactam and meropenem/vaborbactam. These enzymes, including KPC, OXA-48, NDM, VIM, and IMP, are types of carbapenemases that make bacteria resistant to multiple antibiotics, posing a significant concern in treating serious infections [ 1 ]. Each enzyme has distinct characteristics, with KPC commonly found in Enterobacteriaceae, OXA-48 in Klebsiella and E. coli, NDM widespread globally, and VIM and IMP often found in Pseudomonas and Acinetobacter species.

Treatment Options

• For KPC-producing CRE infections, ceftazidime/avibactam and meropenem/vaborbactam are strongly recommended as first-line treatments due to their efficacy and safety profiles [ 1 ].
• Imipenem/relebactam and cefiderocol may also be considered as alternative options, although the evidence for their use is less strong [ 1 ].
• For metallo-β-lactamase (MBL)-producing CRE infections, such as those caused by NDM, VIM, or IMP, the combination of ceftazidime/avibactam plus aztreonam is preferred, with cefiderocol being a conditional alternative [ 1 ].

Rationale

The recommendations are based on the latest evidence from observational studies and clinical trials, which highlight the benefits of novel β-lactam agents over traditional antibiotic regimens in terms of clinical efficacy and safety [ 1 ]. The choice of treatment should consider the specific enzyme, local epidemiology, and susceptibility testing to ensure effective treatment and prevent the spread of these highly resistant organisms in healthcare settings. Rapid identification of these resistance mechanisms is crucial, as conventional antibiotic regimens will likely fail [ 1 ].

From the FDA Drug Label

VABOMERE demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: KPC, SME, TEM, SHV, CTX-M, CMY, and ACT. VABOMERE is not active against bacteria that produce metallo-beta lactamases or oxacillinases with carbapenase activity

• KPC: VABOMERE has in vitro activity against KPC-producing Enterobacteriaceae.
• OXA-48: VABOMERE is not active against bacteria that produce oxacillinases with carbapenemase activity, which includes OXA-48.
• NDM: VABOMERE is not active against bacteria that produce metallo-beta lactamases, which includes NDM.
• VIM: VABOMERE is not active against bacteria that produce metallo-beta lactamases, which includes VIM.
• IMP: VABOMERE is not active against bacteria that produce metallo-beta lactamases, which includes IMP. 2

From the Research

Carbapenemase-Producing Enterobacterales

• KPC, OXA-48, NDM, VIM, and IMP are types of carbapenemases that have been identified in Enterobacterales, which are a group of Gram-negative bacteria 3.
• These enzymes confer resistance to carbapenem antibiotics, which are often considered the last line of defense against bacterial infections 3.

Epidemiology of Carbapenemase Resistance

• The global emergence of carbapenemase-producing bacteria is a significant public health concern, with reports of these bacteria in various parts of the world 3.
• KPC, VIM, OXA-48, NDM, and IMP are among the most prevalent types of carbapenemases, with KPC being the most common in some regions 4.
• The spread of carbapenemase-producing bacteria is often facilitated by horizontal gene transfer, which allows the bacteria to share resistance genes with other bacteria 3.

Detection and Treatment of Carbapenemase-Producing Bacteria

• Rapid detection of carbapenemase-producing bacteria is crucial for effective treatment, with methods such as multiplex immunochromatographic assays available for detection 5.
• Treatment options for carbapenemase-producing bacteria are limited, but ceftazidime-avibactam has shown promise in treating OXA-48-producing Klebsiella pneumoniae 6.
• Cefepime-enmetazobactam is a new β-lactam/β-lactamase inhibitor combination that has shown activity against carbapenem-resistant Enterobacterales, including OXA-48 producers 7.

Resistance Patterns

• OXA-48 producers have shown high susceptibility to cefepime-enmetazobactam, similar to ceftazidime-avibactam 7.
• KPC producers have shown resistance to ceftazidime-avibactam and cefiderocol, with higher MICs observed in strains with mutated blaKPC 4.
• NDM, VIM, and IMP producers have also been reported, with varying levels of resistance to different antibiotics 3.