What is Carbapenem-resistant Enterobacteriaceae Infection?

CRE stands for Carbapenem-Resistant Enterobacterales. Enterobacterales are an order of germs, specifically bacteria. Many different types of Enterobacterales can develop resistance, including Klebsiella pneumoniae and Escherichia coli (E. coli). These bacteria can cause infections including pneumonia, bloodstream infections, urinary tract infections, wound infections, and meningitis.

In healthcare settings, CRE are transmitted from person to person, often via the hands of healthcare personnel or through contaminated medical equipment. Additionally, sink drains and toilets are increasingly recognized as an environmental reservoir and CRE transmission source.

To date, the best clinical management of CRE infections has not been established, because clinical trials have been never performed to establish the optimal treatment strategies. Challenges that are unique to these agents from the antibiotic stewardship point of view relate to their rapid streamlined development, which resulted in fewer clinical trials being conducted before regulatory approval.

Current practice has reverted to the use of ‘older’ antimicrobials, such as polymyxins, tigecycline, and fosfomycin, to combat invasive CRE infections. However, the recent approval of ceftazidime-avibactam has added another treatment option to the current antimicrobial armamentarium. Resistance among the ‘older’ agents is still rare but has been reported.

Nonetheless, as newer agents with activity against carbapenem-resistant organisms become available for clinical use, approaches to treatment selection and optimization become important considerations. At present, numerous agents are under investigation as well as a combination therapy that looks promising in the treatment of CRE infections.

The increase in Market Size is a direct consequence of increasing incident population of CRE infection patients in the 7MM. For patients with CRE colonizing their digestive tract, taking antibiotics can increase the amount of CRE in the body and the chances of developing an infection or spreading CRE to other patients. Several antibiotics have been associated with getting CRE, including carbapenems, cephalosporins, fluoroquinolones, and vancomycin. In 2017, CRE caused an estimated 13,100 infections in hospitalized patients, and 1,100 estimated deaths in the United States.

In the prospective, multinational European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) study (2017), 37% of carbapenem-nonsusceptible K. pneumoniae and 19% of carbapenem-nonsusceptible E. coli were confirmed to possess a carbapenemase gene, with those encoding KPC (42%) and OXA-48 (38%) carbapenemases being found most frequently [62]. However, 29.3% (353/1203) of K. pneumoniae and 60.3% (117/194) of E. coli isolates were confirmed to also have other resistance mechanisms.

The occurrence of carbapenem resistance among Enterobacteriaceae is a major health challenge which reduce the antibiotics choices that use to treat the infections which cause by these bacteria.

The scientific community has focused its efforts on identifying new strategies for combating drug resistance by repositioning non-antibiotic drugs in the antimicrobial arsenal or reconceptualizing old antibiotics. One of the methodologies in the post-antibiotic era is the use of non-antibiotic drugs for the treatment of multidrug-resistant infections. The benefits are considerable; the details of these drugs’ pharmacokinetics and toxicity are already known, and therefore the drugs can be passed directly into phase 2 of clinical trials. However, the costly disadvantage of clinical trials and patent rights remains [16].

Several drugs administered either alone or in conjunction with classical antibiotics have been shown to be effective in removing resistance in CRE, such as antiretroviral compounds (Zidovudine), antifungals (Cyclopirox), anticancer compounds (Gallium, Mitotane, Tamoxifen), and antidepressants (Sertraline).

Regarding novel antibacterial drugs, they can be differentiated in two groups: newly approved antibiotics and molecules in development stages. The latest antibiotics approved and already being used to treat CRE infections are ceftazidime/avibactam, meropenem/vaborbactam, plazomicin and eravacycline. Ceftazidime/avibactam (Allergan) is a novel ß-lactam/ß-lactamase inhibitor combination. The novelty of this combination relies on avibactam, which is a synthetic non-ß-lactam ß-lactamase inhibitor active against ß-lactamases from Ambler classes A, C and D.

Similarly, meropenem/vaborbactam (Melinta) is also a new ß-lactam/ß-lactamase inhibitor consisting of a carbapenem and a novel boron-containing serine-ß-lactamase inhibitor that potentiates the activity of meropenem. This combination inhibits Ambler classes A and C serine carbapenemases. Plazomicin (Achaogen) is a next-generation semisynthetic aminoglycoside with activity against bacteria producing aminoglycoside-modifying enzymes. Lastly, eravacycline (Tetraphase) is a synthetic fluorocycline with broad-spectrum antimicrobial activity against Gram-positive, Gram-negative and anaerobic bacteria, regardless of resistance to other antibiotic classes.

In addition to these already approved drugs, there are six molecules in early developmental stages: SPR206 (SperoTherapeutics), zidebactam (Wockhardt), nacubactam (Fedora Pharmaceuticals) and VNRX 5133 (VenatoRx Pharmaceuticals). The future development of new modalities in CRE Infection treatment appears promising during the forecast period [2021–2030].

Several approved therapies drive the current therapeutic landscape of CRE infection in the US. The market for CRE infection is estimated to increase by 2030. The major reason for market upsurge is the launch of the most anticipated therapies, which are considered as a threat to the current market.

Improvement in the diagnosis methodologies, rising awareness of the diseases, incremental healthcare spending across the world, and estimated launch of emerging therapies is expected to change the dynamics of the market.

Companies across the globe are thoroughly working toward the development of new treatment therapies for CRE infection. Some of the key players include Urovant Sciences, Taiho Pharmaceutical, Taris Bio, Recordati and Dong-A ST are involved in developing therapies for Carbapenem-Resistant Enterobacteriaceae (CRE) Infection.

Original Source:-  Carbapenem-resistant Enterobacteriaceae Infection Market Research Report