[Newsmp]

Amid growing voices warning about the era of ‘antibiotic uselessness’ due to relentless evolution and rapid spread of resistance, the multidrug-resistant antifungal antibiotic Zerbaxa (Ceftolozane/Tazobactam) recently received reimbursement.

It is expected that Zerbaxa will slow the increase of resistant bacteria, which is getting faster while providing new treatment opportunities to patients with resistant bacteria.

In addition, it is interesting to see if Zerbaxa’s reimbursement will affect the movement of other antibiotics that are hesitant to enter Korea.

Although the pace of antibiotic development has been getting shorter and shorter, there are concerns among infectious disease experts recently that no antibiotics will work soon, that is, the same condition as before the advent the penicillin.

Accordingly, academia is proposing a two-track strategy to prevent misuse of antibiotics to prevent new resistance, while developing and introducing new drugs that can respond to the current resistant bacteria.

However, there are few antibiotics that have emerged in the last 10 years. This is because clinical research itself is difficult to secure infected patients who are subject to antibiotics.

Since it is not easy to prove its superiority, it is strenuous to be recognized for its value through drug price even if it is developed at a huge cost.

In particular, Korea is known to have a high antibiotic resistance rate, but due to the rigid drug price system, the introduction of new antibiotics has rarely made, prompting experts to call for improved accessibility.

Among the new antibiotics, Zerbaxa, the only antibiotic approved by the Ministry of Food and Drug Safety, received reimbursement earlier in October after more than five years of hardship.

Zerbaxa demonstrated noninferiority to meropenem in hospital-acquired bacterial pneumonia and intrabdominal infections and levofloxacin in the treatment of complicated urinary-tract infections during major clinical trials.

Based on these research findings, Zerbaxa applied for health insurance registration in 2018 and followed the related procedures but failed to overcome the limitations of economic feasibility.

It was virtually impossible to get recognition for the value of new antibiotics through economic evaluation based on research on noninferiority to existing antibiotics.

Accordingly, a public opinion was created around experts to improve access to new antibiotics, and the government came up with a plan to enhance the accessibility of adding antibiotics to the exemption from economic evaluation when considering the growing risk of antibiotic resistance.

Since then, a new reimbursement standard was established through the drug price negotiation process, and as of Oct. 1, benefits have been applied to cases where carbapenems antibiotics have failed or multidrug-resistant Pseudomonas aeruginosa has been proven in the treatment of complicated urinary tract infection, hospital-acquired bacterial pneumonia, and intrabdominal infection.

In this regard, MSD Korea held a press conference at the Koreana Hotel in Jung-gu, Seoul on Oct. 27 to commemorate the registration of Zerbaxa.

“Antibiotic resistance is one of the most serious health problems in the world, and notably, Korea is also suffering greatly from antibiotic resistance,” said Professor Choo Eun-joo of the department of infectious diseases at Soonchunhyang University Bucheon Hospital.

“In the case of Acinetobacter, more than 80% are resistant to carbapenem, the last available antibiotic. Even in the early 2000s, carbapenem resistance was rarely considered, but in just over 8 years, it has greatly increased to more than 80%.”

Furthermore, Professor Choo pointed out two major problems in Korea regarding antibiotic resistance, excessive use of antibiotics, and few available antibiotics.

“In order to reduce antibiotic resistance, it is helpful to use even a little less antibiotic,” she pointed out. “However, if you look at the patients, it is not easy to judge the need for antibiotics, so they tend to use a little more antibiotics.”

“There should be treatable drugs when infected with resistant bacteria, but until recently, there have been few drugs that can be used for carbapenem resistance,” Choo said. “For this reason, we were mainly using colistin, which is not recommended by overseas guidelines.”

Colistin is a drug developed in 1980 that causes renal toxicity and is rarely used, but rather many susceptible patients have been using it as a last resort.

“If you use colistin, renal toxicity occurs in more than 30%, and if renal toxicity occurs, the mortality rate of patients increases rapidly,” Choo added. “So, it is not recommended by overseas guidelines such as the United States, but in Korea, we only use this medicine in Korea, since there is no other drug to replace.”

“With the efforts of doctors, Korea’s treatment performance is not lower than that of foreign countries, but there is a limit to the weapon itself,” she said. “As a result, the treatment performance for resistant bacteria is lower than in other countries.”

She further stressed, “There should be an appropriate weapon, but there is no drug recommended (in the guideline). We need new drugs to come in quickly.”

Zerbaxa’s reimbursement allowed us to take a breather when the introduction of new antibiotics was urgent.

It is evaluated that Zerbaxa will prevent an increase in resistance on the one hand and provide new opportunities for patients with resistant bacteria infection who had to rely on colistin alone.

“Zerbaxa showed a high susceptibility of 97.1% to Pseudomonas aeruginosa to Korean critical care patients who were hospitalized for lower respiratory tract infections,” Choo said. “Moreover, the carbapenem antibiotics meropenem and piperacillin/tazobactam-resistant Pseudomonas aeruginosa showed a high susceptibility of over 90%, so it will be an effective treatment option for patients suffering from multidrug-resistant Pseudomonas aeruginosa.”

“Ordinary gram-negative bacteria such as P. aeruginosa develops resistant bacteria if carbapenem is used continuously. Using Zerbaxa rather than carbapenem will help suppress the expression of resistant bacteria.”

“In multidrug-resistant P. aeruginosa, the effect of carbapenem is low, but it is found in about 19% of nosocomial pneumonia patients,” Choo added. “We have used colistin because there has been no medicine, but Zerbaxa can prevent kidney function worsening, and we are looking forward to it because of its good clinical effect.”

Furthermore, Choo hoped that Zerbaxa’s registration would lead to the introduction of other new antibiotics.

However, she emphasized that Zerbaxa should not be used excessively like broad-spectrum antibiotics. She believes that good antibiotics should be saved to use for a long time.

“In the past, critical care patients were forced to use broad-spectrum antibiotics for fear of getting worse while looking for antibiotics suitable for patients, but recently, we are trying not to use broad-spectrum antibiotics as much as possible,” she gave an example. “Even if broad-spectrum antibiotics are used in cases where judgment cannot be made, they are recommended to be used as short as possible and replaced with appropriate antibiotics.”

“The right use of antibiotics is the way to produce fewer resistant bacteria and save the next treatment,” Choo added.

Meanwhile, MSD Korea showed pride in the legacy of the antibiotic field leading to Zerbaxa from the first antibiotic, penicillin, during World War II.

Kim Yo-han, managing director of the MSD's medical department, said, “MSD has been focusing on antibiotic research and development for decades since the commercialization of penicillin in 1942 and saved countless lives in World War II.

“As the demand for antibiotic resistance is increasing, the development and introduction of new antibiotics require cooperation from medical staff and health authorities,” Kim added. “Zerbaxa’s insurance benefit was possible because of the efforts of the medical staff and health authorities who sympathized with the need for new drugs.”

“Through continuous R&D, we will try to solve the absence of new antibiotics and increase access to antibiotics,” he said.

“We are happy to mark a new milestone in MSD’s history of leading the development of treatments and vaccines against infectious diseases,” said, Kim Hyun, business unit director of the MSD's hospital specialty franchise. “MSD will continue to make efforts to contribute to eradicating antibiotic resistance as an important partner in the health care industry.”