The discovery of antibiotics is one of the greatest inventions in human history, saving countless lives and significantly increasing human life expectancy. However, as bacterial resistance to antibiotics continues to emerge, bacterial infections are more and more challenging and effective treatments are gradually becoming unavailable.
Bacterial resistance has become a global problem. On April 30, 2014, the World Health Organization released a report stating that antibiotic-resistant bacteria are spreading across the globe. The 2014 Review on Antimicrobial Resistance, published by Jim O'Neill in the UK, estimated that if no action is taken, the number of deaths from bacterial resistance could exceed 10 million cases per year globally by 2050, with one million deaths per year in China. In 2016, the Chinese government launched the National Action Plan to Combat Bacterial Resistance, making the approval of new drugs against drug-resistant bacteria a primary goal to be accomplished by 2020. The U.S. Department of Health and Human Services (HHS) released the second edition of the National Action Plan for Combating Antibiotic-Resistant Bacteria in 2020, with implementation including advancing the development of more than 10 innovative and valuable treatments for bacterial infections by 2022 and achieving the goal of having more than three new antimicrobial drugs in the NDA filing stage by 2025.
The growing problem of multidrug-resistant (MDR) Gram-positive bacteria, including vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and methicillin-resistant coagulase-negative staphylococci (MRCNS), is the reason why the search for effective treatment of multidrug-resistant Gram-positive bacteria is one of the hottest topics in the research of anti-infective drugs today. MRSA is one of the most clinically common drug-resistant bacteria, which can lead to life-threatening and serious infections. According to 2008 epidemiological statistics, the number of deaths due to MRSA infection in the United States each year is equivalent to the number of patients with AIDS, tuberculosis, and viral hepatitis combined. A 2018 European Centre for Disease Prevention and Control study also showed that MRSA is the second most infectious and deadly drug-resistant bacterium in Europe. China Antimicrobial Surveillance Network (CHINET) reveals that the clinical detection rate of MRSA in China has been maintained at more than 30% in recent years, and the detection rate in tertiary hospitals can be up to more than 60%. The Expert Consensus on Prevention and Treatment of Methicillin-resistant Staphylococcus aureus Infection issued by the Chinese Medical Association mentions that the prevalence of MRSA infection is a serious clinical problem and public health threat, and China is a region with a relatively high prevalence of MRSA infection. The mortality rate of MRSA-infected patients is 64%, higher than that of non-drug-resistant bacterial infections, and is classified as a highly serious drug-resistant bacteria by the World Health Organization.
Multidrug-resistant Gram-negative bacteria (MDR-GNB) are mainly classified as carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB). MDR-GNB can cause infections in the lung (pneumonia), urinary tract, skin, wounds, blood, etc. The mortality rate of infections by MDR-GNB is significantly higher than that of the same infections caused by non-resistant Gram-negative bacteria.
Reports from CHINET reveal a significant upward trend in CRE drug resistance in China during the period of 2015 to 2019: the drug resistance rate of Klebsiella pneumoniae increased from 31.5% to 52.1%, while that of CRPA fluctuated within 20%~35%, and CRAB was 65%~80%. MDR-GNB infection has therefore become a serious threat to global public health.
In 2017, the World Health Organization released a list of 12 multidrug-resistant bacteria and made a global call for the development of new, clinically urgent antibiotics to address the global public health threat posed by the "superbugs".